Meta-Analysis Open Access
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2015; 21(20): 6361-6373
Published online May 28, 2015. doi: 10.3748/wjg.v21.i20.6361
Meta-analysis of subtotal stomach-preserving pancreaticoduodenectomy vs pylorus preserving pancreaticoduodenectomy
Wei Huang, Mei-Hua Wan, Qing Xia, Sichuan Provincial Pancreatitis Center, Department of Integrated Traditional Chinese Medicine and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Jun-Jie Xiong, Xu-Bao Liu, Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Peter Szatmary, Shameena Bharucha, Ilias Gomatos, Quentin M Nunes, Robert Sutton, NIHR Liverpool Pancreas Biomedical Research Unit, Royal Liverpool University Hospital, Liverpool L69 3BX, United Kingdom
Author contributions: Huang W and Xiong JJ contributed equally to this work; Liu XB, Sutton R and Xia Q designed the research, corrected and approved the final manuscript; Xiong JJ, Huang W, Wan MH, Szatmary P, Bharucha S, Gomatos I and Nunes QM developed the literature search and carried out the statistical analysis of studies; Xiong JJ, Huang W, Wan MH and Szatmary P carried out the extraction of data; Xiong JJ, Huang W, Wan MH and Szatmary P wrote the manuscript; all authors read and approved the final manuscript.
Supported by Research Special Fund for Public Welfare Industry of Health, No. 201202007; Science and Technology Support Program of Sichuan Province, No. 2013SZ0078; and National Institute for Health Research BRU Award.
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 Xia, MD, Sichuan Provincial Pancreatitis Center, Department of Integrated Traditional Chinese Medicine and Western Medicine, West China Hospital, Sichuan University, Guo Xue Road 37, Chengdu 610041, Sichuan Province, China. xiaqing@medmail.com.cn
Telephone: +86-28-85422373 Fax: +86-28-85423373.
Received: September 3, 2014
Peer-review started: September 4, 2014
First decision: September 27, 2014
Revised: October 10, 2014
Accepted: December 1, 2014
Article in press: December 1, 2014
Published online: May 28, 2015
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Abstract

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD).

METHODS: Major databases including PubMed (Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying (DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%CI) were calculated using either a fixed-effects or random-effects model.

RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE (OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation (OR = 2.68; 95%CI: 0.77-4.58, P < 0.00001), with a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter inpatient stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79), pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).

CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.

Key Words: Pancreaticoduodenectomy; Pylorus preserving Subtotal stomach preserving pancreaticoduodenectomy; Delayed gastric emptying; Pancreatic surgery; Meta-analysis

Core tip: As far as we know, pancreatoduodenectomy is one of the most complicated gastrointestinal operations and is associated with a number of serious postoperative complications. Modifications of standard operating techniques aim to reduce the incidence of complications and improve quality of life of patients while maintaining oncological effectiveness. Subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) was specifically designed to reduce the incidence of delayed gastric emptying (DGE) and thus shorten recovery time in patients with pancreatic head and periampullary tumors. This study clarified that, compared to pylorus preserving pancreaticoduodenectomy (PPPD), SSPPD has a lower rate of DGE, shorter operation time and a shorter period of nasogastric intubation, albeit with no significant difference in pancreatic fistula and other postoperative complications. Therefore, SSPPD can improve intraoperative and short-term postoperative outcomes compared to PPPD for patients with pancreatic head and periampullary lesions.



INTRODUCTION

In 1935, Whipple introduced a two-stage pancreaticoduodenectomy for patients with carcinoma of the ampulla of Vater[1]. In 1941, he reported a one-stage pancreaticoduodenectomy with resection of distal stomach and duodenum[2]. Soon afterwards, the first pylorus preserving pancreaticoduodenectomy (PPPD) was performed by Watson[3] in 1944. PPPD was also used by Traverso and Longmire[4] to preserve gastrointestinal function in 1978 and since then this procedure has been extensively applied to patients with tumors of the pancreatic head as well as periampullary malignancies.

