effect of antecolic versus retrocolic reconstruction for gastro/duodenojejunostomy on delayed...

Effect of antecolic versus retrocolic reconstruction forgastro/duodenojejunostomy on delayed gastric emptyingafter pancreaticoduodenectomy: A meta-analysis

Shuang-Shuang Cao,* Qi-Yuan Lin, Man-Xi He and Guang-Quan ZhangDepartment of Hepatobiliary Surgery, Sixth People’s Hospital of Chengdu, Chengdu, China.

Aim: The aim of this meta-analysis was to assess whether antecolic reconstruction is superior toretrocolic reconstruction for gastro/duodenojejunostomy with respect to delayed gastric emptying afterpancreaticoduodenectomy.Patients and Methods: A literature search of Medline (PubMed), EMBASE, OVID, EBSCO and the Cochranedatabase was done to identify randomized, controlled trials (RCT) comparing antecolic and retrocolic gastro/duodenojejunostomy after pancreaticoduodenectomy from January 1991 to April 2012. Four RCT involving 189patients, and comparing antecolic reconstruction with retrocolic reconstruction, were identified for inclusion.Results: The meta-analysis revealed that there was no significant difference between the two groups interms of operation time [mean difference (MD): 4.39, 95 per cent confidence interval (CI): −19.51 to 28.28,P = 0.72], intraoperative blood loss (MD: 22.51, 95 per cent CI: −160.56 to 205.58, P = 0.81), blood replace-ment (MD: −0.19; 95 per cent CI: −0.62 to 0.23, P = 0.38), mortality [odds ratio (OR): 0.32, 95 per cent CI:0.01–8.26, P = 0.49], morbidity (OR: 2.25, 95 per cent CI: 0.57–8.82, P = 0.24), delayed gastric emptying (OR:0.31, 95 per cent CI: 0.08–1.26, P = 0.10) and length of postoperative hospital stay (MD: −2.35, 95 per cent CI:−7.56 to 2.86, P = 0.38).Conclusion: Compared to retrocolic reconstruction, antecolic reconstruction for gastro/duodenojejunostomydoes not seem to offer an advantage with respect to delayed gastric emptying afterpancreaticoduodenectomy.

Key words: antecolic reconstruction, delayed gastric emptying, meta-analysis, pancreaticoduodenectomy,retrocolic reconstruction.

Introduction

Pancreatoduodenectomy (PD) has been accepted asa safe and primary treatment, offering the only chanceof cure for patients with periampullary malignancies.1

The first successful PD, in which the distal stomach,pylorus and duodenum were removed, was reportedindependently by Whipple2 and Trimble et al.3 in 1941.However, this procedure (classic PD) was associatedwith significant morbidity and mortality. Several yearslater, pylorus-preserving PD, which preserved thewhole stomach and 2.5 cm of the duodenum, andsubtotal stomach-preserving PD, which involvedremoving the duodenum, pyloric ring and 2 cm of thedistal stomach, were performed to decrease the inci-dence of postoperative complications.4,5 Despite the

improvements in surgical techniques, perioperativemanagement and interventional radiology, postopera-tive morbidities, including pancreatic fistula (PF),delayed gastric emptying (DGE), haemorrhage andintraabdominal abscess, still remain high.6,7 Thereported incidence of DGE varies from 9 per cent to 37per cent of patients, regardless of the type of PD.6,8,9

Although DGE is transient and not lethal, it not onlyleads to patient discomfort, but also increases the riskof aspiration pneumonia and prolongs hospital staysignificantly, which contribute to prohibitive hospitalexpenses.10,11 The occurrence of DGE was stronglyaffected by the reconstruction technique.12,13 There-fore, many modifications of the reconstruction methodhave been attempted to reduce the incidence of DGE.

There are two reconstruction routes for gastro/duodenojejunostomy: the antecolic route and theretrocolic route. Both methods have been widelyaccepted and commonly used according to surgeons’preferences. The antecolic route has recently been

*Author to whom all correspondence should be addressed.Email: [email protected] 6 December 2012; accepted 27 February 2013.

bs_bs_bannerSurgical Practicedoi:10.1111/1744-1633.12055 Original Article

© 2014 College of Surgeons of Hong Kong Surgical Practice (2014) 18, 72–81

mailto:[email protected]

advocated by some authors to decrease the incidenceof DGE.13–17 The incidence of DGE has been reportedto be greater than 30 per cent for the retrocolic routeand less than 15 per cent for the antecolic route,respectively.16 In contrast, two randomized, controlledtrials (RCT) and a retrospective study showed that theincidence of DGE did not differ between the tworeconstruction routes.18–20 In light of the ongoingcontroversy, the present meta-analysis provides anevidence-based evaluation. The primary outcome ofinterest was DGE.

