World J Gastroenterol 2015 May 14; 21(18): 5719-5734 ISSN 1007-9327 (print) ISSN 2219-2840 (online)
Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.3748/wjg.v21.i18.5719
© 2015 Baishideng Publishing Group Inc. All rights reserved.
META-ANALYSIS
Systematic review and meta-analysis of prophylactic abdominal drainage after pancreatic resection Chang-Wei Dou, Zhi-Kui Liu, Yu-Li Jia, Xin Zheng, Kang-Sheng Tu, Ying-Min Yao, Qing-Guang Liu drainage is necessary after pancreatic resection.
Chang-Wei Dou, Zhi-Kui Liu, Yu-Li Jia, Xin Zheng, KangSheng Tu, Ying-Min Yao, Qing-Guang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of the Medical College of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Author contributions: Dou CW, Liu ZK, Zheng X, Tu KS, Yao YM and Liu QG designed the research; Dou CW, Liu ZK and Jia YL performed the research; Dou CW, Liu ZK and Zheng X analyzed the data; Dou CW, Liu ZK and Zheng X wrote the paper; Dou CW and Liu ZK contributed equally to this article. Supported by National Natural Scientific Foundation of China (No. 81272645 and No. 81072052 to Liu QG, and No. 81301743 to Zheng X); Research Fund for the Doctoral Program of High Education of China from Ministry of Education, (No. 20120201120090 to Zheng X). Conflict-of-interest: No potential conflicts of interest relevant to this article were reported. Data sharing: No additional data are available. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ Correspondence to: Qing-Guang Liu, PhD, MD, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’ an Jiaotong University, 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. [email protected] Telephone: +86-29-85323905 Fax: +86-29-85323209 Received: October 10, 2014 Peer-review started: October 10, 2014 First decision: November 14, 2014 Revised: November 30, 2014 Accepted: December 19, 2014 Article in press: January 5, 2015 Published online: May 14, 2015
METHODS: PubMed, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published before January 2014. Publications were retrieved if they met the selection criteria. The outcomes of interest included: mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CRPF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Subgroup analyses were also performed for pancreaticoduodenectomy (PD) and for distal pancreatectomy. Begg’s funnel plot and the Egger regression test were employed to assess potential publication bias. RESULTS: Nine eligible studies involving a total of 2794 patients were identified and included in this meta-analysis. Of the included patients, 1373 received prophylactic abdominal drainage. A fixedeffects model meta-analysis showed that placement of prophylactic drainage did not have beneficial effects on clinical outcomes, including morbidity, POPF, CRPF, reoperation, interventional radiology drainage, and length of hospital stay (P s > 0.05). In addition, prophylactic drainage did not significantly increase the risk of abdominal abscess. Overall analysis showed that omitting prophylactic abdominal drainage resulted in higher mortality after pancreatectomy (OR = 1.56; 95%CI: 0.93-2.92). Subgroup analysis of PD showed similar results to those in the overall analysis. Elimination of prophylactic abdominal drainage after PD led to a significant increase in mortality (OR = 2.39; 95%CI: 1.22-4.69; P = 0.01). CONCLUSION: Prophylactic abdominal drainage after pancreatic resection is still necessary, though more evidence from randomized controlled trials assessing prophylactic drainage after PD and distal pancreatectomy are needed.
Abstract AIM: To investigate whether prophylactic abdominal
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection [6]
Key words: Prophylactic abdominal drainage; Pancreatic resection; Systemic review; Meta-analysis
study by Heslin et al showed that intra-abdominal drainage did not significantly reduce the rate of major complications after pancreaticoduodenectomy (PD). In [7] addition, a prospective cohort study by Fisher et al demonstrated that a no drainage policy was associated with a decreased incidence of delayed gastric emptying and wound infection. The first randomized controlled [8] trial (RCT) by Conlon et al showed that omitting prophylactic drainage was not associated with a significant increase in mortality or morbidity. However, [9] Correa-Gallego et al showed that eliminating routine abdominal drainage resulted in a higher mortality rate based on the results of 739 patients. The latest randomized prospective multicenter trial by Van [10] Buren et al demonstrated that omitting prophylactic drainage after PD was associated with higher morbidity and mortality. The results of these studies are conflicting, and the value of prophylactic abdominal drainage in pancreatic resection has been intensively debated in recent years. Therefore, this meta-analysis was conducted to clarify whether prophylactic drainage is necessary for all patients after pancreatic resection.
© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: The elimination of prophylactic abdominal drainage resulted in an increase in mortality rate after pancreatic resection, especially in patients who underwent pancreaticoduodenectomy (PD). Therefore, prophylactic abdominal drainage is still necessary after pancreatic resection. Randomized controlled trials assessing the value of prophylactic abdominal drainage after PD and distal pancreatectomy are required to provide more powerful evidence. Based on current evidence, future prophylactic abdominal drainage may not be routine due to advances in surgical techniques and perioperative management. Moreover, drainage strategy after pancreatic resection should be tailored based on the characteristics of each patient. Dou CW, Liu ZK, Jia YL, Zheng X, Tu KS, Yao YM, Liu QG. Systematic review and meta-analysis of prophylactic abdominal drainage after pancreatic resection. World J Gastroenterol 2015; 21(18): 5719-5734 Available from: URL: http://www.wjgnet. com/1007-9327/full/v21/i18/5719.htm DOI: http://dx.doi. org/10.3748/wjg.v21.i18.5719
MATERIALS AND METHODS Search strategy
PubMed, Web of Science, and the Cochrane Library were searched to obtain relevant articles published up until January 2014. The following medical subject heading (Mesh) terms were used in combination with Boolean operators AND or OR: pancreatico duodenectomy, Whipple, pancreatectomy, pancreatic resection, drain, and drainage. Furthermore, the references in relevant articles were screened manually to identify additional eligible studies. No language restriction was imposed during the electronic search.
INTRODUCTION Prophylactic abdominal drainage, which is considered routine and mandatory after pancreatic resection, is a highly invasive surgery with a morbidity rate as high as 40%. This traditional practice is based on the concept that prophylactic drainage can evacuate anastomotic leakage fluid and abdominal collections. Drainage fluid can serve as a warning sign of anastomotic leakage, intra-abdominal hemorrhage, and abdominal infection. Therefore, it can facilitate the early detection and timely management of postoperative complications. However, prospective studies have demonstrated that prophylactic drainage does not result in any benefit after other abdominal surgeries including [1] [2,3] cholecystectomy , hepatectomy , and colorectal [4] surgery . Some surgeons have begun to question the significance of prophylactic drainage after pancreatic resection, and studies assessing the value of prophylactic drainage after pancreatic resection have been conducted. [5] As early as 1992, Jeekel reported that 22 patients who underwent Whipple’s procedure without abdominal drainage had acceptable postoperative outcomes. The study concluded that abdominal drainage was not mandatory after Whipple’s procedure. In the following two decades, comparative studies were conducted to examine the value of prophylactic abdominal drainage. A retrospective
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Selection criteria
Studies eligible for this meta-analysis had to fulfill the following inclusion criteria: (1) comparative study evaluating the efficacy of prophylactic abdominal drainage after pancreatic resection; (2) at least one postoperative outcome was reported, including mortality, morbidity, pancreatic fistula, abdominal abscess, interventional radiology drainage, reoperation rate, or length of hospital stay; and (3) the study was published as a full-length article. Abstracts, letters, case reports, editorials, expert opinions, reviews, animal studies, and articles not reporting outcomes of interest were excluded.
Outcomes of interest
The outcomes of interest included mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CR-PF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Table 1
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 1 Definitions of clinical outcomes in each included study Author
Mortality
Morbidity
POPF
Heslin et al[6]
NA
NA
Drain output at a rate of ≥ 30 mL/d or more and lasting for more than 7 d
Conlon et al[8]
Deaths within 30 d of surgery
NA
Fisher et al[7]
Deaths within 30 d of surgery. NA
CTCAE (v4.0)[35]
Deaths within 90 d of surgery
Clavien classification[37]
Correa-Gallego et Deaths within 90 d al[9] of surgery
CTCAE (v4.0)[35]
Lim et al[27]
Clavien classification[37] Clavien classification[37] CTCAE (v4.0)[35]
Paulus et al[26]
Adham et al[29]
Mehta et al[28] Van Buren et al[10]
Clavien classification[37] Deaths within 30 d of surgery Deaths within 90 d of surgery
NA
Abdominal abscess
Abdominal collection associated with fever and a positive culture requiring either percutaneous or operative drainage yielding positive cultures Drain output on postoperative day 5 or > 30 Abdominal collection associated with fever mL and amylase level > 150 IU/L and/or three and a positive culture requiring either times greater than the serum value surgical or radiologic drainage ISGPF[36] Abdominal collection with a positive Gram stain or cultures ISGPF[36] Abdominal collection associated with fever, abnormal blood routine test, and positive cultures ISGPF[36] Abdominal collection associated with fever and a positive culture requiring surgical drain or interventional treatment Clinical signs and symptoms with amylase-rich Clinical signs and symptoms or radiologic drainage > 50 mL/d beyond postoperative day diagnosis of abdominal abscess or 10 peritonitis ISGPF[36] NA ISGPF[36]
NA
ISGPF[36]
NA
NA: Not available; CTCAE (v4.0): Common terminology criteria for adverse effects, version 4.0; ISGPF: International Study Group of Pancreatic Fistula.
[12]
shows the definition of clinical outcomes in each study.
based on the Cochrane Collaboration guidelines . The statistical tests were two-sided, and P < 0.05 was regarded as statistically significant. The Cochrane Q test was conducted to assess statistical heterogeneity; P < 0.1 indicated statistically significant heterogeneity, thus the fixed-effects model was used. Otherwise, the 2 random-effects model was employed. The I statistic, 2 which was transformed from the Cochrane Q test [I = 100% × (Q-df)/Q], was also used to assess statistical 2 heterogeneity. An I value of < 25% indicated low heterogeneity, a value of > 50% indicated high heterogeneity and a value between 25 and 50% [12] indicated moderate heterogeneity . To determine the influence of non-RCTs (NRCTs) on pooled results, we performed a restricted analysis of RCTs. A sensitivity test was conducted by reanalyzing the data after removing each trial to assess the robustness of pooled results. As distal pancreatectomy (DP) and PD are two distinct operations, subgroup analyses were conducted to evaluate the efficacy of prophylactic abdominal drainage in PD and in DP. Begg’s funnel plot and the Egger’s regression test were employed to assess potential publication bias in this meta-analysis. A P > 0.1 in the Egger’s test indicated no significant publication bias.
Study extraction and quality assessment
The titles and abstracts of the search results were scanned for potentially eligible studies. Then, the full texts of potentially eligible studies were screened to determine whether they should be included based on the selection criteria. Data from the included articles were extracted independently by two reviewers, and inconsistencies were resolved by consensus. The quality of RCTs was assessed using the Cochrane Risk of Bias Tool, while that of cohort studies and the case-control study was assessed using the modified Newcastle-Ottawa Scale.
Data synthesis and statistical analysis
This meta-analysis was conducted based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, using Review Manager 5 software (The Cochrane Collaboration, Oxford, United Kingdom). Dichotomous variables are presented as ORs with 95%CI, while continuous variables are presented as mean difference (MD) with 95%CI. If the mean value was not available, median values were converted to [11] means for pooled analysis based on Hozo’s method . If the standard deviation (SD) was not available and the range value was available, the SD was calculated [11] from the range value according to Hozo’s formula . If the SD was not reported and the P value or interquartile range value was available, the SD was calculated from the P value or interquartile range value
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RESULTS Figure 1 illustrates the process of study selection. Initially, a total of 5432 articles were obtained through a search of PubMed (n = 2063), Web of Science (n
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Records identified through PubMed (n = 2063)
Records identified through Web of Science (n = 2935)
Records identified through the Cochrane Library (n = 434)
Records after duplicates removed (n = 2101)
Eligibility
Screening
Identification
Dou CW et al . Prophylactic abdominal drainage after pancreatic resection
Records screened (n = 3331)
Records excluded (n = 3308): Non-related articles, reviews, comments, letters, case reports, not enough data for extraction
Full-text articles assessed for eligibility (n = 23)
Full-text articles excluded, with reasons (n = 14) Not comparative studies (n = 1) Review (n = 8) Early vs late removal of drain tube (n = 2) Not related (n = 3)
Included
Studies included in qualitative synthesis (n = 9)
Studies included in quantitative synthesis (meta-analysis) (n = 9)
Figure 1 Flow diagram of literature search and selection.
