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Somatostatin analogues for pancreatic surgery

  1. Kurinchi Selvan Gurusamy*,
  2. Rahul Koti,
  3. Giuseppe Fusai,
  4. Brian R Davidson

Editorial Group: Cochrane Upper Gastrointestinal and Pancreatic Diseases Group

Published Online: 30 APR 2013

Assessed as up-to-date: 14 FEB 2013

DOI: 10.1002/14651858.CD008370.pub3


How to Cite

Gurusamy KS, Koti R, Fusai G, Davidson BR. Somatostatin analogues for pancreatic surgery. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD008370. DOI: 10.1002/14651858.CD008370.pub3.

Author Information

  1. Royal Free Campus, UCL Medical School, Department of Surgery, London, UK

*Kurinchi Selvan Gurusamy, Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital,, Rowland Hill Street, London, NW3 2PF, UK. kurinchi2k@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 APR 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 
Summary of findings for the main comparison. Somatostatin analogues for pancreatic surgery

Somatostatin analogues for pancreatic surgery

Patient or population: people with pancreatic surgery
Settings: secondary or tertiary care
Intervention: somatostatin analogues

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

Assumed riskCorresponding risk

ControlSomatostatin analogues

Perioperative mortality49 per 100040 per 1000
(28 to 57)
RR 0.8
(0.56 to 1.16)
2210
(18 studies)
⊕⊝⊝⊝
very low1,2,3

Treatment withdrawal8 per 100013 per 1000
(5 to 35)
RR 1.55
(0.56 to 4.33)
1220
(9 studies)
⊕⊝⊝⊝
very low1,2,3,4

Re-operation102 per 1000108 per 1000
(70 to 166)
RR 1.06
(0.69 to 1.63)
687
(7 studies)
⊕⊝⊝⊝
very low1,2,3,4,5

Anastomotic leak48 per 100039 per 1000
(25 to 61)
RR 0.81
(0.51 to 1.27)
1585
(9 studies)

Pancreatic fistula (clinically significant)151 per 1000104 per 1000
(46 to 191)
RR 0.69
(0.38 to 1.29)
292
(4 studies)
⊕⊝⊝⊝
very low1,2,3,4

Infected abdominal collections61 per 100056 per 1000
(40 to 80)
RR 0.93
(0.66 to 1.32)
1965
(13 studies)

Shock29 per 100029 per 1000
(14 to 63)
RR 1
(0.46 to 2.15)
812
(4 studies)

*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; RR: risk 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 Most trials were of high risk of bias.
2 Confidence intervals overlap 1 and 0.75 or 1.25.
3 A total of fewer than 300 events in the comparison.
4 Fewer than 10 trials were included for this outcome. So, there is a suspicion of selective outcome reporting, which can indicate publication bias.
5 There was moderate heterogeneity as indicated by I² of 30%, tau² of 0.27; and lack of overlapping of confidence intervals.

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of the condition

Pancreatic resection is performed to treat pancreatic diseases, including malignancy and chronic pancreatitis. The overall morbidity following pancreatic surgery varies between 30% and 60%, and the mortality rate is about 5% (Alexakis 2004; Gouma 2000; Sohn 2000). The major complication following pancreatic resection is postoperative pancreatic leak or fistula. Reviews have described an incidence of pancreatic leak or fistula of around 37% (Connor 2005). Various methods, such as pancreaticogastrostomy rather than pancreaticojejunostomy after pancreatic resections (McKay 2006) and the use of fibrin sealant (Ohwada 1998), have been suggested to decrease the incidence of pancreatic complications, but one of the most common approaches has been the use of somatostatin or its synthetic analogues. However, their use is controversial and some randomised clinical trials and systematic reviews recommend routine prophylactic somatostatin analogues in pancreatic resections (Buchler 1992; Connor 2005; Montorsi 1995) while others do not (Alghamdi 2007; Hesse 2005; Lange 1992).

 

Description of the intervention

Somatostatin or its analogues are administered prophylactically during pancreatic surgery.

 

How the intervention might work

Somatostatin and its analogues inhibit pancreatic exocrine secretions (Lembcke 1987). The theory is that by decreasing the volume of pancreatic secretion, the incidence of pancreatic leak or fistula could be decreased. Considering that pancreatic fistulas can be life-threatening (Bassi 2005), a decrease in clinically significant pancreatic fistula might decrease perioperative mortality, morbidity and postoperative hospital stay.

 

Why it is important to do this review

The use of somatostatin and its analogues during pancreatic surgery is controversial. They may potentially decrease morbidity and mortality following pancreatic surgery but it is also possible that they may have no therapeutic benefit and may be associated with negative outcomes.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We included only randomised controlled trials of parallel design, irrespective of blinding, sample size, publication status or language. We excluded quasi-randomised trials (see below) and other study designs.

 

Types of participants

People who were undergoing a pancreatic surgical procedure (pancreatic resection, pancreatic duct drainage procedures or cyst drainage procedures) for any pancreatic disease.

 

Types of interventions

Administration of perioperative somatostatin (or an analogue of this hormone, such as octreotide) versus a comparator of placebo or no intervention.

 

Types of outcome measures

 

Primary outcomes

  1. Postoperative mortality.
  2. Drug-related complications.
    1. Treatment withdrawal.
    2. Number with adverse effects due to treatment.
  3. Quality of life.

 

Secondary outcomes

  1. Postoperative complications.
    1. Re-operation.
    2. Anastomotic leak.
    3. Pancreatic fistula. Pancreatic fistula has been graded as A, B and C by consensus among surgeons (Bassi 2005). We included any pancreatic fistula; however it was defined by the authors, as one of the outcomes. We also included clinically significant pancreatic fistulas as another outcome. For this outcome, we included only trials in which data on grade B or C were available separately from grade A (not clinically significant).
    4. Postoperative pancreatitis.
    5. Sepsis.
    6. Renal failure.
    7. Bleeding.
    8. Abdominal collections.
    9. Infected abdominal collections.
    10. Delayed gastric emptying.
    11. Pulmonary complications.
    12. Shock.
    13. Number of complications.
    14. Number of people with any complications.
  2. Hospital stay.
    1. Total hospital stay.
    2. Intensive treatment unit (ITU) stay.

 

Search methods for identification of studies

 

Electronic searches

We searched:

  1. the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Controlled Trials Register (Appendix 1; Forman 2009);
  2. the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1) (Appendix 1);
  3. MEDLINE via PubMed (1987 to February 2013) (Appendix 2);
  4. EMBASE via OVID SP (1987 to February 2013) (Appendix 3) and
  5. Science Citation Index Expanded (Royle 2003) to February 2013 (Appendix 4).

 

Searching other resources

We also searched the references of the identified trials to identify further relevant trials.

 

Data collection and analysis

We followed the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), and the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Module (Forman 2009). We imputed the standard deviation from P values according to the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), and used the median for the meta-analysis when the mean was not available. If it was not possible to calculate the standard deviation from the P value or confidence intervals (CIs), we imputed the standard deviation as the highest standard deviation noted for that group under that outcome.

 

Selection of studies

KG and RK identified the trials for inclusion, independently of each other. We listed the excluded trials with reasons for exclusion.

 

Data extraction and management

KG and RK extracted the data for the review independently. In addition, we extracted the population characteristics (such as sex, age, proportion of pancreaticoduodenectomies, the disease aetiology) and the interventions used in each trial. We assessed the risk of bias of the trials independently, without masking of the trial names. We sought any unclear or missing information by contacting the authors of the individual trials. If there was any doubt whether the trials shared the same participants - completely or partially (by identifying common authors and centres) - we contacted the authors of the trials to ascertain whether the trial report had been duplicated. We resolved any differences in opinion through discussion.