Methods

Study selection

Both an Internet-based search and a manual searchwere used to acquire relevant studies. Multipledatabases and resources, including Medline(PubMed), EMBASE, OVID, EBSCO and the Cochranedatabase, were searched for RCT that evaluatedantecolic versus retrocolic reconstruction for gastro/duodenojejunostomy after any type of PD fromJanuary 1991 to April 2012. In addition, further articleswere identified by a manual search of reference listsfrom the retrieved publications. The following medi-cal subject headings or keywords were used withthe appropriate combinations: pancreaticoduo-denectomy, gastrojejunostomy, duodenojejunostomy,delayed gastric emptying, antecolic reconstructionand retrocolic reconstruction. Citations were limited:humans and English language and year = 1991.1–2012.1’ and randomized, controlled trials.

Inclusion and exclusion criteria

All included studies in the meta-analysis had tofulfil the following criteria: (i) explicitly reporting theindication of PD; (ii) comparing the results of ante-colic versus retrocolic reconstruction for gastro/duodenojejunostomy after PD; (iii) reporting on theoutcomes of DGE; and (iv) when two or multiplestudies were published by the same institution and/orauthors, either one of the higher-quality, or the mostrecent, article was included in the analysis. NonRCTand RCT with the number of patients less than 30 wereexcluded.

Study eligibility assessment

Two reviewers (SSC and YZ) independently identifiedand screened the search findings for potentially-eligible studies. Abstracts and full articles wereobtained for detailed evaluation, and eligible trialswere included into the meta-analysis. Any disagree-ments during the selection process were resolved

through discussions by the two reviewers, and whenthis did not resolve the differences, a third person(BLT) made a final decision on the eligibility of thestudy.

Data extraction and quality assessment

Data were independently extracted from each studyusing a standardized data-extraction tool by the tworeviewers (SSC and YZ), and then cross-checked.Data extracted from each study included first author,study period, study design, inclusion and exclusioncriteria, participant characteristics, interventions used,technique of reconstruction, definition of DGE, numberof DGE, morbidity and mortality rates, postoperativetime to remove nasogastric tube (NGT) and start liquidmeals and solid foods and length of hospital stay.Any disagreements were resolved applying the samemethod mentioned earlier. The Jadad scoring sys-tem, which evaluates studies based on appropriaterandomization, proper blinding and an adequatedescription of withdrawals and dropouts, was used toassess the quality of RCT in the study.21

Statistical analysis

Meta-analysis was performed in line with the recom-mendations of the Cochrane Collaboration using theRevman version 5.0 software package (CochraneLibrary). For continuous variables, the mean differ-ence (MD) was calculated with its 95 per cent confi-dence interval (CI). For dichotomous variables, theodds ratio (OR) was calculated with a 95 per cent CI.OR was defined as the odds of an adverse eventoccurring in the antecolic group compared with theretrocolic group, and it was considered statisticallysignificant at P < 0.05 if the 95 per cent CI did notcross the value 1. MD represented the differencebetween the two groups in the continuous variablesand was considered statistically significant at P < 0.05if the 95 per cent CI did not cross the value 0. Thedegree of heterogeneity between studies was meas-ured using χ2 and I2, with significance set at a P < 0.1and I2 > 50 per cent. Pooled effect was calculatedusing either the fixed-effect model or the random-effects model.

Results

Literature search results and theirgeneral characteristics

According to the literature searching strategies, fourRCT16–19 were identified for inclusion. The specific lit-erature screening process is shown in Figure 1. Thefour studies included a total of 189 patients: 93 in the

Antecolic versus retrocolic method 73


antecolic group, and 96 in the retrocolic group. Thedetails of the included studies are summarized inTable 1. There were no significant differences betweenthe two groups with respect to these baseline charac-teristics. Of the four studies, only one16 reported thelength of follow up. The surgical procedure of thereconstruction for gastro/duodenojejunostomy andthe definition of DGE are shown in Table 2. There wassome variation in postoperative management, includ-ing the indication to remove NGT and the administra-tion of somatostatin analogues (SSA), antacid andprokinetic agents (PA).

