The impact of prevention of delayed gastric emptying on long-term prognosis and nutritional status after pancreaticoduodenectomy: a single-center retrospective cohort study

Abstract

Background

Delayed gastric emptying (DGE) remains an unsolved complication after pancreaticoduodenectomy (PD). The aim of this study was to evaluate the effectiveness of a modified reconstruction technique -anchored straight stomach reconstruction (ASSR) - in reducing the incidence of DGE, and its impact on survival after PD.

Methods

A retrospective analysis of 121 consecutive PD patients was conducted: 100 of them had undergone ASSR and the remaining 21 had undergone conventional modified Child method of reconstruction. The two groups were then compared with regard to the incidence of DGE and long-term outcome including postoperative nutritional status.

Results

The incidence of significant DGE in the ASSR group (5%) was significantly lower than that in the conventional group (29%) (p < 0.001). The 5- and 10-year overall survival rates were significantly better in the ASSR group (60% and 49%, respectively) than in the conventional group (45% and 9%, respectively) (p = 0.024). Multivariate analyses showed that the type of reconstruction (ASSR or conventional) was a significant independent post-PD prognostic factor (p = 0.001). Comparison of nutritional status showed that ASSR facilitated a prompt recovery of body weight (BW) and serum albumin level at 6 months after PD. At 12 months after PD, BW gain was significantly better in the ASSR group than in the conventional group (p = 0.032).

Conclusion

Anchored straight stomach reconstruction is able to reduce the incidence of DGE in patients undergoing PD. The prevention of DGE by ASSR might improve their nutritional status, possibly resulting in a better survival rate after PD.

Background

Although pancreaticoduodenectomy (PD) is still a standard surgical treatment for malignant neoplasms in the periampullary region, the rate of postoperative morbidity remains high. Among various complications after PD, delayed gastric emptying (DGE) is frequent. DGE was originally described as gastroparesis (primary DGE), associated particularly with pylorus-preserving pancreaticoduodenectomy (PPPD), with an incidence of 17–46% [1–3]. Previous studies have reported various factors affecting prognosis after PD, including major complications such as pancreatic fistula, and the use of preoperative biliary drainage [4–6]. Although DGE itself is not life-threatening, it necessitates prolongation of the hospital stay, thus increasing medical costs and decreasing the quality of life. A recent report has also indicated that DGE can negatively impact cancer-specific survival [7]. However, the impact of DGE on long-term prognosis after PD has not been fully clarified, as well as the reasons why DGE may have a negative impact.

We have been using a modified reconstruction technique - anchored straight stomach reconstruction (ASSR) - designed to place the stomach straight by anchoring it with a feeding jejunostomy tube, in order to reduce the incidence of DGE after PD. The aim of this study was to evaluate the effectiveness of ASSR for reducing DGE, and its impact on survival after PD.

Methods

Patient selection and clinical data

A consecutive series of 121 patients who underwent PD between July 2007 and May 2021 was used as the target patient group. In order to reduce DGE, we have mostly performed a modified reconstruction technique - anchored straight stomach reconstruction (ASSR) -, except patients who had a history of lower abdominal surgery (e.g., sigmoidectomy for colon cancer or colostomy), due to dense adhesion. However, because the benefits of ASSR were not clear at the time of surgery, the final decision to perform either ASSR or conventional reconstruction without ASSR was made at the discretion of the surgeon. In this study, DGE was evaluated according to the International Study Group of Pancreatic Surgery (ISGPS) grading classification [8]. Grades B and C usually required adjustment of clinical management and were defined as “clinically significant DGE” in this study. Previous studies have utilized the terms “primary” and “secondary” DGE: secondary DGE is concomitant with intra-abdominal complications, whereas primary DGE is not. In the present study, secondary DGE was excluded to clarify the influence of primary DGE on long-term prognosis. Postoperative complications were graded according to the classification system proposed by Clavien et al [9]. We defined any major postoperative complication worse than grade II as a complication. Pancreatic fistula was classified according to the International Study Group of Pancreatic Fistula (ISGPF) clinical criteria [10],and grade B or more was regarded as “clinically significant pancreatic fistula” in this study. For follow-up, clinical parameters such as tumor markers were evaluated closely every 3 months for 2 years and then every 6 months for 3 to 5 years postoperatively. Other imaging modalities, such as computed tomography or magnetic resonance imaging, were added according to requirement. After the follow-up period, information on outcome was obtained from the other clinics or hospitals to which the patients had been referred. 

Surgical procedures

After pancreatectomy, reconstruction was performed using a modified Child method in all patients. End-to-side duodenojejunostomy for PPPD and gastrojejunostomy for subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) were performed in a two-layer manner, antecolically, and a Braun anastomosis was constructed in all patients.In ASSR, a modest-caliber soft catheter with several openings was inserted into the proximal efferent jejunal loop toward the Braun anastomosis. The feeding tube was fixed on the jejunal wall using Witzel’s method, and brought out through a stab wound in the abdominal wall in the left lower quadrant to place the stomach in as straight and vertical a position as possible (Fig.1). Anchoring sutures were placed between the jejunum and the parietes to completely seal off the area of the catheter. This Witzel jejunostomy contributed to straight placement of the anastomosed duodenum and stomach to allow smoother flow of food into the efferent jejunum by gravity when the patient was upright, regardless of stasis (Fig.2a). 

