Description of the condition
Pancreatic cancer ranks thirteenth in terms of the most common cancers and eighth as the cause of cancer death from a global viewpoint (Anderson 2006; Dragovich 2011; Lowenfels 2006). Regional differences exist in the incidence, the number of new patients diagnosed per year (Anderson 2006; Dragovich 2011; Lowenfels 2006). The overall incidence of pancreatic cancer is approximately 4 to 10 cases per 100,000 persons per year (Anderson 2006; Dragovich 2011; Lowenfels 2006). The most common cause of pancreatic cancer is heavy tobacco usage (Anderson 2006; Dragovich 2011; Lowenfels 2006).
Although the exact incidence of chronic pancreatitis worldwide is unknown, it is approximately six cases per 100,000 persons per year in Europe and probably all western countries (Spanier 2008). The prevalence (the total number of patients at a designated time) of chronic pancreatitis in United Kingdom, France, Japan, and south India is 3 cases, 26 cases, 4 cases, and 114 to 200 cases per 100,000 persons, respectively (Bornman 2001; Braganza 2011; Garg 2004; Lévy 2006). The most common cause of chronic pancreatitis is alcohol abuse (Braganza 2011; Spanier 2008).
Pancreatic surgery, which was first introduced by Wandesleben in 1841 (Schnelldorfer 2008; Schnelldorfer 2010), is performed to treat various pancreatic and extra-pancreatic diseases, including pancreatic cancers, chronic pancreatitis, biliary and duodenal malignancy, etc (Connor 2005; Gurusamy 2012). Although the mortality (the proportion of deaths after operation) of pancreatic surgery has been reduced to less than 5% currently, the overall morbidity (the proportion of patients with any postoperative complications) is still high, ranging from 30% to 60% (Bassi 2005; Connor 2005; Giovinazzo 2011; Gurusamy 2012; Wente 2007a; Wente 2007b). The most common complications after pancreatic surgery include delayed gastric emptying (19% to 23%) (Wente 2007a; Wente 2007b), pancreatic fistula (an abnormal communication between the pancreas and bowel leading to leakage of pancreatic juice from the pancreatic duct into the abdominal cavity) (2% to 30%) (Bassi 2005; Hackert 2011; Wente 2007a; Wente 2007b), intra-abdominal abscess (9% to 10%) (Wente 2007a; Wente 2007b), wound infection (5% to 15%) (Andrén-Sandberg 2011; Halloran 2002), and post-operative bleeding (1% to 8%) (Wente 2007a; Wente 2007b).
Description of the intervention
As a measure to reduce post-operative complications, prophylactic drains are traditionally placed in the subhepatic space near both the biliary and pancreatic anastomoses after pancreatic resection (Conlon 2001; Fisher 2011). Abdominal drainage, which was first reported by Hippocrates, has been in use for over 1000 years (Memon 2001).
Surgical drains are artificial tubes used to remove blood, pus, or other body fluids from wounds (Durai 2009). There are two main types of surgical drains, open drains and closed drains (Durai 2009; Gurusamy 2007a; Wang 2011). An open drain communicates with the atmosphere (for example corrugated drain, Penrose drain, sump drain) (Durai 2009; Gurusamy 2007a; Wang 2011). A closed drain consists of a tube draining into a collection bag or bottle where the contents are not exposed to the atmosphere (Durai 2009; Gurusamy 2007a; Wang 2011). Closed drains may either be active drains (suction drains under low or high pressure, for example Jackson-Pratt drain, Redivac) or passive drains (drains without suction, for example Robinson drain, Pigtail drain) (Durai 2009; Gurusamy 2007a; Wang 2011).
How the intervention might work
Surgeons have routinely used drains after pancreatic surgery because of the fear of collection of bile, pancreatic juice, or blood requiring additional procedures (Giovinazzo 2011; Gurusamy 2007a). Abdominal drainage is a therapeutic tool for drainage of intra-abdominal dirty collections (for example bile, pancreatic juice, pus). It may also serve as a diagnostic tool for early identification and monitoring of any fistula or bleeding. Theoretically, it has the potential to prevent or control postoperative complications (for example intra-abdominal abscess, pancreatic or biliary fistula, bleeding). However, abdominal drainage may be associated with some rare adverse events such as bowel perforation, hernia, and bleeding (Cameron-Strange 1985; Henkus 1999; Makama 2010; Nomura 1998; Reed 1992; Sahu 2008; Srivastava 2007; Van Hee 1983). In addition, it may increase the risk of post-operative infectious complications (Gurusamy 2007b; Inoue 2011).