Meta-analysis of operative outcomes

Operation time (min)

There were four studies providing information regard-ing operating time, on which we calculated the MD.The fixed-effect model was used because of nonsig-nificant heterogeneity (P = 0.25, I2 = 26 per cent)between studies, and the result of the pooled analysisshowed no statistically-significant difference betweenthe two groups (MD: 4.39, 95 per cent CI: −19.51 to28.28, P = 0.72) (Fig. 2a).

Intraoperative blood loss (mL)

All studies reported on intraoperative blood loss,which showed no significant difference between theantecolic group and the retrocolic group (MD: 22.51,95 per cent CI: −160.56 to 205.58, P = 0.81). This

finding was not associated with significant heteroge-neity between studies (P = 0.66, I2 = 0 per cent)(Fig. 2b).

Blood replacement (units)

The blood replacement showed similar results in bothgroups (MD: −0.19, 95 per cent CI: −0.62 to 0.23,P = 0.38), with only two articles providing adequatedata for pooling (Fig. 2c).

Meta-analysis of postoperative outcomes

Mortality

All four studies reported on hospital mortality. Of all the189 patients, only one patient died from acute haem-orrhagic shock because of a Dieulafoy’s-type gastriculcer in the retrocolic group. The pooling of the indi-vidual results revealed no difference in mortality (OR:0.32, 95 per cent CI: 0.01–8.26, P = 0.49) (Fig. 3a).

Morbidity

Only one study, which included 35 patients, was usedto analyse the overall postoperative morbidity. Nostatistically-significant difference was achieved: 52.9per cent (antecolic group) versus 33.3 per cent(retrocolic group). All studies provided data on DGErate and PF rate. The summarized effect of DGE withthe random-effects model (P = 0.03, I2 = 67 per cent)revealed a nonstatistically-significant result (OR: 0.31,95 per cent CI: 0.08–1.26, P = 0.10) (Fig. 4a). Similarly,

Fig. 1. Flowchart showing the search strategy used to identify studies.

SS Cao et al.74


the difference in the occurrence of PF between the twogroups was not statistically significant: 8.6 per centversus 13.5 per cent (OR: 0.60, 95 per cent CI: 0.24–1.50, P = 0.27) (Fig. 4b). Two studies also reportedon the grade of DGE, with no significant differencenoted: grade A (OR: 0.70, 95 per cent CI: 0.22–2.21,P = 0.54), grade B (OR: 0.55, 95 per cent CI: 0.17–1.73, P = 0.30) and grade C (OR: 0.97, 95 per cent CI:0.06–16.74, P = 0.98). There was no significant differ-ence between the antecolic group and retrocolicgroup in haemorrhage with respect to other complica-tions (OR: 1.34, 95 per cent CI: 0.35–5.10, P = 0.67)(Fig. 4c), intraabdominal abscesses (OR: 0.94, 95 percent CI: 0.39–2.25, P = 0.89) (Fig. 4d), bile leakage(OR: 1.52, 95 per cent CI: 0.45–5.14, P = 0.50)(Fig. 4e), wound infection (OR: 0.73, 95 per cent CI:0.31–1.69, P = 0.46) (Fig. 4f) and reoperation (OR:0.16, 95 per cent CI: 0.02–1.42, P = 0.10) (Fig. 4g).

Postoperative time to remove NGT (days)

The postoperative time to remove NGT was involved infour studies, and all studies reported the mean andstandard deviation. The random-effects model wasused due to significant heterogeneity (P = 0.09, I2 = 54per cent) between studies, and the overall effect indi-cated no difference between the antecolic group andthe retrocolic group (MD: −0.00, 95 per cent CI: −0.82to 0.81, P = 0.99) (Fig. 3b).

Postoperative time to start liquid meals (days)

Two studies evaluated postoperative time to startliquid meals. A meta-analysis of the two studies withthe fixed-effect model (P = 0.55; I2 = 0 per cent)showed that there was no significant difference in thepostoperative time to start liquid meals (MD: 0.16, 95per cent CI: −0.67 to 0.99, P = 0.71) (Fig. 3c).