Classic Whipple’s and PPPD are now considered to be the most widely employed surgical procedures for the treatment of pancreatic head and periampullary tumors[5-8]. Whereas a classic Whipple’s procedure includes resection of the pancreatic head, duodenum, gallbladder, distal common bile duct, partial jejunum and distal stomach, in a PPPD the proximal duodenum is transected 3 to 4 cm distal to the pylorus ring. While some randomized controlled trials (RCTs) and meta-analyses suggest that these two procedures are comparable in terms of postoperative complications, long-term survival rates and quality of life[6-9], other studies have reported that PPPD is superior to pancreaticoduodenectomy with antrectomy as it results in a reduced occurrence of dumping, diarrhea and bile reflux gastritis, thereby possibly affording patients with an improved nutritional status[10-12].

Delayed gastric emptying (DGE) is regarded as one of the most common postoperative complications of PPPD. This can potentially prolong the hospital stay, affecting patient quality of life and increasing hospital costs[12-16]. Decreasing the occurrence of DGE, therefore, is of particular importance in patients undergoing any type of pancreaticoduodenectomy. Subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) was initially described during the 1990s in Japan. This procedure was intended to preserve the pooling ability of the stomach and minimize the occurrence of DGE[17,18]. It involves division of the stomach 2-3 cm proximal to the pylorus ring with resection of the entire duodenum distal to the site of transection, thereby removing the pylorus but retaining much of the body of the stomach compared to a classical Whipple’s procedure. The rate of postoperative DGE after pancreaticoduodenectomy is controversial and whether SSPPD is able to reduce it and other postoperative complications compared to PPPD remains to be elucidated[19]. We, therefore, carried out a systematic review of the literature to investigate this issue.

MATERIALS AND METHODS
Study selection

Major databases like PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for studies comparing SSPPD with PPPD from January 1978 to July 2014. The following medical search headings (MeSH) were used: “pancreaticoduodenectomy”, “pancreatoduodenectomy”, “Whipple”, “pancreatoduodenal resection”, “pylorus preserving pancreaticoduodenectomy”, “PPPD”, “subtotal stomach preserving pancreaticoduodenectomy”, “SSPPD”, “delayed gastric emptying”“pancreatic surgery”, “comparative study” and combinations of them were used for word searches. References cited in the selected articles were also assessed to identify relevant studies in case studies were missed during the initial database searches. If needed, investigators and experts in the field of pancreatic surgery were contacted to ensure that all relevant studies were identified. Final inclusion of articles was determined by consensus of two researchers; when this failed, a third author adjudicated.

Inclusion and exclusion criteria

Two authors scrutinized potentially eligible studies using the following inclusion criteria: (1) English language full-text articles published in peer-reviewed journals; (2) human clinical trials comparing “PPPD” and “SSPPD”; (3) studies where DGE was mentioned; and (4) where multiple studies came from the same institute and/or authors using the same patient cohorts, the higher quality study was included in the analysis.

Studies were excluded if any of the following conditions existed: (1) abstracts, case reports, letters, editorials, expert opinions and reviews; (2) primary postoperative outcome unavailable; and (3) studies focused on long-term outcomes.

Outcomes of interest

DGE was the primary outcome of interest. Secondary outcomes including operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay were also compared.

Data extraction and quality assessment

Data were collected by two independent researchers using standardized proformas and included: Study characteristics, surgical reconstructions, definition of DGE and postoperative management. Means of the outcomes were used for meta-analysis if not otherwise mentioned. If medians were used in some studies instead of means, the means were estimated using the following formula: (low end of range + median*2 + high end of range)/4 for a sample size smaller than 25. For a sample size greater than 25, means were estimated as the medians. When only a range was given, the standard deviations were estimated as range/4[20].

The qualitative assessment of the RCTs was based on the Jadad scoring system[21] which took into consideration the randomization and double blinding process and the description of withdrawals or dropouts. Note was also made of sample size calculation, sequence generation, allocation concealment and the definitions of outcome parameters. The non-randomized trials were assessed on the basis of the method described by McKay et al[22] which included assessment of the following parameters: prospective vs retrospective data collection; assignment to the PPPD group or the SSPPD group by means other than the surgeon’s preference; and an explicit definition of DGE (studies were given a score of 1 for each of these areas; score 1-4).

