Clinical Analysis of C-Shaped Embedded Pancreaticojejunostomy in Pancreaticoduodenectomy

Background Comparing the effects of C-shaped embedded anastomosis and pancreatic duct-jejunal mucosal anastomosis on the incidence of pancreatic fistula after pancreaticoduodenectomy (PD) to find a better pancreaticojejunal anastomosis method that can reduce the occurrence of complications during the operation and benefit the patients. Methods A retrospective subresearch method was used to select the clinical data of patients who have undergone pancreaticoduodenectomy in our hospital from December 2019 to March 2021. The indicators to be collected for this study include gender, age, body mass index, preoperative liver function (total bilirubin, alanine aminotransferase, and albumin), preoperative comorbidities (diabetes, chronic pancreatitis), and pancreatic condition (texture, pancreatic duct diameter). The patients were divided into two groups according to the method of pancreaticojejunostomy: C-shaped embedded anastomosis group (n = 38) and pancreatic duct-jejunal mucosal anastomosis group (n = 30). The duration of pancreaticojejunostomy, biliary-enteric anastomosis, gastrointestinal anastomosis, intraoperative blood loss, upper abdominal surgery history, pathological type, intraoperative blood loss, pancreaticojejunostomy time, combined pancreatic fistula, biliary fistula, hemorrhage, and abdominal infection were observed and compared. According to the different methods of pancreaticojejunostomy during operation, they were divided into group A: C-shaped embedded pancreaticojejunostomy group (38 cases), and group B: pancreatic duct-jejunal mucosal anastomosis group (30 cases). The postoperative complications were compared between the two groups, and the observed indicators were analyzed with statistical methods. Results The average pancreaticojejunostomy time in group A was 32.13 ± 4.52 min, and the average pancreaticojejunostomy time in group B was 43.23 + 4.31 min. The difference was statistically significant (p < 0.05). Neither group A nor group B had a grade C fistula. The incidence of biochemical fistula in group A was 21.05% (8/38), and the incidence of biochemical fistula in group B was 13.3% (4/30). The difference was not statistically significant (p > 0.05). The incidence of grade B fistula in group A was 5.20% (2/38), and the incidence of grade B fistula in group B was 26.67% (8/30). The difference was statistically significant (p < 0.05). There were no perioperative deaths in the two groups. Conclusion According to the results of data analysis, it can be seen that both the two types of pancreaticojejunostomy have good clinical effects, but that in terms of reducing the grade of pancreatic fistula, the C-shaped embedded pancreaticojejunostomy is obviously better and safer. At the same time, the C-shaped embedded pancreaticojejunostomy can shorten the time of pancreaticojejunostomy and is easier to operate, thus worthy of clinical promotion.


Introduction
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly tumors in gastrointestinal tumors and is also one of the four most common causes of cancer-related deaths [1]. Although the current molecular biology, medical system, treatment technology, and chemotherapy have made great progress, the 5-year survival rate of pancreatic cancer is only 12%. At present, surgical RO resection is still the only possible cure for pancreatic cancer [2,3].
Pancreaticoduodenectomy, also known as Whipple Operation, is the current standard procedure for the treatment of malignant tumors of the pancreatic head and ampulla. In 1898, Codivilla, an Italian physician, for the first time performed pancreaticoduodenectomy (PD), which has been the standard surgical operation for the treatment of benign and malignant lesions in the areas around pancreatic head and ampulla. The reconstruction of digestive tract is the key in the operation, and plays a decisive role in the recovery of patients. With the rapid development of surgical techniques and perioperative management concepts in the past 20 years, the operative mortality rate of pancreaticoduodenectomy has dropped to less than 5% [4]. But the incidence of postoperative complications is still high, because the surgical procedure is complicated, involving quite many organs, and the reconstruction steps are intricate [5]. According to reports from dozens of medical centers in different countries, the incidence of postoperative complications after pancreaticoduodenectomy is 30%-60% [6]. Common postoperative complications include postoperative pancreatic fistula (PF), delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) [7]. Among them, pancreatic fistula is most common, which can cause a significant increase in hospital stay and hospitalization costs, can further lead to severe consequences such as postoperative abdominal bleeding and infection, and can even endanger the patients' lives [8]. Therefore, in the perioperative management, the prevention and treatment of pancreatic fistula are of high priority [9]. In order to better prevent and reduce the incidence of postoperative pancreatic fistula, pancreatic surgeons have invented a variety of approaches for pancreaticojejunostomy. However, the best one has not been found yet. Surgeons have untiringly tired various possible effective methods to reduce the occurrence of PF, such as insertion of drainage tube in the pancreatic duct, preoperative reduction of jaundice, and application of somatostatin [10][11][12][13]. However, the general conditions of patients before surgery, such as gender, age, and whether with diabetes or chronic pancreatitis, are objective and unchangeable. Therefore, the treatment of the pancreatic stump as a controllable factor seems to be particularly important in reducing the occurrence of PF. Theoretically, pancreaticogastrostomy (PG) has more advantages, but most studies currently show that the incidence of PF after PG is not lower than that of pancreaticojejunostomy (PJ), so most surgeons still favor the PJ method, which mainly includes invagination pancreaticojejunostomy (IPJ) and duct-to-mucosa pancreaticojejunostomy (DmPJ) [14][15][16]. Based on these, many scholars have improved and innovated a large number of PJ methods, with more than 100 methods currently. The author's team has improved and innovated on this basis and gradually formed its own PJ method, which is "C-shaped embedded pancreaticojejunostomy." The main purpose of this article is to compare the occurrence of PF and other complications of the two anastomosis methods, C-shaped embedded pancreaticojejunostomy and pancreatic duct-jejunal mucosal anastomosis, so as to provide reference for future clinical practice.