 

Assessment of risk of bias in included studies

According to empirical evidence (Kjaergard 2001; Moher 1998; Schulz 1995; Wood 2008) we assessed the risk of bias of the trials based on sequence generation, allocation concealment, blinding (of participants, personnel and outcome assessors), incomplete outcome data, selective outcome reporting and other sources of bias. Quality components were based on the Cochrane Handbook for Systematic Reviews of Interventions (Gurusamy 2009; Higgins 2011).

 

Sequence generation

  • Low risk of bias (the method used is either adequate (e.g. computer-generated random numbers, table of random numbers) or unlikely to introduce confounding).
  • Uncertain risk of bias (there is insufficient information to assess whether the method used is likely to introduce confounding).
  • High risk of bias (the method used (e.g. quasi-randomised trials) is improper and likely to introduce confounding).

 

Allocation concealment

  • Low risk of bias (the method used (e.g. central allocation) is unlikely to induce bias in the final observed effect).
  • Uncertain risk of bias (there is insufficient information to assess whether the method used is likely to induce bias in the estimate of effect).
  • High risk of bias (the method used (e.g. open random allocation schedule) is likely to induce bias in the final observed effect).

 

Blinding of participants, personnel and outcome assessors

  • Low risk of bias (blinding was performed adequately, or the outcome measurement is not likely to be influenced by lack of blinding).
  • Uncertain risk of bias (there is insufficient information to assess whether the type of blinding used is likely to induce bias in the estimate of effect).
  • High risk of bias (no blinding or incomplete blinding, and the outcome or the outcome measurement is likely to be influenced by lack of blinding).

 

Incomplete outcome data

  • Low risk of bias (the underlying reasons for missing data are unlikely to make treatment effects depart from plausible values, or proper methods have been employed to handle missing data).
  • Uncertain risk of bias (there is insufficient information to assess whether the missing data mechanism in combination with the method used to handle missing data is likely to induce bias in the estimate of effect).
  • High risk of bias (the crude estimate of effects (e.g. complete case estimate) will clearly be biased due to the underlying reasons for data being missing, and the methods used to handle missing data are unsatisfactory).

 

Selective outcome reporting

  • Low risk of bias (the trial protocol is available and all of the trial's pre-specified outcomes that are of interest in the review have been reported or similar).
  • Uncertain risk of bias (there is insufficient information to assess whether the magnitude and direction of the observed effect is related to selective outcome reporting).
  • High risk of bias (not all of the trial's pre-specified primary outcomes have been reported or similar).

 

Source of funding bias

  • Low risk of bias (the trial's source(s) of funding did not come from any parties that might have a conflicting interest (e.g. pharmaceutical company).
  • Uncertain risk of bias (the source of funding was not clear).
  • High risk of bias (the trial was funded by a pharmaceutical company).

We considered trials that were classified as low risk of bias in all the above domains as low bias-risk trials.

 

Measures of treatment effect

For dichotomous outcomes, we calculated the risk ratio (RR) with 95% CI. For continuous outcomes we calculated mean difference (MD) or standardised mean difference (SMD) with 95% CI. We also calculated the risk difference (RD) with 95% CI but planned to report the results if they were different from the RR. We identified no such results.

 

Unit of analysis issues

All the trials included in this review were simple parallel group design and the unit of analysis was each person recruited into the trial.

 

Dealing with missing data

We performed the analysis on an 'intention-to-treat' basis (Newell 1992), whenever possible. Otherwise, we adopted the 'available case analysis'.

 

Assessment of heterogeneity

We explored heterogeneity by Chi² test with significance set at a P value 0.10, and the quantity of heterogeneity was measured by the I² statistic (Higgins 2002). An I² statistic of > 30% was considered statistically significant heterogeneity.

 

Assessment of reporting biases

We used a funnel plot to explore bias (Egger 1997; Macaskill 2001). We used asymmetry in a funnel plot of trial size against treatment effect to assess bias. We performed the linear regression approach described by Egger et al to determine the funnel plot asymmetry (Egger 1997).

 

Data synthesis

We performed the meta-analyses according to the recommendations of The Cochrane Collaboration (Higgins 2011). We used the software package Review Manager (RevMan) provided by The Cochrane Collaboration (RevMan 2011). We used a random-effects model (DerSimonian 1986) and a fixed-effect model (DeMets 1987). In case of discrepancy between the two models, we reported both results; otherwise we have reported only the results from the fixed-effect model.

 

Subgroup analysis and investigation of heterogeneity

We planned the following subgroup analyses for the primary outcomes.

  • Trials with low risk of bias versus those with high risk of bias.
  • Different interventions (somatostatin and octreotide).
  • Different aetiologies (malignancy and chronic pancreatitis).
  • Different procedures (pancreatoduodenectomy, distal pancreatectomy and pancreatic drainage procedures).
  • Different methods of management of pancreatic stump (pancreatogastrostomy and pancreatojejunostomy).

We performed the Chi² test for subgroup differences, setting a P value of 0.05 to identify any differences.

 

Sensitivity analysis

In the event that we found 'zero-event' trials for statistically significant outcomes, we intended to perform a sensitivity analysis with and without empirical continuity correction factors, as suggested by Sweeting et al (Sweeting 2004). However, we did not find any such outcomes.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Results of the search

We identified 1352 references through the electronic searches of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Controlled Trials Register and CENTRAL in The Cochrane Library (N = 77), MEDLINE (N = 567), EMBASE (N = 356) and Science Citation Index Expanded (N = 352). We have shown the flow of references in Figure 1. We excluded 315 duplicates and 979 clearly irrelevant references through reading abstracts. We retrieved 58 references for further assessment. No references were identified through scanning reference lists of the identified randomised trials. Of the 58 references, we excluded 21 for the reasons listed in the 'Characteristics of excluded studies' table. Four of the 21 references corresponded to two studies (Lowy 1997; Wang 2012), hence the inclusion of only 19 studies in the table. Of the remaining 37 references, 16 were multiple reports resulting in 21 randomised trials that fulfilled the inclusion criteria.

 FigureFigure 1. Study flow diagram.

 

Included studies

All the 21 trials were completed trials and 19 of these provided data for the analyses. Details of the trials are shown in the 'Characteristics of included studies' table. Overall, the 21 trials included 2348 participants. Three hundred and four participants were involved in seven trials comparing somatostatin versus control (Beguiristain 1995; Buccoliero 1992; Gouillat 2001; Katsourakis 2010; Klempa 1991; Shan 2005; Tulassay 1993) and 1702 participants were involved in 13 trials comparing octreotide versus control (Briceño Delgado 1998; Buchler 1992; Fernandez-Cruz 2012; Friess 1995; Hesse 2005; Kollmar 2008; Kurumboor 2012; Lange 1992; Matheus 2009; Montorsi 1995; Pederzoli 1994; Suc 2004; Yeo 2000). The remaining participants were involved in one trial comparing vapreotide versus control (Sarr 2003). Overall 1608 participants underwent pancreatoduodenectomy, 1196 participants had malignancy and 596 participants had chronic pancreatitis in the trials that reported these characteristics. The mean age of the individuals in the trials varied between 43 and 65 years. The mean proportion of females varied between 15% and 48%. There was no difference in the characteristics of participants in the intervention group or control in any of the trials that reported these baseline characteristics.

 

Excluded studies

The reasons for exclusion of studies are listed in the 'Characteristics of excluded studies' table. None of these studies were randomised clinical trials.

 

Risk of bias in included studies

The risk of bias is summarised in the 'Risk of bias' graph (Figure 2) and 'Risk of bias' summary (Figure 3). We classified two trials as low risk of bias (Gouillat 2001; Kollmar 2008).

 FigureFigure 2. Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
 FigureFigure 3. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

 

Allocation

The generation of allocation sequence was adequate in five trials (Gouillat 2001; Hesse 2005; Kollmar 2008; Shan 2005; Suc 2004) and allocation concealment was adequate in three trials (Gouillat 2001; Kollmar 2008; Suc 2004).