= 2935) and the Cochrane Library (n = 434). After scanning the titles and abstracts, 2101 duplicates and 3308 irrelevant articles were excluded. Full texts of the remaining 23 potentially eligible articles were screened [5] for detailed assessment. One study was excluded [13,14] due to lack of a control group. Two studies comparing early removal with late removal of drain [15-22] tubes and eight review articles were excluded. [23-25] Three articles were irrelevant and were excluded [6-10,13,26-28] after full-text assessment. Nine studies were finally included in the meta-analysis.
the type of pancreatic resection was uniformly PD. In [7,8,10,26,29] the other four studies , the type of surgery included DP, PD, and other types of pancreatic resection. The study conducted by Correa-Gallego [9] et al included two distinct subgroups of patients. Patients in one subgroup underwent PD, while those in the other subgroup underwent DP. Basic medical information (including comorbidity, preoperative treatment, preoperative biochemical tests, pathology, length of operation, and estimated blood loss) was also reported in the nine included studies. A summary of the comparability of patients in the two groups in each study is shown in Table 3. Most aspects were comparable between the two groups in each study.
Characteristics of the included studies
Basic information on the nine included studies, such as author, year of publication, country, study design, baseline demographics, and surgical procedures are [8,10] listed in Table 2. Of the nine included studies, two [27] were RCTs, one study was a case-control study [6,7,9,26,28,29] and the other six were observational cohort studies. A total of 2794 patients were included in this meta-analysis; 1373 patients received prophylactic abdominal drainage and the remaining 1421 patients did not. The average age of the patients in each study ranged from 62 to 69 years, and the percentage of [6,10,27,28] males varied from 29.6 to 58.1. In four studies ,
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Quality assessment of the included studies
The risk of bias in six cohort studies and one casecontrol study were assessed by the modified Newcastle[6,7,9,26,28,29] Ottawa scale. In the six cohort studies , the exposed cohorts in most studies were representative of the patients who had prophylactic drainage after pancreatic resection. The non-exposed cohorts were selected from the same patient base as the exposed cohorts in most studies. The cohort study by Heslin
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 2 Characteristics of included studies Author, year Heslin et al[6] 1998 Conlon et al[8] 2001 Fisher et al[7] 2011 Paulus et al[26] 2012 Adham et al[29] 2013 Correa-Gallego et al[9] 2013
Lim et al[27] 2013 Mehta et al[28] 2013 Van Buren et al[10] 2013
Country
Design
No. of patients
Group
Age (yr)
Male:female
Operation type: No. of patients
United States
OCS
89
United States
RCT
179
United States
OCS
228
United States
OCS
59
France
OCS
242
United States
OCS
Drain No drain Drain No drain Drain No drain Drain No drain Drain No drain Drain No drain
65 ± 2 65 ± 2 66 (23-81) 69 (33-87) 63 (53-72) 59 (51-70) 52 (44-66) 58 (52-68) 61.5 (20-85) 66.5 (19-85) NA NA
18:20 (58.1) 32:19 46:42 (49.7) 43:48 78:101 (40.7) 19:40 NA NA 66:64 (52.4) 61:51 NA NA
PD: 51 PD: 38 PD: 73, DP: 15 PD: 66, DP: 25 PD: 123, DP: 56 PD: 30, DP: 17 DP: 39 DP: 30 PD: 79, DP: 29, Others: 22 PD: 69, DP: 37, Others: 6 PD: 386 PD: 353
Drain No drain
NA NA
NA NA
DP: 154 DP: 196
Drain No drain Drain No drain Drain No drain
62 (40-76) 62 (38-78) 60 62.5 62.1 ± 11.7 64.3 ± 12.6
8:19 (29.6) 8:19 130:121 232:236 37:31 38:31
PD: 27 PD: 27 PD: 251 PD: 458 PD: 68 PD: 69
France
OCS
739 (Subgroup A of PD) 350 (Subgroup B of DP) 54
United States
OCS
709
United States
RCT
137
OCS: Observational comparative study; PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy; Others: Enucleation and Central pancreatectomy; NA: Not available.
Table 3 Comparability between drained patients and non-drained patients Author
Comorbidity
Preoperative treatment
Preoperative biochemical test
Pathology
Length of operation
Estimated blood loss
Texture of pancreas
Diameter of pancreatic duct
Heslin et al[6] Conlon et al[8] Fisher et al[7]
Comparable NA Significant difference NA Comparable
Comparable Comparable NA
Comparable Comparable Comparable
NA Comparable Comparable
NA NA Comparable
Comparable Comparable
Comparable NA
Comparable Comparable Significant difference Comparable NA
NA NA Comparable
NA Comparable
Comparable NA Significant difference NA Comparable
Comparable NA
NA
NA
Comparable
NA
Comparable
NA
NA
NA
Comparable
Comparable Comparable
Comparable Comparable
Comparable Comparable
Comparable Comparable
Van Buren et al[10]
Comparable
Comparable
Comparable
Comparable
Significant difference Significant difference Comparable Significant difference Comparable
Significant difference NA
Lim et al[27] Mehta et al[28]
Significant difference Significant difference Comparable Significant difference Comparable
Paulus et al[26] Adham et al[29] Correa-Gallego et al[9] PD subgroup DP subgroup
Comparable NA Comparable
Comparable Significant difference Comparable Significant difference Comparable
NA: Not available; PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy.
Effect of prophylactic drainage on patients’ clinical outcomes
[6]
et al reported an independent assessment of the [6,26] clinical outcomes. Two studies did not have a clear description of the length of follow-up. In the case [27] control study , the comparability of cases and controls was ensured by one-to-one matching. The risk of bias [8,10] in the two RCTs was evaluated by the Cochrane Risk of Bias Tool. The two RCTs had a low risk of bias in random sequence generation, allocation concealment and selective reporting. The study by Van Buren et [10] al did not report the blinding assessment of clinical outcomes. The results of the quality assessment for the nine included studies are shown in Table 4.
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The results of this meta-analysis are summarized in Table 5. Forest plots representing the results of the overall analysis are displayed in Figure 2. Forest plots representing the results of subgroup analyses of PD and DP are shown in Figures 3 and 4.
Mortality
Seven of nine studies reported mortality. The mortality rate in the non-prophylactic drainage group was higher than that in the prophylactic drainage group (2.96%
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 4 Quality of assessment of included studies Cohort studies Heslin et al[6] Paulus et al[26] Fisher et al[7] Adham et al[29] Correa-Gallego et al[9] Metha et al[28] Case-control study Lim et al[27] RCTs
Conlon et al[8] Van Buren et al[10]
Representativeness of Selection of the non- Ascertainment of Comparability between the exposed cohort exposed cohort exposure the two cohorts Potential selection bias Same patient base Surgical record No restriction/matching Representative Representative
Same patient base Different patient base Representative Same patient base Representative Same patient base Representative Same patient base Representativeness of Selection of Controls the cases Potential selection bias Hospital control Random sequence Allocation generation concealment Low risk Low risk
Low risk Low risk
Surgical record Surgical record
No restriction/matching No restriction/matching
Surgical record No restriction/matching Surgical record No restriction/matching Surgical record No restriction/matching Ascertainment of Comparability of cases exposure and controls Surgical record One to one matching Blinding of Blinding of outcome participants and assessment personnel High risk Low risk High risk Unclear risk
Assessment of outcome Independent assessment Surgical record Surgical record
Length of followup NM
Surgical record Surgical record Surgical record Assessment of outcome Surgical record Incomplete outcome data
90 d 90 d 90 d Definition of Controls and cases Surgical record Selective reporting
Unclear risk Low risk
Low risk Low risk
NM 30 d
RCT: Randomized controlled trial.
Table 5 Summary of results Outcome of interest Mortality Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Overall morbidity Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP POPF Overall analysis Subgroup analysis of PD Subgroup analysis of DP CR-PF Overall analysis Subgroup analysis of PD Abdominal abscess Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Interventional radiology drainage Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP Reoperation Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP Length of hospital stay Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP
Studies
Patients
Results
Pooled estimates
P value P value for HG
I2
No drainage
Drainage
No drainage
Drainage
(95%CI)
7 2 5
1353 160 954
1283 150 911
2.96% 6.25% 3.35%
1.87% 2.56% 1.32%
1.56 (0.93-2.62) 2.55 (0.79-8.30) 2.39 (1.22-4.69)
0.09 0.12 0.01
0.31 0.25 0.52
15% 26% 0%
9 2 5 2
1421 160 945 226
1373 150 783 193
43.54% 66.88% 46.35% 27.88%
52.59% 67.31% 51.34% 33.68%
0.69 (0.52-0.92) 1.00 (0.58-1.72) 0.69 (0.56-0.84) 1.29 (0.24-6.81)
0.01 1.00 < 0.01 0.76
0.01 0.26 0.23 < 0.01
58% 20% 28% 89%
7 4 2
1292 907 226
1234 732 193
13.78% 13.34% 16.81%
27.55% 26.23% 24.87%
0.55 (0.42-0.72) 0.46 (0.35-0.59) 0.39 (0.07-2.21)
< 0.01 < 0.01 0.29
0.07 0.24 0.17
46% 28% 46%
6 3
743 554
694 346
9.02% 8.84%
13.26% 15.32%
0.72 (0.33-1.59) 0.61 (0.14-2.66)
0.42 0.51
< 0.01 < 0.01
69% 81%
7 2 3
414 160 134
582 150 146
11.84% 15.00% 14.18%
8.59% 7.70% 6.85%
1.29 (0.84-1.98) 1.95 (0.53-7.16) 2.12 (0.95-4.72)
0.25 0.32 0.07
0.34 0.09 0.13
11% 65% 50%
8 2 5 2
1309 160 945 226
1243 150 783 193
11.38% 14.38% 10.16% 18.14%
12.31% 10.90% 12.52% 20.73%
1.05 (0.69-1.62) 1.35 (0.26-6.97) 0.87 (0.65-1.19) 1.03 (0.38-2.80)
0.81 0.72 0.39 0.95
0.03 0.02 0.13 0.13
52% 81% 43% 57%
9 2 5 2
1421 160 945 226
1373 150 783 193
4.71% 16.67% 4.02% 3.54%
4.73% 6.41% 2.68% 6.22%
1.01 (0.70-1.47) 1.11 (0.17-7.29) 1.26 (0.73-2.17) 0.80 (0.29-2.17)
0.95 0.91 0.41 0.66
0.59 0.07 0.51 0.46
0% 70% 0% 0%
9 2 5 2
1421 160 945 226
1373 150 783 193
-
-
-0.96 [-1.74-(-0.18)] 0.78 (-0.40-1.97) -0.75 (-1.73-0.24) -2.10 [-2.46-(-1.73)]
0.02 0.19 0.14 < 0.01
< 0.01 0.49 < 0.01 0.29
92% 0% 85% 11%
PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy; RCT: Randomized clinical trial.