Postoperative time to start solid foods (days)

There were three studies reporting the postoperativetime to start solid foods. The summarized effect withthe fixed-effect model (P = 0.33, I2 = 11 per cent)revealed no difference between the two groups (MD:−1.22, 95 per cent CI: −2.86 to 0.42, P = 0.15)(Fig. 3d).

Length of postoperative hospital stay (days)

The length of postoperative hospital stay wasdiscussed in four studies, and was found to bestatistically nonsignificant between the two groups(MD: −2.35, 95 per cent CI: −7.56 to 2.86, P =0.38). However, there was statistically-significantTa

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SS Cao et al.76


heterogeneity between the groups in all availablestudies for the pooled analysis (P = 0.05, I2 = 61 percent) (Fig. 3e).

Heterogeneity analysis

A significant heterogeneity between the two groupswas observed in the DGE, grade C DGE, postopera-tive time to remove NGT and length of postoperativehospital stay. Given the heterogeneity, the random-effects model was applied for the analysis.

Discussion

DGE after PD was first reported by Warshaw andTorchiana in the 1980s.22 Although the exact mecha-nism of DGE has not been fully clarified, it is probablycaused by a complex interaction of various factors,including pylorospasm, caused by vagotomy anddecreased vascular supply to the antropyloric region,23

diminished circulating levels of motilin,24 torsion orangulation of the gastro/duodenojejunostomy25 and

other intraabdominal complications, such as ana-stomotic leakage, abscess and local inflammation.26

Despite Traverso and Kozuschek27 reporting adecade ago that antecolic reconstruction for gastro/duodenojejunostomy seems to be preferred, thereconstructive method of choice remains controver-sial. Several retrospective studies have recently pro-posed that an antecolic reconstruction for gastro/duodenojejunostomy during PD could significantlydecrease the rate of DGE. The authors of those studiesspeculated that antecolic gastro/duodenojejunostomycan avoid angulation, venous congestion and oedemaof the reconstructed alimentary tract.15,20,28,29 However,two RCT failed to find an advantage of antecolicreconstruction. This systematic review with a meta-analysis of RCT demonstrated that antecolic recon-struction for gastro/duodenojejunostomy could notdecrease the incidence of DGE after PD, which indi-cates that underpowered studies potentially over-estimate the benefits of antecolic reconstruction forgastro/duodenojejunostomy on DGE.

(a)

Study or subgroup

Total (95 per cent CI) 93 96 100

SD

AG RG Mean difference

Total

Heterogeneity: χ2 = 4.07, df = 3 (P = 0.25); I2 = 26%Test for overall effect: Z = 0.36 (P = 0.72)

17322420

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Mean difference

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Chijiiwa 2009Gangavatiker 2011Kurahara 2011Tani 2006

(b)

Study or subgroup


SD

AG RG Mean difference Mean difference

Heterogeneity: χ2 = 1.61, df = 3 (P = 0.66); I2 = 0%Test for overall effect: Z = 0.24 (P = 0.81)

Total

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(per cent) IV, fixed, 95 per cent CI

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Study or subgroup SD


Total IV, fixed, 95 per cent CIWeight


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32 1.1 36Gangavatiker 2011

Total (95 per cent CI) 52 56 100Heterogeneity: χ2 = 0.03, df = 1 (P = 0.86); I2 = 0%Test for overall effect: Z = 0.89 (P = 0.38)

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Fig. 2. Forest plot displaying the results of the meta-analysis on operative outcomes: operative time (a), intraoperative blood loss (b)and blood replacement (c). AG, antecolic group; CI, confidence interval; RG, retrocolic group; SD, standard deviation.



(a)

Study or subgroup


AG RG Odds ratio

Total

Total eventsHeterogeneity: Not applicable Test for overall effect: Z = 0.69 (P = 0.49)

17322420

M-H, random, 95 per cent CI

Odds ratio

M-H, random, 95 per cent CIWeight

(per cent)

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100

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Total

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00

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00

1

0 1


(b)

Study or subgroup


SD


Heterogeneity: Tau2 = 0.30; χ2 = 6.53, df = 3 (P = 0.09); I2 = 54%Test for overall effect: Z = 0.01 (P = 0.99)

Total

17322420

IV, random, 95 per cent CIWeight

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–100 –50 500AG RG

100

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Mean

1.1

4.54.4

18.9


(d)



Total

1732



–100 –50 500AG RG

100

SD Total

1836

Mean

8.48.9

Mean

Chijiiwa 2009Gangavatiker 2011


20

35.663.21.2

5.15.4

34.3 208.1

10.29.6

19.7Tani 2006

(e)

