Observational Study Open Access
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2016; 22(34): 7797-7805
Published online Sep 14, 2016. doi: 10.3748/wjg.v22.i34.7797
Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy
Bing-Yang Hu, Tao Wan, Wen-Zhi Zhang, Jia-Hong Dong, Institute and Hospital of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China
Jia-Hong Dong, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
Author contributions: Hu BY and Dong JH contributed equally to this work; Hu BY and Dong JH designed the research; Hu BY collected and analyzed the data and drafted the manuscript; Zhang WZ and Wan T contributed analytical tools; all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the Chinese People’s Liberation Army General Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
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: Dr. Jia-Hong Dong, Institute and Hospital of Hepatobiliary Surgery, Chinese PLA General Hospital; Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, 168 Litang Road, Beijing 102218, China. zhangwenzhi301301@163.com
Telephone: +86-10-66938331 Fax: +86-10-68241383
Received: April 17, 2016
Peer-review started: April 18, 2016
First decision: May 12, 2016
Revised: June 28, 2016
Accepted: July 31, 2016
Article in press: August 1, 2016
Published online: September 14, 2016

Abstract
AIM

To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy.

METHODS

We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis.

RESULTS

A total of 269 (49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy, including 71 (13.17%) cases of grade A pancreatic fistula, 178 (33.02%) cases of grade B, and 20 (3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula (POPF) and the following factors: age, hypertension, alcohol consumption, smoking, history of upper abdominal surgery, preoperative jaundice management, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, operative time, intraoperative blood transfusion, Braun anastomosis, and pancreaticoduodenectomy (with or without pylorus preservation). Conversely, a significant correlation was observed between POPF and the following factors: gender (male vs female: 54.23% vs 42.35%, P = 0.008), diabetes (non-diabetic vs diabetic: 51.61% vs 39.19%, P = 0.047), body mass index (BMI) (≤ 25 vs > 25: 46.94% vs 57.82%, P = 0.024), blood glucose level (≤ 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%, P = 0.002), pancreaticojejunal anastomosis technique (pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis: 57.54% vs 35.46%, P = 0.000), diameter of the pancreatic duct (≤ 3 mm vs > 3 mm: 57.81% vs 38.36%, P = 0.000), and pancreatic texture (soft vs hard: 56.72% vs 29.93%, P = 0.000). Multivariate logistic regression analysis showed that gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

CONCLUSION

Gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

Key Words: Pancreaticoduodenectomy, Pancreatic fistula, Pancreaticojejunal anastomosis, Pancreatic duct, Complications

Core tip: Pancreaticoduodenectomy remains the standard surgical approach for tumors involving the lower bile duct, the pancreatic head, the duodenal papilla, and the ampulla. This operation is considered risky because of high rates of postoperative mortality and complications. In this study, we collected a large sample of 539 cases and analyzed several potential risk factors for pancreatic fistula. A statistical analysis of the case data showed that gender (male), pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.
INTRODUCTION

Pancreaticoduodenectomy is the primary treatment for malignant tumors involving the pancreatic head, the lower bile duct, and the duodenal ampulla[1,2]. The safety of pancreaticoduodenectomy has been greatly improved; however, perioperative mortality rate still ranges from 0%-5%[3-5]. Studies have reported that the incidence of pancreatic fistula after pancreaticoduodenectomy is approximately 11.4%-64.3%[6-16]. Pancreatic fistula remains the most common complication after pancreaticoduodenectomy, and this complication prolongs hospital stays and leads to high medical expenses. Pancreatic fistula is associated with delayed gastric emptying, abdominal abscesses, infection at the incision, sepsis, and bleeding after pancreaticoduodenectomy[17-20]. Several approaches may reduce the incidence of pancreatic fistula after pancreaticoduodenectomy; however, to date, a definitive approach that prevents pancreatic fistula is still lacking[21-23]. In this study, we conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed over more than 3 years in the Department of Hepatobiliary Surgery of the PLA General Hospital, China, to determine the potential risk factors for pancreatic fistula.