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection No drainage Study or subgroup Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Lim 2013 Mehta 2013 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
5 2 11 1 1 1 11 8
112 91 353 196 47 27 458 39
7 2 3 3 1 1 5 2
130 88 386 154 179 27 251 68
26.1% 8.4% 11.7% 14.1% 1.7% 4.1% 26.5% 7.5%
0.82 [0.25, 2.66] 0.97 [0.13, 7.01] 4.11 [1.14, 14.84] 0.26 [0.03, 2.51] 3.87 [0.24, 63.04] 1.00 [0.06, 16.85] 1.21 [0.42, 3.52] 4.33 [0.88, 21.18]
1283
100.0%
1.56 [0.93, 2.62]
Total (95%CI) 1353 Total events 40 24 2 2 Heterogeneity: χ = 8.26, df = 7 (P = 0.31); I = 15% Test for overall effect: Z = 1.70 (P = 0.09)
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
A. Mortality No drainage Study or subgroup
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
45 52 105 43 22 15 15 248 20 55
112 91 353 196 47 38 27 458 30 69
83 55 139 50 117 23 19 171 15 50
130 88 386 154 179 51 27 251 39 68
11.7% 10.3% 15.8% 12.5% 9.5% 6.9% 4.7% 15.5% 5.6% 7.5%
0.38 [0.23, 0.64] 0.80 [0.44, 1.46] 0.75 [0.55, 1.02] 0.58 [0.36, 0.94] 0.47 [0.24, 0.89] 0.79 [0.34, 1.86] 0.53 [0.17, 1.62] 0.55 [0.40, 0.76] 3.20 [1.18, 8.67] 1.41 [0.64, 3.14]
Total (95%CI) 1421 1373 100.0% Total events 620 722 2 2 2 Heterogeneity: Tau = 0.10; χ = 21.40, df = 9 (P = 0.01); I = 58% Test for overall effect: Z = 2.58 (P = 0.010)
0.69 [0.52, 0.92]
Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Odds ratio M-H, Random, 95%CI
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
B. Morbidity No drainage Study or subgroup
Routine drainage
Risk ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
14 59 38 5 0 48 0 14
112 353 196 47 27 458 30 69
21 104 42 79 6 61 6 21
130 386 154 179 27 251 39 68
12.0% 24.1% 19.8% 7.9% 0.9% 21.5% 0.9% 13.0%
0.77 [0.41, 1.45] 0.62 [0.47, 0.82] 0.71 [0.48, 1.04] 0.24 [0.10, 0.56] 0.08 [0.00, 1.30] 0.43 [0.31, 0.61] 0.10 [0.01, 1.70] 0.66 [0.37, 1.18]
Total (95%CI) 1292 1234 100.0% Total events 178 340 2 2 2 Heterogeneity: Tau = 0.06; χ = 12.95, df = 7 (P = 0.07); I = 46% Test for overall effect: Z = 4.35 (P < 0.0001)
0.55 [0.42, 0.72]
Adham 2013 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Risk ratio M-H, Random, 95%CI
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
C. POPF No drainage Study or subgroup Adham 2013 Fisher 2011 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
13 5 0 35 0 14
112 47 27 458 30 69
12 21 5 41 6 7
130 179 27 251 39 68
22.1% 19.5% 5.8% 26.4% 5.9% 20.2%
Total (95%CI) 743 694 100.0% Total events 67 92 2 2 2 Heterogeneity: Tau = 0.56; χ = 16.07, df = 5 (P = 0.007); I = 69% Test for overall effect: Z = 0.81 (P = 0.42)
1.29 0.90 0.07 0.42 0.08 2.22
[0.56, [0.32, [0.00, [0.26, [0.00, [0.83,
Odds ratio M-H, Random, 95%CI
2.96] 2.52] 1.42] 0.69] 1.56] 5.90]
0.72 [0.33, 1.59]
0.01
0.1
1
Favours (No drainage)
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Odds ratio
Odds ratio
Events
Total
Events
Drainage Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
15 6 2 0 1 7 18
112 91 47 38 27 30 69
16 6 10 3 1 8 6
130 88 179 51 27 39 68
35.4% 15.7% 11.0% 8.2% 2.7% 14.7% 12.3%
1.10 [0.52, 2.34] 0.96 [0.30, 3.11] 0.75 [0.16, 3.55] 0.18 [0.01, 3.59] 1.00 [0.06, 16.85] 1.18 [0.37, 3.72] 3.65 [1.35, 9.87]
582
100.0%
1.29 [0.84, 1.98]
Total (95%CI) 414 Total events 49 50 2 2 Heterogeneity: χ = 6.77, df = 9 (P = 0.34); I = 11% Test for overall effect: Z = 1.16 (P = 0.25)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
E. Abdominal abscess No drainage Study or subgroup Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
7 49 34 5 1 1 29 7 16
91 353 196 47 38 27 458 30 69
11 68 35 4 2 1 21 5 6
88 386 154 179 51 27 251 39 68
10.9% 21.5% 18.9% 7.3% 2.8% 2.1% 17.7% 8.0% 10.8%
Total (95%CI) 1309 1243 100.0% Total events 149 153 2 2 2 Heterogeneity: Tau = 0.18; χ = 16.65, df = 8 (P = 0.03); I = 52% Test for overall effect: Z = 0.24 (P = 0.81)
Odds ratio M-H, Random, 95%CI
0.58 [0.22, 1.58] 0.75 [0.51, 1.12] 0.71 [0.42, 1.21] 5.21 [1.34, 20.24] 0.66 [0.06, 7.58] 1.00 [0.06, 16.85] 0.74 [0.41, 1.33] 2.07 [0.58, 7.32] 3.12 [1.14, 8.54] 1.05 [0.69, 1.62]
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
F. Interventional radiology drainage No drainage Study or subgroup Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
17 4 2 0 0 3 1 26 8 6
112 91 353 196 47 38 27 458 30 69
16 8 2 1 8 1 2 14 11 2
130 88 386 154 179 51 27 251 39 68
22.4% 13.9% 3.4% 3.0% 6.3% 1.4% 3.4% 30.4% 12.5% 3.3%
1.27 [0.61, 2.66] 0.46 [0.13, 1.59] 1.09 [0.15, 7.81] 0.26 [0.01, 6.44] 0.21 [0.01, 3.75] 4.29 [0.43, 42.92] 0.48 [0.04, 5.64] 1.02 [0.52, 1.99] 0.93 [0.32, 2.69] 3.14 [0.61, 16.16]
1373
100.0%
1.01 [0.70, 1.47]
Total (95%CI) 1421 Total events 67 65 2 2 Heterogeneity: χ = 7.50, df = 9 (P = 0.59); I = 0% Test for overall effect: Z = 0.07 (P = 0.95)
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection G. Reoperation Mean difference
Mean difference
Study or subgroup
Mean
No drainage SD
Total
Routine drainage Mean
SD
Total
Weight
IV, Random, 95%CI
IV, Random, 95%CI
Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
17.8 9 7 5 7 12 10 11.3 6.5 8
20.67 9.75 2.96 1.48 0.75 1 4.5 9.63 0.75 5.19
112 91 353 196 47 38 27 458 30 69
16.2 9 8 7 7 12 15 13.8 9 7
16 7.5 2.96 2.22 1 1 11.25 9.63 2.5 2.22
130 88 386 154 179 51 27 251 39 68
2.3% 5.7% 14.1% 14.2% 14.5% 14.2% 2.4% 9.6% 12.6% 10.3%
1.06 [-1.33, 6.13] 0.00 [-2.54, 2.54] -1.00 [-1.27, -0.57] -2.00 [-2.41, -1.59] 0.00 [-0.26, 0.26] 0.00 [-0.42, 0.42] -5.00 [-9.57, -0.43] -2.50 [-3.98, -1.02] -2.50 [-3.33, -1.67] 1.00 [-0.33, 2.33]
Total (95%CI) 1421 1373 100.0% -0.96 [-1.74, -0.18] 2 2 2 Heterogeneity: Tau = 1.07; χ = 113.60, df = 9 (P < 0.00001); I = 92% -100 -50 0 50 100 Test for overall effect: Z = 2.42 (P = 0.02) Favours (No drainage) Favours (Drainage) H. Length of hospital stay
Figure 2 Forest plots of clinical outcomes in patients with prophylactic drainage vs those without prophylactic drainage after pancreatic resection. The effect of prophylactic abdominal drainage on A: Mortality; B: Morbidity; C: Postoperative pancreatic fistula (POPF); D: Clinically relevant pancreatic fistula (CR-PF); E: Abdominal abscess; F: Interventional radiology drainage; G: Reoperation; and H: Length of hospital stay.
vs 1.87%), although the difference was not statistically significant (OR = 1.56, 95%CI: 0.93-2.92; P = 0.09; 2 I = 15%). Pooled analysis of the two RCTs showed consistent results. The sensitivity test showed that eliminating prophylactic drainage was associated with a significant increase in mortality (OR = 1.83, 95%CI: 2 1.02-3.28; P = 0.04; I = 13%), after excluding the [29] study by Adham et al .
formation between the two groups and showed discordant results. Prophylactic drainage did not lead to a significantly higher rate of abdominal abscess 2 formation (OR = 1.29, 95%CI: 0.84-1.98; P < 0.25; I = 11%). Restricted analysis of the RCTs confirmed this result. This was unchanged after the sensitivity test.
Interventional radiology drainage
Eight studies reported the rate of postoperative interventional drainage. The frequency of interventional radiology drainage was not different between the 2 groups (OR = 1.05, 95%CI: 0.69-1.62; P = 0.81; I = 52%). This result was also supported by restricted analysis of the two RCTs. The result was not altered after the sensitivity test.
Morbidity
All nine studies reported morbidity. Pooled results favored the elimination of prophylactic drainage due to significantly lower morbidity in the non-drainage group 2 (OR = 0.69, 95%CI: 0.52-0.92; P = 0.01; I = 58%). However, restricted analysis of the two RCTs showed that omitting prophylactic drainage was not associated with reduced morbidity (OR = 1.00, 95%CI: 0.58-1.72; 2 P = 1.00; I = 58%). The sensitivity test demonstrated that the difference in morbidity between the groups was not significant after excluding the study by Mehta [28] 2 et al (OR = 0.73, 95%CI: 0.53-1.01; P = 0.06; I = 60%).
Reoperation
All nine studies reported the rate of reoperation after pancreatic resection. Four studies reported higher reoperation rates in the non-prophylactic drainage group, while the other five studies reported the opposite results. The reoperation rates were similar 2 (OR = 1.01, 95%CI: 0.70-1.47; P = 0.95; I = 0%) between the two groups. Restricted analysis of the RCTs showed a similar result. The robustness of this result was confirmed by the sensitivity test.
POPF and CR-PF
Seven studies reported the rate of POPF and CR-PF. The pooled results suggested that omitting prophylactic drainage was associated with a significantly lower rate 2 of POPF (OR = 0.55, 95%CI: 0.42-0.72; P < 0.01; I = 46%). The difference in the rate of CR-PF was not statistically different between the groups (OR = 0.72, 2 95%CI: 0.33-1.59; P = 0.42; I = 69%). Restricted analysis of the RCTs showed consistent results. The sensitivity test for POPF and CR-PF confirmed the above results.