Statistical analysis

Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Continuous variables and categorical variables were expressed as weighted mean difference (WMD) and odds ratio (OR) with their respective corresponding 95% confidence interval (CI). Chi-square test was used to assess heterogeneity and a P < 0.1 was considered significant. I2 values were used for the evaluation of statistical heterogeneity: an I2 value of 50% or more was indicative of presence of heterogeneity[23]. The fixed-effects model was initially used for all outcomes[24], while the random-effects model was used if the test rejected the assumption of homogeneity of studies[25]. Descriptive methods were also used if the data were considered to be inappropriate for meta-analysis. Sensitivity analyses were performed by removing individual studies from the data set and analyzing the effect on the overall results, identifying sources of significant heterogeneity. Subgroup analyses were undertaken by including studies with the International Study Group of Pancreatic Surgery (ISGPS) definitions, reconstruction with pancreaticojejunostomy or pancreaticogastrostomy, RCTs or non-RCTs, and D1 or D2 lymph node dissection. Funnel plots[26] were constructed to evaluate potential publication bias based on the primary outcome - DGE.

RESULTS
Description of included trials in the meta-analysis

The search strategy initially identified 148 relevant clinical trials. After filtering the studies using the inclusion criteria, ten studies[17,27-35] with full-text were identified to investigate the details. Of these, two studies[32,34] were excluded: one study[34] focused on the long-time outcomes of the same cohorts reported by their previous study; another study[32] had no data available. Finally, eight studies were identified for inclusion: two RCTs[29,35], one prospective non-randomized trials[27] and five retrospective studies[17,28,30,31,33]. Pancreaticojejunostomy was used in 6 studies[17,27,29,31,33,35], while pancreaticogastrostomy was used in two studies[28,30]. A total of 650 patients were included: 294 and 356 patients in the PPPD and SSPPD groups respectively. The ISGPS definition of DGE was used in six studies[28-31,33,35]. Indications for removal of nasogastric tube were reported in six studies[27-29,31,33,35]. All the included studies were from Japan. Figure 1 shows the process of selecting comparative studies included in our meta-analysis. The study characteristics and quality assessments are shown in Table 1. The surgical reconstruction, definition of DGE and postoperative management are listed in Table 2.

Table 1 Characteristics of the included studies.
Ref.CountryYearDesignGroupnSex (M/F)Age1Benign/malignantQuality score
Hayashibe et al[17]Japan2007RetroPPPD124/860.9 ± 8.50/121 (McKay)
SSPPD218/1364.3 ± 9.51/20
Akizuki et al[27]Japan2008PNRPPPD3420/14 18/1266 (28-78)15/192 (McKay)
SSPPD3065 (39-79)4/26
Kurahara et al[28]Japan2010RetroPPPD4826/22 38/2664.418/301 (McKay)
SSPPD6466.811/53
Oida et al[30]Japan2011RetroPPPD2521/466.2 ± 4.70/251 (McKay)
SSPPD4230/1265.8 ± 5.80/42
Kawaiet al[29]Japan2011RCTPPPD6433/31 38/2868 ± 912/523 (Jadad)
SSPPD6667 ± 914/52
Fujii et al[31]Japan2012RetroPPPD3319/1463.8 (35-83)0/331 (McKay)
SSPPD5628/2864.6 (41-84)0/56
Nanashima et al[33]Japan2013RetroPPPD2821/768 ± 87/211 (McKay)
SSPPD2715/1266 ± 125/22
Matsumoto et al[35]Japan2014RCTPPPD5029/21 35/1566 ± 1018/323 (Jadad)
SSPPD5067 ± 921/29
Figure 1
Figure 1 Flow diagram depicting the study selection process in accordance with PRISMA guidelines.
Table 2 Surgical reconstruction, definition of delayed gastric emptying and postoperative management.
Ref.ReconstructionDefinition of DGEIndication for removing NGTPPIPA
Hayashibe et al[17]Duct to mucosa and end-to-side pancreaticojejunostomy, end-to-side antecolic gastrojejunostomy, and side-to-side jejunojejunostomy (Braun anastomosis)(1) NGT ≥ POD 10UnknownUnknownUnknown
(2) inability to tolerate a solid diet ≥ POD 14
Akizuki et al[27]Duct-to-mucosa and end-to-side pancreaticojejunostomy,end duodenal (or stomach)-to-side jejunal, Braun anastomosis was made(1) NGT ≥ POD 10The fluid of NGT < 500 mL per night, generally removed on POD 1YesYes
(2) inability to tolerate a solid diet ≥ POD 14
Kurahara et al[28]End-to-side pancreaticogastrostomy with an internal stent, end-to-side duodenojejunostomy (PPPD) or gastrojejunostomy (SSPPD)ISGPSThe fluid of NGT < 500 mL per nightYesYes
Oida et al[30]Pancreaticogastrostomy and end to end duodenojejunostomy (PPPD)ISGPSUnknownUnknownUnknown
Pancreaticogastrostomy and end to end gastrojejunostomy (SSPPD)
Kawai et al[29]Duct-to-mucosa, end-to-side pancreatojejunostomy with internal stentISGPSAll removed on POD 1NoNo
Duodenojejunostomy (PPPD), gastrojejunostomy (SSPPD)
Fujii et al[31]End-to-side pancreatojejunostomy and end-to-side antecolic gastrojejunostomy in SSPPD or a duodenojejunostomy in PPPDISGPSGenerally removed on POD 1, or on POD 2 if the fluid of NGT > 500 mL per nightUnknownUnknown
Nanashima et al[33]End-to-side with external stent pancreatojejunostomyISGPSThe fluid of the NGT < 300 mL per nightYesUnknown
Matsumoto et al[35]End-to-side pancreatojejunostomy, end-to-side duodenojejunostomy (PPPD) and gastrojejunstomy (SSPPD)ISGPSThe fluid of the NGT < 200 mL per nightYesUnknown
Results of meta-analysis