 

Blinding

Blinding was adequate in 10 trials (Buchler 1992; Friess 1995; Gouillat 2001; Kollmar 2008; Lange 1992; Montorsi 1995; Pederzoli 1994; Sarr 2003; Tulassay 1993; Yeo 2000).

 

Incomplete outcome data

Five trials were free from bias due to incomplete outcome data (Gouillat 2001; Hesse 2005; Katsourakis 2010; Kollmar 2008; Suc 2004). In eight trials there were post-randomisation drop-outs (Buchler 1992; Friess 1995; Klempa 1991; Montorsi 1995; Pederzoli 1994; Sarr 2003; Shan 2005; Yeo 2000) resulting in a high risk of bias from incomplete outcome data. In these trials with post-randomisation drop-outs, a significant proportion of participants underwent pancreatic surgery. There was no information available on these participants. Thus, it was not possible even to perform an available case analysis and we had to perform a per protocol analysis. In the remaining trials, it was not clear whether there were post-randomisation drop-outs (Beguiristain 1995; Briceño Delgado 1998; Buccoliero 1992; Katsourakis 2010; Matheus 2009; Lange 1992; Tulassay 1993).

 

Selective reporting

Nine trials were free from bias due to selective reporting (Briceño Delgado 1998; Buchler 1992; Friess 1995; Gouillat 2001; Kollmar 2008; Montorsi 1995; Pederzoli 1994; Suc 2004; Yeo 2000).

 

Other potential sources of bias

Three trials were free from other potential sources of bias (Kollmar 2008; Sarr 2003; Yeo 2000).

 

Effects of interventions

See:  Summary of findings for the main comparison Somatostatin analogues for pancreatic surgery

 

Somatostatin analogues versus none (Analysis 1.1 to Analysis 1.20)

 

Primary outcomes

 
Mortality

There was no difference in the perioperative mortality between the two groups (RR 0.80; 95% CI 0.56 to 1.16).

 
Drug-related complications

There was no significant difference in treatment withdrawal (RR 1.55; 95% CI 0.56 to 4.33) between the groups. The number of people with adverse effects due to treatment was significantly higher in the somatostatin analogues group than the control group by the fixed-effect model (RR 1.36; 95% CI 1.02 to 1.82) but not by the random-effects model (RR 2.09; 95% CI 0.83 to 5.24).

 
Quality of life

This was not reported in any of the trials.

 

Secondary outcomes

 
Postoperative complications

There were statistically significant lower incidences of pancreatic fistula (RR 0.66; 95% CI 0.55 to 0.79) and sepsis (RR 0.42; 95% CI 0.21 to 0.85) in the somatostatin analogues group than in the control group. There was a statistically significant lower number of complications (RR 0.70; 95% CI 0.60 to 0.82) and lower number of participants with any complication (RR 0.70; 95% CI 0.61 to 0.80) in the somatostatin analogues group than the control group. There was no significant difference in the re-operation rates (RR 1.06; 95% CI 0.69 to 1.63), incidence of anastomotic leak (RR 0.81; 95% CI 0.51 to 1.27), clinically significant pancreatic fistulas (RR 0.69; 95% CI 0.38 to 1.28), postoperative pancreatitis (RR 0.63; 95% CI 0.32 to 1.22), renal failure (RR 0.67; 95% CI 0.25 to 1.77), bleeding (RR 1.00; 95% CI 0.70 to 1.44), abdominal collections (RR 0.76; 95% CI 0.56 to 1.05), infected abdominal collections (RR 0.93; 95% CI 0.66 to 1.32), delayed gastric emptying (RR 0.79; 95% CI 0.51 to 1.23), pulmonary complications (RR 0.89; 95% CI 0.57 to 1.39) or shock (RR 1.00; 95% CI 0.46 to 2.15) between the groups.

 
Hospital stay

There was no difference in the duration of hospital stay (MD -1.29 days; 95% CI -2.60 to 0.03) or in the duration of ITU stay (MD 0.90 days; 95% CI -1.76 to 3.56) between the groups.

 

Subgroup analysis

We performed the following planned subgroup analyses.

  • Different interventions (somatostatin and octreotide).
  • Different aetiologies (malignancy and chronic pancreatitis).
  • Different procedures (pancreatoduodenectomy).

We were unable to perform subgroup analysis based on the risk of bias in the trials as only two trials were of low risk of bias. We were unable to perform a planned subgroup analysis of distal pancreatectomy and pancreatic drainage procedures, and the different methods of management of pancreatic stump (pancreatogastrostomy and pancreatojejunostomy), as the outcome data for the different subgroups were not available from the trials.

There was no significant difference in any of the primary outcomes between intervention and control groups in the different subgroups ( Analysis 2.1;  Analysis 2.2;  Analysis 2.3;  Analysis 3.1;  Analysis 3.2;  Analysis 3.3;  Analysis 4.1;  Analysis 4.2;  Analysis 4.3).

 

Variations in statistical analysis

We observed no change in results by adopting the random-effects model or by calculating the RD except for the outcome 'number with adverse effects due to treatment'. We did not perform the sensitivity analysis using empirical continuity correction factors as suggested by Sweeting 2004, as there were no statistically significant outcomes in the main comparison with zero event trials.

 

Reporting bias

The funnel plot of perioperative mortality did not show any reporting bias (Figure 4). The Egger's linear regression approach to identify publication bias (Egger 1997) did not reveal any bias for the outcome perioperative mortality (P value = 0.7721). We performed the Egger's approach using the statistical software StatsDirect 2.7.2. No funnel plot was calculated for adverse effects of the drug because of the few trials reporting this outcome. None of the trials reported participant quality of life.

 FigureFigure 4. Funnel plot of comparison: 1 Somatostatin analogues versus none, outcome: 1.1 Perioperative mortality.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Summary of main results

Somatostatin analogues did not decrease perioperative mortality and re-operation rates in people undergoing pancreatic surgery.

The main indication for re-operation is the presence of a pancreatic fistula, associated sepsis or organ dysfunction (Bassi 2005). There is no universal definition of pancreatic fistula or pancreatic leak and the incidence can vary depending on the definition used. An international study group of surgeons have graded postoperative pancreatic fistulas by consensus as A, B and C (Bassi 2005). Grade A is the transient fistula that does not have any clinical impact. Grade B fistulas require alteration in the management of the person. Grade C fistulas require major alterations in the management of the person and usually require re-operation. Grade B and C fistulas have significant clinical impact and may contribute to increased morbidity and mortality. In this review, we included only trials in which data on grade B or C were available separately from grade A for the outcome clinically significant pancreatic fistula (grades B or C). The overall incidence of pancreatic fistula was lower in the somatostatin analogues group. Only four trials distinguished between any pancreatic fistula and clinically significant pancreatic fistula (Gouillat 2001; Hesse 2005; Kollmar 2008; Kurumboor 2012). There was no difference between the somatostatin analogues group and control in the incidence of clinically significant pancreatic fistula. It is likely that some of the pancreatic fistulas that were reported in the other trials were clinically significant. However, in the absence of data on the proportion of these fistulas that were clinically significant, such trials could not be included for the outcome 'clinically significant pancreatic fistulas' and could be included only for the outcome 'all pancreatic fistulas'. The few trials included under the outcome 'clinically significant pancreatic fistulas' may be the reason for the lack of a statistically significant difference between the somatostatin analogues and control. Alternatively, the lack of a statistically significant difference may be due to the lack of effect.

The overall postoperative complications were significantly lower in the intervention group than the control group. However, there was no significant difference in total hospital stay between the two groups for the main analysis. Possible reasons for the absence of difference in total hospital stay include a lack of effect of somatostatin analogues with regards to the incidence of re-operation, anastomotic leak or clinically significant pancreatic fistulas; or could be because of the management of the pancreatic fistulas at the person's home (community-based treatment). Pancreatic fistulas amenable for community-based treatment might decrease the quality of life of people during the time it takes for these fistulas to close, increase the convalescence period resulting in a later return to work with major cost implications for the person, person's carers and the person's employers, and increase the costs associated with the provision of community-based treatment, even though they do not prolong hospital stay. In the absence of any information on the quality of life of the participants, it was not possible to assess the impact of pancreatic fistulas that did not prolong hospital stay.

