Pancreatic fistula (pancreatic fistula) is a pathological phenomenon in which the pancreatic ducts are connected to internal organs or to the outside world through abnormal channels after pancreatic diseases and their surgical procedures, and the pancreatic fluid flows out from non-physiological pathways, the former being called intrapancreatic fistula and the latter being called extrapancreatic fistula. Extrapancreatic fistula is a serious complication of pancreatic surgery. The definition of postoperative pancreatic fistula given by Howard l998 in the journal Surgery is: 1. postoperative drainage of fluid or fluid exuding from the abdominal wound; 2. duration of more than 5 days; greater than 10 ml per day; 3. fluid with amylase and lipase content more than 3 times that of plasma. According to the daily drainage of pancreatic fluid, extra-pancreatic fistulas can be divided into 3 categories: 1, low-flow pancreatic fistulas, pancreatic fluid drainage <200ml/d; 2, medium-flow pancreatic fistulas, pancreatic fluid drainage of 200-500m1/d; 3, high-flow pancreatic fistulas, pancreatic fluid drainage >500m1/d. Some authors have also divided pancreatic fistulas into partial fistulas and complete fistulas. The difference is whether there is pancreatic fluid drainage into the intestine. It is reported that about 75% of pancreatic fistulas close within 1 year, and the remaining 25% of pancreatic fistulas take more than 1 year to close. With the increase in acute pancreatitis, pancreatic trauma and pancreatic surgery, the incidence of pancreatic fistulas has increased. Pancreatic fistula is also a more common complication after pancreatic head and duodenectomy and is one of the most common causes of death after pancreatic surgery, with an incidence of about 10% to 18% and a few reports as high as 40%. The morbidity and mortality rate can be 7%-30%. The incidence has gradually decreased in recent years. After the pancreatic fluid leaks into the abdominal cavity, pancreatic protease and pancreatic lipase leach surrounding tissues and organs, which can cause uncontrollable abdominal infection, such as pancreatic fluid erosion of the large blood vessels in the abdominal cavity, can cause hemorrhagic shock, and its morbidity and mortality rate can be as high as 50%. Moreover, pancreatic leakage is often one of the important causes of other complications. Therefore, the prevention and treatment of pancreatic leakage has been of great concern. A. Etiology 1, pancreatic trauma Pancreatic trauma is a common cause of pancreatic fistula, the incidence of which is about 14.4 to 37.2%. (1) After damage to the pancreas, especially blunt injuries caused by contusions, lacerations or crush injuries to the pancreas, the actual extent of damage to the pancreatic tissue is often larger than what can be seen with the naked eye. Therefore, if this factor is neglected during pancreatic debridement or repair, the residual damaged pancreatic tissue may continue to necrotize after surgery, and once the pancreatic duct is involved, pancreatic fistula will occur; (2) Although the damaged pancreatic duct is ligated during surgery, pancreatic fistula is still likely to occur after surgery if secondary infection occurs; (3) If the large pancreatic duct or main pancreatic duct is injured, it is more difficult to obtain successful pancreatic duct anastomosis if the pancreatic duct is of normal size, and pancreatic fistula is likely to occur. 2, severe acute pancreatitis necrotic pancreatic tissue after surgical removal or self-exfoliation of the pancreatic duct exposed, or pancreatic tail removal, due to tissue inflammation, infection does not heal, so that pancreatic secretion continues to flow from the drainage port, resulting in pancreatic fistula. In severe acute pancreatitis, the incidence of pancreatic fistula is about 15%. 