Results of the analyses are shown in Figures 2 and 3 and summarized in Table 3.

Figure 2
Figure 2 Forest plots demonstrating primary outcome. Forest plots illustrating results of delayed gastric emptying in the form of meta-analysis comparing PPPD with SSPPD. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the fixed-effects model. PPPD: Pylorus preserving pancreaticoduodenectomy; SSPPD: Subtotal stomach-preserving pancreaticoduodenectomy.
Table 3 Summary results for studies comparing pylorus-preserving pancreaticoduodenectomy and subtotal stomach-preserving pancreaticoduodenectomy.
Outcome of interestNo. ofstudiesNo. ofpatientsOR/WMD = (95%CI)P valueHeterogeneity P valueI2
Delayed gastric emptying86502.75 (1.75-4.30)< 0.000010.1043%
Operation time8650-5.30 (-43.44-32.84)0.790.000377%
Intraoperative blood loss8650-217.70 [-429.77-(-5.63)]0.040.00468%
Pancreatic fistula75830.91 (0.56-1.49)0.70.970%
Postoperative hemorrhage54610.51 (0.15-1.74)0.290.950%
Intra-abdominal abscess54611.05 (0.54-2.05)0.890.650%
Wound infection53940.88 (0.39-1.97)0.750.880%
Time of start liquid diet42862.97 (-0.43-6.38)0.090.00182%
Time of start solid diet43163.69 (-0.46-7.83)0.08< 0.0000191%
Time of nasogastric intubation64382.68 (0.77-4.58)0.006< 0.0000196%
Reinsertion of nasogastric tube43491.90 (0.91-3.97)0.090.580%
Mortality64710.31 (0.05-2.01)0.221.000%
Hospital stay42553.92 (-0.37-8.22)0.070.0464%
Figure 3
Figure 3 Forest plots demonstrating secondary outcomes. Forest plots illustrating results of operation time (A), intraoperative blood loss (B), pancreatic fistula (C), postoperative hemorrhage (D), intraabdominal abscess (E), wound infection (F), time to starting liquid diet (G), time to starting solid diet (H), period of nasogastric intubation (I), reinsertion of nasogastric tube (J), mortality (K), hospital stay (L) in the form of meta-analysis comparing PPPD with SSPPD. Pooled odds ratios (ORs) or weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated using the fixed effects model or the random-effects model. PPPD: Pylorus preserving pancreaticoduodenectomy; SSPPD: Subtotal stomach-preserving pancreaticoduodenectomy.

All included studies reported the occurrence rate of DGE. Patients in the SSPPD group had a lower incidence of DGE compared to those in the PPPD group (OR = 2.75, 95%CI: 1.75-4.30; P < 0.00001) and the period of nasogastric intubation was also shorter in the SSPPD group (WMD = 2.68, 95%CI: 0.77-4.58; P = 0.006). Furthermore, there was a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter hospital stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although the latter three did not reach statistical significance. PPPD was, however, associated with less intraoperative blood loss compared to SSPPD (WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04). There were no differences in operating time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79) or outcomes such as pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09), mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22) and hospital stay.