As far as the interventions are concerned, somatostatin has to be administered by continuous intravenous infusion for approximately one week. This can decrease the mobility of the person. Octreotide, in contrast, is administered subcutaneously three times a day allowing good mobility. The other advantage is that it can be administered even in people with difficult venous access thereby increasing compliance. The adverse effects associated with the intervention were mainly minor adverse effects, such as pain at the injection site. There were no serious adverse effects reported in any of the trials. Of the trials that reported the withdrawal of intervention, the treatment was stopped in about 1.3% of the 610 participants. In high-income countries, the cost of the entire course of octreotide is less than the cost of one additional day at the hospital. There was no difference in the hospital stay between the two groups. The lack of information on pancreatic fistulas (i.e. whether they were clinically significant or not) does not help in reaching a conclusion as to whether the somatostatin analogues should be routinely recommended. However, on a balance, considering the lack of serious adverse effects, low costs and the potential benefit in reducing the proportion of people who developed any complication and in the number of people who developed pancreatic fistulas, somatostatin analogues are recommended routinely for people undergoing pancreatic surgery. Further cost-effectiveness evaluation of somatostatin analogues in pancreatic surgery is necessary.

 

Overall completeness and applicability of evidence

This review included people undergoing pancreatic surgery for malignancy and chronic pancreatitis using pancreatoduodenectomy, distal pancreatectomy and pancreatic drainage procedures. Hence, this review is applicable to most people undergoing pancreatic surgery.

 

Quality of the evidence

Most of the trials were of high risk of bias. Allocation was unclear in most of the trials. Blinding was not performed in some of the trials. Considering that many of the outcomes were subjective, this could have resulted in overestimation of treatment effects (Wood 2008). Some of the trials had a significant proportion of post-randomisation drop-outs. A significant proportion of these people underwent pancreatic surgery. Thus, we had to adopt the per protocol analysis for some trials. In spite of all the preoperative staging investigations, such as computerised tomography (CT) scan, endoscopic ultrasound (EUS), diagnostic laparoscopy (DL) or a combination of these investigations, between 8% and 33% of people are found to have unresectable pancreatic cancer on laparotomy (Mayo 2009). Considering that the intervention was started preoperatively in the majority of the people, it appears that post-randomisation drop-outs are inevitable. Considering that no pancreatic surgery is carried out in people with unresectable disease (they may undergo palliative bypass procedures such as gastrojejunostomy or cholecystojejunostomy), it is reasonable to exclude these participants from the analysis for outcomes related to postoperative complications or hospital stay. Thus, an available case analysis may be appropriate in such circumstances when the drop-outs are not related to the intervention (Gurusamy 2009) (we can be sure that octreotide does not cause unresectability). However, exclusion of participants for any other reason will lead to a biased effect estimate. It is also important to report all the pre-specified outcomes in order to avoid selective reporting. Some of the trials did not report all the pre-specified outcomes. It will also be useful in reporting the outcomes according to their severity. In spite of its deficiencies, the only validated classification of postoperative complications is the Clavien-Dindo classification (Clavien 2009; Dindo 2004). It is also important to report the quality of life in participants so that a formal cost-effectiveness analysis can be undertaken. Reporting of the outcomes stratified by the aetiology, type of pancreatic resection and method of management of pancreatic stump will enable the evaluation of the effect of somatostatin analogues in the different subgroups, as they may be useful in some subgroups but not in others.

 

Potential biases in the review process

We followed the Cochrane Handbook for Systematic Reviews of Interventions for this review (Higgins 2011). There were no language, publication status or sample size restrictions. Thus, we minimised the bias due to selection of trials. There was no reporting bias in perioperative mortality as suggested by the funnel plot and Egger's linear regression approach (Egger 1997).

We have used per protocol analysis when intention-to-treat analysis or available case analysis was not possible. This could lead to bias favouring the intervention. Inadequate reporting of the pancreatic fistulas also make it difficult to judge whether somatostatin analogues are useful.

We have used median for the meta-analysis when the mean was not available for hospital stay. We have also imputed the standard deviation from P values according to the formulae stated in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If the trials stated a P value < 0.05, we calculated the standard deviation using a P value equal to 0.05. If standard deviation could not be calculated because the trial reports just stated that there was no statistical significance without mentioning the exact P value, we used the highest standard deviation among the other trials included in the outcome. This imputation of standard deviation may have introduced bias. We also performed a sensitivity analysis by excluding the trials that did not report the mean and standard deviation of the hospital stay in the two groups. There was no change in the results either in the overall analysis or in the different subgroup analyses when we performed this sensitivity analysis.

 

Agreements and disagreements with other studies or reviews

Of the systematic reviews, that by Connor et al concluded that somatostatin and its analogues should be used in pancreatic surgery based on a reduction in the incidence of pancreatic fistula (Connor 2005). The other systematic review by Alghamdi et al concluded that octreotide decreased the incidence of pancreatic fistula, and that further trials are necessary to confirm the findings of the meta-analysis and to identify subgroups of people undergoing pancreatic surgery who may benefit from octreotide (Alghamdi 2007). We have made a recommendation of routine use of somatostatin analogues in pancreatic surgery because of the low costs of the drug, lack of any serious adverse effects in the postoperative setting and the potential to decrease the complication rates after pancreatic surgery.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 

Implications for practice

Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials of low risk of bias are necessary. Based on current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.

 
Implications for research

Further trials with low risk of bias are necessary.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

We would like to thank the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group for the support that they provided for the completion of this review.

We would also like to acknowledge and thank the authors of the original protocol, Eva Morris, Moritz N Wente, Christoph M Seiler, Meg Finch-Jones, Markus W Büchler and Derek Alderson.

This project was funded by the National Institute for Health Research.
Disclaimer of the Department of Health: "The views and opinions expressed in the review are those of the authors and do not necessarily reflect those of the National Institute for Health Research (NIHR), National Health Services (NHS), or the Department of Health".

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
Download statistical data

 
Comparison 1. Somatostatin analogues versus none

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

 1 Perioperative mortality182210Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.56, 1.16]

 2 Treatment withdrawal91220Risk Ratio (M-H, Fixed, 95% CI)1.55 [0.56, 4.33]

 3 Number with adverse effects due to treatment81199Risk Ratio (M-H, Random, 95% CI)2.09 [0.83, 5.24]

 4 Re-operation7687Risk Ratio (M-H, Random, 95% CI)1.26 [0.58, 2.70]

 5 Anastomotic leak91585Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.51, 1.27]

 6 Pancreatic fistula (all)172206Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.55, 0.79]

 7 Pancreatic fistula (clinically significant)4292Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.38, 1.28]

 8 Postoperative pancreatitis111667Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.32, 1.22]

 9 Sepsis71092Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.21, 0.85]

 10 Renal failure5998Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.25, 1.77]

 11 Bleeding141814Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.70, 1.44]

 12 Abdominal collections81589Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.56, 1.05]

 13 Infected abdominal collections131965Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.66, 1.32]

 14 Delayed gastric emptying5434Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.51, 1.23]

 15 Pulmonary complications91210Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.57, 1.39]

 16 Shock4812Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.46, 2.15]

 17 Number of complications7Rate Ratio (Fixed, 95% CI)0.70 [0.60, 0.82]

 18 Number with any complication121903Risk Ratio (M-H, Fixed, 95% CI)0.70 [0.61, 0.80]

 19 Hospital stay101314Mean Difference (IV, Fixed, 95% CI)-1.29 [-2.60, 0.03]

 
Comparison 2. Somatostatin analogues versus none (stratified by different interventions)