Grouping.
According to the different anastomosis methods, they are divided into group A: C-shaped embedded anastomosis, and group B: pancreatic duct-jejunal mucosal anastomosis.

Preoperative Preparation
The following is the preoperative preparation: (1) Rehydration is performed to correct acid-base imbalance and electrolyte ion disorder (2) Improving preoperative anemia, hypoproteinemia, and jaundice and for patients unable to eat, intravenous nutritional support shall be given (3) Liver protection treatment was performed for patients with abnormal liver function, and the patients shall be advised to eat more high-protein foods before surgery (4) For patients complicated with basic diseases such as heart disease, hypertension, and diabetes, relevant departments shall be invited for consultation, and the patient's diet will be adjusted and arranged based 2 Journal of Oncology on the consultation's opinions to ensure the patient can undergo surgery normally (5) Before operation, food and water are prohibited, a gastric tube will be placed, and broad-spectrum antibiotics will be applied 0.5-1 hour before operation to prevent infection

Surgical Approach
4.1. C-Shaped Embedded Anastomosis Method. A C-shaped embedded anastomosis method was used in group A. Insert the pancreatic duct drainage tube into the main pancreatic duct for about 6-7 cm, and use a 15 cm 3.0 absorbable thread to penetrate the pancreas, pancreatic duct, and pancreatic duct drainage twice to form a U-shaped suture which fixed the tube in the pancreatic duct (see Figure 1(a)). Use a 50 cm 3.0 Prolene thread to penetrate the whole pancreas at pancreas superior margin and anastomosis with the seromuscular layer of the jejunum twice (see Figure 1(b)). Go on to suture the posterior wall of the pancreas and the seromuscular layer of the jejunum with a continuous suture (see Figure 1(c)); then penetrate the whole pancreas at pancreas inferior margin and anastomosis with the seromuscular layer of the jejunum twice (see Figure 1(d)) so that the jejunum wrapped the upper, posterior, and lower edges of the 3 Journal of Oncology pancreas by about 1 cm to form a C-shaped embedded anastomosis. Use an electric hook to make a 0.5 cm incision at the edge of the mesangium of the jejunum, and then insert the pancreatic duct drainage tube into the cavity of the jejunum for about 10 cm through the incision. Then, use a 15 cm 3.0 absorbable thread to perform a purse string suture around the incision of the jejunum (see Figure 1(e)). After tightening the knot, continue with the first 3.0 Prolene thread to suture the anterior wall of the pancreas and the jejunum to complete the C-shaped embedded anastomosis of the pancreas and jejunum (see Figure 1(f)). Finally, we also captured the key steps of the operation to supplement the description of the anastomosis method, as shown in Figure 2. PF, can be diagnosed as pancreatic fistula. According to different standards, it is divided into biochemical fistula, grade B fistula, and grade C fistula (see Table 1).

Diagnosis of Postoperative Biliary
Fistula. According to ISGPS definition, biliary fistula can be diagnosed if the concentration of bilirubin in abdominal drainage fluid exceeds 3 times of the upper limit of normal blood bilirubin concentration at any time from the third day after surgery. Imaging examination suggested that fluid accumulation around the biliary anastomosis could provide indirect evidence for biliary fistula and provide guidance for the treatment of biliary fistula. Patients with biliary fistula often have higher amylase levels due to the presence of pancreatic fluid in the intestinal cavity (see Table 2).

