Covering reinforced staples with polyethylene glycolic acid felt-covered fibrin sealant to prevent pancreatic fistula after distal pancreatomy : a retrospective comparative study

doi:10.21203/rs.3.rs-1566336/v1

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Covering reinforced staples with polyethylene glycolic acid felt-covered fibrin sealant to prevent pancreatic fistula after distal pancreatomy : a retrospective comparative study

https://doi.org/10.21203/rs.3.rs-1566336/v1

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Background

In accordance with previous reports of the utility of polyethylene glycolic acid (PGA) felt and fibrin glue for postoperative pancreatic fistula (POPF), we usually perform distal pancreatectomy (DP) with a PGA felt reinforcement stapler when treating a pancreatic stump with DP, then cover the stump with PGA felt and fibrin glue (the PPF method).

Methods

127 DP performed in our department between January 2008 and June 2021 were retrospectively analyzed to compare the risk factors of POPF and the postoperative course of patients receiving the PPF method of treatment versus those receiving the conventional treatment.

Results

In the PPF method, CR-POPF tended to decrease, and POPF showed a significant decrease. The duration of drainage and the length of postoperative hospitalization were also significantly shorter with the PPF method. The risk of CR-POPF significantly decreased with the PPF method if the pancreas was thick (> 13.5 mm) or the patients were obese.

Conclusions

The PPF method is useful for POPF in DP and is particularly effective when a thick pancreas or an obese patient is involved. Removing the drainage tube early in the PPF method may lead to early discharge.

postoperative pancreatic fistula

distal pancreatectomy

polyethylene glycolic acid felt

fibrin glue.

Postoperative pancreatic fistulas (POPF) are the most frequent complication of distal pancreatectomy (DP) and occur in 13–64% of cases [1–3]. POPF often cause various problems leading to wound infection, intra-abdominal abscess, hemorrhage, and sepsis, which result in a longer hospital stay and higher medical costs. Thus, the best approach to preventing POPF should be considered when performing a pancreatectomy. Many surgeons attempt to control POPF by applying various surgical techniques, but the ensuing results have been mostly unsuccessful in alleviating the problem [4, 5].

Polyethylene glycolic acid (PGA) felt is a soft, flexible, absorbable, nonwoven material widely used for tissue reinforcement [6–8]. Its adhesion to tissue is greatest when used with a fibrin sealant. Herein, we examined a combination therapy consisting of reinforcement mesh, PGA felt wrapping, and fibrin sealant application (the PPF method) with the aim of evaluating the efficacy of this method in preventing POPF after DP.

Patient demographics and clinical presentations

Between January 2008 and June 2021, 127 consecutive patients underwent DP under general anesthesia at Tokyo Metropolitan Tama Medical Center. The patient data were retrieved from prospectively maintained databases and included baseline patient characteristics, such as demographic data, preoperative risk factors, co-morbidities, operative characteristics, and postoperative outcomes.

All the patients routinely underwent a preoperative enhanced computed tomography (CT). The imaging findings were assessed for main pancreatic duct (MPD) size, thickness of the pancreas, and pancreatitis. Pancreatic duct dilatation was defined as a main pancreatic duct diameter > 3 mm on CT; a thick pancreas was defined as thickness > 13.5 mm; and pancreatitis was defined as peripancreatic infiltration or fluid collection on CT. Based on Youden's index using receiver operating characteristic (ROC) analysis of the CR-POPF, the 127 patients were divided into two groups based on MPD diameter, pancreatic thickness, operation time, and intraoperative blood loss.

POPF was evaluated using the International Study Group for Pancreatic Fistula (ISGPF) definition [9]. All the operations were performed after obtaining the patients’ informed consent. The study was performed in accordance with the guidelines of the Helsinki Declaration and its later amendments.

Statistical analysis

Categorical variables were expressed as a number (%) and were compared using the chi-square test or Fisher’s exact test, as appropriate. Continuous variables were expressed as the median [interquartile range (IQR)] and were compared using Wilcoxon’s rank sum test. P < 0.05 was considered to indicate statistical significance. All statistical analyses were performed using the commercially available software JMP® 13 (SAS Institute Inc., Cary, NC, USA).