Postoperative management 

The nasogastric tube (NGT) was removed on postoperative day 1 or 2, or when the volume of gastric output was less than 200 ml/day. We performed contrast gastrography on postoperative day (POD) 3 to verify the absence of anastomotic leakage and passage of the medium, and thereafter progressed to a regular diet (Fig.2b). Prokinetic agents were initiated on a clinical need basis and not as prophylaxis. The feeding jejunostomy tube was mostly removed within 3 weeks, unless required for feeding purposes, in which case it was employed for early enteral nutrition.

Statistical analysis

Data are presented as means ± standard deviation or as medians with the range. Statistical analysis was performed using Student’s t test and Fisher’s exact test. Survival analysis was performed using the Kaplan–Meier method and differences were evaluated by log-rank tests. The Cox proportional hazards model was used to assess potential predictors of survival. Variables that affected overall survival with P values of <0.05 in univariate analyses were included in the multivariate model. Differences at P <0.05 were considered significant. 

Results

Patient background factors and incidence of delayed gastric emptying

Among the 121 patients treated by PD, 100 who underwent ASSR were assigned to the ASSR group. The remaining 21 who underwent reconstruction without ASSR were assigned to the conventional surgery group. The relevant patient characteristics and perioperative details are shown in Table 1. The median patient age was 73 years in the ASSR group and 69 years in the conventional group, and patients in the ASSR group were significantly older at the time of surgery (p=0.01). As for the type of procedure, PPPD was used in 87% of the ASSR group and in 52% of the conventional group, the difference being significant (p<0.001). There were no significant inter-group differences in other patient background factors, including diagnoses, UICC stage, pancreatic fistula, major complications and adjuvant chemotherapy. The observed DGE grades are listed in Table 2. In the ASSR group, the interval for removal of NGT tended to be shorter, and the period until resumption of a solid diet was significantly shorter than in the conventional group (p=0.002). Consequently, the incidence of significant DGE in the ASSR group (5%; n=5) was significantly lower than that in the conventional group (29%; n=6) (p<0.001). 

Impact of anchored straight stomach reconstruction on long-term outcome

The patients were followed up for a mean period of 3.8 ± 3.2 years (range, 0.3-14 years). No perioperative deaths (within 90 days) occurred in any of the 121 patients. Of 121, the 5- and 10-year overall survival rates were significantly better in the ASSR group (60% and 49%, respectively) than in the conventional group (45% and 9%, respectively) (p=0.024) (Fig.3a). On the other hand, the 3- and 5-year recurrence-free survival rates in the ASSR group (57% and 55%, respectively) were higher than those in the conventional group (34% and 34%, respectively), but not to a significant degree (Fig.3b). Analysis of the post-PD prognostic usefulness of six factors revealed that outcome was significantly poorer for a higher ASA-PS classification (p=0.006), pancreatic cancer (p<0.001), UICC Stage III (p=0.026) and conventional reconstruction (p=0.011); other factors had no significant influence (Table 3). Multivariate analysis using these four factors revealed ASA-PS classification (p=0.016), diagnosis (p=0.005) and type of reconstruction (p=0.001) to be independent prognostic factors after PD.  

Long-term nutritional status in the two groups

To investigate the reasons why ASSR affected survival after PD, postoperative nutritional status was compared between the two groups. To avoid any influence of recurrence, we excluded patients whose follow-up period was less than one year after surgery and those who developed recurrent disease within one year after surgery. As a result, 69 patients in the ASSR group and 15 in the conventional group were evaluated. Figure 4 shows the changes in body weight (BW) and serum albumin level in the two groups before surgery, and 3, 6 and 12 months after surgery, respectively. Body weight was decreased at 3 months after surgery in both groups (p<0.01). At 6 and 12 months, the ASSR group showed a significant weight increase relative to that at 3 months (p=0.041) and 6 months (p=0.002), respectively, whereas in the conventional group it showed a continuous decrease for up to 12 months post-surgery. At 12 months, BW in the ASSR group was significantly higher than that in the conventional group (p=0.032). The serum albumin level in the ASSR group was unchanged at 3 months after surgery, and at 6 months had increased significantly relative to that at 3 months (p=0.005). Although the serum albumin level at 6 and 12 months remained persistently higher in the ASSR group than in the conventional group, the inter-group difference was not significant.