Length of hospital stay
Nine studies reported the length of hospital stay. Pooled results showed that eliminating prophylactic drainage resulted in a significantly shorter length of hospital stay [MD = -0.96, 95%CI: -1.74-(-0.18); P = 0.02]. Noteworthy was the high statistical heterogeneity 2 between the studies (I = 92%). Restricted analysis of the RCTs showed consistent results. However, the results were altered after removing the study by Mehta [28] 2 et al (MD = -0.80, 95%CI: -1.61-0.01; P = 0.05; I
Abdominal abscess
Seven studies compared the rate of abdominal abscess
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection No drainage Study or subgroup
Routine drainage
Odds ratio
Odds ratio
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
Events
Total
Events
Total
Weight
Correa-Gallego 2013 (a)
11
353
3
386
22.7%
4.11 [1.14, 14.84]
Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
1 1 11 8
47 27 458 39
1 1 5 2
179 27 251 68
3.3% 7.9% 51.5% 14.6%
3.87 [0.24, 63.04] 1.00 [0.06, 16.85] 1.21 [0.42, 3.52] 4.33 [0.88, 21.18]
911
100.0%
2.39 [1.22, 4.69]
Total (95%CI) 954 Total events 32 12 2 2 Heterogeneity: χ = 3.26, df = 4 (P = 0.52); I = 0% Test for overall effect: Z = 2.54 (P = 0.01)
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
A. Mortality Study or subgroup Correa-Gallego 2013 (a) Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
No drainage Events Total 105 353 15 38 15 27 248 458 55 69
Routine drainage Events Total 139 386 23 51 19 27 171 251 50 68
Total (95%CI) 945 Total events 438 402 2 2 Heterogeneity: χ = 5.57, df = 4 (P = 0.23); I = 28% Test for overall effect: Z = 3.62 (P = 0.0003)
783
Weight 41.4% 5.3% 3.8% 45.0% 4.5%
Odds ratio M-H, Fixed, 95%CI 0.75 [0.55, 1.02] 0.79 [0.34, 1.86] 0.53 [0.17, 1.62] 0.55 [0.40, 0.76] 1.41 [0.64, 3.14]
100.0%
0.69 [0.56, 0.84]
Odds ratio M-H, Fixed, 95%CI
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
B. Morbidity No drainage Study or subgroup Correa-Gallego 2013 (a) Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
Risk ratio
Risk ratio
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
Events
Total
Events
Total
Weight
59 0 48 14
353 27 458 69
104 6 61 21
386 27 251 68
49.6% 3.6% 40.0% 9.6%
0.54 0.06 0.36 0.57
732
100.0%
0.46 [0.35, 0.59]
Total (95%CI) 907 Total events 121 192 2 2 Heterogeneity: χ = 4.19, df = 3 (P = 0.24); I = 28% Test for overall effect: Z = 6.02 (P < 0.00001)
[0.38, 0.78] [0.00, 1.13] [0.24, 0.55] [0.26, 1.24]
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
C. POPF Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
0 35 14
27 458 69
5 41 7
27 251 68
16.3% 44.7% 38.9%
0.07 [0.00, 1.42] 0.42 [0.26, 0.69] 2.22 [0.14, 2.66]
Total (95%CI) 554 346 100.0% Total events 49 53 2 2 2 Heterogeneity: Tau = 1.21; χ = 10.71, df = 2 (P = 0.005); I = 81% Test for overall effect: Z = 0.66 (P = 0.51)
0.61 [0.14, 2.66]
Study or subgroup Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
D. CR-PF No drainage Study or subgroup Heslin 1998 Lim 2013 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
0 1 18
38 27 69
3 1 6
51 27 68
35.3% 11.5% 53.2%
0.18 [0.01, 3.59] 1.00 [0.06, 16.85] 3.65 [1.35, 9.87]
146
100.0%
2.12 [0.95, 4.72]
Total (95%CI) 134 Total events 19 10 2 2 Heterogeneity: χ = 4.02, df = 2 (P = 0.13); I = 50% Test for overall effect: Z = 1.84 (P = 0.07)
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Odds ratio
Odds ratio
Events
Total
Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
49 1 1 29 16
353 38 27 458 69
68 2 1 21 6
386 51 27 251 68
63.1% 1.9% 1.1% 28.7% 5.2%
0.75 [0.51, 1.12] 0.66 [0.06, 7.58] 1.00 [0.06, 16.85] 0.74 [0.41, 1.33] 3.12 [1.14, 8.54]
783
100.0%
0.87 [0.65, 1.19]
Correa-Gallego 2013 (a) Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
Total (95%CI) 945 Total events 96 98 2 2 Heterogeneity: χ = 7.03, df = 4 (P = 0.13); I = 43% Test for overall effect: Z = 0.86 (P = 0.39)
F. Interventional radiology drainage No drainage Study or subgroup Events Total Correa-Gallego 2013 (a) 2 353 Heslin 1998 3 38 Lim 2013 1 27 Mehta 2013 26 458 Van Buren 2013 6 69
0.01 0.1 1 Favours (No drainage)
Routine drainage Events Total 2 386 1 51 2 27 14 251 2 68
Total (95%CI) 945 Total events 38 21 2 2 Heterogeneity: χ = 3.28, df = 4 (P = 0.51); I = 0% Test for overall effect: Z = 0.82 (P = 0.41)
783
Weight 8.1% 3.3% 8.2% 72.6% 7.8%
Odds ratio M-H, Fixed, 95%CI 1.09 [0.15, 7.81] 4.29 [0.43, 42.92] 0.48 [0.04, 5.64] 1.02 [0.52, 1.99] 3.14 [0.61, 16.16]
100.0%
1.26 [0.73, 2.17]
10 100 Favours (Drainage)
Odds ratio M-H, Fixed, 95%CI
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
G. Reoperation No drainage
Mean difference
Mean difference
SD
Total
Mean
SD
Total
Weight
IV, Random, 95%CI
IV, Random, 95%CI
2.96 1 4.5 9.63 5.19
353 38 27 458 69
8 12 15 13.8 7
2.96 1 11.25 9.63 2.22
386 51 27 251 68
29.1% 29.1% 4.0% 18.1% 19.7%
-1.00 [-1.43, -0.57] 0.00 [-0.42, 0.42] -5.00 [-9.57, -0.43] -2.50 [-3.98, -1.02] 1.00 [-0.33, 2.33]
Total (95%CI) 945 783 100.0% 2 2 2 Heterogeneity: Tau = 0.82; χ = 26.27, df = 4 (P < 0.0001); I = 85% Test for overall effect: Z = 1.49 (P = 0.14)
-0.75 [-1.73, 0.24]
Study or subgroup
Mean
Correa-Gallego 2013 (a) 7 Heslin 1998 12 Lim 2013 10 Mehta 2013 11.3 Van Buren 2013 8
Routine drainage
-100 -50 0 Favours (No drainage)
50 100 Favours (Drainage)
H. Length of hospital stay
Figure 3 Forest plots of subgroup analysis of patients who underwent pancreaticoduodenectomy. For patients who underwent pancreaticoduodenectomy (PD), the effect of prophylactic abdominal drainage on A: Mortality; B: Morbidity; C: Postoperative pancreatic fistula (POPF); D: Clinically relevant pancreatic fistula (CR-PF); E: Abdominal abscess; F: Interventional radiology drainage; G: Reoperation; and H: Length of hospital stay. [26]
2
= 93%) or the study by Paulus et al (MD = -0.74, 2 95%CI: -1.53-0.05; P = 0.07; I = 91%).
(OR = 0.61, 95%CI: 0.14-2.66; P = 0.51; I = 81%), abdominal abscess (OR = 2.12, 95%CI: 0.95-4.72; 2 P = 0.07; I = 50%), reoperation rate (OR = 1.26, 2 95%CI: 0.73-2.17; P = 0.41; I = 0%), postoperative interventional drainage (OR = 0.87, 95%CI: 0.65-1.19; 2 P = 0.39; I = 43%) and length of hospital stay (MD 2 = -0.75, 95%CI: -1.73-0.24; P = 0.14; I = 85%), no significant differences were observed between the groups.
Subgroup analysis
Subgroup analysis of patients who underwent PD: Mortality in the non-prophylactic drainage group after PD was significantly higher than that in the prophylactic drainage group with a pooled estimate 2 of 2.39 (95%CI: 1.22-4.69; P = 0.01; I = 0%). This indicated that omission of prophylactic drainage after PD resulted in significantly higher mortality. However, patients who underwent PD without prophylactic abdominal drainage had a significantly lower rate of morbidity (OR = 0.69, 95%CI: 0.56-0.84; P < 2 0.01; I = 28%) and POPF (OR = 0.46, 95%CI: 2 0.35-0.59; P < 0.01; I = 28%). In terms of CR-PF
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Subgroup analysis of patients who underwent DP: Only two studies were eligible for the subgroup analysis of patients who underwent DP. No significant difference was found between the groups with respect to morbidity (OR = 1.29, 95%CI: 0.24-6.81; P = 0.76; 2 I = 89%), POPF (OR = 0.39, 95%CI: 0.07-2.21; P
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
43 20
196 30
50 15
154 39
53.4% 46.6%
0.58 [0.36, 0.94] 3.20 [1.18, 8.67]
Total (95%CI) 226 193 100.0% Total events 63 65 2 2 2 Heterogeneity: Tau = 1.29; χ = 9.11, df = 1 (P = 0.003); I = 89% Test for overall effect: Z = 0.30 (P = 0.76)
1.29 [0.24, 6.81]
Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
A. Mortality Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
38 0
196 30
42 6
154 39
75.4% 24.6%
0.64 [0.39, 1.06] 0.08 [0.00, 1.56]
Total (95%CI) 226 193 100.0% Total events 38 48 2 2 2 Heterogeneity: Tau = 0.98; χ = 1.86, df = 1 (P = 0.17); I = 46% Test for overall effect: Z = 1.06 (P = 0.29)
0.39 [0.07, 2.21]
Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
B. POPF No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
34 7
196 30
35 5
154 39
90.7% 9.3%
0.71 [0.42, 1.21] 2.07 [0.58, 7.32]
193
100.0%
0.84 [0.52, 1.36]
Total (95%CI) 226 Total events 41 40 2 2 Heterogeneity: χ = 2.32, df = 1 (P = 0.13); I = 57% Test for overall effect: Z = 0.71 (P = 0.48)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
C. Interventional radiology drainage No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
0 8
196 30
1 11
154 39
19.3% 80.7%
0.26 [0.01, 6.44] 0.93 [0.32, 2.69]
193
100.0%
0.80 [0.29, 2.17]
Total (95%CI) 226 Total events 8 12 2 2 Heterogeneity: χ = 0.54, df = 1 (P = 0.46); I = 0% Test for overall effect: Z = 0.44 (P = 0.66)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
D. Reoperation No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
Mean difference
Mean difference
IV, Fixed, 95%CI
IV, Fixed, 95%CI
Mean
SD
Total
Mean
SD
Total
Weight
5 6.5
1.48 0.75
196 30
7 9
2.22 2.5
154 39
80.6% -2.00 [-2.41, -1.59] 19.4% -2.50 [-3.33, -1.67]
193
100.0% -2.10 [-2.46, -1.73]
Total (95%CI) 226 2 2 Heterogeneity: χ = 1.13, df = 1 (P = 0.29); I = 11% Test for overall effect: Z = 11.24 (P < 0.00001)
-100 -50 0 Favours (No drainage)
50 100 Favours (Drainage)
E. Length of hospital stay
Figure 4 Forest plots of subgroup analysis of patients who underwent distal pancreatectomy. For patients who underwent distal pancreatectomy (DP), the effect of prophylactic abdominal drainage on A: Morbidity; B: Postoperative pancreatic fistula (POPF); C: Interventional radiology drainage; D: Reoperation; and E: Length of hospital stay. 2
2
= 0.29; I = 46%), reoperation (OR = 0.80, 95%CI: 2 0.29-2.17; P = 0.66; I = 0%), or interventional radiology drainage (OR = 1.03, 95%CI: 0.38-2.80; P
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= 0.95; I = 57%). Eliminating prophylactic drainage was associated with a significantly reduced length of hospital stay [MD = -2.10, 95%CI: -2.46-(-1.73); P
Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.3748/wjg.v21.i18.5719
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META-ANALYSIS
Systematic review and meta-analysis of prophylactic abdominal drainage after pancreatic resection Chang-Wei Dou, Zhi-Kui Liu, Yu-Li Jia, Xin Zheng, Kang-Sheng Tu, Ying-Min Yao, Qing-Guang Liu drainage is necessary after pancreatic resection.