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

 1 Perioperative mortality171935Risk Ratio (IV, Fixed, 95% CI)0.81 [0.54, 1.20]

    1.1 Somatostatin
7304Risk Ratio (IV, Fixed, 95% CI)0.39 [0.20, 0.76]

    1.2 Octreotide
101631Risk Ratio (IV, Fixed, 95% CI)1.19 [0.73, 1.93]

 2 Treatment withdrawal91220Risk Ratio (IV, Fixed, 95% CI)1.45 [0.45, 4.65]

    2.1 Somatostatin
2142Risk Ratio (IV, Fixed, 95% CI)6.82 [0.36, 127.64]

    2.2 Octreotide
71078Risk Ratio (IV, Fixed, 95% CI)1.08 [0.30, 3.85]

 3 Number with adverse effects due to treatment81199Risk Ratio (M-H, Fixed, 95% CI)1.33 [0.99, 1.77]

    3.1 Somatostatin
2142Risk Ratio (M-H, Fixed, 95% CI)3.47 [0.58, 20.68]

    3.2 Octreotide
61057Risk Ratio (M-H, Fixed, 95% CI)1.27 [0.95, 1.71]

 
Comparison 3. Somatostatin analogues versus none (stratified by different aetiologies)

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

 1 Perioperative mortality5844Risk Ratio (IV, Fixed, 95% CI)0.68 [0.29, 1.60]

    1.1 Malignancy
4400Risk Ratio (IV, Fixed, 95% CI)0.48 [0.18, 1.24]

    1.2 Chronic pancreatitis
3444Risk Ratio (IV, Fixed, 95% CI)2.75 [0.42, 17.87]

 2 Treatment withdrawal2Risk Ratio (IV, Fixed, 95% CI)Totals not selected

    2.1 Malignancy
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Chronic pancreatitis
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Number with adverse effects due to treatment1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

    3.1 Chronic pancreatitis
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Somatostatin analogues versus none (pancreatoduodenectomy)

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

 1 Perioperative mortality8639Risk Ratio (M-H, Fixed, 95% CI)1.39 [0.72, 2.69]

 2 Treatment withdrawal4387Risk Ratio (M-H, Fixed, 95% CI)5.15 [0.61, 43.28]

 3 Number with adverse effects due to treatment4387Risk Ratio (M-H, Fixed, 95% CI)13.05 [2.67, 63.92]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Appendix 1. CENTRAL search strategy

#1 (randomized controlled trial):pt
#2 (controlled clinical trial):pt
#3 (randomized):ab
#4 (placebo):ab
#5 MeSH descriptor Drug Therapy, this term only
#6 (randomly):ab
#7 (trial):ab
#8 (groups):ab
#9 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8)
#10 (pancreas):ti,ab
#11 (pancrea*):ti,ab
#12 MeSH descriptor Pancreas, this term only
#13 MeSH descriptor Islets of Langerhans, this term only
#14 MeSH descriptor Pancreas, Exocrine, this term only
#15 MeSH descriptor Pancreatic Ducts, this term only
#16 (#10 OR #11 OR #12 OR #13 OR #14 OR #15)
#17 MeSH descriptor Carcinoma, this term only
#18 MeSH descriptor Adenocarcinoma, this term only
#19 MeSH descriptor Carcinoma, Ductal, this term only
#20 MeSH descriptor Carcinoma, Islet Cell, this term only
#21 (cancer)
#22 (cancer*)
#23 MeSH descriptor Neoplasms explode all trees
#24 (tumo*)
#25 (#17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24)
#26 (#16 AND #25)
#27 MeSH descriptor Pancreatitis explode all trees
#28 (pancreatitides)
#29 (#26 OR #27 OR #28)
#30 MeSH descriptor Surgical Procedures, Operative explode all trees
#31 MeSH descriptor General Surgery explode all trees
#32 (surger*)
#33 (operatio*)
#34 (operative therap*)
#35 (resection*):kw
#36 MeSH descriptor Pancreatectomy explode all trees
#37 MeSH descriptor Pancreaticojejunostomy explode all trees
#38 MeSH descriptor Pancreaticoduodenectomy explode all trees
#39 (pancreaticoduodenectom*):ti,ab
#40 (pancreatectomy):ab,ti
#41 (pancreaticojejunostomy):ab,ti
#42 (duodenopancreatectom*):ab,ti
#43 (#30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42)
#44 MeSH descriptor Somatostatin explode all trees
#45 MeSH descriptor Octreotide explode all trees
#46 (somatostatin):ab,ti
#47 (octreotide):ab,ti
#48 (lanreotide):ab,ti
#49 (pasireotide):ab,ti
#50 (vapreotide):ab,ti
#51 (#44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50)
#52 (#9 AND #29 AND #43 AND #51)

 

Appendix 2. MEDLINE search strategy

1. randomized controlled trial [pt]
2. controlled clinical trial [pt]
3. randomized [tiab]
4. placebo [tiab]
5. drug therapy [sh]
6. randomly [tiab]
7. trial [tiab]
8. groups [tiab]
9. #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8
10. animals [mh] not (humans [mh] and animals [mh])
11. #9 not #10
12. Pancreatic Neoplasms [MeSH]
13. Pancreatitis[MeSH]
14. pancreas cancer [tiab]
15. pancreas cancers [tiab]
16. pancreas neoplasm [tiab]
17. pancreas neoplasms [tiab]
18. pancreas carcinoma [tiab]
19. pancreas tumor [tiab]
20. pancreas tumors [tiab]
21. pancreas tumour [tiab]
22. pancreas tumours [tiab]
23. pancreatitis [tiab]
24. pancreatitides [tiab]
25. #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24
26. Surgical Procedures, Operative[MeSH]
27. Surgery[MeSH]
28. operation OR operations[tiab]
29. operative therapy [tiab]
30. operative therapies [tiab]
31. surgery OR surgeries [tiab]
32. resection OR resections [tiab]
33. #26 or #27 or #28 or #29 or #30 or #31 or #32
34. #25 and #33
35. Pancreatectomy[MeSH]
36. Pancreaticojejunostomy[MeSH]
37. Pancreaticoduodenectomy[MeSH]
38. pancreaticoduodenectomy [tiab]
39. pancreatectomy [tiab]
40. pancreaticojejunostomy [tiab]
41. pancreaticogastrostomy [tiab]
42. pancreaticoduodenectomies [tiab]
43. duodenopancreatectomy [tiab]
44. duodenopancreatectomies [tiab]
45. #35 or #36 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44
46. #34 or #45
47. Somatostatin[Mesh]
48. Octreotide[Mesh]
49. lanreotide [Substance Name]
50. pasireotide[Substance Name]
51. vapreotide [Substance Name]
52. somatostatin [tiab]
53. octreotide [tiab]
54. lanreotide [tiab]
55. pasireotide [tiab]
56. vapreotide [tiab]
57. #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56
58. #46 and #57
59. #58 and #11

 