MATERIALS AND METHODS
Patients and data collection

We reviewed the data from 539 successive cases of pancreaticoduodenectomy performed in the Department of Hepatobiliary Surgery of the PLA General Hospital, China, from March 2012 to October 2015. The following patient data were collected: gender, age, hypertension, diabetes, alcohol consumption, smoking, body mass index (BMI), history of upper abdominal surgery, preoperative jaundice management, blood sugar, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, intraoperative blood transfusion, operative time, pancreaticojejunal anastomosis technique, Braun anastomosis, pylorus preservation, diameter of the pancreatic duct, and pancreatic texture. Additionally, all postoperative complications and postoperative pathological findings (especially information about pancreatic fistula) were recorded. All 539 cases were included in this comprehensive study.

Preoperative preparation

Prior to surgery, the patients underwent routine tests, examinations, and evaluations of organ function. To date, no uniform standard exists for preoperative jaundice management. We believe that patients with obstructive jaundice who have a poor mental state, severe dehydration, poor nutrition, or severe jaundice should undergo jaundice management and supportive therapy to improve their nutritional intake and replenish fluids. Patients should subsequently undergo surgery after their general condition has improved.

Surgical approach

In this study, 275 patients underwent classic pancreaticoduodenectomy, of whom 13 had portal vein resection and reconstruction. Additionally, 264 patients underwent pylorus-preserving pancreaticoduodenectomy, of whom six had portal vein resection and reconstruction. Child’s technique (pancreaticojejunal anastomosis, biliary-jejunal anastomosis, and gastrojejunal anastomosis in sequential order) was used for the gastrointestinal reconstruction. A support tube was placed in the pancreatic duct of all patients. The support tube was drained via the jejunal loop to outside the body in 127 patients. In the remaining patients, the tube was placed in the jejunum via biliary-jejunal anastomosis. The following two approaches were used for pancreaticojejunal anastomosis: (1) pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis in 398 patients; and (2) pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis in 141 patients.

Classification and detailed definition of postoperative pancreatic fistula

Pancreatic fistula was defined according to the International Study Group on Pancreatic Fistula (ISGPF) as any measurable volume of drainage fluid output via operatively or postoperatively placed drains on or after postoperative day 3 with amylase content greater than three times the upper normal serum value. Three grades of pancreatic fistulas were determined according to their clinical severity. The grades were determined only after complete healing of the fistula (Table 1)[24].

Table 1 Criteria utilized to grade postoperative pancreatic fistula.
Grade A B C
Clinical conditions Well Often well Ill appearing/bad
Specific treatment1 No Yes/no Yes
US/CT (if obtained) Negative Negative/positive Positive
Persistent drainage (after 3 wk)2 No Usually yes Yes
Reoperation No No Yes
Death related to POPF No No Possibly yes
Signs of infection No Yes Yes
Sepsis No No Yes
Readmission No Yes/no Yes/no
1Partial (peripheral) or total parenteral nutrition, antibiotics, enteral nutrition, somatostatin analogue, and/or minimally invasive drainage;
2With or without a drain in situ. CT: Computed tomography; POPF: Postoperative pancreatic fistula; US: Ultrasonography.
Statistical analysis

All clinical data were entered into an Excel spreadsheet, and SPSS 19.0 software was used for statistical analyses. Measurement data are expressed as the mean ± SD. A t-test was performed for between-group comparisons. Categorical variables were analyzed using Fisher’s exact test and the χ2 test. All variables were incorporated into a univariate analysis. P < 0.05 was considered statistically significant. Statistically significant variables demonstrated in the univariate analysis were incorporated into a multivariate logistic regression analysis to identify the independent risk factors for pancreatic fistula after pancreaticoduodenectomy.

RESULTS
Overall characteristics of patients and complications

This study included 343 male patients and 196 female patients with a mean age of 56.42 ± 10.75 years. The mean hospital stay was 30.03 ± 8.86 d. The condition (confirmed by postoperative pathology) of the 539 patients is shown in Table 2. Among the 539 patients, 349 (64.75%) experienced complications, and 269 (49.9%) had POPF, including 71 (13.17%) cases of grade A pancreatic fistula, 178 (33.02%) cases of grade B, and 20 (3.71%) cases of grade C. Additionally, 198 (36.73%) patients had clinically relevant POPFs. The following complications were identified: 25 (4.64%) cases of abdominal bleeding, 59 (10.95%) cases of bile leakage, 120 (22.63%) cases of delayed gastric emptying, 9 (1.67%) cases of pancreaticojejunal anastomotic bleeding, 66 (12.24%) cases of abdominal infection, and 45 (8.35%) cases of incision infection. Moreover, 15 (2.78%) patients underwent a second operation, and 6 (1.11%) patients died after surgery due to abdominal bleeding associated with a pancreatic fistula.