Chang-Wei Dou, Zhi-Kui Liu, Yu-Li Jia, Xin Zheng, KangSheng Tu, Ying-Min Yao, Qing-Guang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of the Medical College of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China Author contributions: Dou CW, Liu ZK, Zheng X, Tu KS, Yao YM and Liu QG designed the research; Dou CW, Liu ZK and Jia YL performed the research; Dou CW, Liu ZK and Zheng X analyzed the data; Dou CW, Liu ZK and Zheng X wrote the paper; Dou CW and Liu ZK contributed equally to this article. Supported by National Natural Scientific Foundation of China (No. 81272645 and No. 81072052 to Liu QG, and No. 81301743 to Zheng X); Research Fund for the Doctoral Program of High Education of China from Ministry of Education, (No. 20120201120090 to Zheng X). Conflict-of-interest: No potential conflicts of interest relevant to this article were reported. Data sharing: No additional data are available. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ Correspondence to: Qing-Guang Liu, PhD, MD, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’ an Jiaotong University, 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. [email protected] Telephone: +86-29-85323905 Fax: +86-29-85323209 Received: October 10, 2014 Peer-review started: October 10, 2014 First decision: November 14, 2014 Revised: November 30, 2014 Accepted: December 19, 2014 Article in press: January 5, 2015 Published online: May 14, 2015
METHODS: PubMed, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published before January 2014. Publications were retrieved if they met the selection criteria. The outcomes of interest included: mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CRPF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Subgroup analyses were also performed for pancreaticoduodenectomy (PD) and for distal pancreatectomy. Begg’s funnel plot and the Egger regression test were employed to assess potential publication bias. RESULTS: Nine eligible studies involving a total of 2794 patients were identified and included in this meta-analysis. Of the included patients, 1373 received prophylactic abdominal drainage. A fixedeffects model meta-analysis showed that placement of prophylactic drainage did not have beneficial effects on clinical outcomes, including morbidity, POPF, CRPF, reoperation, interventional radiology drainage, and length of hospital stay (P s > 0.05). In addition, prophylactic drainage did not significantly increase the risk of abdominal abscess. Overall analysis showed that omitting prophylactic abdominal drainage resulted in higher mortality after pancreatectomy (OR = 1.56; 95%CI: 0.93-2.92). Subgroup analysis of PD showed similar results to those in the overall analysis. Elimination of prophylactic abdominal drainage after PD led to a significant increase in mortality (OR = 2.39; 95%CI: 1.22-4.69; P = 0.01). CONCLUSION: Prophylactic abdominal drainage after pancreatic resection is still necessary, though more evidence from randomized controlled trials assessing prophylactic drainage after PD and distal pancreatectomy are needed.
Abstract AIM: To investigate whether prophylactic abdominal
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection [6]
Key words: Prophylactic abdominal drainage; Pancreatic resection; Systemic review; Meta-analysis
study by Heslin et al showed that intra-abdominal drainage did not significantly reduce the rate of major complications after pancreaticoduodenectomy (PD). In [7] addition, a prospective cohort study by Fisher et al demonstrated that a no drainage policy was associated with a decreased incidence of delayed gastric emptying and wound infection. The first randomized controlled [8] trial (RCT) by Conlon et al showed that omitting prophylactic drainage was not associated with a significant increase in mortality or morbidity. However, [9] Correa-Gallego et al showed that eliminating routine abdominal drainage resulted in a higher mortality rate based on the results of 739 patients. The latest randomized prospective multicenter trial by Van [10] Buren et al demonstrated that omitting prophylactic drainage after PD was associated with higher morbidity and mortality. The results of these studies are conflicting, and the value of prophylactic abdominal drainage in pancreatic resection has been intensively debated in recent years. Therefore, this meta-analysis was conducted to clarify whether prophylactic drainage is necessary for all patients after pancreatic resection.
© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: The elimination of prophylactic abdominal drainage resulted in an increase in mortality rate after pancreatic resection, especially in patients who underwent pancreaticoduodenectomy (PD). Therefore, prophylactic abdominal drainage is still necessary after pancreatic resection. Randomized controlled trials assessing the value of prophylactic abdominal drainage after PD and distal pancreatectomy are required to provide more powerful evidence. Based on current evidence, future prophylactic abdominal drainage may not be routine due to advances in surgical techniques and perioperative management. Moreover, drainage strategy after pancreatic resection should be tailored based on the characteristics of each patient. Dou CW, Liu ZK, Jia YL, Zheng X, Tu KS, Yao YM, Liu QG. Systematic review and meta-analysis of prophylactic abdominal drainage after pancreatic resection. World J Gastroenterol 2015; 21(18): 5719-5734 Available from: URL: http://www.wjgnet. com/1007-9327/full/v21/i18/5719.htm DOI: http://dx.doi. org/10.3748/wjg.v21.i18.5719
MATERIALS AND METHODS Search strategy
PubMed, Web of Science, and the Cochrane Library were searched to obtain relevant articles published up until January 2014. The following medical subject heading (Mesh) terms were used in combination with Boolean operators AND or OR: pancreatico duodenectomy, Whipple, pancreatectomy, pancreatic resection, drain, and drainage. Furthermore, the references in relevant articles were screened manually to identify additional eligible studies. No language restriction was imposed during the electronic search.
INTRODUCTION Prophylactic abdominal drainage, which is considered routine and mandatory after pancreatic resection, is a highly invasive surgery with a morbidity rate as high as 40%. This traditional practice is based on the concept that prophylactic drainage can evacuate anastomotic leakage fluid and abdominal collections. Drainage fluid can serve as a warning sign of anastomotic leakage, intra-abdominal hemorrhage, and abdominal infection. Therefore, it can facilitate the early detection and timely management of postoperative complications. However, prospective studies have demonstrated that prophylactic drainage does not result in any benefit after other abdominal surgeries including [1] [2,3] cholecystectomy , hepatectomy , and colorectal [4] surgery . Some surgeons have begun to question the significance of prophylactic drainage after pancreatic resection, and studies assessing the value of prophylactic drainage after pancreatic resection have been conducted. [5] As early as 1992, Jeekel reported that 22 patients who underwent Whipple’s procedure without abdominal drainage had acceptable postoperative outcomes. The study concluded that abdominal drainage was not mandatory after Whipple’s procedure. In the following two decades, comparative studies were conducted to examine the value of prophylactic abdominal drainage. A retrospective
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Selection criteria
Studies eligible for this meta-analysis had to fulfill the following inclusion criteria: (1) comparative study evaluating the efficacy of prophylactic abdominal drainage after pancreatic resection; (2) at least one postoperative outcome was reported, including mortality, morbidity, pancreatic fistula, abdominal abscess, interventional radiology drainage, reoperation rate, or length of hospital stay; and (3) the study was published as a full-length article. Abstracts, letters, case reports, editorials, expert opinions, reviews, animal studies, and articles not reporting outcomes of interest were excluded.
Outcomes of interest
The outcomes of interest included mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CR-PF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Table 1
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 1 Definitions of clinical outcomes in each included study Author
Mortality
Morbidity
POPF
Heslin et al[6]
NA
NA
Drain output at a rate of ≥ 30 mL/d or more and lasting for more than 7 d
Conlon et al[8]
Deaths within 30 d of surgery
NA
Fisher et al[7]
Deaths within 30 d of surgery. NA
CTCAE (v4.0)[35]
Deaths within 90 d of surgery
Clavien classification[37]
Correa-Gallego et Deaths within 90 d al[9] of surgery
CTCAE (v4.0)[35]
Lim et al[27]
Clavien classification[37] Clavien classification[37] CTCAE (v4.0)[35]
Paulus et al[26]
Adham et al[29]
Mehta et al[28] Van Buren et al[10]
Clavien classification[37] Deaths within 30 d of surgery Deaths within 90 d of surgery
NA
Abdominal abscess
Abdominal collection associated with fever and a positive culture requiring either percutaneous or operative drainage yielding positive cultures Drain output on postoperative day 5 or > 30 Abdominal collection associated with fever mL and amylase level > 150 IU/L and/or three and a positive culture requiring either times greater than the serum value surgical or radiologic drainage ISGPF[36] Abdominal collection with a positive Gram stain or cultures ISGPF[36] Abdominal collection associated with fever, abnormal blood routine test, and positive cultures ISGPF[36] Abdominal collection associated with fever and a positive culture requiring surgical drain or interventional treatment Clinical signs and symptoms with amylase-rich Clinical signs and symptoms or radiologic drainage > 50 mL/d beyond postoperative day diagnosis of abdominal abscess or 10 peritonitis ISGPF[36] NA ISGPF[36]
NA
ISGPF[36]
NA
NA: Not available; CTCAE (v4.0): Common terminology criteria for adverse effects, version 4.0; ISGPF: International Study Group of Pancreatic Fistula.
[12]
shows the definition of clinical outcomes in each study.
based on the Cochrane Collaboration guidelines . The statistical tests were two-sided, and P < 0.05 was regarded as statistically significant. The Cochrane Q test was conducted to assess statistical heterogeneity; P < 0.1 indicated statistically significant heterogeneity, thus the fixed-effects model was used. Otherwise, the 2 random-effects model was employed. The I statistic, 2 which was transformed from the Cochrane Q test [I = 100% × (Q-df)/Q], was also used to assess statistical 2 heterogeneity. An I value of < 25% indicated low heterogeneity, a value of > 50% indicated high heterogeneity and a value between 25 and 50% [12] indicated moderate heterogeneity . To determine the influence of non-RCTs (NRCTs) on pooled results, we performed a restricted analysis of RCTs. A sensitivity test was conducted by reanalyzing the data after removing each trial to assess the robustness of pooled results. As distal pancreatectomy (DP) and PD are two distinct operations, subgroup analyses were conducted to evaluate the efficacy of prophylactic abdominal drainage in PD and in DP. Begg’s funnel plot and the Egger’s regression test were employed to assess potential publication bias in this meta-analysis. A P > 0.1 in the Egger’s test indicated no significant publication bias.
Study extraction and quality assessment
The titles and abstracts of the search results were scanned for potentially eligible studies. Then, the full texts of potentially eligible studies were screened to determine whether they should be included based on the selection criteria. Data from the included articles were extracted independently by two reviewers, and inconsistencies were resolved by consensus. The quality of RCTs was assessed using the Cochrane Risk of Bias Tool, while that of cohort studies and the case-control study was assessed using the modified Newcastle-Ottawa Scale.
Data synthesis and statistical analysis
This meta-analysis was conducted based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, using Review Manager 5 software (The Cochrane Collaboration, Oxford, United Kingdom). Dichotomous variables are presented as ORs with 95%CI, while continuous variables are presented as mean difference (MD) with 95%CI. If the mean value was not available, median values were converted to [11] means for pooled analysis based on Hozo’s method . If the standard deviation (SD) was not available and the range value was available, the SD was calculated [11] from the range value according to Hozo’s formula . If the SD was not reported and the P value or interquartile range value was available, the SD was calculated from the P value or interquartile range value
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RESULTS Figure 1 illustrates the process of study selection. Initially, a total of 5432 articles were obtained through a search of PubMed (n = 2063), Web of Science (n
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Records identified through PubMed (n = 2063)
Records identified through Web of Science (n = 2935)
Records identified through the Cochrane Library (n = 434)
Records after duplicates removed (n = 2101)
Eligibility
Screening
Identification
Dou CW et al . Prophylactic abdominal drainage after pancreatic resection
Records screened (n = 3331)
Records excluded (n = 3308): Non-related articles, reviews, comments, letters, case reports, not enough data for extraction
Full-text articles assessed for eligibility (n = 23)
Full-text articles excluded, with reasons (n = 14) Not comparative studies (n = 1) Review (n = 8) Early vs late removal of drain tube (n = 2) Not related (n = 3)
Included
Studies included in qualitative synthesis (n = 9)
Studies included in quantitative synthesis (meta-analysis) (n = 9)
Figure 1 Flow diagram of literature search and selection.