Why it is important to do this review
Routine use of prophylactic abdominal drainage in patients undergoing pancreatic surgery is controversial. The use of surgical drains has been considered as mandatory after pancreatic surgery (Allen 2011). Recent studies have suggested that routine placement of prophylactic abdominal drains may be unnecessary and may be associated with an increased complication rate (Conlon 2001; Diener 2011; Fisher 2011; Paulus 2012). Up to now, there has been no Cochrane review assessing the role of prophylactic abdominal drainage for pancreatic surgery.
To assess the benefits and harms of routine abdominal drainage after pancreatic surgery.
To determine the comparative effects of different types of surgical drain after pancreatic surgery.
To determine the optimal time for drain removal after pancreatic surgery.
Criteria for considering studies for this review
Types of studies
We will include randomized controlled trials (RCTs) comparing drain use with no drain use, comparing different types of drains, and comparing early versus late drain removal in patients undergoing elective pancreatic surgery. We will exclude quasi-randomized trials (where the allocation is done on the basis of a pseudo-random sequence, for example odd and even hospital numbers or date of birth, alternation) and non-randomized studies (Reeves 2011).
Types of participants
We will include patients (irrespective of age, sex, or race) who are about to undergo elective pancreatic resections for any pancreatic or extra-pancreatic disease.
Types of interventions
- Routine drain use versus no drain use.
- One type of drain versus another.
- Early versus late drain removal (no more than four days versus more than four days).
Types of outcome measures
- peri-operative mortality;
- long-term mortality.
- Infectious complications:
- wound infections;
- intra-abdominal infections.
- Drain-related complications.
- Length of hospital stay.
- Hospital costs.
- Additional procedures for abdominal collection:
- open procedure;
- radiological drainage requiring insertion of drain;
- radiological drainage requiring percutaneous aspiration.
- Pain, quality of life.
Main outcomes for ‘Summary of findings’ table
- Infectious complications.
- Drain-related complications.
- Length of hospital stay.
Search methods for identification of studies
We will design the search strategies before searching; we will not have any restrictions for year of publication, language, or publication type.
Electronic searches will be conducted on the following databases (Royle 2003).
- Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, contained within the Cochrane Central Register of Controlled Trials (CENTRAL) (Appendix 1).
- MEDLINE via PubMed (Appendix 2).
- EMBASE via EMBASE.com (Appendix 3).
- Science Citation Index Expanded (Appendix 4).
- Chinese Biomedical Literature Database (CBM) (Appendix 5).
Searching other resources
We will search the following databases which include ongoing trials.
- World Health Organization International Clinical Trials Registry Platform search portal (http://apps.who.int/trialsearch/).
- ClinicalTrials.gov (http://www.clinicaltrials.gov/).
- Current Controlled Trials (http://www.controlled-trials.com/).
- European (EU) Clinical Trials Register (https://www.clinicaltrialsregister.eu/).
- Chinese Clinical Trial Register (http://www.chictr.org/).
We will also search the reference lists in relevant publications and meeting abstracts (via http://www.asco.org/ASCOv2/Meetings and Science Citation Index Expanded) to explore further relevant clinical trials. We plan to communicate with the authors of included randomized controlled trials (RCTs) for information required in the review, if necessary.
Data collection and analysis
We will conduct the systematic review according to the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2011a) and Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Module (Forman 2011).
Selection of studies
After completing all searches, we will merge the search results using the software package Endnote X5 (reference management software) and remove duplicate records of the same report. Two independent review authors (Wu S, Lu J) will scan the title and abstract of every record identified by the search for inclusion. We will retrieve the full text for further assessment if the inclusion criteria are unclear from the abstract. We plan to detect duplicate publications by identifying common authors, centres, details of the interventions, numbers of participants, and baseline data (Higgins 2011b). We intend to correspond with the authors of the RCTs to confirm whether the trial results had been duplicated, if necessary. We will exclude papers not meeting the inclusion criteria and list the reasons for the exclusion. A third review author (Cheng Y) will resolve any discrepancy between the two authors by discussion and, if required, by consultation with the UGPD Review Group's editors.