Table 2 Disease composition.
Pathological type n
Pancreatic head cancer 126
Neuroendocrine tumor of the pancreatic head 12
Benign tumor of the pancreatic head 12
Solid pseudopapillary tumor of the pancreatic head 16
Autoimmune pancreatitis 3
Chronic pancreatitis 11
Lower bile duct cancer 145
Benign tumor of the lower bile duct 13
Ampullary cancer 76
Benign ampullary tumor 6
Duodenal stromal tumor 7
Duodenal cancer 10
Chronic mucosal inflammation of the descending duodenum 3
Duodenal papillary cancer 90
Benign duodenal papillary tumor 6
Duodenal papillary neuroendocrine tumor 3
Total 539
Univariate analysis

Univariate analysis showed no significant correlation between POPF and the following factors: age, hypertension, alcohol consumption, smoking, history of upper abdominal surgery, preoperative jaundice management, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, operative time, intraoperative blood transfusion, Braun anastomosis, and pancreaticoduodenectomy (with or without pylorus preservation). Conversely, a significant correlation was observed between POPF and the following factors: gender (male vs female: 54.23% vs 42.35%, P = 0.008), diabetes (non-diabetic vs diabetic: 51.61% vs 39.19%, P = 0.047), BMI (≤ 25 vs > 25: 46.94% vs 57.82%, P = 0.024), blood glucose level (≤ 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%, P = 0.002), pancreaticojejunal anastomosis technique (pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis: 57.54% vs 35.46%, P = 0.000), diameter of the pancreatic duct (≤ 3 mm vs > 3 mm: 57.81% vs 38.36%, P = 0.000), and pancreatic texture (soft vs hard: 56.72% vs 29.93%, P = 0.000) (Table 3).

Table 3 Risk factors for pancreatic fistula according to univariate analysis.
Variable POPF occurrence
Yes No χ2 P value
Sex 7.042 0.008
Male 186 157
Female 83 113
Age (yr) 2.132 0.144
≥ 60 99 116
< 60 170 154
Body mass index (kg/m2) 5.066 0.024
> 25 85 62
≤ 25 184 208
Hypertension 0.938 0.332
Yes 62 53
No 207 217
Diabetes mellitus 3.941 0.047
Yes 29 45
No 240 225
Drinking history 0.169 0.681
Yes 77 73
No 193 197
Smoking history 1.426 0.232
Yes 78 66
No 191 204
Epigastrium surgery 0.640 0.424
Yes 18 23
No 251 247
Preoperative biliary drainage 0.406 0.524
Yes 65 59
No 204 211
Preoperative total bilirubin (μmol/L) 0.378 0.539
> 171 73 67
≤ 171 196 203
Serum albumin (g/L) 0.000 0.985
< 35 41 41
≥ 35 228 229
Blood glucose (mmol/L) 9.157 0.002
≤ 6.0 190 157
> 6.0 79 113
Pancreaticojejunostomy 20.323 0.000
Double-layer mucosa-to-mucosa 229 169
Single-layer mucosa-to-mucosa 50 91
Blood loss (mL) 0.134 0.715
> 600 34 37
≤ 600 235 225
Pancreatic duct diameter (mm) 19.687 0.000
≤ 3 185 135
> 3 84 135
Pylorus-preserving 0.017 0.897
Yes 131 133
No 138 137
Pancreatic duct drainage 0.016 0.900
External 64 63
Enteral 205 207
Intraoperative blood infusion 1.310 0.252
Yes 36 46
No 233 224
Operative time (min) 0.299 0.584
> 300 196 191
≤ 300 73 79
Braun anastomosis 2.274 0.132
Yes 78 94
No 192 175
Pancreatic texture 29.330 0.000
Soft 228 174
Hard 41 96
Multivariate logistic regression analysis

The risk factors for pancreatic fistula (gender, diabetes, BMI, blood glucose level, pancreaticojejunal anastomosis technique, the diameter of the pancreatic duct, and pancreatic texture) demonstrated in the univariate analysis were incorporated into the logistic regression analysis. The results showed that gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy (Table 4).