= 2935) and the Cochrane Library (n = 434). After scanning the titles and abstracts, 2101 duplicates and 3308 irrelevant articles were excluded. Full texts of the remaining 23 potentially eligible articles were screened [5] for detailed assessment. One study was excluded [13,14] due to lack of a control group. Two studies comparing early removal with late removal of drain [15-22] tubes and eight review articles were excluded. [23-25] Three articles were irrelevant and were excluded [6-10,13,26-28] after full-text assessment. Nine studies were finally included in the meta-analysis.
the type of pancreatic resection was uniformly PD. In [7,8,10,26,29] the other four studies , the type of surgery included DP, PD, and other types of pancreatic resection. The study conducted by Correa-Gallego [9] et al included two distinct subgroups of patients. Patients in one subgroup underwent PD, while those in the other subgroup underwent DP. Basic medical information (including comorbidity, preoperative treatment, preoperative biochemical tests, pathology, length of operation, and estimated blood loss) was also reported in the nine included studies. A summary of the comparability of patients in the two groups in each study is shown in Table 3. Most aspects were comparable between the two groups in each study.
Characteristics of the included studies
Basic information on the nine included studies, such as author, year of publication, country, study design, baseline demographics, and surgical procedures are [8,10] listed in Table 2. Of the nine included studies, two [27] were RCTs, one study was a case-control study [6,7,9,26,28,29] and the other six were observational cohort studies. A total of 2794 patients were included in this meta-analysis; 1373 patients received prophylactic abdominal drainage and the remaining 1421 patients did not. The average age of the patients in each study ranged from 62 to 69 years, and the percentage of [6,10,27,28] males varied from 29.6 to 58.1. In four studies ,
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Quality assessment of the included studies
The risk of bias in six cohort studies and one casecontrol study were assessed by the modified Newcastle[6,7,9,26,28,29] Ottawa scale. In the six cohort studies , the exposed cohorts in most studies were representative of the patients who had prophylactic drainage after pancreatic resection. The non-exposed cohorts were selected from the same patient base as the exposed cohorts in most studies. The cohort study by Heslin
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 2 Characteristics of included studies Author, year Heslin et al[6] 1998 Conlon et al[8] 2001 Fisher et al[7] 2011 Paulus et al[26] 2012 Adham et al[29] 2013 Correa-Gallego et al[9] 2013
Lim et al[27] 2013 Mehta et al[28] 2013 Van Buren et al[10] 2013
Country
Design
No. of patients
Group
Age (yr)
Male:female
Operation type: No. of patients
United States
OCS
89
United States
RCT
179
United States
OCS
228
United States
OCS
59
France
OCS
242
United States
OCS
Drain No drain Drain No drain Drain No drain Drain No drain Drain No drain Drain No drain
65 ± 2 65 ± 2 66 (23-81) 69 (33-87) 63 (53-72) 59 (51-70) 52 (44-66) 58 (52-68) 61.5 (20-85) 66.5 (19-85) NA NA
18:20 (58.1) 32:19 46:42 (49.7) 43:48 78:101 (40.7) 19:40 NA NA 66:64 (52.4) 61:51 NA NA
PD: 51 PD: 38 PD: 73, DP: 15 PD: 66, DP: 25 PD: 123, DP: 56 PD: 30, DP: 17 DP: 39 DP: 30 PD: 79, DP: 29, Others: 22 PD: 69, DP: 37, Others: 6 PD: 386 PD: 353
Drain No drain
NA NA
NA NA
DP: 154 DP: 196
Drain No drain Drain No drain Drain No drain
62 (40-76) 62 (38-78) 60 62.5 62.1 ± 11.7 64.3 ± 12.6
8:19 (29.6) 8:19 130:121 232:236 37:31 38:31
PD: 27 PD: 27 PD: 251 PD: 458 PD: 68 PD: 69
France
OCS
739 (Subgroup A of PD) 350 (Subgroup B of DP) 54
United States
OCS
709
United States
RCT
137
OCS: Observational comparative study; PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy; Others: Enucleation and Central pancreatectomy; NA: Not available.
Table 3 Comparability between drained patients and non-drained patients Author
Comorbidity
Preoperative treatment
Preoperative biochemical test
Pathology
Length of operation
Estimated blood loss
Texture of pancreas
Diameter of pancreatic duct
Heslin et al[6] Conlon et al[8] Fisher et al[7]
Comparable NA Significant difference NA Comparable
Comparable Comparable NA
Comparable Comparable Comparable
NA Comparable Comparable
NA NA Comparable
Comparable Comparable
Comparable NA
Comparable Comparable Significant difference Comparable NA
NA NA Comparable
NA Comparable
Comparable NA Significant difference NA Comparable
Comparable NA
NA
NA
Comparable
NA
Comparable
NA
NA
NA
Comparable
Comparable Comparable
Comparable Comparable
Comparable Comparable
Comparable Comparable
Van Buren et al[10]
Comparable
Comparable
Comparable
Comparable
Significant difference Significant difference Comparable Significant difference Comparable
Significant difference NA
Lim et al[27] Mehta et al[28]
Significant difference Significant difference Comparable Significant difference Comparable
Paulus et al[26] Adham et al[29] Correa-Gallego et al[9] PD subgroup DP subgroup
Comparable NA Comparable
Comparable Significant difference Comparable Significant difference Comparable
NA: Not available; PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy.
Effect of prophylactic drainage on patients’ clinical outcomes
[6]
et al reported an independent assessment of the [6,26] clinical outcomes. Two studies did not have a clear description of the length of follow-up. In the case [27] control study , the comparability of cases and controls was ensured by one-to-one matching. The risk of bias [8,10] in the two RCTs was evaluated by the Cochrane Risk of Bias Tool. The two RCTs had a low risk of bias in random sequence generation, allocation concealment and selective reporting. The study by Van Buren et [10] al did not report the blinding assessment of clinical outcomes. The results of the quality assessment for the nine included studies are shown in Table 4.
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The results of this meta-analysis are summarized in Table 5. Forest plots representing the results of the overall analysis are displayed in Figure 2. Forest plots representing the results of subgroup analyses of PD and DP are shown in Figures 3 and 4.
Mortality
Seven of nine studies reported mortality. The mortality rate in the non-prophylactic drainage group was higher than that in the prophylactic drainage group (2.96%
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Table 4 Quality of assessment of included studies Cohort studies Heslin et al[6] Paulus et al[26] Fisher et al[7] Adham et al[29] Correa-Gallego et al[9] Metha et al[28] Case-control study Lim et al[27] RCTs
Conlon et al[8] Van Buren et al[10]
Representativeness of Selection of the non- Ascertainment of Comparability between the exposed cohort exposed cohort exposure the two cohorts Potential selection bias Same patient base Surgical record No restriction/matching Representative Representative
Same patient base Different patient base Representative Same patient base Representative Same patient base Representative Same patient base Representativeness of Selection of Controls the cases Potential selection bias Hospital control Random sequence Allocation generation concealment Low risk Low risk
Low risk Low risk
Surgical record Surgical record
No restriction/matching No restriction/matching
Surgical record No restriction/matching Surgical record No restriction/matching Surgical record No restriction/matching Ascertainment of Comparability of cases exposure and controls Surgical record One to one matching Blinding of Blinding of outcome participants and assessment personnel High risk Low risk High risk Unclear risk
Assessment of outcome Independent assessment Surgical record Surgical record
Length of followup NM
Surgical record Surgical record Surgical record Assessment of outcome Surgical record Incomplete outcome data
90 d 90 d 90 d Definition of Controls and cases Surgical record Selective reporting
Unclear risk Low risk
Low risk Low risk
NM 30 d
RCT: Randomized controlled trial.
Table 5 Summary of results Outcome of interest Mortality Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Overall morbidity Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP POPF Overall analysis Subgroup analysis of PD Subgroup analysis of DP CR-PF Overall analysis Subgroup analysis of PD Abdominal abscess Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Interventional radiology drainage Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP Reoperation Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP Length of hospital stay Overall analysis Restricted analysis of RCTs Subgroup analysis of PD Subgroup analysis of DP
Studies
Patients
Results
Pooled estimates
P value P value for HG
I2
No drainage
Drainage
No drainage
Drainage
(95%CI)
7 2 5
1353 160 954
1283 150 911
2.96% 6.25% 3.35%
1.87% 2.56% 1.32%
1.56 (0.93-2.62) 2.55 (0.79-8.30) 2.39 (1.22-4.69)
0.09 0.12 0.01
0.31 0.25 0.52
15% 26% 0%
9 2 5 2
1421 160 945 226
1373 150 783 193
43.54% 66.88% 46.35% 27.88%
52.59% 67.31% 51.34% 33.68%
0.69 (0.52-0.92) 1.00 (0.58-1.72) 0.69 (0.56-0.84) 1.29 (0.24-6.81)
0.01 1.00 < 0.01 0.76
0.01 0.26 0.23 < 0.01
58% 20% 28% 89%
7 4 2
1292 907 226
1234 732 193
13.78% 13.34% 16.81%
27.55% 26.23% 24.87%
0.55 (0.42-0.72) 0.46 (0.35-0.59) 0.39 (0.07-2.21)
< 0.01 < 0.01 0.29
0.07 0.24 0.17
46% 28% 46%
6 3
743 554
694 346
9.02% 8.84%
13.26% 15.32%
0.72 (0.33-1.59) 0.61 (0.14-2.66)
0.42 0.51
< 0.01 < 0.01
69% 81%
7 2 3
414 160 134
582 150 146
11.84% 15.00% 14.18%
8.59% 7.70% 6.85%
1.29 (0.84-1.98) 1.95 (0.53-7.16) 2.12 (0.95-4.72)
0.25 0.32 0.07
0.34 0.09 0.13
11% 65% 50%
8 2 5 2
1309 160 945 226
1243 150 783 193
11.38% 14.38% 10.16% 18.14%
12.31% 10.90% 12.52% 20.73%
1.05 (0.69-1.62) 1.35 (0.26-6.97) 0.87 (0.65-1.19) 1.03 (0.38-2.80)
0.81 0.72 0.39 0.95
0.03 0.02 0.13 0.13
52% 81% 43% 57%
9 2 5 2
1421 160 945 226
1373 150 783 193
4.71% 16.67% 4.02% 3.54%
4.73% 6.41% 2.68% 6.22%
1.01 (0.70-1.47) 1.11 (0.17-7.29) 1.26 (0.73-2.17) 0.80 (0.29-2.17)
0.95 0.91 0.41 0.66
0.59 0.07 0.51 0.46
0% 70% 0% 0%
9 2 5 2
1421 160 945 226
1373 150 783 193
-
-
-0.96 [-1.74-(-0.18)] 0.78 (-0.40-1.97) -0.75 (-1.73-0.24) -2.10 [-2.46-(-1.73)]
0.02 0.19 0.14 < 0.01
< 0.01 0.49 < 0.01 0.29
92% 0% 85% 11%
PD: Pancreaticoduodenectomy; DP: Distal pancreatectomy; RCT: Randomized clinical trial.