Data extraction and management
Two authors (Wu S, Lu J) will independently extract the data, check and enter the data into an electronic data collection form (Microsoft Word) (Figure 1). We will resolve any discrepancies between the two authors by consensus.
|Figure 1. Data collection form (Microsoft Word)|
Assessment of risk of bias in included studies
Two review authors (Cheng Y, Yang C) will assess the methodological quality of the included trials independently. We plan to use the quality checklist recommended by the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (Higgins 2011c). We will assess the risk of bias of the trials based on the following domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias (Gurusamy 2009; Higgins 2011c). In all cases, 'Low risk' indicates a low risk of bias, 'High risk' indicates high risk of bias, and 'Unclear risk' indicates that insufficient details are reported of what happened in the study (Higgins 2011c). We will resolve any disagreements by discussion and referral to a third author (Cheng N) for adjudication. We intend to present the results for the risk of bias in two figures (a 'Risk of bias' graph and a 'Risk of bias' summary) generated using Review Manager 5 (RevMan 2011).
Measures of treatment effect
We will perform the meta-analyses using the software package Review Manager 5 (RevMan 2011). For dichotomous outcomes, we will calculate the risk ratio (RR) with 95% confidence interval (Deeks 2011). For continuous outcomes, we will calculate the mean difference (MD) with 95% confidence interval (Deeks 2011). For continuous outcomes with different measurement scales in different RCTs, we will calculate the standardized mean difference (SMD) with 95% confidence interval (Deeks 2011).
Unit of analysis issues
The unit of analysis is each patient. We will analyze data using the generic inverse-variance method in Review Manager 5 for cluster-randomized trials (Higgins 2011a). We will combine groups to create a single pair-wise comparison for trials with multiple intervention groups (Higgins 2011a).
Dealing with missing data
We will contact the original investigators to request further information in the case of missing data. If there is no reply, we will perform the analysis using the 'intention-to-treat' (ITT) principle, if applicable (Newell 1992). Otherwise, we will use only the available data in the analysis.
Assessment of heterogeneity
We plan to describe the heterogeneity by using the Chi² test (Deeks 2011). A P value less than 0.10 is considered to indicate significant heterogeneity (Deeks 2011). We also plan to use the I² statistic to measure the quantity of heterogeneity. In the case of significant heterogeneity, we will perform the meta-analysis and interpret the result cautiously. We will explore the clinical heterogeneity by comparing the characteristics of participants, interventions, controls, outcome measures, and study designs in the included studies. We plan to undertake the following approaches for explanation and solution.
- Check that the data are correct.
- Change the effect measure.
- Use the random-effects model for analysis.
- Carry out a sensitivity analysis by excluding potentially biased trials.
- Carry out subgroup analysis or meta-regression.
- Present all trials and provide a narrative discussion (Deeks 2011).
Assessment of reporting biases
If meta-analysis is possible, we plan to use funnel plots to assess reporting biases (Sterne 2011). Visual asymmetry in funnel plots will be used to determine the reporting biases (Sterne 2011). We will not perform funnel plots if the number of included trials is less than 10 (Sterne 2011).
We will perform the meta-analyses using Review Manager 5 software provided by The Cochrane Collaboration (RevMan 2011). Two review authors (Lin Y, Zhou R) will enter all data into Review Manager independently. Any disagreement will be resolved by consensus. For all analyses, we will employ the random-effects model. We will perform the meta-analysis if there are sufficient trials of similar comparisons reporting the same outcomes. Otherwise, we will describe the results of the included RCTs and provide a narrative discussion (Deeks 2011).
Subgroup analysis and investigation of heterogeneity
If there is significant heterogeneity among the RCTs we plan to perform the following subgroup analyses.
- RCTs with low risk of bias versus RCTs with high risk of bias.
- Different etiologies (pancreatic cancer, chronic pancreatitis, and others).
- The type of operation (proximal, distal, and central pancreatectomy).
We will perform sensitivity analyses to see whether conclusions are robust to decisions made during the review process using the following methods.
- Changing between a fixed-effect model and a random-effects model.
- Changing between risk ratios (RR), risk differences (RD), and odds ratios (OR) for dichotomous outcomes.
- Changing between mean differences (MD) and standardized mean differences (SMD) for continuous outcomes.
- Changing between worst-case scenario analysis and best-case scenario analysis for missing data.
If the results do not change, they are considered to have low sensitivity. If the results change, they are considered to have high sensitivity.
We would like to thank the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group including Karin Dearness who assisted in the development of the protocol, Racquel Simpson who developed the search strategies and ran the literature searches.