Table 4 Logistic regression for the predictors of pancreatic fistula following pancreaticoduodenectomy.
Variable B SE Wals P value OR 95%CI
Sex 0.579 0.196 8.688 0.003 1.784 1.214-2.622
Body mass index 0.518 0.213 5.941 0.015 1.679 1.107-2.546
Pancreaticojejunostomy 0.743 0.217 11.723 0.001 2.102 1.374-3.216
Pancreatic duct diameter 0.724 0.192 14.254 0.000 2.062 1.416-3.003
Pancreatic texture 1.115 0.227 24.102 0.000 3.048 1.953-4.757
DISCUSSION

The causes of pancreatic fistula include pancreaticojejunal anastomotic leak, leak from pancreatic resection, leak associated with damage to the pancreatic capsule, and leak via the puncture channel. Pancreatic fistula after pancreaticoduodenectomy is a common and serious complication and the most important cause of subsequent complications and death after this procedure[8,24-26]. The dilemma of pancreatic fistula after pancreaticoduodenectomy has not yet been resolved[27]. Currently, researchers believe that the following factors are related to pancreatic fistula: gender, age, preoperative jaundice, intraoperative blood loss, operative time, pancreatic texture, BMI, diameter of the main pancreatic duct, and pancreaticojejunal anastomosis[14,28-32]. Peng et al[33] suggested that bundled pancreaticogastrostomy was a safe and effective anastomosis technique to prevent the leakage of pancreatic juice from pancreaticojejunal anastomosis. Shubert et al[34] believed that the clinical risk score for pancreatic fistula (CRS-PF) could effectively predict pancreatic fistula after pancreaticoduodenectomy. In this study, multivariate logistic regression analysis showed that gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

Kawai retrospectively analyzed the perioperative data from 1239 patients treated at 11 medical facilities from 2005 to 2009 and summarized that the male gender was a risk factor for pancreatic fistula after pancreaticoduodenectomy[35]. This study included 343 male patients (POPF rate: 54.23%) and 196 female patients (POPF rate: 42.35%). Univariate analysis showed that the difference in the POPF rate was significant (P = 0.008), suggesting that male patients were at a higher risk than female patients for the development of pancreatic fistula after pancreaticoduodenectomy. Additionally, multivariate logistic regression analysis showed that the difference was significant (P = 0.003), suggesting that gender (male) was a risk factor for pancreatic fistula after pancreaticoduodenectomy. The odds ratio (OR = 1.784; 95%CI: 1.214-2.622) showed that the risk of developing pancreatic fistula after pancreaticoduodenectomy was 1.784-fold higher in male patients than in female patients.

El Nakeeb et al[36] analyzed 471 cases of pancreaticoduodenectomy and found that BMI > 25 was a risk factor for POPF. Gaujoux et al[28] analyzed 100 successive cases of pancreaticoduodenectomy and similarly found that BMI > 25 was a risk factor for pancreatic fistula after pancreaticoduodenectomy. In our study, 392 patients had a BMI ≤ 25 (POPF rate: 46.94%), and 147 patients had a BMI > 25 (POPF rate: 57.82%). Univariate analysis showed that the difference in the POPF rates was significant (P = 0.024), suggesting that patients with a BMI > 25 were at a higher risk of developing pancreatic fistula after pancreaticoduodenectomy than patients with a BMI ≤ 25. Additionally, multivariate logistic regression analysis showed that the difference was significant (P = 0.015 < 0.05), which indicated that BMI > 25 was a risk factor for pancreatic fistula after pancreaticoduodenectomy. The OR (1.679, 95%CI: 1.107-2.546) showed that the risk of developing a pancreatic fistula after pancreaticoduodenectomy was 1.679-fold higher in patients with a BMI > 25 than in patients with a BMI ≤ 25. The higher incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a BMI > 25 may be associated with the following factors: increased difficulty in exposing the pancreas during surgery due to a higher volume of abdominal fat and peripancreatic fat, a higher risk of damage to the pancreatic capsule during separation due to a soft and brittle pancreas, and a higher risk of pancreatic leakage caused by damage to the pancreatic tissue and fine pancreatic ducts due to suturing and knotting during pancreaticojejunal anastomosis.