Postoperative Delayed Gastric
Emptying. In this study, the diagnostic standard for postoperative gastric emptying delay adopted the postpancreatectomy delayed gastric emptying (DEG) standard proposed by the International Study Group on Pancreatic Surgery (ISGPs). Before diagnosis, the abnormal gastric emptying caused by mechanical obstruction should be ruled out, and the gastrojejunal or duodenal-jejunal anastomosis should be unobstructed by endoscopy or upper gastrointestinal angiography (see Table 3).

Diagnosis of Postoperative
Hemorrhage. In this study, the postoperative hemorrhage classification adopted the postpancreatectomy hemorrhage standard proposed by the  According to the bleeding time, it is divided into early postoperative hemorrhage (less than or equal to 24 h after surgery) and late postoperative hemorrhage (more than 24 h after surgery) (see Table 4).  Table 5).

Statistical
Methods. The statistical software SPSS26.0 was used for data analysis. All measurement data conforming to the normal distribution were described and represented by the mean ± standard deviation (χ ± s), and the difference between the groups was performed by two independent sample t tests; measurement data such as postoperative complications were performed by a χ 2 test. The difference was statistically significant with p < 0:05.

Comparison of Preoperative Situation of Patients with C-Shaped Embedded Anastomosis and Pancreatic Duct-Jejunal
Mucosal Anastomosis. 68 patients were included in this study, of which 38 patients underwent C-shaped embedded anastomosis and 30 patients underwent pancreatic ductjejunal mucosal anastomosis. The average age of all patients was 61:98 ± 7:98 years old. As shown in the table, the preoperative albumin level of patients with C-shaped embedded anastomosis (hereinafter referred to as group A) was 34:89 ± 2:54 g/L, and the preoperative albumin level of patients with pancreatic duct-jejunal mucosal anastomosis (hereinafter referred to as group B) was 34:71 ± 4:08 g/L. The two groups had no statistical significance after statistical analysis. The preoperative serum bilirubin level of group A was 116:89 ± 59:97 μmol/L, and the preoperative serum bilirubin level of group B was 97:64 ± 30:11 μmol/L. The two groups had no statistical significance after statistical analysis. The average intraoperative blood loss in group A was 432:61 ± 205:38 mL, and the average intraoperative blood loss of group B was 481:38 ± 142:67 mL. The two groups had no statistical significance after statistical analysis (p = 0:078). Generally speaking, the two groups had no statistical significance in terms of preoperative general conditions, pancreatic conditions (texture, pancreatic duct diameter), intraoperative blood loss, and case types (p > 0:05). The specific results are shown in Table 6.     Table 7. The difference between the two groups was not statistically significant in the comparison of biochemical fistula, while the difference was statistically significant (p < 0:05) in the comparison of grade B fistula. And there was no significant difference in the incidence of bile leakage, abdominal bleeding, delayed gastric emptying, and abdominal infection between group A and group B. The specific results are shown in Table 8.