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection No drainage Study or subgroup Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Lim 2013 Mehta 2013 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
5 2 11 1 1 1 11 8
112 91 353 196 47 27 458 39
7 2 3 3 1 1 5 2
130 88 386 154 179 27 251 68
26.1% 8.4% 11.7% 14.1% 1.7% 4.1% 26.5% 7.5%
0.82 [0.25, 2.66] 0.97 [0.13, 7.01] 4.11 [1.14, 14.84] 0.26 [0.03, 2.51] 3.87 [0.24, 63.04] 1.00 [0.06, 16.85] 1.21 [0.42, 3.52] 4.33 [0.88, 21.18]
1283
100.0%
1.56 [0.93, 2.62]
Total (95%CI) 1353 Total events 40 24 2 2 Heterogeneity: χ = 8.26, df = 7 (P = 0.31); I = 15% Test for overall effect: Z = 1.70 (P = 0.09)
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
A. Mortality No drainage Study or subgroup
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
45 52 105 43 22 15 15 248 20 55
112 91 353 196 47 38 27 458 30 69
83 55 139 50 117 23 19 171 15 50
130 88 386 154 179 51 27 251 39 68
11.7% 10.3% 15.8% 12.5% 9.5% 6.9% 4.7% 15.5% 5.6% 7.5%
0.38 [0.23, 0.64] 0.80 [0.44, 1.46] 0.75 [0.55, 1.02] 0.58 [0.36, 0.94] 0.47 [0.24, 0.89] 0.79 [0.34, 1.86] 0.53 [0.17, 1.62] 0.55 [0.40, 0.76] 3.20 [1.18, 8.67] 1.41 [0.64, 3.14]
Total (95%CI) 1421 1373 100.0% Total events 620 722 2 2 2 Heterogeneity: Tau = 0.10; χ = 21.40, df = 9 (P = 0.01); I = 58% Test for overall effect: Z = 2.58 (P = 0.010)
0.69 [0.52, 0.92]
Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Odds ratio M-H, Random, 95%CI
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
B. Morbidity No drainage Study or subgroup
Routine drainage
Risk ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
14 59 38 5 0 48 0 14
112 353 196 47 27 458 30 69
21 104 42 79 6 61 6 21
130 386 154 179 27 251 39 68
12.0% 24.1% 19.8% 7.9% 0.9% 21.5% 0.9% 13.0%
0.77 [0.41, 1.45] 0.62 [0.47, 0.82] 0.71 [0.48, 1.04] 0.24 [0.10, 0.56] 0.08 [0.00, 1.30] 0.43 [0.31, 0.61] 0.10 [0.01, 1.70] 0.66 [0.37, 1.18]
Total (95%CI) 1292 1234 100.0% Total events 178 340 2 2 2 Heterogeneity: Tau = 0.06; χ = 12.95, df = 7 (P = 0.07); I = 46% Test for overall effect: Z = 4.35 (P < 0.0001)
0.55 [0.42, 0.72]
Adham 2013 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Risk ratio M-H, Random, 95%CI
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
C. POPF No drainage Study or subgroup Adham 2013 Fisher 2011 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
13 5 0 35 0 14
112 47 27 458 30 69
12 21 5 41 6 7
130 179 27 251 39 68
22.1% 19.5% 5.8% 26.4% 5.9% 20.2%
Total (95%CI) 743 694 100.0% Total events 67 92 2 2 2 Heterogeneity: Tau = 0.56; χ = 16.07, df = 5 (P = 0.007); I = 69% Test for overall effect: Z = 0.81 (P = 0.42)
1.29 0.90 0.07 0.42 0.08 2.22
[0.56, [0.32, [0.00, [0.26, [0.00, [0.83,
Odds ratio M-H, Random, 95%CI
2.96] 2.52] 1.42] 0.69] 1.56] 5.90]
0.72 [0.33, 1.59]
0.01
0.1
1
Favours (No drainage)
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Odds ratio
Odds ratio
Events
Total
Events
Drainage Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
15 6 2 0 1 7 18
112 91 47 38 27 30 69
16 6 10 3 1 8 6
130 88 179 51 27 39 68
35.4% 15.7% 11.0% 8.2% 2.7% 14.7% 12.3%
1.10 [0.52, 2.34] 0.96 [0.30, 3.11] 0.75 [0.16, 3.55] 0.18 [0.01, 3.59] 1.00 [0.06, 16.85] 1.18 [0.37, 3.72] 3.65 [1.35, 9.87]
582
100.0%
1.29 [0.84, 1.98]
Total (95%CI) 414 Total events 49 50 2 2 Heterogeneity: χ = 6.77, df = 9 (P = 0.34); I = 11% Test for overall effect: Z = 1.16 (P = 0.25)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
E. Abdominal abscess No drainage Study or subgroup Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Routine drainage
Odds ratio
Events
Total
Events
Total
Weight M-H, Random, 95%CI
7 49 34 5 1 1 29 7 16
91 353 196 47 38 27 458 30 69
11 68 35 4 2 1 21 5 6
88 386 154 179 51 27 251 39 68
10.9% 21.5% 18.9% 7.3% 2.8% 2.1% 17.7% 8.0% 10.8%
Total (95%CI) 1309 1243 100.0% Total events 149 153 2 2 2 Heterogeneity: Tau = 0.18; χ = 16.65, df = 8 (P = 0.03); I = 52% Test for overall effect: Z = 0.24 (P = 0.81)
Odds ratio M-H, Random, 95%CI
0.58 [0.22, 1.58] 0.75 [0.51, 1.12] 0.71 [0.42, 1.21] 5.21 [1.34, 20.24] 0.66 [0.06, 7.58] 1.00 [0.06, 16.85] 0.74 [0.41, 1.33] 2.07 [0.58, 7.32] 3.12 [1.14, 8.54] 1.05 [0.69, 1.62]
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
F. Interventional radiology drainage No drainage Study or subgroup Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
17 4 2 0 0 3 1 26 8 6
112 91 353 196 47 38 27 458 30 69
16 8 2 1 8 1 2 14 11 2
130 88 386 154 179 51 27 251 39 68
22.4% 13.9% 3.4% 3.0% 6.3% 1.4% 3.4% 30.4% 12.5% 3.3%
1.27 [0.61, 2.66] 0.46 [0.13, 1.59] 1.09 [0.15, 7.81] 0.26 [0.01, 6.44] 0.21 [0.01, 3.75] 4.29 [0.43, 42.92] 0.48 [0.04, 5.64] 1.02 [0.52, 1.99] 0.93 [0.32, 2.69] 3.14 [0.61, 16.16]
1373
100.0%
1.01 [0.70, 1.47]
Total (95%CI) 1421 Total events 67 65 2 2 Heterogeneity: χ = 7.50, df = 9 (P = 0.59); I = 0% Test for overall effect: Z = 0.07 (P = 0.95)
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection G. Reoperation Mean difference
Mean difference
Study or subgroup
Mean
No drainage SD
Total
Routine drainage Mean
SD
Total
Weight
IV, Random, 95%CI
IV, Random, 95%CI
Adham 2013 Conlon 2001 Correa-Gallego 2013 (a) Correa-Gallego 2013 (b) Fisher 2011 Heslin 1998 Lim 2013 Mehta 2013 Paulus 2012 Van Buren 2013
17.8 9 7 5 7 12 10 11.3 6.5 8
20.67 9.75 2.96 1.48 0.75 1 4.5 9.63 0.75 5.19
112 91 353 196 47 38 27 458 30 69
16.2 9 8 7 7 12 15 13.8 9 7
16 7.5 2.96 2.22 1 1 11.25 9.63 2.5 2.22
130 88 386 154 179 51 27 251 39 68
2.3% 5.7% 14.1% 14.2% 14.5% 14.2% 2.4% 9.6% 12.6% 10.3%
1.06 [-1.33, 6.13] 0.00 [-2.54, 2.54] -1.00 [-1.27, -0.57] -2.00 [-2.41, -1.59] 0.00 [-0.26, 0.26] 0.00 [-0.42, 0.42] -5.00 [-9.57, -0.43] -2.50 [-3.98, -1.02] -2.50 [-3.33, -1.67] 1.00 [-0.33, 2.33]
Total (95%CI) 1421 1373 100.0% -0.96 [-1.74, -0.18] 2 2 2 Heterogeneity: Tau = 1.07; χ = 113.60, df = 9 (P < 0.00001); I = 92% -100 -50 0 50 100 Test for overall effect: Z = 2.42 (P = 0.02) Favours (No drainage) Favours (Drainage) H. Length of hospital stay
Figure 2 Forest plots of clinical outcomes in patients with prophylactic drainage vs those without prophylactic drainage after pancreatic resection. The effect of prophylactic abdominal drainage on A: Mortality; B: Morbidity; C: Postoperative pancreatic fistula (POPF); D: Clinically relevant pancreatic fistula (CR-PF); E: Abdominal abscess; F: Interventional radiology drainage; G: Reoperation; and H: Length of hospital stay.
vs 1.87%), although the difference was not statistically significant (OR = 1.56, 95%CI: 0.93-2.92; P = 0.09; 2 I = 15%). Pooled analysis of the two RCTs showed consistent results. The sensitivity test showed that eliminating prophylactic drainage was associated with a significant increase in mortality (OR = 1.83, 95%CI: 2 1.02-3.28; P = 0.04; I = 13%), after excluding the [29] study by Adham et al .
formation between the two groups and showed discordant results. Prophylactic drainage did not lead to a significantly higher rate of abdominal abscess 2 formation (OR = 1.29, 95%CI: 0.84-1.98; P < 0.25; I = 11%). Restricted analysis of the RCTs confirmed this result. This was unchanged after the sensitivity test.
Interventional radiology drainage
Eight studies reported the rate of postoperative interventional drainage. The frequency of interventional radiology drainage was not different between the 2 groups (OR = 1.05, 95%CI: 0.69-1.62; P = 0.81; I = 52%). This result was also supported by restricted analysis of the two RCTs. The result was not altered after the sensitivity test.
Morbidity
All nine studies reported morbidity. Pooled results favored the elimination of prophylactic drainage due to significantly lower morbidity in the non-drainage group 2 (OR = 0.69, 95%CI: 0.52-0.92; P = 0.01; I = 58%). However, restricted analysis of the two RCTs showed that omitting prophylactic drainage was not associated with reduced morbidity (OR = 1.00, 95%CI: 0.58-1.72; 2 P = 1.00; I = 58%). The sensitivity test demonstrated that the difference in morbidity between the groups was not significant after excluding the study by Mehta [28] 2 et al (OR = 0.73, 95%CI: 0.53-1.01; P = 0.06; I = 60%).
Reoperation
All nine studies reported the rate of reoperation after pancreatic resection. Four studies reported higher reoperation rates in the non-prophylactic drainage group, while the other five studies reported the opposite results. The reoperation rates were similar 2 (OR = 1.01, 95%CI: 0.70-1.47; P = 0.95; I = 0%) between the two groups. Restricted analysis of the RCTs showed a similar result. The robustness of this result was confirmed by the sensitivity test.
POPF and CR-PF
Seven studies reported the rate of POPF and CR-PF. The pooled results suggested that omitting prophylactic drainage was associated with a significantly lower rate 2 of POPF (OR = 0.55, 95%CI: 0.42-0.72; P < 0.01; I = 46%). The difference in the rate of CR-PF was not statistically different between the groups (OR = 0.72, 2 95%CI: 0.33-1.59; P = 0.42; I = 69%). Restricted analysis of the RCTs showed consistent results. The sensitivity test for POPF and CR-PF confirmed the above results.
