Blumgart anastomosis with polyglycolic acid felt reduces the incidence of pancreatic fistula after pancreaticoduodenectomy: A propensity score analysis

Abstract Polyglycolic acid (PGA) felt has been used to prevent clinically relevant postoperative pancreatic fistula (CR‐POPF) after pancreaticoduodenectomy (PD). However, there has been no related research on Blumgart anastomosis. Therefore, this study aimed to investigate the practical significance of Blumgart anastomosis with our new method involving PGA felt to prevent CR‐POPF following PD. Data from 133 consecutive patients who underwent Blumgart anastomosis during PD between June 2015 and November 2021 were reviewed. We applied PGA felt to 35 of these patients starting from July 2020. Surgical outcomes were analyzed by propensity score matching. Thirty‐five (35.7%) of the 98 patients in the without‐PGA group were matched with an equal number from the with‐PGA group after adjusting for covariates. CR‐POPF was found in 17 patients (49%) in the without‐PGA group and two patients (6%) in the with‐PGA group (P < .001). The multivariate analysis results indicated that male sex, pancreatic duct size <3 mm, soft pancreatic texture, and nonuse of PGA were independently associated with CR‐POPF after PD. In conclusion, Blumgart anastomosis with our new penetrating method for PGA felt reduces the incidence of CR‐POPF after PD.

Blumgart anastomosis is the tension-free approximation of the jejunum to the pancreatic stump by transfixing mattress sutures, 4 which has been modified in various institutions with good outcomes. 5 Therefore, Blumgart anastomosis has been adopted by many institutions.
Polyglycolic acid (PGA) felt is a bioabsorbable recombinant membrane made of a synthetic polymer with a cellulose-like structure and has been widely used to reinforce tissues such as the lung and bronchi in thoracic surgery. Recently, PGA felt has been used to prevent POPF in pancreatic surgery. [6][7][8][9][10] Regarding PD, some retrospective studies indicated that the incidence of CR-POPF was lower in patients with PGA than in those without PGA. 7,8 In contrast, some other studies did not show a significant difference in the incidence of CR-POPF between patients with and without PGA. 9,10 In addition, the pancreaticojejunostomy of these studies was not performed by Blumgart anastomosis, and the PGA felt was wrapped around the anastomotic site as a method of reinforcement. Recently, we developed a new method for the PGA felt to adhere without wrapping during Blumgart anastomosis. Therefore, this study aimed to investigate the practical significance of Blumgart anastomosis with PGA felt to prevent CR-POPF following PD.

| Surgical procedure
After review by a multidisciplinary board, all pancreatic disease cases were assessed by pancreatic surgeons to determine resectability and the most appropriate surgical procedure. The subtotal stomachpreserving method was the standard procedure for PD. In patients with malignant disease, lymph nodes were dissected at the hepatoduodenal ligament, around the common hepatic artery, around the superior mesenteric artery (SMA), and around the pancreatic head.
Transection of the pancreatic parenchyma was performed with an electric scalpel. A modified Child method, with duct-to-mucosa pancreatojejunostomy, was chosen for organ reconstruction in all cases.
The modified Blumgart mattress suture was performed for pancreatic remnant reconstruction. 5,11 In all cases, a 4-Fr polyethylene tube was placed through the pancreatojejunal anastomotic site as an external stent. Three silastic flexible drains were routinely placed adjacent to the anastomosis and at both the cranial and caudal sites of the pancreatojejunostomy and choledochojejunostomy.
In the PGA group, 0.3-mm-thick PGA felts (Neoveil; Gunze, Osaka, Japan) were prepared as eight pieces cut into sizes of 7 × 7 mm. After the seromuscular layer of the jejunum was threaded through using straight needles with 4-0 monofilament nonabsorbable sutures, 7 × 7 mm PGA felts were penetrated by each needle to reinforce the dorsal side ( Figure 1A). The pancreatic parenchyma was sutured penetratingly ( Figure 1B). For reinforcement of the ventral side, 7 × 7 mm PGA felts were penetrated by each needle ( Figure 2A). Anastomosis between the main pancreatic duct and the jejunal wall was performed with 6-8 interrupted 5-0 monofilament absorbable sutures ( Figure 2B). The seromuscular layer of the jejunum was threaded through with the former four straight needles ( Figure 3A). Each of the two threads was tied ( Figure 3B). The space between the ligated threads was reinforced with 4-0 monofilament nonabsorbable sutures ( Figure 4A). Next, the caudal side was reinforced with 4-0 monofilament nonabsorbable sutures ( Figure 4B).
Application of fibrin glue around the anastomotic site and the administration of somatostatin analogs were not used in either group.
In this study, period laparoscopic PD was performed in two patients (with PGA group). However, pancreatojejunostomy of both patients was performed in the same manner as above under a small laparotomy.