Appendix 1. CENTRAL search strategy
- MeSH descriptor Pancreas, explode all trees
- MeSH descriptor Common Bile Duct, explode all trees
- MeSH descriptor Ampulla of Vater, explode all trees
- MeSH descriptor Duodenum, explode all trees
- (pancrea*):ti,ab,kw (Title, Abstract,or Keyword)
- (#1 OR #2 OR #3 OR #4 OR #5 )
- MeSH descriptor Carcinoma, this term only
- MeSH descriptor Adenocarcinoma, this term only
- MeSH descriptor Carcinoma, Ductal, this term only
- MeSH descriptor Carcinoma, Islet Cell, this term only
- MeSH descriptor Neoplasms explode all trees
- (cancer$ OR neoplas* OR cyst$ OR growth$ OR adenocarcin* OR malig*)
- (tumo* OR tumour$ OR tumor$ )
- (carcin* OR carcinoma$)
- (#7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14)
- (#6 AND #15)
- MeSH descriptor Pancreatitis explode all trees
- (pancreatiti*) ti,ab,kw
- (#16 OR #17 OR #18)
- MeSH descriptor Surgical Procedures, Operative explode all trees
- MeSH descriptor General Surgery explode all trees
- (surger*) ti,ab,kw
- (operati*) ti,ab,kw
- (operative therap*) ti,ab,kw
- (resection*) ti,ab,kw
- (#20 OR #21 OR #22 OR #23 OR #24 OR #25)
- (#19 AND #26)
- MeSH descriptor Pancreatectomy explode all trees
- MeSH descriptor Pancreaticojejunostomy explode all trees
- MeSH descriptor Pancreaticoduodenectomy explode all trees
- (pancreaticogastrostom*) ti,ab,kw
- (duodenopancreatectom*) ti,ab,kw
- (#27 OR #28 OR#29 OR #30 OR #31 OR #32)
- MeSH descriptor Drainage, explode all trees
- MeSH descriptor Suction, explode all trees
- MeSH descriptor Negative-pressure wound therapy, explode all trees
- (drain*) ti,ab,kw
- (suction*) ti,ab,kw
- (negative-pressure wound therap*) ti,ab,kw
- (#34 OR #35 OR #36 OR #37 OR #38 OR #39)
- (#33 AND #40)
Appendix 2. MEDLINE (PubMed) search strategy
- randomized controlled trial [pt]
- controlled clinical trial [pt]
- randomized [tiab]
- placebo [tiab]
- drug therapy [sh]
- randomly [tiab]
- trial [tiab]
- groups [tiab]
- (1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8)
- animals [mh] NOT humans [mh]
- (#9 NOT #10)
- Pancreatic Neoplasms [MeSH]
- Common Bile Duct Neoplasms [Mesh]
- Ampulla of Vater [Mesh]
- Duodenal Neoplasms [Mesh]
- pancrea* cancer* [tiab]
- pancrea* carcinoma* [tiab]
- pancrea* tumo* [tiab]
- Pancreatitis [MeSH]
- pancreatiti* [tiab]
- (#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20)
- Surgical Procedures, Operative [MeSH]
- General Surgery [MeSH]
- operati* [tiab]
- operative therap* [tiab]
- surger* [tiab]
- resection* [tiab]
- (#22 OR #23 OR #24 OR #25 OR #26 OR #27)
- (#21 AND #28)
- Pancreas/surgery [MeSH]
- Pancreatectomy [MeSH]
- Pancreaticojejunostomy [MeSH]
- Pancreaticoduodenectomy [MeSH]
- pancreaticogastrostom* [tiab]
- duodenopancreatectom* [tiab]
- (#29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35)
- Drainage [MeSH]
- Suction [MeSH]
- Negative-pressure wound therapy [MeSH]
- drain* [tiab]
- suction* [tiab]
- negative-pressure wound therap* [tiab]
- (#37 OR #38 OR #39 OR #40 OR #41 OR #42)
- (#9 OR #36 OR #43)
Appendix 3. EMBASE search strategy
- 'clinical trial'/exp OR 'clinical trial'
- 'randomized controlled trial'/exp OR 'randomized controlled trial'
- 'randomization'/exp OR 'randomization'
- 'single-blind method'/exp OR 'single-blind method'
- 'double-blind method'/exp OR 'double-blind method'
- 'cross-over studies'/exp OR 'cross-over studies'
- 'random allocation'/exp
- 'placebo'/exp OR 'placebo'
- 'randomi?ed controlled trial$'
- 'random allocation'
- 'randomly allocated'
- 'allocated randomly'
- allocated AND random*
- 'single blind$'
- 'double blind$'
- 'treble blind$' OR 'triple blind$'
- 'prospective study'/exp OR 'prospective study'
- (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19)
- 'case study'/exp OR 'case study'
- 'case report'
- 'abstract report'/exp OR 'abstract report' OR 'letter'/exp OR 'letter'