Length of hospital stay
Nine studies reported the length of hospital stay. Pooled results showed that eliminating prophylactic drainage resulted in a significantly shorter length of hospital stay [MD = -0.96, 95%CI: -1.74-(-0.18); P = 0.02]. Noteworthy was the high statistical heterogeneity 2 between the studies (I = 92%). Restricted analysis of the RCTs showed consistent results. However, the results were altered after removing the study by Mehta [28] 2 et al (MD = -0.80, 95%CI: -1.61-0.01; P = 0.05; I
Abdominal abscess
Seven studies compared the rate of abdominal abscess
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection No drainage Study or subgroup
Routine drainage
Odds ratio
Odds ratio
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
Events
Total
Events
Total
Weight
Correa-Gallego 2013 (a)
11
353
3
386
22.7%
4.11 [1.14, 14.84]
Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
1 1 11 8
47 27 458 39
1 1 5 2
179 27 251 68
3.3% 7.9% 51.5% 14.6%
3.87 [0.24, 63.04] 1.00 [0.06, 16.85] 1.21 [0.42, 3.52] 4.33 [0.88, 21.18]
911
100.0%
2.39 [1.22, 4.69]
Total (95%CI) 954 Total events 32 12 2 2 Heterogeneity: χ = 3.26, df = 4 (P = 0.52); I = 0% Test for overall effect: Z = 2.54 (P = 0.01)
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
A. Mortality Study or subgroup Correa-Gallego 2013 (a) Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
No drainage Events Total 105 353 15 38 15 27 248 458 55 69
Routine drainage Events Total 139 386 23 51 19 27 171 251 50 68
Total (95%CI) 945 Total events 438 402 2 2 Heterogeneity: χ = 5.57, df = 4 (P = 0.23); I = 28% Test for overall effect: Z = 3.62 (P = 0.0003)
783
Weight 41.4% 5.3% 3.8% 45.0% 4.5%
Odds ratio M-H, Fixed, 95%CI 0.75 [0.55, 1.02] 0.79 [0.34, 1.86] 0.53 [0.17, 1.62] 0.55 [0.40, 0.76] 1.41 [0.64, 3.14]
100.0%
0.69 [0.56, 0.84]
Odds ratio M-H, Fixed, 95%CI
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
B. Morbidity No drainage Study or subgroup Correa-Gallego 2013 (a) Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
Risk ratio
Risk ratio
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
Events
Total
Events
Total
Weight
59 0 48 14
353 27 458 69
104 6 61 21
386 27 251 68
49.6% 3.6% 40.0% 9.6%
0.54 0.06 0.36 0.57
732
100.0%
0.46 [0.35, 0.59]
Total (95%CI) 907 Total events 121 192 2 2 Heterogeneity: χ = 4.19, df = 3 (P = 0.24); I = 28% Test for overall effect: Z = 6.02 (P < 0.00001)
[0.38, 0.78] [0.00, 1.13] [0.24, 0.55] [0.26, 1.24]
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
C. POPF Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
0 35 14
27 458 69
5 41 7
27 251 68
16.3% 44.7% 38.9%
0.07 [0.00, 1.42] 0.42 [0.26, 0.69] 2.22 [0.14, 2.66]
Total (95%CI) 554 346 100.0% Total events 49 53 2 2 2 Heterogeneity: Tau = 1.21; χ = 10.71, df = 2 (P = 0.005); I = 81% Test for overall effect: Z = 0.66 (P = 0.51)
0.61 [0.14, 2.66]
Study or subgroup Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
D. CR-PF No drainage Study or subgroup Heslin 1998 Lim 2013 Van Buren 2013
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
0 1 18
38 27 69
3 1 6
51 27 68
35.3% 11.5% 53.2%
0.18 [0.01, 3.59] 1.00 [0.06, 16.85] 3.65 [1.35, 9.87]
146
100.0%
2.12 [0.95, 4.72]
Total (95%CI) 134 Total events 19 10 2 2 Heterogeneity: χ = 4.02, df = 2 (P = 0.13); I = 50% Test for overall effect: Z = 1.84 (P = 0.07)
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Odds ratio
Odds ratio
Events
Total
Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
49 1 1 29 16
353 38 27 458 69
68 2 1 21 6
386 51 27 251 68
63.1% 1.9% 1.1% 28.7% 5.2%
0.75 [0.51, 1.12] 0.66 [0.06, 7.58] 1.00 [0.06, 16.85] 0.74 [0.41, 1.33] 3.12 [1.14, 8.54]
783
100.0%
0.87 [0.65, 1.19]
Correa-Gallego 2013 (a) Heslin 1998 Lim 2013 Mehta 2013 Van Buren 2013
Routine drainage
Total (95%CI) 945 Total events 96 98 2 2 Heterogeneity: χ = 7.03, df = 4 (P = 0.13); I = 43% Test for overall effect: Z = 0.86 (P = 0.39)
F. Interventional radiology drainage No drainage Study or subgroup Events Total Correa-Gallego 2013 (a) 2 353 Heslin 1998 3 38 Lim 2013 1 27 Mehta 2013 26 458 Van Buren 2013 6 69
0.01 0.1 1 Favours (No drainage)
Routine drainage Events Total 2 386 1 51 2 27 14 251 2 68
Total (95%CI) 945 Total events 38 21 2 2 Heterogeneity: χ = 3.28, df = 4 (P = 0.51); I = 0% Test for overall effect: Z = 0.82 (P = 0.41)
783
Weight 8.1% 3.3% 8.2% 72.6% 7.8%
Odds ratio M-H, Fixed, 95%CI 1.09 [0.15, 7.81] 4.29 [0.43, 42.92] 0.48 [0.04, 5.64] 1.02 [0.52, 1.99] 3.14 [0.61, 16.16]
100.0%
1.26 [0.73, 2.17]
10 100 Favours (Drainage)
Odds ratio M-H, Fixed, 95%CI
0.01 0.1 1 Favours (No drainage)
10 100 Favours (Drainage)
G. Reoperation No drainage
Mean difference
Mean difference
SD
Total
Mean
SD
Total
Weight
IV, Random, 95%CI
IV, Random, 95%CI
2.96 1 4.5 9.63 5.19
353 38 27 458 69
8 12 15 13.8 7
2.96 1 11.25 9.63 2.22
386 51 27 251 68
29.1% 29.1% 4.0% 18.1% 19.7%
-1.00 [-1.43, -0.57] 0.00 [-0.42, 0.42] -5.00 [-9.57, -0.43] -2.50 [-3.98, -1.02] 1.00 [-0.33, 2.33]
Total (95%CI) 945 783 100.0% 2 2 2 Heterogeneity: Tau = 0.82; χ = 26.27, df = 4 (P < 0.0001); I = 85% Test for overall effect: Z = 1.49 (P = 0.14)
-0.75 [-1.73, 0.24]
Study or subgroup
Mean
Correa-Gallego 2013 (a) 7 Heslin 1998 12 Lim 2013 10 Mehta 2013 11.3 Van Buren 2013 8
Routine drainage
-100 -50 0 Favours (No drainage)
50 100 Favours (Drainage)
H. Length of hospital stay
Figure 3 Forest plots of subgroup analysis of patients who underwent pancreaticoduodenectomy. For patients who underwent pancreaticoduodenectomy (PD), the effect of prophylactic abdominal drainage on A: Mortality; B: Morbidity; C: Postoperative pancreatic fistula (POPF); D: Clinically relevant pancreatic fistula (CR-PF); E: Abdominal abscess; F: Interventional radiology drainage; G: Reoperation; and H: Length of hospital stay. [26]
2
= 93%) or the study by Paulus et al (MD = -0.74, 2 95%CI: -1.53-0.05; P = 0.07; I = 91%).
(OR = 0.61, 95%CI: 0.14-2.66; P = 0.51; I = 81%), abdominal abscess (OR = 2.12, 95%CI: 0.95-4.72; 2 P = 0.07; I = 50%), reoperation rate (OR = 1.26, 2 95%CI: 0.73-2.17; P = 0.41; I = 0%), postoperative interventional drainage (OR = 0.87, 95%CI: 0.65-1.19; 2 P = 0.39; I = 43%) and length of hospital stay (MD 2 = -0.75, 95%CI: -1.73-0.24; P = 0.14; I = 85%), no significant differences were observed between the groups.
Subgroup analysis
Subgroup analysis of patients who underwent PD: Mortality in the non-prophylactic drainage group after PD was significantly higher than that in the prophylactic drainage group with a pooled estimate 2 of 2.39 (95%CI: 1.22-4.69; P = 0.01; I = 0%). This indicated that omission of prophylactic drainage after PD resulted in significantly higher mortality. However, patients who underwent PD without prophylactic abdominal drainage had a significantly lower rate of morbidity (OR = 0.69, 95%CI: 0.56-0.84; P < 2 0.01; I = 28%) and POPF (OR = 0.46, 95%CI: 2 0.35-0.59; P < 0.01; I = 28%). In terms of CR-PF
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Subgroup analysis of patients who underwent DP: Only two studies were eligible for the subgroup analysis of patients who underwent DP. No significant difference was found between the groups with respect to morbidity (OR = 1.29, 95%CI: 0.24-6.81; P = 0.76; 2 I = 89%), POPF (OR = 0.39, 95%CI: 0.07-2.21; P
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Dou CW et al . Prophylactic abdominal drainage after pancreatic resection Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
43 20
196 30
50 15
154 39
53.4% 46.6%
0.58 [0.36, 0.94] 3.20 [1.18, 8.67]
Total (95%CI) 226 193 100.0% Total events 63 65 2 2 2 Heterogeneity: Tau = 1.29; χ = 9.11, df = 1 (P = 0.003); I = 89% Test for overall effect: Z = 0.30 (P = 0.76)
1.29 [0.24, 6.81]
Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
A. Mortality Odds ratio
Odds ratio
Events
No drainage Total
Events
Total
Weight
M-H, Random, 95%CI
M-H, Random, 95%CI
38 0
196 30
42 6
154 39
75.4% 24.6%
0.64 [0.39, 1.06] 0.08 [0.00, 1.56]
Total (95%CI) 226 193 100.0% Total events 38 48 2 2 2 Heterogeneity: Tau = 0.98; χ = 1.86, df = 1 (P = 0.17); I = 46% Test for overall effect: Z = 1.06 (P = 0.29)
0.39 [0.07, 2.21]
Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
0.01
0.1
1
Favours (No drainage)
10
100
Favours (Drainage)
B. POPF No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
34 7
196 30
35 5
154 39
90.7% 9.3%
0.71 [0.42, 1.21] 2.07 [0.58, 7.32]
193
100.0%
0.84 [0.52, 1.36]
Total (95%CI) 226 Total events 41 40 2 2 Heterogeneity: χ = 2.32, df = 1 (P = 0.13); I = 57% Test for overall effect: Z = 0.71 (P = 0.48)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
C. Interventional radiology drainage No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Odds ratio
Odds ratio
Events
Total
Routine drainage Events
Total
Weight
M-H, Fixed, 95%CI
M-H, Fixed, 95%CI
0 8
196 30
1 11
154 39
19.3% 80.7%
0.26 [0.01, 6.44] 0.93 [0.32, 2.69]
193
100.0%
0.80 [0.29, 2.17]
Total (95%CI) 226 Total events 8 12 2 2 Heterogeneity: χ = 0.54, df = 1 (P = 0.46); I = 0% Test for overall effect: Z = 0.44 (P = 0.66)
0.01 0.1 1 10 100 Favours (No drainage) Favours (Drainage)
D. Reoperation No drainage Study or subgroup Correa-Gallego 2013 (b) Paulus 2012
Routine drainage
Mean difference
Mean difference
IV, Fixed, 95%CI
IV, Fixed, 95%CI
Mean
SD
Total
Mean
SD
Total
Weight
5 6.5
1.48 0.75
196 30
7 9
2.22 2.5
154 39
80.6% -2.00 [-2.41, -1.59] 19.4% -2.50 [-3.33, -1.67]
193
100.0% -2.10 [-2.46, -1.73]
Total (95%CI) 226 2 2 Heterogeneity: χ = 1.13, df = 1 (P = 0.29); I = 11% Test for overall effect: Z = 11.24 (P < 0.00001)
-100 -50 0 Favours (No drainage)
50 100 Favours (Drainage)
E. Length of hospital stay
Figure 4 Forest plots of subgroup analysis of patients who underwent distal pancreatectomy. For patients who underwent distal pancreatectomy (DP), the effect of prophylactic abdominal drainage on A: Morbidity; B: Postoperative pancreatic fistula (POPF); C: Interventional radiology drainage; D: Reoperation; and E: Length of hospital stay. 2
2
= 0.29; I = 46%), reoperation (OR = 0.80, 95%CI: 2 0.29-2.17; P = 0.66; I = 0%), or interventional radiology drainage (OR = 1.03, 95%CI: 0.38-2.80; P
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= 0.95; I = 57%). Eliminating prophylactic drainage was associated with a significantly reduced length of hospital stay [MD = -2.10, 95%CI: -2.46-(-1.73); P