Pancreaticojejunal anastomosis is a critical step during pancreaticoduodenectomy and affects the surgical outcome. However, pancreaticojejunal anastomosis is a complex procedure during pancreaticoduodenectomy, and the choice of an appropriate pancreaticojejunal anastomosis technique should reduce the incidence of pancreatic fistula[33,37-40]. Fu et al[32] retrospectively analyzed 532 cases of pancreaticoduodenectomy and found that the pancreaticojejunal anastomosis technique was a risk factor for pancreatic fistula after pancreaticoduodenectomy. In this study, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis was performed in 398 patients (POPF rate: 57.54%), and pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis was performed in 141 patients (POPF rate: 35.46%). Univariate analysis showed that the difference in the POPF rates was significant (P = 0.000), suggesting that patients who underwent pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis were at a higher risk of developing pancreatic fistula after pancreaticoduodenectomy than patients who underwent pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis. Additionally, multivariate logistic regression analysis showed that the difference was significant (P = 0.001), suggesting that pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis was an independent risk factor for pancreatic fistula after pancreaticoduodenectomy. The OR (2.102, 95%CI: 1.374-3.216) indicated that the risk of developing a pancreatic fistula after pancreaticoduodenectomy was 2.102-fold higher in patients who underwent pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis than in patients who underwent pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis. The higher incidence of pancreatic fistula after pancreaticoduodenectomy in patients who underwent pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis may be related to the following factors: use of the 6-0 PDS II suture during pancreatic duct-jejunum anastomosis because the fine suture can easily cut the pancreatic duct during suturing and knotting, thereby resulting in a pancreaticojejunal anastomotic leak, and the use of the 5-0 PDS II suture to suture the pancreatic section and the jejunal seromuscular layer because this suture can easily cut the pancreas and fine pancreatic ducts during suturing and may not tightly secure the pancreatic section and the jejunal seromuscular layer, thereby resulting in pancreatic leakage and leakage from the fine pancreatic ducts. In contrast, the 4-0 Vicryl suture is used for full-layer suturing of the pancreas, the pancreatic duct, and the jejunum during pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis; therefore, the suture is secure and reduces the risk of cutting the pancreas. Moreover, the jejunal seromuscular layer covers the entire pancreatic section and presses the fine pancreatic ducts at the pancreatic section, thereby reducing pancreatic leakage[38].

A soft pancreas is a risk factor for pancreatic fistula after pancreaticoduodenectomy[35-37,41,42]. The pancreatic stumps of all cases were submitted for pathological diagnosis of the degree of pancreatic fibrosis. All cases of pancreatic texture were divided into two groups (normal soft pancreas with no significant fibrosis, as shown in Figure 1A, and hard pancreas with fibrosis, as shown in Figure 1B). In this study, 402 patients had a soft pancreas (POPF rate: 56.72%), and 137 patients had a hard pancreas (POPF rate: 29.93%). Univariate analysis showed that the difference in the POPF rates was significant (P = 0.000), suggesting that patients with a soft pancreas were at a higher risk of developing a pancreatic fistula after pancreaticoduodenectomy than patients with a hard pancreas. Additionally, multivariate logistic regression analysis demonstrated that the difference was significant (P = 0.000), which indicated that a soft pancreas was an independent risk factor for pancreatic fistula after pancreaticoduodenectomy. The OR (3.048, 95%CI: 1.953-4.757) showed that the risk of developing a pancreatic fistula after pancreaticoduodenectomy was 3.048-fold higher in patients with a soft pancreas than in patients with a hard pancreas. The higher incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a soft pancreas may be related to insecure suturing and knotting, which can result in unsatisfactory pancreaticojejunal anastomosis and a higher risk of damage to the pancreatic tissue and fine pancreatic ducts during suturing and knotting of a soft pancreas, resulting in pancreatic leakage. The lower incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a hard pancreas may be related to pancreatic exocrine dysfunction due to prolonged pancreatic duct obstruction and pancreatic fibrosis, secure pancreaticojejunal anastomosis, and obstructed minor ducts at the cut-surface of the hard pancreas, and this could help reduce POPF[43] and risk of damage to the pancreatic tissue and fine pancreatic ducts during suturing and knotting. Pancreatic texture is the most significant single predictor of POPF, and clinicians should select a pancreaticojejunal anastomosis technique based on the texture of the pancreas to reduce the incidence of POPF[44].

Figure 1
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Figure 1 Photomicrographs of the pathological examination for pancreatic fibrosis. A: No significant fibrosis; B: Severe fibrosis (hematoxylin-eosin staining; original magnification, × 100).

