An analysis of risk factors for clinically relevant pancreatic fistulas after laparoscopic pancreaticoduodenectomy : Medicine

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Research Article: Observational Study

An analysis of risk factors for clinically relevant pancreatic fistulas after laparoscopic pancreaticoduodenectomy

Chen, Guoli MDa,*; Zheng, Zhifang MDb; Yi, Haizhao MDa; Yue, Qiuju MDa; Li, Lijie MDa

Author Information
Medicine 102(20):p e33759, May 19, 2023. | DOI: 10.1097/MD.0000000000033759
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1. Introduction

Pancreaticoduodenectomy (PD) is a standard surgical method for treating pancreatic head and periampullary tumors.[1] It requires the simultaneous resection of the pancreatic head, duodenum, gallbladder, distal bile duct, and distal stomach, followed by gastrointestinal anastomoses.[2,3] Pancreaticojejunal anastomosis, bile duct-jejunal anastomosis, and stomach-jejunal anastomosis are performed sequentially.[4,5] However, PD is considered one of the most challenging and complex procedures in general surgery owing to many factors, such as large surgical resection range, complex reconstruction of the digestive tract, and numerous potential postoperative complications.[6]

Recent advances in medicine and medical technology have enabled a new era of minimally invasive surgery and functional surgery, and the emergence of laparoscopic technology is the most representative.[6] The application of laparoscopic techniques in PD has lagged behind other abdominal procedures.[6,7] Laparoscopic pancreaticoduodenectomy (LPD), one of the most challenging abdominal surgical procedures, has been gradually applied in the resection of periampullary and pancreatic head tumors.[8] In 1994, Gagner and Pomp performed the first laparoscopic pancreaticoduodenectomies and opened the way for the development of laparoscopic technology in this field.[9–11] However, the postoperative recovery of the patients was unsatisfactory.[9–11] Due to the surgical complexity and the high rate of postoperative complications, the clinical development of LPD has been questioned, and its clinical application has been halted.

Contemporary hepatobiliary and pancreatic surgeons have focused on the minimally invasive advantages of laparoscopy and the reduced incidence of related complications. Through the continuous innovation of laparoscopic instruments, improvement of surgical methods and concepts, and strengthening of perioperative management, perioperative mortality after LPD has decreased.[12] The most common postoperative complication after LPD is a pancreatic fistula (PF), with an incidence of 4.5% to 52.3%.[13] The occurrence and progression of PF are often closely related to abdominal abscesses, early or delayed bleeding, the need for revision surgery, and even death.[14] Importantly, when a clinical PF above grade B develops, it can lead to prolonged hospitalization, increased costs, and requires the doctor-in-charge to invest a lot of energy to deal with it. Therefore, the prevention of PF after LPD must span the entire perioperative period.[15,16] It is imperative to analyze the risk factors and establish a prediction model for PF after LPD, which may eventually become a routine operation in various centers. This study retrospectively analyzed the clinical data of 80 patients who underwent LPD and aimed to explore the possible risk factors associated with clinically relevant PF after LPD.

2. Materials and methods

2.1. Study participants

The clinical data of 80 patients who underwent LPD in the Department of Liver and Gallbladder Surgery at our hospital, from January 2018 to January 2022, were collected. This study was approved by the Ethics Committee of our hospital. The eligibility criteria were as follows; The general condition of the patient was favorable, without serious underlying diseases, and the patient was deemed suitable for surgery and anesthesia; A history of laparotomy without the involvement of the upper abdomen; Vascular reconstruction was included in the intraoperative LPD only, without combined organ resection, such as total pancreatectomy or splenectomy; Patients and their family members consented to the LPD.

2.2. Surgical process

The entire surgical process was optimized based on published reports, and the specific surgical procedure is described with reference to the literature.[17,18] After general anesthesia, the patient was positioned supine, with their legs apart. The abdominal cavity was explored using 4 additional holes at the level of the umbilicus on the lateral border of the right and left rectus abdominis and 2 cm below the rib edge on the right and left anterior axillary lines. The gastrocolic ligament, hepatic colic ligament, and anterior lobe of the right transverse colonic mesentery were opened to fully expose the pancreas. Subsequently, the right peritoneum was opened, and the descending and horizontal parts of the duodenum and the head of the pancreas were freed, followed by the greater and lesser curves of the stomach. Approximately 50% of the distal stomach was cut, the perigastric lymph nodes were cleared, the common hepatic artery was freed, and the neck of the pancreas was cut. The jejunum was dissected at 15 cm from the ligament of Treitz. The pancreatic hook was dissected near the common hepatic artery and the adipose lymphatic tissues continued to be cleared along the portal vein. The gallbladder was removed in a retrograde manner, and then, the common bile duct was freed and transected. The pancreatic duct support tube was placed into the jejunum through this area, the pouch was tightened. The pancreatic duct was then brought close to the pancreatic section, and the parenchyma of the pancreas and the pulpy muscle layer of the jejunum were sutured continuously. The pancreaticojejunal anastomosis was reinforced with interrupted horizontal sutures. A drainage tube was placed below and on the oral side of the pancreatic-intestinal anastomosis through the posterior part of the biliopancreatic-intestinal anastomosis. Finally, the specimen was removed through the subumbilical poke hole for pathological examination.