| Statistical analysis
Continuous data are expressed as the medians (ranges). The statistical analyses were performed using chi-square tests, Mann-Whitney U tests, or Fisher's exact probability tests, as appropriate. To overcome biases owing to the different distribution of covariates among patients who underwent Blumgart anastomosis with PGA and without PGA, propensity score matching was carried out. Using multivariate logistic regression analysis, we estimated propensity scores for these patients. The following covariates were selected by the forward selection method from age, sex, preoperative serum albumin concentration, body mass index (BMI), pancreatic ductal adenocarcinoma (PDAC), pancreatic duct size, and pancreatic texture, as these variables were shown to be prognostically significant in other studies. Subsequently, a one-to-one match between the two groups was performed by the nearest-neighbor matching method within 0.05. The balance of covariates between the groups was assessed by the absolute standardized mean difference (ASMD) before and after the matching procedure.
The variables identified as potentially significant by univariate analysis were selected for multivariate analysis with a logistic regression model to identify the independent predictors of CR-POPF.
All P values were two-sided, and P < .05 was considered to indicate a statistically significant difference. All statistical calculations were performed using the IBM SPSS Statistics 27 software package (IBM, Tokyo, Japan).

| Propensity score matching analysis
The patient flow chart, including the propensity score matching analysis, is outlined in Figure S1. Thirty-five (35.7%) of the 98 patients in the without-PGA group were matched with an equal number from the with-PGA group after adjusting for covariates.

| Patient characteristics
The patient demographics and clinical characteristics are shown in Table S1. Before propensity score matching, the percentages of age (≥70 y), sex, BMI (≥24 kg/m 2 ), PDAC, pancreatic duct size (<3 mm), and soft pancreatic texture did not differ between the two groups.
However, the percentage of serum albumin (<3.5 g/dl) was significantly higher in the without-PGA group than in the with-PGA group (41% vs 17%, P = .013).
After propensity score matching, the percentages of age (≥70 y), sex, serum albumin (<3.5 g/dl), BMI (≥24 kg/m 2 ), PDAC, pancreatic duct size (<3 mm), and soft pancreatic texture did not differ between the two groups. Table 1 shows the surgical outcomes after Blumgart anastomosis with/without PGA. After propensity score matching, the operation time was significantly longer in the without-PGA group than in the with-PGA group (441 min vs 377 min, P = .023). The total blood loss volume, portal vein resection rate, and drain fluid amylase concentration (DFAC) d 1 did not differ between the two groups. DFAC d 3 in the with-PGA group was one-third lower than that in the without-PGA group, but there was no significant difference.

| Predictors of CR-POPF after Blumgart anastomosis
The multivariate analysis results indicated that male sex (odds ratio  (Table S2).

