Delayed gastric emptying after pancreatoduodenectomy: comparison between two different pancreatic reconstruction techniques

Background The association between delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) and pancreatic reconstruction technique remain unclear. The aim of this study is to investigate whether the occurrence of DGE differs between pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). A total of 83 patients who underwent subtotal stomach-preserving pancreatoduodenectomy was retrospectively analyzed, and the factors associated with clinically relevant DGE were explored. These patients were divided into a PG group and a PJ group according to the pancreatic reconstruction. DGE occurrence and its association with intra-abdominal complications was compared between the two types of pancreatic reconstruction.

The association between delayed gastric emptying (DGE) after pancreatoduodenectomy (PD) and pancreatic reconstruction technique remain unclear. The aim of this study is to investigate whether the occurrence of DGE differs between pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG).

Methods
A total of 83 patients who underwent subtotal stomach-preserving pancreatoduodenectomy was retrospectively analyzed, and the factors associated with clinically relevant DGE were explored. These patients were divided into a PG group and a PJ group according to the pancreatic reconstruction. DGE occurrence and its association with intra-abdominal complications was compared between the two types of pancreatic reconstruction.

Results
The overall incidence of DGE was 27.7%. Intra-abdominal complications including pancreatic fistula were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. In addition, DGE with intraabdominal complications tended to be more frequent in PG, despite the fact that intraabdominal complications occurred at a similar frequency in both groups.

Conclusions
Intra-abdominal complications were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. We speculate that intra-abdominal complications affected patients with PG more and resulted in frequent occurrence of DGE.

Background
The mortality rate after pancreatoduodenectomy (PD) is declining to a very low level in specialized centers. However, the postoperative morbidity rate remains high (approximately 50%) [1,2], and delayed gastric emptying (DGE) is the most predominant morbidity, with an incidence varying from 19% to 57% [1,3]. Although not life-threatening, DGE is associated with a decreased quality of life, increased postoperative length of stay, and increased healthcare costs.
Because of the variation in the definition of DGE, it has not been possible to compare studies of DGE [4]. To resolve this issue, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition in 2006 based on two clinical parameters [4]: number of days that nasogastric drainage is required, and the number of days until solid food is tolerated. As a result, reports about DGE defined according to this generalized definition have been accumulating [5][6][7]. Regarding the pathogenesis of DGE, denervation of the antropyloric region, pyloric and antral ischemia, and decreased levels of motilin have been suggested [8][9][10]. Furthermore, strong associations with other postoperative complications, especially intra-abdominal complications (IACs) such as pancreatic fistula (PF) and intra-abdominal abscesses (IAAs), have been reported [4-6, 11, 12]. Considering the association between DGE and IACs, the procedure for remnant pancreatic reconstruction would likely be a crucial factor related to DGE occurrence, because its disruption would result in various kinds of IACs. To minimize the risk of pancreatic anastomosis failure, pancreaticogastrostomy (PG) has been adopted instead of pancreaticojejunostomy (PJ) by several surgeons [13,14]. However, there has been no definite evidence showing increased safety with PG [15], and, moreover, there have been few reports comparing the incidence of DGE between the two types of pancreatic reconstruction.

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The aim of the present study was to compare the occurrence of clinically relevant DGE and its association with IACs between these two different pancreatic reconstruction techniques.

Methods
Of a consecutive series of 93 patients undergoing elective PD from May 2002 to March 2012 in the Steel Memorial Muroran Hospital, a retrospective review of 83 patients who recovered and were discharged from hospital was carried out. The following 10 patients were excluded from this analysis: two patients who died from postoperative complications, one patient who died from recurrence during hospitalization, and seven patients whose clinical data were not available. All of the patients underwent subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Prior to 2008, PG was used exclusively for remnant pancreatic reconstruction; in 2009, PJ was adopted for reconstruction instead of PG. All operations were performed by experienced surgeons.

Descriptions of the operative procedures
The procedure for the resection at the time of SSPPD was the same for the PG and PJ groups; the gallbladder, distal common bile duct, head of the pancreas, duodenum, and about 10 cm of the proximal jejunum were removed. The antrum was resected 3 cm oral to the pyloric ring. The reconstruction procedures for the PG and PJ groups were as follows.
PG group PG was performed with an invagination technique, hand-sewn with absorbable monofilament sutures, on the posterior wall of the gastric body, and a short internal stent was used. The proximal jejunum was brought through the transverse mesocolon by the retrocolic route, end-to-side choledochojejunostomy was performed using interrupted absorbable monofilament sutures with or without tube drainage, according to duct size.

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Further downstream, side-to-side antecolic gastrojejunostomy and side-to-side jejunojejunostomy with hand suturing were performed.

PJ group
The jejunal loop was brought in the same manner as in the PG group. PJ with end-to-side technique was performed between the pancreatic duct and the jejunal mucosa using 8 to 12 interrupted absorbable monofilament sutures according to duct size. A pancreatic duct tube was routinely placed in the main pancreatic duct. Further downstream, end-to-side choledochojejunostomy, side-to-side antecolic gastrojejunostomy and side-to-side jejunojejunostomy were performed in a similar manner to PG group.Closed suction was placed posterior to the biliary and pancreatic anastomosis in both groups.