2.3. Observational indicators

2.3.1. Intraoperative indicators

The intraoperative indicators were operative time, intraoperative blood loss, number of dissected lymph nodes, tumor location, and diameter.

2.3.2. Postoperative indicators

A PF diagnosis was made according to the 2016 International Study Group of Pancreatic Surgery recommended PF diagnostic and classification criteria, The diagnostic criteria for PF included amylase concentration of the pancreatic stump or anastomotic drainage >3 times the upper limit of normal, and clinically relevant symptoms 3 days or more after surgery. PF was divided into biochemical leakage, B-grade PF, and C-grade PF, according to the different clinical manifestations.[19]

2.4. Statistical analysis

Statistical analysis was performed using SPSS version 22.0. The continuous variables were reported as mean ± standard deviation and compared by using the t test. The categorical variables were reported as frequency distributions and compared by using the χ2 test. A P value < .05 was considered significant.

3. Results

3.1. General information

The clinical data of the 80 LPD cases performed by our team between 2018 and 2022 are shown in Table 1. The mean operation time was 298.75 ± 37.66 minutes. The mean resection time was 162.58 ± 29.11 minutes. The mean digestive tract reconstruction time was 97.45 ± 10.88 minutes. The average time for the pancreaticojejunostomy was 32.71 ± 5.39 minutes. The average time for the gastrointestinal anastomosis was 22.58 ± 4.63 minutes. The mean time for the biliary anastomosis was 23.19 ± 3.86 minutes. The mean intraoperative bleeding volume was 162.77 ± 29.58 mL (range, 50–1200 mL).

Table 1 - The General information of the patient.
Parameters All patients (n = 80)
Age (yr)
 ≥65 51 (63.75%)
 <65 29 (36.25)
 Male 60 (75%)
 Female 20 (25%)
 Yes 26 (32.5%)
 No 54 (67.5%)
 Yes 15 (18.75%)
 No 65 (81.25%)
ASA score
 I 18 (22.5%)
 II 62 (77.5%)
 Operation time 298.75 ± 37.66 min
 Resection time 162.58 ± 29.11 min
 Digestive tract reconstruction time 97.45 ± 10.88 min
 The average time of pancreaticojejunostomy 32.71 ± 5.39 min
 The average time of gastrointestinal anastomosis 22.58 ± 4.63 min
 The mean time of biliary anastomosis 23.19 ± 3.86 min
 The mean intraoperative bleeding volume 162.77 ± 29.58 mL

3.2. Postoperative pathological information

O the 80 patients, 36 had pancreatic cancer, 20 had duodenal papillary carcinoma, 12 had cholangiocarcinoma, 9 had intraductal papillary myxoma, and 3 had pancreatic neuroendocrine tumors. The tumor diameter was 2.18 ± 0.76 cm (Table 2).

Table 2 - The intraoperative information on LPD.
Parameters n
 Pancreatic cancer 36
 Duodenal papilla carcinoma 20
 Cholangiocarcinoma 12
 Intraductal papillary myxoma 9
Pancreatic neuroendocrine tumor 3
Tumor diameter 2.18 ± 0.76 cm
The number of positive lymph nodes 5.07 ± 0.69
LPD = laparoscopic pancreaticoduodenectomy.

3.3. The risk factors for clinically relevant PF after LPD

The 80 patients were divided into 2 groups based on the presence or absence of a clinically relevant PF: PF group (n = 9) and non-PF group (n = 71). Univariate analyses were performed to examine potential risk factors for clinically relevant PF after LPD. The results showed that pancreatic duct diameter (P < .001), pancreatic texture (P < .001), abdominal infection (P = .002), and reoperation (P < .001) were associated with clinically relevant PF (Table 3). Results from the multivariate logistic regression analysis showed that the pancreatic duct diameter (P = .002) and texture (P = .016) were significant independent risk factors (Table 4).