| DISCUSS ION
Our new penetrating method, like previous methods, was developed with the concept of reinforcing the pancreatic parenchyma from injury caused by the suture. In addition, our PGA felt fills and reinforces the jejunum and pancreas. Furthermore, reinforcing the space between the ligated threads ( Figure 4A) and the caudal side ( Figure 4B) of the Blumgart anastomosis improves the close contact of the anastomosis and prevents pancreatic juice leakage. Our method is expected to be able to adhere to the anastomotic site for a longer time than the wrapping method.
Consequently, in this study using propensity score analysis, the rate of CR-POPF was significantly lower in the with-PGA group (6%) than in the without-PGA group (49%) (P < .001). Furthermore, an independent predictor of CR-POPF after Blumgart anastomosis. Additionally, DFAC-d 3 in the with-PGA group was one-third lower than that in the without-PGA group. There were no significant differences between the two groups in terms of intraabdominal abscess. However, the rate of intraabdominal abscess tended to be higher in the with-PGA group than in the without-PGA group. Since our drain-management strategy has not changed, 12 the reason for the increase in intraabdominal abscess may be due to latent POPF after using PGA felt.
Although there have been remarkable recent advances in pancreatic surgery, CR-POPF still occurs at a high rate. 2,3 In addition to surgical methods and instruments, various additional substances have been used to reduce the incidence of CR-POPF after PD. Fibrin glue may be used to reduce the incidence of CR-POPF in pancreatic anastomosis. However, a recent randomized control trial and metaanalysis that evaluated the use of fibrin glue in pancreatic surgery showed no significant effect. 13 Application of fibrin glue around the anastomotic site and administration of somatostatin analogs were not employed in this study. As an additional substance, PGA has attracted attention in recent years, and PGA felt has been used to prevent POPF in pancreatic surgery. [6][7][8][9][10] PGA felt is a bioabsorbable tissue-reinforcing material that is made of PGA and does not remain as a foreign substance in the human body.
When PGA felt is attached to a tissue, inflammatory cells and fibroblasts gather around the PGA fibers as a biological reaction; these cells then infiltrate the felt and proliferate, with consequent formation of granulation tissue. The mechanism of reinforcement is that the granulation tissue becomes fibrotic with decomposition of the PGA felt and is replaced with autologous tissue.
Regarding distal pancreatectomy, Jang et al 6 demonstrated in a randomized controlled trial that application of PGA felt to the cut surface of the pancreas is associated with a significantly reduced rate of CR-POPF. In that study, the rate of CR-POPF was 11.4% in the PGA group and 28.3% in the control group (P = .04). For PD, there are only a few retrospective studies of CR-POPF after PD with PGA.
Ochiai et al 7 reported that CR-POPF occurred in 5.6% of the PGA group and 38.9% of the control group (P = .016). Kang et al 8 reported that the rate of CR-POPF was significantly lower in the PGA group (12.6%) than in the control group (22.4%) (P = .024). On the other hand, some other studies did not show a significant difference in the incidence of CR-POPF between patients with and without PGA. 9,10 Although the Blumgart anastomosis has been modified in various institutions with good outcomes, the pancreaticojejunostomy in these TA B L E 1 Surgical outcomes of patients who underwent Blumgart anastomosis with/without PGA before and after propensity score matching This investigation has some limitations that should be mentioned. First, it was a single-center retrospective study. However, the strength of this study is that the surgical techniques and postoperative management were unified. In addition, propensity score matching controlled for possible selection biases. Second, the rate of CR-POPF after PD was higher than that in previous studies. It is possible that a learning curve was present in the Blumgart anastomosis of this study. The rationale is that the operation time was significantly longer in the without-PGA group than in the with-PGA group. In the future, large-series multicenter prospective studies evaluating the clinical impact of PGA felt will help to compensate for the limitations of this investigation.
In conclusion, the results of our study indicate that Blumgart anastomosis with our new penetrating method for PGA felt reduces the incidence of CR-POPF after PD. We therefore propose the application of PGA felt by the penetrating method to prevent CR-POPF after PD.

ACK N OWLED G M ENTS
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