Appendix 3. EMBASE search strategy

1 randomized controlled trial/
2 controlled clinical trial/
3 randomized.ab.
4 placebo.ab.
5 drug therapy/
6 randomly.ab.
7 trial.ab.
8 groups.ab. (641427)
9 6 or 3 or 7 or 2 or 8 or 1 or 4 or 5
10 animals/
11 humans/
12 11 and 10
13 10 not 12
14 9 not 13
15 pancreas.ab,ti.
16 pancrea$.ab,ti.
17 pancreas/ or "islets of langerhans"/ or pancreas, exocrine/ or pancreatic ducts/
18 16 or 17 or 15
19 carcinoma/ or adenocarcinoma/ or carcinoma, ductal/ or carcinoma, islet cell/
20 cancer.tw.
21 cancer$.tw.
22 exp neoplasms/
23 tumo$.tw.
24 22 or 21 or 23 or 19 or 20
25 18 and 24
26 exp Pancreatitis/
27 pancreatitides.tw.
28 27 or 25 or 26
29 exp Surgical Procedures, Operative/
30 exp Surgery/
31 surger$.tw.
32 operatio$.tw.
33 operative therap$.tw.
34 resection$.mp.
35 exp Pancreatectomy/
36 exp Pancreaticojejunostomy/
37 exp Pancreaticoduodenectomy/
38 pancreaticoduodenectom$.ab,ti.
39 pancreatectomy.ab,ti.
40 pancreaticojejunostomy.ab,ti.
41 pancreaticogastrostomy.ab,ti.
42 duodenopancreatectom$.ab,ti.
43 35 or 33 or 32 or 39 or 40 or 36 or 41 or 42 or 38 or 34 or 30 or 37 or 29 or 31
44 exp Somatostatin/
45 exp Octreotide/
46 somatostatin.ab,ti.
47 octreotide.ab,ti.
48 lanreotide.ab,ti.
49 pasireotide.ab,ti.
50 vapreotide.ab,ti.
51 50 or 49 or 46 or 45 or 44 or 48 or 47
52 28 and 51 and 43 and 14

 

Appendix 4. Science Citation Index Expanded search strategy

#1 TS=(randomized controlled trial OR controlled clinical trial OR randomized OR placebo OR drug therapy OR randomly OR trial OR groups)
#2 TS=(Pancreatic Neoplasms OR Pancreatitis OR pancreas cancer OR pancreas cancers OR pancreas neoplasm OR pancreas neoplasms OR pancreas carcinoma OR pancreas tumor OR pancreas tumors OR pancreas tumour OR pancreas tumours OR pancreatitis OR pancreatitides)
#3 TS=(Operative Surgical Procedures OR Surgery OR operation OR operations OR operative therapy OR operative therapies OR surgery OR surgeries OR resection OR resections)
#4 #2 AND #3
#5 (Pancreatectomy OR Pancreaticojejunostomy OR Pancreaticoduodenectomy OR pancreaticoduodenectomy OR pancreatectomy OR pancreaticojejunostomy OR pancreaticogastrostomy OR pancreaticoduodenectomies OR duodenopancreatectomy OR duodenopancreatectomies)
#6 #4 OR #5
#7 TS=(Somatostatin OR Octreotide OR lanreotide OR pasireotide OR vapreotide OR somatostatin OR octreotide OR lanreotide OR pasireotide OR vapreotide)
#8 #1 AND #6 AND #7

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Last assessed as up-to-date: 14 February 2013.


DateEventDescription

16 February 2013New search has been performedSearch results updated and two more trials included in the analysis. Numerous subgroup analyses which increase the possibility of type I error have been removed and subgroup analyses have now been performed for primary outcomes only.

30 January 2012New citation required but conclusions have not changedTwo trials included in analyses. Conclusions unchanged.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Protocol first published: Issue 4, 2003
Review first published: Issue 2, 2010


DateEventDescription

13 February 2012AmendedContact details updated.

20 September 2010AmendedContact details updated.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

KS Gurusamy wrote the review, assessed the trials for inclusion and extracted data on included trials. R Koti wrote sections of the review, independently assessed the trials for inclusion and extracted data on included trials. K Fusai and BR Davidson provided advice for improving the review.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

None.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Internal sources

  • University College London, UK.

 

External sources

  • No sources of support supplied

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

We have revised the protocol as follows.

  1. The importance of the outcomes has been changed. We have stated primary outcomes as perioperative mortality and re-operation. The other postoperative complications have been changed to the secondary outcomes.
  2. We have excluded time to fistula closure in people with pancreatic leaks/fistula as one of the outcomes. This is because of the lack of universal definition of pancreatic fistula (grade A fistula is not clinically significant - Bassi 2005) and consider that this outcome is not a significant patient-oriented outcome.
  3. We have restricted the electronic search to the four main databases, which results in the identification of more than 97% of the randomised clinical trials (Royle 2003).
  4. Assessment of risk of bias in the trials and the statistical methods used have been revised according to the then current version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008).

 

Differences between previous version and this version

  1. The outcomes have been re-ordered according to the latest version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
  2. Assessment of risk of bias in the trials and the statistical methods used have been revised according to the latest version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
  3. Numerous subgroup analysis on secondary outcomes have been removed since this will result in error because of the numerous repeated testing performed.

 

Notes

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

This review was developed based on a Cochrane protocol written by a different group of authors and published in The Cochrane Library in 2003. The protocol was withdrawn from publication in early 2009, as the original authors were unable to complete the review. The authors of the present review have developed the review based on the original protocol, which has been quality assured during the editorial process. Details of changes to the protocol are noted in Differences between protocol and review. Further revisions to the methods of the review were made according to the guidelines of the most recent version of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Details of changes are noted in a sub-heading in Differences between protocol and review.

 

Index terms

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Medical Subject Headings (MeSH)

Gastrointestinal Agents [*therapeutic use]; Length of Stay; Octreotide [therapeutic use]; Pancreas [secretion; *surgery]; Pancreatectomy [*adverse effects; mortality]; Pancreatic Diseases [surgery]; Pancreatic Fistula [*prevention & control]; Pancreaticoduodenectomy [adverse effects; mortality]; Postoperative Complications [mortality; *prevention & control]; Publication Bias; Randomized Controlled Trials as Topic; Reoperation [statistics & numerical data]; Sepsis [prevention & control]; Somatostatin [*analogs & derivatives]