Discussion
At present, cancer has become one of the main factors affecting public health. Pancreatic cancer is the most common one with high degree of malignancy. Since the early diagnosis rate is not high, its mortality rate ranks the fourth in all cancers globally. The National Comprehensive Cancer Network (NCCN) recommends pancreaticoduodenectomy (PD) as the only potential cure for pancreatic cancer in the clinical practice guidelines. In 1994, Dr. Ganger and Dr. Pomp from Canada performed the world's first laparoscopic pancreaticoduodenectomy (LPD) for a patient with chronic pancreatitis. Since then, more and more surgeons have begun to pay   Pancreaticoduodenectomy is a relatively complicated surgical method, which can greatly affect the body and potentially cause a lot of complications. In recent years, more and more innovative anastomosis methods have been proposed, the safety of the perioperative period has been greatly improved, and the techniques have become more mature. It has become a commonly used surgical method in high-volume centers. Pancreaticojejunostomy is the most commonly used gastrointestinal reconstruction method in pancreaticoduodenectomy, and it is also a key factor determining the effect of surgery. Over the years, pancreatic surgeons have made multiple attempts in the methods and techniques of pancreaticojejunostomy. Various pancreaticojejunostomies emerged one after another, all aimed at achieving biological healing through a firm mechanical anastomosis. However, there is no pancreaticojejunostomy that can completely avoid pancreatic fistula so far. Among them, the pancreatic duct-to-jejunal mucosal anastomosis is achieved by suturing the pancreatic duct mucosa and the jejunum mucosa and making the pancreas section and the jejunum serous membrane closely attached. Theoretically, it can effectively prevent the occurrence of pancreatic fistula and related complications and become the first choice for pancreatic anastomosis. However, the results of recent prospective studies and meta-analysis showed that the pancreatic duct-to-jejunal mucosal anastomosis has not significantly reduced the incidence of pancreatic fistula, and for patients with soft pancreas or small pancreatic duct diameter (<3 mm), it requires considerable techniques and experience to conduct pancreatic duct-to-jejunal mucosal anastomosis. If not, it is more likely to cause serious complications such as postoperative pancreatic fistula. In recent years, with the gradual development of laparoscopic and robotic pancreaticoduodenectomy, the pancreaticojejunostomy has encountered a technical bottleneck. The traditional open pancreaticojejunostomy method is not suitable for minimally invasive pancreaticojejunostomy. How to conduct a minimally invasive pancreaticojejunostomy easily and safely has become the exploration target of pancreatic surgeons. Excessively tight pancreaticojejunostomy in the past can affect the blood supply of the anastomosis, excessive anastomotic tension can cause pancreatic tissue edema, resulting in severe suture cutting injury, and multilayer and overdense sutures can also cause penetrating injury to the pancreas, resulting in pancreatic juice leakage through the needle hole to form a pancreatic fistula. Based on the above understanding of traditional pancreaticojejunostomy, combined with a large number of laparoscopic and robotic pancreaticojejunostomy experiences, the author has gradually formed a simple and convenient C-shaped embedded pancreaticojejunostomy through continuous optimization of the suture method.
The results of this study showed that the average time of pancreaticojejunostomy in patients who underwent Cshaped embedded pancreaticojejunostomy was 32:13 ± 4:52 min, while the average time of pancreaticojejunostomy was 43:23 ± 4:31 min in patients who underwent pancreatic duct-jejunal mucosal anastomosis. The difference was statistically significant (p < 0:05). Neither of the two groups of patients had a Grade C fistula, but it can be clearly found from the data that in terms of reducing the grade of pancreatic fistula, the C-shaped embedded pancreaticojejunostomy is better and safer. There was no perioperative death in the two groups. In terms of operation time, the C-shaped embedded pancreaticojejunostomy was also relatively shorter and easier to operate. There were few patients with gastric emptying disorders, bile leakage, and abdominal infections after surgery, and none of the remaining patients had complications required surgical intervention. In this study, due to limited conditions, not many patients were included. At the same time, the procedure is currently in the learning curve stage. However, from the previous results, this procedure is efficient in time and simple in steps, which is very suitable for large-scale clinical applications. It can not only significantly reduce the incidence of postoperative pancreatic fistula and related complications but is also a safe and effective method of pancreaticojejunostomy. If its role in reducing the incidence of postoperative pancreatic fistula can be further confirmed in a large sample of patients, it will be revolutionary in the change of the concept of pancreaticojejunostomy and the promotion of pancreaticoduodenectomy. The C-shaped embedded pancreaticojejunostomy is simple and convenient to operate and strives to achieve the fastest biological healing with minimal mechanical damage. The suture of the pancreas section and the jejunum serosa muscle layer can be achieved with one thread, which with an assistant U shaped suture and purse suture, still simplified the whole process a little longer and guarantee a reduced rate of postoperative complication.

Conclusions
The C-shaped embedded anastomosis method proposed in this study is an innovative anastomosis method based on the original pancreaticojejunal end-to-side anastomosis. By including the cases of both pancreatic duct-jejunum anastomosis and C-shaped embedded anastomosis methods, the data further confirmed that the C-shaped embedded anastomosis method is safe and feasible. Besides, it also has the advantages of less hemorrhage, shorter postoperative hospital stay, and lower hospitalization costs. Compared with pancreaticojejunal anastomosis, C-shaped embedded anastomosis has higher technical advantages for doctors and lower perioperative mortality and postoperative complications for the patient. All in all, the anastomosis method is simple and easy to operate, the incidence of postoperative pancreatic fistula is low, and it has good safety and effectiveness. It is suitable for promotion and application in both open and minimally invasive pancreaticoduodenectomy.

Data Availability
All data included in this study are available upon request by contact with the corresponding author. 8 Journal of Oncology