Table 3 - Univariate analysis of clinically relevant PF.
Parameters Non-PF (n = 71) PF (n = 9) P value
Age .064
 ≥65 32 7
 <65 39 2
Gender .838
 Male 53 7
 Female 18 2
Hypertension .344
 Yes 18 1
 No 53 8
Diabetes .14
 Yes 10 3
 No 61 6
Operation time (min) .273
 ≥280 20 1
 <280 51 8
Pancreatic duct diameter (mm) <.001
 ≥3 16 8
 <3 55 1
Pancreas texture <.001
 Soft 56 2
 Hard 15 7
Abdominal infection .002
 Yes 1 2
 No 70 7
Reoperation <.001
 Yes 2 3
 No 69 6
Pulmonary infection .217
 Yes 2 1
 No 69 8
Delayed gastric emptying .08
 Yes 4 2
 No 67 7
Chronic pancreatitis .07
 Yes 8 3
 No 63 6
PF = pancreatic fistulas.

Table 4 - Multivariate analysis of postoperative complications of pancreatic fistula.
Parameters β OR 95% CI P value
Pancreatic duct diameter 1.009 2.487 1.006–3.698 .002
Pancreas texture 1.107 1.505 1.082–2.301 .016
Abdominal infection 0.025 0.071 0.039–1.267 .542
Reoperation 0.327 1.523 0.693–3.142 .329

4. Discussion

LPD is one of the most difficult procedures in abdominal surgery. Additional to the difficulty and complexity of the operation, most doctors are “deterred” by the high incidence and severity of complications.[17] However, with the continuous development of LPD, its application in the field of hepatobiliary and pancreatic surgery has improved progressively. With innovative laparoscopic instruments being developed, continuous updating of surgical methods and concepts, as well as improvements in perioperative management, standardized diagnosis, and treatment of postoperative complications, the perioperative mortality of patients after LPD surgery has gradually declined. Hence, the risk of postoperative complications should no longer be a deterrent for surgeons.[20,21]

Currently, the perioperative complications of LPD include PF, bile leakage, bleeding, abdominal infection, and delayed gastric emptying. Among them, PF is one of the most common and serious complications. PF often causes serious sequelae, such as postoperative abdominal infection and bleeding, and in the most complicated cases, may cost the patients their lives.[13,22,23] The incidence is 4.5% to 52.3%.[13,22,23] At present, there are few studies on the risk factors of PF after LPD, and there is no consensus. Early identification of high-risk patients with PF after LPD will provide important guidance for LPD management.[24] Many different risk factors may be associated with PF after LPD. The most frequently mentioned risk factors include sex, body mass index, preoperative albumin level, operation duration, intraoperative blood loss, pancreatic texture, pathological type, and pancreatic duct diameter.[22,25] Of them, soft pancreas, pancreatic duct stenosis, and high body mass index are widely considered independent risk factors for PF after LPD.

As an important complication of LPD, PF is closely associated with patient prognosis.[26–28] Our results showed that patients with PF had a higher probability of abdominal infection, an increased number of individual complications, and a higher rate of reoperation. The superimposition of these factors increases the length of hospital stay and costs, and increases the psychological and economic burdens on patients. Even if prognosis of the patient with PF is not poor, the overall recovery time is prolonged, and may affect some patients choice of future treatment including postoperative chemotherapy, which in turn, may affect their quality of life, and even their survival. Clinically, the prevention and treatment of PF are very important, both for recovery and patient survival following LPD. The results of this study may be useful for guiding clinical practice.

The limitations of this study are as follows. First, as a retrospective analysis, there may be some information bias and selection bias in the patient data. Further prospective trials to verify the results of this study are warranted. Second, the sample size was small. Third, this was a single-center study. However, our results are encouraging. In the future, multicenter studies and randomized controlled trials with larger sample sizes are necessary to ascertain the risk factors for PF after LPD.

5. Conclusion

LPD, performed as a routine procedure, is safe and feasible for teams with extensive laparoscopic experience. The risk factors for clinically relevant PF after LPD are pancreatic duct diameter and pancreatic texture.

Author contributions

Conceptualization: Guoli Chen, Qiuju Yue.

Data curation: Guoli Chen.

Formal analysis: Guoli Chen.

Funding acquisition: Guoli Chen, Haizhao Yi.

Investigation: Guoli Chen, Haizhao Yi.

Methodology: Guoli Chen, Haizhao Yi.

Project administration: Zhifang Zheng, Haizhao Yi, Lijie Li.

Resources: Zhifang Zheng, Haizhao Yi, Qiuju Yue, Lijie Li.

Software: Zhifang Zheng, Qiuju Yue, Lijie Li.

Supervision: Zhifang Zheng, Lijie Li.

Validation: Lijie Li.

Visualization: Lijie Li.


laparoscopic pancreaticoduodenectomy
pancreatic fistulas


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clinically relevant pancreatic fistula; laparoscopic; pancreaticoduodenectomy; risk factors

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