MeSH check words

Humans

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. Additional references
  24. References to other published versions of this review
Beguiristain 1995 {published data only}
  • Beguiristain A, Espi A, Balen E, Pardo F, Hernandez Lizoain JL, Alvarez Cienfuegos J. Somatostatin prophylaxis following cephalic duodenopancreatectomy. Revista Espanola de Enfermedades Digestivas 1995;87(3):221-4.
Briceño Delgado 1998 {published data only}
  • Briceño Delgado FJ, López Cillero P, Rufián Peña S, Solórzano Peck G, Miño Fugarolas G, Pera Madrazo C. Prospective and randomized study on the usefulness of octreotide in the prevention of complications after cephalic duodeno-pancreatectomy. Revista Espanola de Enfermedades Digestivas 1998;90(10):687-94.
Buccoliero 1992 {published and unpublished data}
  • Buccoliero F, Pansini GC, Mascoli F, Mari C, Donini A, Navarra G. Somatostatin in duodenocephalopancreatectomy for neoplastic pathology. Minerva Chirurgica 1992;47(8):713-6.
Buchler 1992 {published data only}
  • Buchler M, Friess H. Inhibition of pancreatic secretion to prevent postoperative complications following pancreatic resection. Acta Gastroenterologica Belgica 1993; Vol. 56, issue 3-4:271-8.
  • Buchler M, Friess H. Prevention of postoperative complications following pancreatic surgery. Digestion 1993;54(Suppl 1):41-6.
  • Buchler M, Friess H, Klempa I, Hermanek P, Sulkowski U, Becker H, et al. Role of octreotide in the prevention of postoperative complications following pancreatic resection. American Journal of Surgery 1992;163(1):125-31.
  • Friess H, Klempa I, Hermanek P, Sulkowski U, Uhl W, Beger HG, et al. Prophylaxis of complications after pancreatic surgery: results of a multicenter trial in Germany. Digestion 1994; Vol. 55, issue Suppl 1:35-40.
Fernandez-Cruz 2012 {published data only}
  • Fernandez-Cruz L, Chavarria EJ, Taura P, Vallejos R, Lopez-Boado MA, Ferrer J. Prospective, randomized trial of the effect of octreotide on pancreatic juice output after pancreatoduodenectomy in relation to histological diagnosis, duct size and leakage. HPB 2012;14:91-2.
Friess 1995 {published data only}
  • Buchler MM, Gaus W. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. authors' reply. British Journal of Surgery 1996; Vol. 83, issue 3:422-3.
  • Friess H, Beger HG, Sulkowski U, Becker H, Hofbauer B, Dennler HJ, et al. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis. British Journal of Surgery 1995;82(9):1270-3.
  • Friess H, Beger HG, Sulkowski U, Becker H, Hofbauer B, Dennler HJ, et al. Randomized controlled multicentre study of the prevention of complications by octreotide in patients undergoing surgery for chronic pancreatitis (vol 82, pg 1270, 1995). British Journal of Surgery 1996; Vol. 83, issue 1:126.
  • Friess H, Hofbauer B, Buchler MW. The role of somatostatin and octreotide in pancreatic surgery and in acute and chronic pancreatitis. Digestive Surgery 1994;11(3-6):445-50.
Gouillat 2001 {published and unpublished data}
  • Gouillat C, Chipponi J, Baulieux J, Partensky C, Saric J, Gayet B. Randomized controlled multicentre trial of somatostatin infusion after pancreaticoduodenectomy. British Journal of Surgery 2001;88(11):1456-62.
  • Gouillat C, Faucheron JL, Balique JG, Gayet B, Saric J, Partensky C, et al. Natural history of the pancreatic stump after duodenopancreatectomy of the pancreatic head. Annales de Chirurgie 2002;127(6):467-76.
Hesse 2005 {published data only}
  • Hesse UJ, De Decker C, Houtmeyers P, Demetter P, Ceelen W, Pattyn P, et al. Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy. World Journal of Surgery 2005;29(10):1325-8.
  • Hesse UJ, De Decker C, Houtmeyers P, Demetter P, Ceelen W, Pattyn P, et al. Prospectively randomized trial using perioperative low dose octreotide to prevent organ related and general complications following pancreatic surgery and pancreatico-jejunostomy. Acta Chirurgica Belgica 2005; Vol. 105, issue 4:383-7.
Katsourakis 2010 {published data only}
  • Katsourakis A, Oikonomou L, Chatzitheoklitos E, Noussios G, Pitiakoudis M, Polychronidis A, et al. The role of somatostatin in 67 consecutive pancreatectomies: a randomized clinical trial. Clinical and Experimental Gastroenterology 2010;3(1):179-83.
  • Katsourakis A, Zezos P, Noussios G, Kouklakis G, Chatzitheoklitos E, Simopoulos K, et al. Does prophylactic administration of somatostatin decrease the rates of complications after pancreatic resection?: a clinical and electron microscopy study. Pancreas 2013;42(1):37-41.
Klempa 1991 {published data only}
  • Klempa I, Baca I, Menzel J, Schuszdiarra V. Effect of somatostatin on basal and stimulated exocrine pancreatic secretion after partial duodenopancreatectomy. A clinical experimental study. Der Chirurg 1991; Vol. 62, issue 4:293-9.
Kollmar 2008 {published and unpublished data}
  • Kollmar O, Moussavian MR, Richter S, de Roi P, Maurer CA, Schilling MK. Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: results of a prospective randomized double-blinded placebo-controlled trial. European Journal of Surgical Oncology 2008;34(8):868-75.
Kurumboor 2012 {published data only}
  • Kurumboor P, Kamalesh NP, Pramil K, Vipin IS, Shylesh A, Varma D, et al. A prospective randomized controlled trial on use of octreotide in patients with soft pancreas undergoing pancreaticoduodenectomy: interim analysis. HPB 2012;14:225.
Lange 1992 {published data only}
  • Lange JR, Steinberg SM, Doherty GM, Langstein HN, White DE, Shawker TH, et al. A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas. Surgery 1992;112(6):1033-8.
Matheus 2009 {published data only}
  • Matheus A, Montagnini A, Abe E, Haddad L, Penteado S, Abdo E, et al. Octreotide in patients with high risk to develop pancreatic fistula after pancreaticoduodenectomy: a prospective randomized trial. HPB 2010;12(Suppl S1):218-9.
  • Matheus AS, Montagnini AL, Jukemura J, Abe ES, Penteado S, Haddad LB, et al. Octreotide in patients with high risk to develop pancreatic fistula after pancreaticoduodenectomy - a prospective randomized trial. European Journal of Surgical Oncology 2010;36(9):814.
  • Matheus AS, Montagnini AL, Jukemura J, Perini MV, Haddad LB, Abe ES, et al. Does octreotide have any beneficial effect in patients with high risk to develop pancreatic fistula after pancreaticoduodenectomy: a prospective randomized trial. Gastroenterology 2009;136(5 Suppl 1):A-881.
Montorsi 1995 {published data only}
  • Montorsi M, Zago M, Mosca F, Capussotti L, Zotti E, Ribotta G, et al. Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial. Surgery 1995;117(1):26-31.
Pederzoli 1994 {published data only}
  • Bassi C, Falconi M, Lombardi D, Briani G, Vesentini S, Camboni MG, et al. Prophylaxis of complications after pancreatic surgery: results of a multicenter trial in Italy. Italian Study Group. Digestion 1994;55(Suppl 1):41-7.
  • Pederzoli P, Bassi C, Falconi M, Camboni MG. Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. British Journal of Surgery 1994;81(2):265-9.
Sarr 2003 {published data only}
  • Ramos-De la Medina A, Sarr MG. Somatostatin analogues in the prevention of pancreas-related complications after pancreatic resection. Journal of Hepatobiliary Pancreatic Surgery 2006;13(3):190-3.
  • Sarr MG. The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial. Journal of the American College of Surgeons 2003;196(4):556-65.
Shan 2005 {published data only}
  • Shan YS, Sy ED, Lin PW. Role of somatostatin in the prevention of pancreatic stump-related morbidity following elective pancreaticoduodenectomy in high-risk patients and elimination of surgeon-related factors: prospective, randomized, controlled trial. World Journal of Surgery 2003;27(6):709-14.
  • Shan YS, Sy ED, Tsai ML, Tang LY, Li PS, Lin PW. Effects of somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy: increased delayed gastric emptying and reduced plasma motilin. World Journal of Surgery 2005;29(10):1319-24.
Suc 2004 {published data only}
  • Oberlin P, Suc B, Pezet D, Fagniez PL, Hay JM. Prevention of intra-abdominal complications after pancreatic resection by octreotide. A prospective, multicenter, randomized trial. Gastroenterology 2000;118(4):A463.
  • Suc B, Msika S, Piccinini M, Fourtanier G, Hay JM, Flamant Y, et al. Octreotide in the prevention of intra-abdominal complications following elective pancreatic resection: a prospective, multicenter randomized controlled trial. Archives of Surgery 2004;139(3):288-94.
Tulassay 1993 {published data only}
  • Tulassay Z, Flautner L, Fehervari I, Sandor Z, Nemeth J. Somatostatin in the prevention of postoperative increase of pancreatic enzyme after pancreatic surgery. Orvosi Hetilap 1992;133(13):777-80.
  • Tulassay Z, Flautner L, Sandor Z, Fehervari I. Perioperative use of somatostatin in pancreatic surgery. Acta Biomedica Ateneo Parmense 1993;64(5-6):205-11.
Yeo 2000 {published data only}
  • Yeo CJ, Cameron JL, Lillemoe KD, Sauter PK, Coleman J, Sohn TA, et al. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. Annals of Surgery 2000;232(3):419-29.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. Additional references
  24. References to other published versions of this review
Barnett 2004 {published data only}
  • Barnett SP, Hodul PJ, Creech S, Pickleman J, Arahna GV. Octreotide does not prevent postoperative pancreatic fistula or mortality following pancreaticoduodenectomy. The American Surgeon 2004;70(3):222-7.
Bassi 1994 {published data only}
  • Bassi C, Falconi M, Pederzoli P. Role of somatostatin and somatostatin analogs in the treatment of gastrointestinal-diseases - prevention of complications after pancreatic surgery. Gut 1994;35:S20-2.
Brennan 2000 {published data only}
  • Brennan MF, Yeo CJ, Warshaw AL, O'Leary P, Warren KW, Way LW, et al. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial - discussion. Annals of Surgery 2000;232(3):426-9.
Büchler 2001 {published data only}
  • Büchler MW, Bassi C, Fingerhut A, Klempa I. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy?. Annals of Surgery 2001;234(2):262-3.
Droeser 2013 {published data only}
  • Droeser RA, Jeanmonod P, Schuld J, Moussavian MR, Schilling MK, Kollmar O. Octreotide prophylaxis is not beneficial for biochemical activity and clinical severity of postoperative pancreatic fistula after pancreatic surgery. Digestive Surgery 2013;29(6):484-91.
Elhadad 1998 {published data only}
  • Elhadad A, Rounanier G, Chippoini J. Octreotide in the prevention of surgical complications after pancreatectomy. A prospective randomised multicenter study. Hepatogastroenterology 1998;45(Suppl 2):152.
Falconi 2002 {published data only}
  • Falconi M, Contro C, Ballabio M, Bassi C, Salvia R, Pederzoli P. Evaluation of lanreotide effects on human exocrine pancreatic secretion after a single dose: preliminary study. Digestive and Liver Disease 2002;34(2):127-32.
Frick 1996 {published data only}
Friess 1989 {published data only}
  • Friess H, Buchler M, Meschenmoser L. Effect of octreotide (SMS 201-995) on exocrine pancreatic function in man. Pancreas 1989;4:616.
Friess 1996 {published data only}
  • Friess H, Buchler M. Efficacy of somatostatin and its analogues in pancreatic surgery and pancreatic disorders. Digestion 1996;57 Suppl 1:97-102.
Habib 1998 {published data only}
  • Habib E, Elhadad A, Fourtanier G, Chipponi J, Faniez P L, Hay JM, et al. Octreotide in prevention of surgical complication after pancreatectomy. Annales de Chirurgie 1998;52(7):671-2.
Klempa 1979 {published data only}
  • Klempa I, Schwedes U, Usadel KH. Prevention of postoperative pancreatic complications following duodenopancreatectomy using somatostatin. Der Chirurg 1979;50(7):427-31.
Lowy 1997 {published data only}
  • Lowy AM, Lee JE, Davidson BS, Pisters PWT, Evans DB. The role of octreotide in the prevention of pancreatic fistula after pancreaticoduodenectomy for periampullary malignancy: a prospective randomized trial. Gastroenterology 1996;110(4):A1401.
  • Lowy AM, Lee JE, Pisters PW, Davidson BS, Fenoglio CJ, Stanford P, et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Annals of Surgery 1997;226(5):632-41.
Shatverian 2004 {published data only}
  • Shatverian GA, Ratnikova NP, Mikhailov Iu E, Bedzhanian AL, Sidorov AN, Fisenko EP, et al. Role octreotide in prevention of complications after pancreatoduodenal resections [Rol' oktreotida v profilaktuke oslozhnenii posle pankreatoduodenal'nykh rezektsii]. Khirurgiia 2004;2:56-60.
Van Berge 1997 {published data only}
  • Van Berge Henegouvven MI, Van Gulik TM, Akkermans LMA, Jansen JBMJ, Gouma DJ. The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers. Gut 1997;41(6):758-62.
Van Hee 1998 {published data only}
  • Van Hee R, De Laet I, Salgado R, Ysebaert D. The influence of somatostatin on postoperative outcome after elective pancreatic surgery. Acta Chirurgica Belgica 1998;98(2):62-5.
Wang 2012 {published data only}
  • Tian BL, Su AP, Wang WG, Zhang Y. Does preoperative somatostatin administration decrease the rate of postoperative pancreatic fistula following pancreaticoduodenectomy? A randomized placebo-controlled trial. Journal of Gastroenterology and Hepatology 2012;27 Suppl 5:359.
  • Wang W, Tian B, Babu SR, Zhang Y, Yang M. Randomized, placebo-controlled study of the efficacy of preoperative somatostatin administration in the prevention of postoperative complications following pancreaticoduodenectomy. Hepatogastroenterology 2012;60(123):e1. [DOI: 10.5754/hge12669]
Woltering 2003 {published data only}
  • Woltering EA. The potent somatostatin analogue vapreotide does not decrease pancreas-specific complications after elective pancreatectomy: a prospective, multicenter, double-blinded, randomized, placebo-controlled trial - invited commentary. Journal of the American College of Surgeons 2003;196(4):564-5.
Yeo 1999 {published data only}