Sensitivity and subgroup analysis

Sensitivity analyses were carried out by excluding each study out of each outcome measure. These exclusions did not alter the results obtained from cumulative analyses. The subgroup analyses were undertaken for all outcome measures by including studies with ISGPS definition or other definition, studies with pancreaticogastrostomy or pancreaticojejunostomy, RCTs or non-randomized trials, and D1 or D2 lymph node dissection. Results of the analyses are also summarized in Table 4. The rate of DGE was also shown to be lower in the studies using the ISGPS definition (OR = 8.73; 95%CI: 2.09-36.56; P = 0.003), pancreaticojejunostomy (OR = 3.72; 95%CI: 2.12-6.56; P < 0.00001), RCTs (OR = 2.69; 95%CI: 1.17-6.17; P = 0.02) or non-RCTs (OR = 3.36; 95%CI: 1.25-9.08; P = 0.02).

Table 4 Sensitivity analysis performed for studies comparing pylorus-preserving pancreaticoduodenectomy and subtotal stomach-preserving pancreaticoduodenectomy.
Outcome of interestNo. of studiesNo. of patientsOR (95%CI)P valueHeterogeneityP valueI2
DGE with ISGPS definition
DGE (ISGPS B/C)65538.73 (2.09-36.56)0.003< 0.000182%
Operation time65536.50 (-35.02-48.02)0.760.000580%
Intraoperative blood loss65530.78 (-81.90-83.46)0.990.2033%
Pancreatic fistula54860.92 (0.54-1.55)0.750.930%
Postoperative hemorrhage43970.57 (0.15-2.16)0.410.910%
Intraabdominal abscess43971.07 (0.53-2.18)0.850.490%
Wound infection32971.18 (0.45-3.09)0.740.980%
Time of start liquid diet21893.62 (-2.82-10.06)0.270.0380%
Time of start solid diet32524.77 (-0.11-9.64)0.06< 0.0000194%
Time of nasogastric intubation43413.32 (0.31-6.32)0.03< 0.0000197%
Reinsertion of nasogastric tube32852.15 (0.93-4.96)0.070.440%
Mortality43740.32 (0.03-3.18)0.330.970%
Hospital stay32225.96 (3.46-8.46)< 0.000010.550%
DGE with other definition
DGE2972.29 (0.35-15.21)0.390.1161%
Operation time297-48.51 (-109. 22-12.20)0.120.790%
Intraoperative blood loss297-588.29 [-898.10-(-278.49)]0.00020.790%
Pancreatic fistula2970.86 (0.22-3.33)0.83--
Wound infection2970.44 (0.09-2.08)0.300.880%
Time of start liquid diet2972.30 (-2.30-6.91)0.330.00687%
Time of NGD insertion2971.82 (-2.43-6.06)0.400.02
Mortality2970.29 (0.01-7.26)0.45--
Hospital stay2970.17 (-2.77-3.11)0.910.2427%
Reconstruction with pancreaticojejunostomy
DGE64713.72 (2.12-6.56)< 0.000010.1835%
Operation time6471-11.79 (-32.26-8.68)0.260.2130%
Intraoperative blood loss6471-265.87 (-422.93-108.81)0.00090.1538%
Pancreatic fistula64710.90 (0.55-1.48)0.670.940%
Postoperative hemorrhage43490.61 (0.16-2.38)0.480.930%
Intra-abdominal abscess43491.06 (0.51-2.22)0.880.480%
Wound infection43270.83 (0.34-2.03)0.680.780%
Time of start solid diet32492.29 (-1.97-6.54)0.290.0664%
Time of nasogastric intubation53711.92 (0.38-3.47)0.01< 0.0000189%
Hospital stay31881.23 (-1.64-4.09)0.400.2528%
Reconstruction with pancreaticogastrostomy
DGE21791.51 (0.70-3.26)0.29--
Operation time217949.00 (30.41-67.59)< 0.00001--
Intraoperative blood loss217941.00 (-51.78-133.78)0.39--
Randomized controlled trial
DGE22302.69 (1.17-6.17)0.020.320%
Operation time2230-16.69 (-42.68-9.30)0.210.830%
Intraoperative blood loss2230-120.23 (-364.94-124.48)0.340.770%
Pancreatic fistula22301.08 (0.53-2.20)0.820.910%
Postoperative hemorrhage22300.67 (0.11-4.11)0.670.720%
Intra-abdominal abscess22300.75 (0.14-4.14)0.750.1551%
Wound infection22301.19 (0.38-3.70)0.760.860%
Reinsertion of nasogastric tube22302.17 (0.84-5.59)0.110.2039%
Mortality22300.34 (0.01-8.46)0.51--
Non-randomized controlled trial
DGE64203.36 (1.25-9.08)0.020.0558%
Operation time6420-0.56 (-47.55-46.43)0.980.00772%
Intraoperative blood loss6420-283.77 (-593.42-25.87)0.070.00178%
Pancreatic fistula53530.77 (0.39-1.53)0.460.930%
Postoperative hemorrhage32310.41 (0.08-2.22)0.300.780%
Intra-abdominal abscess32311.21 (0.47-3.13)0.700.830%
Wound infection31640.64 (0.19-2.08)0.450.730%
Time of start liquid diet31863.68 (-0.30, 7.66)0.070.000687%
Time of start solid diet31865.06 (0.39-9.73)0.030.0469%
Time of nasogastric intubation53083.49 (0.82-6.16)0.01< 0.0000195%
Hospital stay3155 4.28 (-0.56-9.12)0.080.0276%
Mortality42400.30 (0.03-2.94)0.300.970%
D1 lymph node dissection
DGE2570.32 (0.07-1.48)0.140.900%
D2 lymph node dissection
DGE21193.07 (1.05-9.02)0.040.530%
Publication bias