Perioperative management
There were no differences in the perioperative management between the two groups.
In both groups, the gastric suction using a nasogastric tube was removed when the daily discharge was less than 500 mL, usually on the first postoperative day. Solid oral intake was initiated 4 days after operation and the patients proceeded to a regular diet within about 14 days.
Classification of delayed gastric emptying (DGE) and pancreatic fistula The preoperative features are summarized in Table 2 for the 23 DGE (+) patients and the 60 DGE (-) patients. There were no significant associations with median age, sex ratio, median body mass index (BMI), underlying disease, and preoperative cholangitis/biliary drainage, although some authors previously reported these as associated factors [5,6,17,18].
Postoperative features were also compared between DGE (+) and DGE (-) patients in Table   2. The DGE (+) group showed a significantly longer postoperative hospital stay, as in previous reports [7]. No significant differences were seen between the DGE (+) and DGE (-) groups in terms of median operative time, median bleeding. On the other hand, IACs, PF, 7 and IAA, were strongly associatedwith DGE(p<0.001, p<0.001, and 0.027, respectively).
As to the pancreatic reconstruction, pancreatic reconstruction procedure was associated with DGE, which occurred more frequently in the PG group than in the PJ group (40.5% vs. 17.4%,respectively, p=0.019). Table 3 shows a comparison of patients' characteristics between the PJ and PG groups. The surgical results were generally similar between the two types of reconstruction, except for DGE occurrence. Remarkably, delayed gastric emptying with intra-abdominal complications tended to be more frequent in pancreaticogastrostomy, despite the fact that intra-abdominal complications occurred at a similar frequency in both groups (36.8% vs. 66.7%, respectively, p=0.07). In particular, DGE with PF was more frequent in PG (37.5% vs. 100%, respectively, p=0.013).
Multivariate analysis using logistic regression identified thee variables as independently associated with the occurrence of DGE: pancreatic fistula, intra-abdominal abscess and pancreatic reconstruction technique .

Discusssion
Recent investigations have reported that DGE should be considered a warning of IACs, such as PF or IAA [7,11,13,17,18]. Similarly, in the present study, most DGE patients (82.6%) had IACs, which confirmed this association (p<0.001). As to surgical procedure, pylorus-preserving pancreaticoduodenectomy (PPPD) [19] and a postcolic route for the GE reconstruction [20] have been reported as typical risk factors for DGE. On the other hand, there have been few reports of the association between DGE and the pancreatic reconstruction procedure. However, the reconstruction method of the pancreatic stump is closely associated with IACs, which have been frequently reported as risk factors for DGE [5,7]. Considering this relationship, a close association between the procedure of pancreatic reconstruction and DGE occurrence is expected. In our institute, PJ was exclusively adopted for pancreatic reconstruction in SSPPD instead of PG since 2009. 8 There was no bias in the selection of patients between PG and PJ even though the present study was retrospective, which adds to the validity of the present analysis. As expected, and this was the most striking result, DGE occurred more frequently in the PG group.
The frequent occurrence of DGE in PG would suggest that the surgical procedure of PG itself affected DGE occurrence. It is possible that the PG resulted in fixation of the subtotal stomach to the posterior wall, thereby disturbing gastric peristalsis.
Next, as to DGE with IACs, safer pancreatic reconstruction with fewer IACs should decrease this type of DGE. Some surgeons prefer PG to PJ for patients at high risk of PF because some observational clinical studies (OCSs) reported a lower incidence of PF with PG [13,14]. However, these reports showed high heterogeneity, and, moreover, no highquality, randomized, controlled trials (RCTs) have yet to provide adequate evidence of greater safety with PG than with PJ [15]. Similarly, in the present study, there were no significant differences in the frequencies of PF and IACs between the PG and PJ groups, but DGE with IACs occurred more frequently in the PG group. As suspected, the present data suggested that the PG group was more vulnerable than the PJ group to the impact of DGE occurring by IACs. Especially with regard to PF, a strong association with DGE was shown in the PG group, but not in the PJ group. In the PJ group, 3 of 8 patients (37.5%) with PF had DGE, whereas all PG patients with PF were affected by DGE (P 0.007). It is probable that, in patients with PJ, the increasing distance from the pancreatic anastomosis would reduce gastric paresis due to PF or peripancreatic inflammation.
Although pancreatic anastomosis should not be chosen based on prevention of DGE alone, PG appeared to have a tendency to induce DGE, and thereby resulted in patient frustration, the need for nutritional support, and prolonged hospital stay. When PG is adopted, surgeons should take care to prevent disturbance of gastric peristalsis, including the anastomotic procedure, by omitting the incision on the anterior gastric wall, or choosing a vertical incision instead of a horizontal incision [21].
Although the ISGPS criteria have enabled comparisons of DGE between investigators using the general definition, interpretation of DGE is sometimes confusing. For example, patients with IACs, including chylorrhea, postoperative hemorrhage, enterocolitis, and gastric ulcer bleeding, may require withdrawal of oral intake despite lacking gastroparesis. DGE was originally described as gastroparesis following PPPD [22]; therefore, in our opinion, these patients should not be categorized as having DGE, whereas some investigators might have interpreted such cases as having DGE. This confusion occurred because the ISGPS criteria did not mention the presence or absence of co-existing complications, exclusion criteria, and the method for evaluating gastroparesis, although the criteria are simple, objective, and clearly measurable. Refinement of the definition is warranted for further analysis of the etiology of DGE.
In conclusion, the occurrence of DGE and its association with IACs was compared between different pancreatic reconstruction techniques. Intra-abdominal complications including PF were strongly associated with DGE. As to the pancreatic reconstruction, DGE developed more frequently in the PG than in the PJ. We speculate that PG itself predisposed patients to DGE by the fixation to the posterior wall and intra-abdominal complications affected patients with PG more, these resulted in frequent occurrence of DGE in PG.

Funding
The authors have no financial ties to disclose.

Availability of data and materials
All data and materials are contained within the manuscript.

Ethics approval and consent to participate
Local ethics committee (Steel Memorial Muroran Hospital) ruled that no formal ethics approval was required in this study.

Consent for publication
Informed consent was obtained from all individual participants included in this study.