- (#21 OR #22 OR #23)
- (#20 NOT #24)
- 'pancreas'/exp OR 'pancreas'
- 'common bile duct'/exp OR 'common bile duct'
- 'Vater papilla'/exp OR 'Vater papilla'
- 'duodenum'/exp OR 'duodenum'
- (#26 OR #27 OR #28 OR #29)
- carcin* OR cancer$ OR neoplas* OR tumour$ OR tumor$ OR cyst$ OR growth$ OR adenocarcin* OR malig*
- (#30 AND #31)
- 'pancreas cancer'/exp OR 'pancreas cancer'
- 'duodenum cancer'/exp OR 'duodenum cancer' OR 'duodenum carcinoma'/exp OR 'duodenum carcinoma' OR 'Vater papilla tumor'/exp OR 'Vater papilla tumor' OR 'Vater papilla carcinoma'/exp OR 'Vater papilla carcinoma' OR 'bile duct carcinoma'/exp OR 'bile duct carcinoma' OR 'bile duct cancer'/exp OR 'bile duct cancer'
- (#32 OR #33 OR #34)
- 'pancreatitis'/exp OR 'pancreatitis'
- (#35 OR #36 OR #37)
- 'surgery'/exp OR 'surgery'
- surger* OR operati* OR 'operative therap$' OR resection*
- (#39 OR #40)
- (#38 AND #41)
- 'pancreas resection'/exp OR 'pancreas resection'
- 'pancreaticojejunostomy'/exp OR 'pancreaticojejunostomy'
- 'pancreaticoduodenectomy'/exp OR 'pancreaticoduodenectomy'
- (#42 OR #43 OR #44 OR #45 OR #46 OR #47)
- 'drain'/exp OR drain
- 'suction'/exp OR suction
- 'abscess drainage'/exp OR 'abscess drainage'
- 'abdominal drainage'/exp OR 'abdominal drainage'
- 'wound drainage'/exp OR 'wound drainage'
- 'surgical drainage'/exp OR 'surgical drainage'
- 'vacuum assisted closure'/exp OR 'vacuum assisted closure'
- 'negative pressure wound therapy'/exp OR 'negative pressure wound therapy'
- (#49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58)
- (#25 AND #48 AND #59)
Appendix 4. Science Citation Index Expanded search strategy
- TS=(randomized controlled trial OR controlled clinical trial OR RCT OR randomized OR placebo OR random* OR trial OR groups AND humans)
- TS=(Pancreatic Neoplasms OR Common Bile Duct Neoplasms OR Malignant Tumor of ampullary OR Benign Tumour of ampullary OR Duodenal Neoplasms OR Pancreatitis OR pancrea* cancer* OR pancrea* neoplasm* OR pancrea* carcinoma* OR pancrea* tumo* OR pancreatiti*)
- TS=(Operative Surgical Procedures OR Surgery OR operati* OR operative therap* OR surger* OR resection* )
- (#2 AND #3)
- TS=(Pancreatectomy OR Pancreaticojejunostomy OR Pancreaticoduodenectomy OR pancreatectom* OR pancreaticojejunostom* OR pancreaticoduodenectom* OR pancreaticogastrostom* OR duodenopancreatectom*)
- (#4 OR #5)
- TS=(drain* OR suction* OR negative pressure wound therap* OR negative-pressure wound therap* OR vacuum-assisted closure OR vacuum assisted closure*)
- (#1 AND #6 AND #7)
Appendix 5. Chinese Biomedical Literature Database (CBM) search strategy
- (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12)
- (#14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33)
- 主题词:吻合术, 外科/全部树/全部副主题词
- (#35 OR #36 OR #37 OR #38 OR #39)
- (#34 AND #40)
- (#41 OR #42 OR #43 OR #44 OR #45 OR #46 OR#47 OR #48 OR #49 OR #50)
- (#52 OR #53 OR #54 OR #55 OR #56 OR #57 OR# 58 OR #59)
- (#13 AND #51 AND #60)
Contributions of authors
- Cheng Y: drafted the protocol, developed the search strategies, will assess the risk of bias of the trials and draft the final review.
- Yang C: drafted the protocol, will assess the risk of bias of the trials and interpret the analysis within the review.
- Wu S: will select which trials to include and extract data from trials.
- Lu J: will select which trials to include and extract data from trials.
- Zhou R: will enter data into Review Manager and carry out the analysis.
- Lin Y: will enter data into Review Manager and carry out the analysis.
- Nansheng Cheng: revised the protocol, will revise the final review.
- Cheng Y and Yang C have contributed equally to developing the protocol.
Declarations of interest
Sources of support
- West China Hospital, Sichuan University, China.
- No sources of support supplied