The funnel plot based on the incidence of DGE is shown in Figure 4. None of the studies lies outside the limits of the 95%CI, indicating there was no evidence of publication bias.

Figure 4
Figure 4 Funnel plot to investigate publication bias. Funnel plot on delayed gastric emptying basing on all studies. The funnel plot revealed no publication bias.
DISCUSSION

Physiologically, gastric emptying requires coordination of the gastric antrum, pylorus and duodenum through paracrine messages and extrinsic stimulation from the vagus nerve[36]. DGE is one of the most common complications after pancreaticoduodenectomy and has been reported to occur in 1%-6% of patients[37]. While this is not a life-threatening complication of pancreatic surgery, it results in a reduced quality of life, impaired oral intake, increased hospital costs and the delayed initiation of adjuvant chemotherapy, where required. The pathogenesis of DGE after PPPD is thought to involve a number of factors, such as: gastric atony caused by vagotomy[38]; pylorospasm[39,40]; ischemia of the pylorus ring due to division of the right gastric artery[41]; congestion around the pylorus ring due to division of the left gastric vein[42]; and gastric dysrhythmia secondary to other complications such as pancreatic fisecon[43,44]. SSPPD was introduced in recent years as an alternative to PPPD to maintain the pooling ability of the stomach and reduce the incidence of DGE[17] by retaining most of the gastric body but resecting the pyloric complex itself. Whereas in a PPPD the proximal duodenum is divided 3 to 4 cm distal to the pylorus ring, in an SSPPD more than 95% of the stomach is preserved.

This meta-analysis of two RCTs and six non-randomized trials (prospective and retrospective) revealed a significant benefit of SSPPD compared with PPPD with regard to DGE and period of nasogastric intubation, albeit with greater intraoperative blood loss. Subgroup analysis specifically looking at trials using the ISGPS definition of DGE, reconstruction with pancreaticojejunostomy, RCTs or non-randomized trials also favored SSPPD with lower rates of DGE. This is the first complete pooled study to date comparing rates of DGE with the two surgical techniques (SSPPD vs PPPD). Apart from obvious potential benefits relating to hospital stay, nutrition and possible quality of life benefits, SSPPD may even lead to shorter postoperative recovery times and even earlier commencement of oral chemotherapy, where required. As a result, we consider SSPPD to have distinct short-term advantages over PPPD.

Due to the lack of an internationally accepted consensus definition for DGE in the past, the differences in reported DGE rates may have reflected differences in definitions rather than true differences in incidence. The ISGPS proposed definition of DGE, which includes a 3 tiered clinical grading system[45] based on clinical impact, allows more accurate comparisons. DGE grades B and C signify a prolonged hospital stay and increased costs. In our subgroup analysis, DGE grades B and C were lower in the SSPPD group compared to the PPPD group.