Discussion

Several techniques for reducing the incidence of DGE after PD have been advocated [11–14], but no definitive conclusions have been reached and the optimal treatment strategy for DGE remains to be clarified. A straight alignment of the stomach following PPPD has recently been reported to reduce the incidence of DGE [13, 14]. However, previous groups transposed the stomach over the left transverse colon and simply mobilized it downward in a straight line, without any anchoring suture or fixation of the stomach to the parietes. In contrast, we anchored the stomach to the parietes in the left lower quadrant of the abdomen, making use of a feeding jejunostomy tube in our technique. This anchoring contributed to straight placement of the anastomosed duodenum and stomach to allow smoother flow of food into the efferent jejunum by gravity when the patient was upright, regardless of stasis. In the present study, although the incidence of PPPD was more frequent in the ASSR group, the incidence of significant DGE in that group was only 5%, being lower than the incidence reported previously (range, 17–46%) [1–3]. As to placement of the feeding jejunostomy tube (FJT) at the time of PD, previous authors have suggested that it increases perioperative morbidity [15]. Contrarily, Sun et al. also reported that FJT placement did not appear to be associated with increased perioperative morbidity or mortality among 2980 patients who underwent gastrectomy [16]. In this study, our technique was simple and safe, with no complications related to jejunostomy, such as bowel occlusion, bowel perforation, or volvulus. Accordingly, this technique was considered acceptable in patients undergoing PD.

Conventionally, DGE is not considered a life-threatening complication. Recently, Futagawa et al. have demonstrated that severe DGE, especially grade C, negatively impacts survival, and is an independent risk factor for cancer-specific survival [7]. In the present study, survival was found to be significantly better in the ASSR group, the type of reconstruction was an independent factor affecting post-PD prognosis, and thus our results were consistent with their findings. Although the reasons why DGE may affect survival are not fully understood, it can be speculated that preservation of almost the whole stomach led to more favorable surgical outcomes, and may have contributed to improved oral intake. This in turn would have led to a more favorable nutritional status, possibly resulting in better survival through an improvement in immune status and compliance with adjuvant chemotherapy [7]. We compared the postoperative nutritional status between the two groups. This showed that ASSR facilitated better recovery in terms of BW and serum albumin level. We consider that, in the ASSR group, earlier resumption of oral feeding may have improved the protein supply, thus contributing to BW gain and an increase in the albumin level. Kawai et al. have suggested that DGE is associated with weight loss and poor nutritional status [17]. They also demonstrated that the incidence of > grade 2 weight loss (10–20% from the baseline) at 6 and 12 months after surgery in PPPD patients was 41.1% and 43.0%, respectively. In our series, on the other hand, the corresponding incidence at 6 and 12 months in the ASSR group was 32.7% and 31.7%, respectively. Further recovery of the serum albumin level in the ASSR group was also better than that observed in their study. Fujii et al. also reported that approximately 12% of BW was lost at 6 months after the surgery, and that the serum albumin level was also decreased at 6 months after surgery [3]. In our series, patients in the ASSR group at 6 months after surgery showed a BW loss of 7% and an increased albumin level. Consequently, ASSR in the present study might have facilitated prompter recovery of postoperative nutritional status in comparison with previous reports. Poor nutrition can delay recovery and is correlated with a higher incidence of complications and a poorer quality of life. Regarding with correlation between postoperative nutritional status and survival, there is mounting evidence that sarcopenia is associated with poorer prognosis after multiple abdominal operations, including gastric, liver, and pancreatic surgery [18–20]. Our results are consistent with those findings, and indicate shed new light on the relationship between DGE, nutritional status, and survival in patients with PD, particularly the degree to which DGE leads to poorer postoperative nutritional status, and its impact on long-term survival. To our knowledge, this is the first study to have investigated the reasons why DGE can impact survival in patients after PD.

Several limitations of this study must be acknowledged. This was a retrospective observational study with a non-randomized design, the number of patients included was relatively small, and thus potential bias could not be excluded. Although further studies with larger numbers of patients are warranted, the cases included were all assessed using acceptable standardized methods, as mentioned previously. Additionally, in this study, a nutritional advantage in patients with ASSR was apparent in comparison with previous reports.

Conclusion

In the present study, this modified anchored straight stomach reconstruction is considered simple and safe, and it can reduce the incidence of DGE, even in PPPD. Consequently, it shows promise for improvement of oral intake, thus conferring a more favorable nutritional status that would enhance survival in patients undergoing PD. In conclusion, prevention of DGE by ASSR has not only nutritional benefits, but also may improve the prognosis on the oncological aspect in patients with malignancy.

Abbreviations

Declarations

Acknowledgements 

The author would like to thank David Douglas ([email protected]) for the English language review.

Authors’ contributions

HS and NI developed the concept of the study and drafted the article. NI, YI, SM, MM and IW participated in the data collection and assisted with data interpretation. HS and IW supervised the manuscript. HS and NI obtained IRB approval for the protocol of the study. All authors read and approved the final manuscript. 

Funding 

No funding was obtained for this study. 

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. 

Ethics approval and consent to participate

The study was conducted in accordance with the principles of the Declaration of Helsinki. This study was approved by the ethics committee of Juntendo University Nerima Hospital (Tokyo, Japan; approval number: 2020076), and the requirement for informed consent was waived because of the retrospective nature of the study and the use of anonymized data.

Consent for publication

Not applicable. 

Competing interests

The authors declare that they have no competing interests. 

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Tables

Tables are available in the Supplemental Files section.