Patient demographics and clinical presentations

Between January 2008 and June 2021, 127 consecutive patients underwent a DP. The median age of all cases was 70 years (IQR: 61–77 years), and the median BMI was 22.2 kg/m2. Examination showed that 46 patients (36.2%) had a soft pancreas and 92 (72.4%) had received a diagnosis of a malignancy. The remaining 35 patients (27.6%) received a diagnosis of a benign disease, including 12 cases (9.4%) of intraductal papillary mucinous neoplasms, ten cases of (7.8%) neuroendocrine tumor, three cases (2.4%) of mucinous cystic neoplasm, three cases (2.4%) of serous cystic neoplasm, and seven cases (5.5%) of other diseases. The surgical procedures included open DP (ODP) in 65 patients (51.2%), laparoscopic DP (LDP) in 61 patients (48.0%), and robot-assisted DP (RDP) in one patient (0.8%). The pancreatic stump was treated with the PPF method in 17 patients (13.4%), reinforced stapler alone in 29 patients (22.8%), stapler alone in 68 patients (53.5%), and MPD ligation in 13 patients (10.2%). The median operation time in all the cases was 334 minutes (IQR: 275–394 minutes), and the median intraoperative blood loss was 340 ml (IQR: 150–870 ml). Pre-firing compression was done in 85 patients, including 17 using the PPF method. POPF occurred in 82 patients (64.6%), and CR-POPF occurred in 56 patients (44.1%). (Table 1)

Comparison of the factors related to CR-POPF

CR-POPF developed in 56 (44.1%) DP, and the all the cases were Grade B. There were no cases of POPF-related death. Most patients in whom a fistula developed after DP were obese.

Pancreatic characteristics, including duct size and gland texture, may be used to identify patients with a high risk of fistula development following a DP. A large MPD (≥3 mm) and thick pancreas (≥13.5 mm) were also associated with a higher fistula rate (38.0% vs. 57.1%; P = 0.032 and 42.3% vs. 60.7%; P = 0.039, respectively). There was no significant difference in the pancreatic gland texture in the present cohort.

The intraoperative factors were also scrutinized. Intraoperative blood loss > 800 ml was associated with a higher fistula rate (12.7% vs. 46.4%; P < 0.001). Minimally invasive procedures, including laparoscopic and robotic surgery and prefiring compression, were not associated significantly with CR-POPF formation (P =0.096 and P =0.452, respectively) (Table 2).

Risk factors associated with POPF

Univariate analysis revealed that soft pancreas (odds ratio (OR): 6.03; P = 0.020), large blood loss (OR: 7.02, P = 0.003), and non-application of the PPF method (OR: 5.65; P = 0.023) were independent predictors of CR-POPF. Multivariate analysis revealed that only large blood loss (OR: 7.64; P < 0.001) was an independent predictor CR-POPF (Table 3). These findings suggested that non-application of the PPF method could be a risk of POPF.

Comparison of postoperative outcomes in the PPF and conventional groups

The PPF group and the conventional group consisted of 17 patients (13.4%) and 110 patients (86.6%), respectively. The overall POPF rate (41.2% vs. 68.2%; P = 0.030) was significantly lower in the PPF group while CR-POPF (13.9% vs. 24.0%; P = 0.006) tended to occur at a lower rate in the PPF group. The rate of other surgical complications, including delayed gastric emptying, postoperative aneurysm, and chyle leakage, was similar between the groups. In addition, the rate of postoperative intra-abdominal fluid collection and elevated drain amylase was significantly lower in the PPF group. Moreover, compared to the control group, the PPF group had a significantly shorter median length of drainage tube insertion and hospital stay (22 days vs. 8 days; P < 0.001 and 28 days vs. 12 days; P < 0.001, respectively) (Table 4).

Comparison of postoperative outcomes in POPF high-risk cases in the PPF and conventional groups

CR-POPF occurrence did notdecrease uniformly in all the cases treated with the PPF method. However, it did decrease significantly among patients in the PPF group with a thick pancreas (> 13.5 mm) or high BMI (P =0.022 and P =0.016, respectively). CR-POPF were also evaluated in patients with a large MPD diameter and soft pancreatic texture, but no significant difference was found between these groups. (Figure 1)

Comparison of postoperative outcomes between the PPF and reinforced stapler-alone groups

A previous study revealed that the use of a stapler with PGA mesh reinforcement independently decreased the risk of post-DP pancreatic fistula formation [10, 11]. It is possible that only the PGA reinforcement without additional PGA mesh wrapping or fibrin glue was enough to prevent post-DP POPF. Thus, we compared the reinforced stapler-alone and PPF methods and found that CR-POPF occurrence decreased to a significantly greater extent in the PPF group than in the reinforced stapler-alone group (P =0.028). (Figure 2)

Previous studies reported several methods of preventing POPF, including main pancreatic duct ligation [12], staple closure [13, 14], pancreatico-intestinal anastomosis [15], and somatostatin analogue [16, 17]. However, the effectiveness of almost of all these methods remains unclear.

Fibrin sealant is widely used to prevent POPF in patients with DP [18, 19]. Suzuki et al. showed intraoperative fibrin sealant was effective to prevent POPF after DP. They revealed POPF decreased significantly in the fibrin sealant group, compared to the control group (15% vs. 40%). Ohwada et al. reported the fibrin sealant sandwich technique. They inserted fibrin sealant between the dorsal and ventral edges of the pancreatic stump. They reported that POPF decreased significantly in the sandwich technique group compared to the simple sealing group (9% vs. 27%).