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. Additional references
  24. References to other published versions of this review
Alexakis 2004
Alghamdi 2007
  • Alghamdi AA, Jawas AM, Hart RS. Use of octreotide for the prevention of pancreatic fistula after elective pancreatic surgery: a systematic review and meta-analysis. Canadian Journal of Surgery 2007;50(6):459-66.
Bassi 2005
Clavien 2009
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Connor 2005
DeMets 1987
DerSimonian 1986
Dindo 2004
  • Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of Surgery 2004;240(2):205-13.
Egger 1997
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Forman 2009
  • Forman D, Delaney B, Kuipers E, Malthaner R, Moayyedi P, Gardener E, et al. Cochrane Upper Gastrointestinal and Pancreatic Diseases Group. About The Cochrane Collaboration (Cochrane Review Groups (CRGs)) 2009, Issue 2. Art. No.: UPPERGI.
Gouma 2000
  • Gouma DJ, van Geenen RC, van Gulik TM, de Haan RJ, de Wit LT, Busch OR, et al. Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Annals of Surgery 2000;232(6):786-95. [PUBMED: 11088073]
Gurusamy 2009
Higgins 2002
Higgins 2008
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Chichester: John Wiley & Sons, 2008.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collsboration, 2011. Available from www.cochrane-handbook.org.
Kjaergard 2001
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Lembcke 1987
  • Lembcke B, Creutzfeldt W, Schleser S, Ebert R, Shaw C, Koop I. Effect of the somatostatin analogue sandostatin (SMS 201-995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men. Digestion 1987;36(2):108-24.
Macaskill 2001
Mayo 2009
  • Mayo SC, Austin DF, Sheppard BC, Mori M, Shipley DK, Billingsley KG. Evolving preoperative evaluation of patients with pancreatic cancer: does laparoscopy have a role in the current era?. Journal of the American College of Surgeons 2009;208(1):87-95.
McKay 2006
Moher 1998
  • Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet 1998;352(9128):609-13.
Newell 1992
Ohwada 1998
  • Ohwada S, Ogawa T, Tanahashi Y, Nakamura S, Takeyoshi I, Ohya T, et al. Fibrin glue sandwich prevents pancreatic fistula following distal pancreatectomy. World Journal of Surgery 1998;22(5):494-8.
RevMan 2011
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Royle 2003
  • Royle P, Milne R. Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches. International Journal of Technology Assessment in Health Care 2003;19(4):591-603.
Schulz 1995
  • Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12.
Sohn 2000
  • Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, et al. Resected adenocarcinoma of the pancreas - 616 patients: results, outcomes, and prognostic indicators. Journal of Gastrointestinal Surgery 2000;4(6):567-79.
StatsDirect 2.7.2
  • StatsDirect Ltd. StatsDirect statistical software. Version 2.7.2. StatsDirect Ltd, 06/09/2008.
Sweeting 2004
Wood 2008
  • Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman GD, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 2008;336:601-5.

References to other published versions of this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. Additional references
  24. References to other published versions of this review
Gurusamy 2010
Koti 2010
Wente 2003
  • Morris E, Wente MN, Seiler CM, Finch-Jones M, Büchler MW, Alderson D. Somatostatin and its analogues in the prevention of complications following pancreatic surgery. Cochrane Database of Systematic Reviews 2003, Issue 4. [DOI: 10.1002/14651858.CD004521]