Pancreatic duct diameter ≤ 3 mm is a risk factor for pancreatic fistula after pancreaticoduodenectomy[14,37]. In this study, the diameter of the pancreatic duct was ≤ 3 mm in 320 patients (POPF rate: 57.81%) and > 3 mm in 219 patients (POPF rate: 38.36%). Univariate analysis showed that the difference in the POPF rates was significant (P = 0.000), suggesting that patients with a pancreatic duct diameter ≤ 3 mm were at a higher risk of developing a pancreatic fistula after pancreaticoduodenectomy than patients with a pancreatic duct diameter > 3 mm. Additionally, multivariate logistic regression analysis indicated that the difference was significant (P = 0.000), suggesting that pancreatic duct diameter ≤ 3 mm was an independent risk factor for pancreatic fistula after pancreaticoduodenectomy. The OR (2.062, 95%CI: 1.416-3.003) showed that the risk of developing a pancreatic fistula after pancreaticoduodenectomy was 2.062-fold higher in patients with a pancreatic duct diameter ≤ 3 mm than in patients with a pancreatic duct diameter > 3 mm. The lower incidence of pancreatic fistula after pancreaticoduodenectomy in patients with a pancreatic duct diameter > 3 mm may be related to pancreatic duct obstruction, pancreatic duct fibrosis, pancreatic fibrosis, ease of suturing, and a lower risk of damage to the pancreatic duct during suturing and knotting. As a result, the incidence of pancreatic fistula after pancreaticoduodenectomy was lower in patients with pancreatic duct dilation than in patients without.

Univariate analysis demonstrated that the incidence of pancreatic fistula after pancreaticoduodenectomy was significantly lower in diabetic patients than in non-diabetic patients (39.19% vs 51.61%, P = 0.047) and was significantly lower in patients with a blood glucose level > 6.0 mmol/L than in patients with a blood glucose level ≤ 6.0 mmol/L (41.14% vs 54.75%, P = 0.002). However, multivariate logistic regression analysis showed that these differences were not significant (P = 0.268 and P = 0.115, respectively); therefore, diabetes was not a risk factor for POPF.

In conclusion, gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.

COMMENTS
Background

Pancreaticoduodenectomy remains the standard surgical treatment for tumors involving the lower bile duct, the pancreatic head, the duodenal papilla, and the ampulla. Pancreaticoduodenectomy is difficult to perform and is associated with high morbidity and mortality. Most complications after pancreaticoduodenectomy are associated with postoperative pancreatic fistula (POPF); however, no definitive approach can prevent pancreatic fistulas.

Research frontiers

The incidence of tumors involving the lower bile duct, the pancreatic head, the duodenal papilla, and the ampulla increases each year, and more patients are undergoing pancreaticoduodenectomy. Surgical techniques and perioperative management are improving; however, the incidence and postoperative mortality of POPF remain high.

Innovations and breakthroughs

Gender (male), BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas are risk factors for pancreatic fistula after pancreaticoduodenectomy. Postoperative complications and deaths are related to pancreatic fistulas. For patients with a small pancreatic duct diameter or a soft pancreas, surgeons should select a pancreaticojejunal anastomosis technique that is associated with a lower incidence of POPF.

Applications

POPF was diagnosed in strict accordance with the definition of pancreatic fistula from the ISGPF. POPFs are more common in patients with relevant risk factors, such as male gender, BMI > 25, pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis, pancreatic duct diameter ≤ 3 mm, and soft pancreas. Care must be taken in patients with any of these risk factors, and an appropriate pancreaticojejunal anastomosis technique should be selected based on the texture of the pancreas and the diameter of the pancreatic duct. Patients must be closely monitored after surgery, and patients with a pancreatic fistula must be treated promptly to reduce the risk of fatal complications.

Terminology

Pancreaticoduodenectomy remains the standard surgical treatment for tumors involving the lower bile duct, the pancreatic head, the duodenal papilla, and the ampulla. POPF is common after pancreaticoduodenectomy and is the leading cause of postoperative complications and death following this procedure.

Peer-review

This retrospective study was well designed, and the statistical analysis was highly accurate. The article has a sufficient number of references. The manuscript language is of high quality, and the conclusions of the study are rational. The findings from this study contribute to our understanding of pancreatic fistula after pancreaticoduodenectomy. Readers with an interest in pancreatic fistulas will find this paper beneficial and informative.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: China

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P- Reviewer: Adhoute X, De Paschale M S- Editor: Qi Y L- Editor: Wang TQ E- Editor: Ma S

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