Polyethylene glycolic acid (PGA) felt (Neoveil; Gunze), a bioabsorbable, recombinant membrane made of a synthetic polymer with a cellulose-like structure, is frequently used with fibrin sealant in thoracic surgery. Several studies revealed that the application of layers of PGA felt on the remnant pancreatic stump and use of fibrin glue with layers PGA mesh are effective in preventing post-DP pancreatic fistula development [20, 21].

Previous studies reported that use of the reinforced stapler [10, 11] in pancreatic transection decreased the risk of postoperative pancreatic fistula formation. The POPF rate with and without a reinforcement stapler was 3.6% and 13.5%, respectively [10]. The present study also examined whether the reinforced stapler alone was sufficient but found that the CR-POPF incidence was significantly lower in PPF method group than the reinforced stapler-alone group.

The present study focused on patients with a high risk of POPF characterized as having a soft pancreas, wide MPD, obesity or thick pancreatic resection. We assumed that pancreatic fistulas were less likely to develop if some method of treating the pancreatic stump was used with pancreatic resection in patients with a low risk of pancreatic fistula formation, such as those with a hard or thin pancreas, a normal-sized main pancreatic duct or normal BMI. Therefore, our investigation of pancreatic resection in patients with a high risk of POPF found that the PPF method is useful in patients with a thick pancreas or obesity, suggesting that using the PPF method in patients with a high risk of POPF may lead to better outcomes.

In addition, the PPF method demonstrated significantly more late, postoperative fluid collection in the pancreatic stump. However, all the cases improved with conservative treatment, such as antibiotic treatment, and did not require surgical intervention (Fig. 3). These results suggested that even if fluid collection in the pancreatic stump, a form of pancreatic fistula, is observed with the PPF method, conservative treatment can improve the patient’s condition sufficiently to enable early removal of the drainage tube. The PPF method is particularly effective in dissecting a thick pancreas, and early removal of the drainage tube in the PPF method has the potential to promote early discharge.

A previous study reported a new method of using PGA felt in conjunction with fibrin sealant in pancreaticojejunal (PJ) anastomosis in pancreaticoduodenectomies but its utility remains controvertial [8, 22]. We hypothesized that the covering of the PJ anastomotic line itself is probably one reason for the disappointing outcomes, i.e., completely wrapping and sealing the PJ anastomosis can cause exudates, including pancreatic juice from the small ductal branches of the cut surface of the pancreatic remnant, to collect, leading to PJ anastomosis infection and eventually POPF formation.

In conclusion, the present study found that the PPF method may be useful for preventing post-DP pancreatic fistula and to be particularly effective when dissecting a thick pancreas or performing a DP in an obese patient. Moreover, removing the drainage tube early in the PPF method may conduce to early discharge.

POPF, postoperative pancreatic fistula; DP, distal pancreatectomy; PGA, polyethylene glycolic acid; CR-POPF, clinically relevant postoperative pancreatic fistula; CT, computed tomography; MPD, main pancreatic duct; ROC, receiver operating characteristic; BMI, body mass index; ISGPF, international study group for pancreatic fistula; IQR, interquartile range; LDP, laparoscopic distal pancreatectomy; RDP, robot-assisted distal pancreatectomy; OR, odds ratio; PJ, pancreaticojejunal

Ethics approval and consent to participate

The study was approved by the ethics committee of the University Hospital Medical Information Network (No. UMIN000047580). Our study was in compliance with the regulations and carried out in accordance with the relevant guidelines. Data collection and analysis followed the ethical guidelines of the World Medical Association Declaration of Helsinki. Informed consent was obtained from all participates.

Consent for publication

Not applicable.

Availability of data and materials

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

Competing interests

The authors declare that they have no competing interests.

Funding

This manuscript did not receive sponsorship for publication.

Authors' contributions

KK and TH designed the study. KK analyzed and interpreted the patient data. KK was involved in acquisition of data. KK was a major contributor in writing the manuscript. TH revised the manuscript. All authors given their final approval to the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.

Acknowledgements

The Authors thank James Robert Valera for professionally editing the English draft of this manuscript.

Authors' information (optional)

Not applicable.