Previous studies have often found associations between DGE and postoperative intraabdominal complications such as biliary fistula, pancreatic fistula, and intraabdominal abscess[16,29,42,46], although causality has never been clearly demonstrated. Our systematic review did not reveal any significant differences between SSPPD and PPPD in the incidence of pancreatic fistula or intraabdominal abscess rates, suggesting that these did not have a simple relationship with DGE.

Coordination of the antro-pyloric region is considered to be impaired after surgery involving lymph node dissection in the area of the hepatoduodenal ligament and can lead to a physiological derangement similar to that seen with truncal vagotomy[39]. In our subgroup analysis, however, degree of nodal dissection (D1 vs D2) did not influence rates of DGE, although the sample size was very small.

Importantly, our study found no statistically significant differences in mortality, post-operative hemorrhage, pancreatic fistula or wound infection rates between the two operative techniques. While time to commencing liquid and solid diet and hospital stay were also not statistically significant, there is a clear tendency favoring SSPPD in relation to these outcomes. It is notable, however, that there seems to be the greatest difference in the retrospective and non-randomized trials, raising the possibility of selection bias. One can envisage, for example, a surgical team introducing diet earlier in patients who underwent SSPPD vs PPPD. Furthermore, it is worth noting that there was no mortality at all in any of the included PPPD groups, whereas there were reports of single patient mortality in the SSPPD groups. While this difference did not reach statistical significance, one has to note that none of the studies were sufficiently powered to detect small differences in infrequent events such as death and this must be addressed in any future randomized controlled trial.

There are a number of limitations to this study. Firstly, all included studies originated from Japan, which may skew both the population under investigation as well as operative techniques. Also, most included studies were non-randomized and retrospective in design. Furthermore, there was significant variability in clinical parameters such as operative time, intraoperative blood loss, time of start of liquid or solid diet, time of nasogastric intubation and hospital stay. This was likely related to the differences in operative technique (pancreaticojejunostomy vs pancreaticogastrostomy, end-to-end vs end-to-side anastomoses, use of pancreatic stents). Due to a lack of detailed information in the included studies, it was not possible to perform a subgroup analysis based on various reconstruction approaches. The greatest shortcoming, however, is that the studies included provided us with insufficient information to conduct a sound comparison of long-term nutritional status, gastrointestinal function and quality of life. Clearly, if there were to be significant long-term complications such as increased rates in dumping syndrome, it would argue strongly against SSPPD as a technique.

In conclusion, this study suggests SSPPD is as safe as PPPD in the studied population and may be superior to PPPD with respect to DGE. However, there is an evident need for well-designed RCTs comparing SSPPD and PPPD with respect to quality of life and survival outcomes.

COMMENTS
Background

Currently, classic pancreaticoduodenectomy and pylorus preserving pancreaticoduodenectomy (PPPD) are considered to be the most widely used surgical procedures for the treatment of pancreatic head and periampullary tumors. Delayed gastric emptying (DGE) is regarded as one of the most common postoperative complications in these two surgical approaches. Recently, a new surgical method, subtotal stomach-preserving pancreaticoduodenectomy (SSPPD), was developed to reduce the incidence of DGE. However, whether this can be achieved in practice is not clear.

Research frontiers

To conduct a meta-analysis comparing perioperative outcomes, especially DGE, after PPPD and SSPPD for the first time.

Innovations and breakthroughs

Based on this meta-analysis, patients undergoing SSPPD had a significantly lower rate of DGE and a shorter period of nasogastric intubation despite being associated with greater intraoperative blood loss.

Applications

SSPPD can reduce DGE as well as improve short-term postoperative outcomes compared with PPPD. However, future randomized trials should compare the advantages between SSPPD and PPPD.

Peer-review

This report was of great interest because it seems to be the first complete pooled study to compare rates of DGE with the two surgical techniques, SSPPD vs PPPD. Of course there are limitations in that most of the studies included in this study were retrospective. However, this study can be the chart for deciding the surgical management for patients requiring pancreaticoduodenectomy and for further studies.

Footnotes

P- Reviewer: Nentwich MF, Sakamoto Y, Sugiyama H S- Editor: Ma YJ L- Editor: Roemmele A E- Editor: Wang CH

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