Study or subgroup


SD


Heterogeneity:Tau2 = 15.45; χ2 = 7.70, df = 3 (P = 0.05); I2 = 61%Test for overall effect: Z = 0.88 (P = 0.38)

12.38.46.25.7

Total

17322420

IV, random, 95 per cent CIWeight

(per cent) IV, random, 95 per cent CI

–100 –50 500AG RG

100

22.635.334.1

8.0

SD

11.19.2

937.7

Total

18362220

Mean

40.8

20.416.3

28.7

Mean

39.4

24.815.3

47.7


(c)



Total IV, fixed, 95 per cent CIWeight


–100 –50 500AG RG

100

SD TotalMean Mean

17 24.0185.4Chijiiwa 2009


0.41.83.1

4

33.11.6

2.72 32

–0.00 (–082, 0.81)

0.10 (–0.14, 0.34)

–14.70 (–30.57, 1.17)–2.20 (–4.96, 0.56)0.40 (–0.41, 1.21)

–1.22 (–2.86, 0.42)

–1.80 (–4.55, 0.95)–0.70 (–2.77, 1.37)

–11.60 (–26.55, 3.45)

–2.35 (–7.56, 2.68)

1.40 (–6.38, 9.18)

–19.00 (–35.71, –2.29)–4.40 (–8.91, 0.11)1.00 (–3.18, 5.18)

0.6 (–0.67, 0.99)

–0.30 (–2.00, 1.40)0.30 (–0.65, 1.25)76.0

0.31.65.936

2.42 366.6

5.76.3Gangavatiker 2011

Fig. 3. Forest plot displaying the results of the meta-analysis on postoperative outcomes: mortality (a), postoperative time to removenasogastric tube (b) and start liquid meals (c) and solid foods (d) and length of postoperative hospital stay (e). AG, antecolic group;CI, confidence interval; RG, retrocolic group; SD, standard deviation.

SS Cao et al.78


Some recent studies have revealed that DGE is notaffected by the type of procedure performed, butrather by blood loss and postoperative complica-tions.11,15,19,26,30 DGE always implicates a state ofgastroparesis, for which prolonged gastric drainage isrequired and delays the return to solid food intake. Inthe present study, the secondary outcomes of opera-tive time, intraoperative blood loss, blood replace-

ment, postoperative morbidity, mortality, postoperativetime to remove NGT and start liquid meals and solidfoods, and length of postoperative hospital stay weresimilar in both groups, which further confirmed theconclusion drawn earlier.

The lack of a generally-accepted definition of DGEmight be one important reason for the different con-clusions in the previous literature.31 Although various

(a)

Study or subgroup

AG RG Odds ratio

Total M-H, random, 95 per cent CI

Odds ratio

M-H, random, 95 per cent CIWeight

(per cent)

1010.10.01AG RG

100

TotalEvents Events

Total (95 per cent CI) 93 96Total eventsHeterogeneity: Tau2 = 1.29; χ2 = 9.22, df = 3 (P = 0.03); I2 = 67%Test for overall effect: Z = 1.63 (P = 0.10)

17322420

18362220

1

511

1

4

1110

18 35

10


0.31 (0.08, 1.26)

0.05 (0.01, 0.47)0.26 (0.07, 0.96)1.36 (0.49, 3.82)0.22 (0.02, 2.19)

100

19.829.232.118.8

Total (95 per cent CI) 93 96Total eventsHeterogeneity: χ2 = 1.53, df = 3 (P = 0.68); I2 = 0%Test for overall effect: Z = 1.10 (P = 0.27)

17322420

18362220

1

33

1

1

66

8 13

0


(b)

Study or subgroup

AG RG Odds ratio

Total M-H, fixed, 95 per cent CI

Odds ratio

M-H, fixed, 95 per cent CIWeight

(per cent)

1010.10.01AG RG

100

TotalEvents Events

0.60 (0.24, 1.50)

3.15 (0.12, 82.16)0.38 (0.08, 1.76)0.52 (0.12, 2.27)

1.06 (0.06, 18.45)

100

3.945.742.77.6

1732

1836

22

10



20 200

4 3

2Tani 2006

(c)

Study or subgroup

AG RG Odds ratio


Odds ratio


(per cent)