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Table 1. Patient demographics and clinical presentations

Variables	Total (n=127)
Age, years (median (range))	70.0 (61.0-77.0)
BMI, kg/m²(median (range))	22.2 (20.4-24.9)
Histological grade (benign vs. malignancy)	92/35
Pancreatic texture (soft vs. hard)	46/81
Minimal invasive surgery (open vs. lap/robot)	65/62
MPD size, mm (median (range))	2.9 (2.3-3.5)
Thickness of resection, mm (median (range))	13.5 (10.9-15.9)
Pancreatitis (Yes vs. No)	63/64
Operation time, min. (median (range))	334.0 (275.0-394.0)
Blood loss, ml (median (range))	340.0 (150.0-870.0)
Pre-compression (Yes vs. No)	85/42
PPF method (Yes vs. No)	17/110
POPF (no-POPF/BL vs. CR-POPF)	71/56

BMI, body mass index; MPD, main pancreatic duct; POPF, postoperative pancreatic fistula; CR-POPF, clinically relevant postoperative pancreatic fistula; BL, biochemical leak

Table 2. Comparison of the factors related to CR-POPF

Variables	No-POPF/BL (n=71)	CR-POPF (n=56)	P value
Age, years (≥75 vs. <75)	24/47	14/41	0.394
BMI, kg/m²(≥20.5 vs. <20.5)	45/26	47/9	0.010
Histological grade (benign vs. malignant)	20/51	15/41	0.863
Pancreatic texture (soft vs. hard)	26/45	20/36	0.916
Minimal invasive surgery (open vs. lap/robot)	30/41	32/24	0.096
MPD size, mm (≥3 vs. <3)	27/44	32/24	0.032
Thickness of resection, mm (≥13.5 vs. <13.5)	30/41	34/22	0.039
Pancreatitis (Yes vs. No)	33/38	26/30	0.427
Operation time, min. (≥445 vs. <445)	5/66	9/47	0.107
Blood loss, ml (≥800 vs. <800)	9/62	26/30	<0.001
Pre-compression (Yes vs. No)	49/21	35/20	0.452
PPF method (Yes vs. No)	13/58	4/52	0.067

BMI, body mass index; MPD, main pancreatic duct; POPF

Table 3. Risk factors associated with POPF

	Univariate analysis		Multivariate analysis
	Hazard ratio	P-value	Hazard ratio	P-value
Age, years (≥75 vs. <75)	1.220 (0.489-3.041)	0.669
BMI, kg/m²(≥20.5 vs. <20.5)	2.612 (0.958-7.123)	0.061
Histological grade (benign vs. malignant)	3.664 (0.858-15.648)	0.080
Pancreatic texture (soft vs. hard)	6.027 (1.336-27.192	0.020	2.356 (0.967-5.740)	0.059
Minimal invasive surgery (open vs. lap/robot)	1.262 (0.403-3.946)	0.690
MPD size, mm (≥3 vs. <3)	1.556 (0.640-3.784)	0.329
Thickness of resection, mm (≥13.5 vs. <13.5)	2.135 (0.842-5.418)	0.110
Pancreatitis (Yes vs. No)	1.152 (0.440-3.017)	0.774
Operation time, min. (≥445 vs. <445)	2.155 (0.481-9.648)	0.315
Blood loss, ml (≥800 vs. <800)	7.019 (1.984-24.836)	0.003	7.643 (2.889-20.217)	<0.001
Pre-compression (Yes vs. No)	1.641 (0.592-4.548)	0.341
PPF method (Yes vs. No)	5.646 (1.270-25.107)	0.023	2.618 (0.740-9.263)	0.136

BMI, body mass index; MPD, main pancreatic duct; POPF

Table 4. Comparison of postoperative outcomes in the PPF and conventional group

Variables	Former (n=110)	PPF (n=17)	P value
POPF (no-POPF vs. POPF)	35/75	10/7	0.030
POPF (no-POPF/BL vs. CR-POPF)	58/52	13/4	0.067
Intra-abdominal fluid collection (Yes vs. No)	2/108	5/12	<0.001
Delayed gastric emptying (Yes vs. No)	13/97	0/17	0.135
Chyle leak (Yes vs. No)	19/91	1/16	0.230
Aneurysm (Yes vs. No)	2/108	0/17	0.575
Elevated drainage amylase from drainage delay (Yes vs. No)	55/55	4/13	0.042
Duration of drainage tube insertion, days	22.0 (10.0-38.0)	8.0 (6.0-14.5)	<0.001
Length of hospital stay, days	28.0 (14.8-40.3)	12.0 (9.5-19.0)	<0.001

POPF, postoperative pancreatic fistula; CR-POPF, clinically relevant postoperative pancreatic fistula; BL, biochemical leak

No competing interests reported.

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You are reading this latest preprint version

Covering reinforced staples with polyethylene glycolic acid felt-covered fibrin sealant to prevent pancreatic fistula after distal pancreatomy : a retrospective comparative study

Status:

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Abstract

Background

Methods

Results

Conclusions

Figures

Introduction

Materials And Methods

Patient demographics and clinical presentations

Statistical analysis

Results

Discussion

Abbreviations

Declarations

References

Tables

Competing Interests

Status:

Version 1