1010.10.01AG RG

100

TotalEvents Events

1.34 (0.35, 5.10)

5.98 (0.28, 129.44)2.27 (0.19, 27.58)

0.18 (0.01, 4.01)11.723.0

100

65.4


17322420

18362220

6

13

1

5

30

11 12

4


(d)

Study or subgroup

AG RG Odds ratio


Odds ratio


(per cent)

1010.10.01AG RG

100

TotalEvents Events

0.94 (0.39, 2.25)

0.21 (0.02, 2.08)0.28 (0.03, 2.87)

8.66 (0.43, 174.42)1.42 (0.34, 5.94)

100

36.728.94.1

30.3

Fig. 4. Forest plot displaying the results of the meta-analysis on postoperative complications: delayed gastric emptying (a),pancreatic fistula (b), haemorrhage (c), intraabdominal abscesses (d), bile leakage (e), wound infection (f) and reoperation (g). AG,antecolic group; CI, confidence interval; RG, retrocolic group; SD, standard deviation.



definitions for DGE exist, in recent years, two defini-tions, applied by Chijiiwa et al. and Gangavatikeret al., seem to be most widely used. In order to makethe comparison of results of different studies possible,the consensual definition of DGE proposed by theInternational Study Group of Pancreatic Surgery(ISGPS) was recommended from 2007.32 According tothe ISGPS, DGE was classified into grades A, B and Cbased on clinical impact. The present study showedthat the occurrence of ISGPS grades A, B and C DGEwas similar in the antecolic and retrocolic reconstruc-tion groups.

This meta-analysis of RCT might have some limita-tions that must be taken into account when consider-ing the final results. First, a test for heterogeneity wassignificant for DGE, grade C DGE, postoperative timeto remove NGT and the length of postoperative hos-pital stay. There are many differences between thestudies that serve as sources of heterogeneity, includ-ing differences in the nuances of surgical tech-

nique (Billroth I or Billroth II, pancreaticojejunostomy orpancreaticogastrostomy), definition of DGE, postop-erative drug use (SSA, antacid and PA) and indicationto remove NGT. Second, potential publication biasmight lie in in this meta-analysis. Studies with signifi-cant results are more prone to be published thanthose with nonsignificant results. Finally, a smallnumber of studies and poor-quality studies with(quality score < 3) were included in the meta-analysis.Due to multifactorial heterogeneity and only fourstudies being included, a subgroup analysis was notperformed. To reach an evidence-based consensuson the effect of antecolic reconstruction for gastro/duodenojejunostomy on DGE, much larger andrigorously-designed studies would be needed thanthose currently available.

In conclusion, the present meta-analysis of RCTshowed that antecolic reconstruction for gastro/duodenojejunostomy could not decrease the inci-dence of DGE after PD.

1732

1836

39

314


Total (95 per cent CI) 69 74 100Total eventsHeterogeneity: χ2 = 0.34, df = 2 (P = 0.84); I2 = 0%Test for overall effect: Z = 0.74 (P = 0.46)

2073.918.7

7.4201

13 18

1Tani 2006

(f)

Study or subgroup

AG RG Odds ratio


Odds ratio


(per cent)

1010.10.01AG RG

100

TotalEvents Events

0.73 (0.31, 1.69)

0.61 (0.22, 1.71)1.07 (0.18, 6.22)

1.00 (0.06, 17.18)

32 74.1360 4Gangavatiker 2011

Total (95 per cent CI) 52 56 100Total eventsHeterogeneity: χ2 = 0.22, df = 1 (P = 0.64); I2 = 0%Test for overall effect: Z = 1.64 (P = 0.10)

20

0.16 (0.02, 1.42)

0.11 (0.01, 2.15)0.32 (0.01, 8.26)25.9200

0 5

1Tani 2006

(g)

Study or subgroup

AG RG Odds ratio


Odds ratio


(per cent)

1010.10.01AG RG

100

TotalEvents Events


17322420

1.52 (0.45, 5.14)

0.32 (0.01, 8.26)0.43 (0.04, 5.16)

6.48 (0.71, 58.79)Not estimable

100

34.447.018.6

18362220

0

15

0

0

21

6 4

1


(e)

Study or subgroup

AG RG Odds ratio


Odds ratio


(per cent)

1010.10.01AG RG

100

TotalEvents Events

Fig. 4. Continued

SS Cao et al.80


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