3, pancreatic surgery Various types of pancreatic surgery may damage the pancreatic duct and form a pancreatic fistula. Common surgeries: (1) Severe acute pancreatitis after laparoscopic drainage. (2) After tumor removal or pancreatic body and tail resection for benign pancreatic tumors; islet cell tumor surgery is usually performed for tumor removal, which is less likely to damage the pancreatic duct. If the tumor is deeper or close to the large pancreatic duct, the pancreatic duct may be damaged and cause pancreatic fistula if care is not taken during surgery. After pancreatic duodenectomy for pancreatic malignant tumors, pancreatic fistula occurs in about 10-25% of cases, which is the most serious complication of the operation and the main cause of death after pancreatic head duodenectomy. Most of them are due to technical errors in the anastomosis between the residual pancreas and the digestive tract after pancreatic head and duodenectomy. The incidence is related to the surgical approach, the treatment of the residual pancreas and the thickness of the pancreatic duct. In general, the incidence of pancreatic fistula after pancreatic head resection is higher than that of distal pancreatic resection; the incidence of pancreatic fistula after pancreatic duct ligation is higher than that of pancreatic-jejunostomy; the incidence of pancreatic fistula with normal caliber pancreatic duct is higher than that of significantly dilated pancreatic duct. Pancreatic leakage can also occur after pancreatic biopsy or pancreatic ductotomy for lithotripsy. In addition to the surgical approach and surgical technique, the risk factors for pancreatic fistula are: ① age > 65 years; ② small caliber of pancreatic duct; ③ failure to place the endopancreatic duct stent; ④ flabby or normal pancreatic parenchyma; ⑤ excessive intraoperative blood loss; ⑥ deep and prolonged preoperative jaundice; ⑦ poor nutritional status and liver function, decreased creatinine clearance; ⑧ prolonged surgery; ⑨ malignant diseases have a higher chance of pancreatic fistula after surgery than benign ones. (3) Anastomotic fistula secondary to external drainage of pancreatic cyst or pancreatic abscess, or internal drainage of pseudocyst. (4) After resection of penetrating ulcers involving the pancreas; splenectomy injury to the pancreas; splenorenal vein or splenic vena cava shunt injury to the tail of the pancreas; surgery on other adjacent organs of the pancreas accidentally injuring the pancreas. (5) Injury to the pancreatic duct by duodenal papillary sphincter plasty or EST. Diagnosis and differentiation The diagnosis of pancreatic fistula needs to be based on medical history, clinical manifestations and auxiliary examinations. 1. History: History of acute pancreatitis, history of surgery on the pancreas or peripancreatic organs, and history of abdominal or pancreatic trauma. 2, clinical manifestations: abdominal drainage tube is the window to observe the changes in the abdominal cavity, and is an important means to diagnose pancreatic leakage and abdominal infection. The presence of fistula and the outflow of pancreatic fluid from the abdominal drainage tube is the main basis for the diagnosis of pancreatic fistula. A pancreatic fistula should be suspected if there is a large amount of drainage near the pancreatic-intestinal anastomosis, the fluid is non-mucous, light in color and lasts for more than 1 week. If necessary, relevant laboratory tests can be performed on the drained fluid. If there are secondary symptoms of pancreatic fistula, the corresponding clinical manifestations may appear. 3, drainage fluid amylase test: pancreatic fistula patients drainage fluid amylase content is significantly elevated, generally above 1000SU/L (sometimes up to 10000U/L) can confirm the diagnosis. Only a few patients need to be confirmed by imaging. 4, fistulography: after injecting 76% pantothenic glucosamine into the fistula for radiographs, the pancreatic duct and fistula can be seen to be connected, and the site, shape, direction and extent of the fistula can be understood. If there is an internal fistula, it is also possible to understand the flow of contrast into the corresponding organ and provide a basis for the choice of surgical approach. Pancreatic fistula needs to be differentiated from other fistulas: (1) Gastrointestinal fistula: the drainage fluid is gastric or intestinal fluid, which can be confirmed by X-ray fistula or gastrointestinal imaging, oral melanoma or activated carbon powder. (2) Biliary fistula: the drainage fluid is bile fluid and the biliary tract is visible on contrast examination. (3) Celiac fistula: the drainage fluid is celiac and the celiac test is positive. (4) renal fistula or bladder fistula: 76% pantopamine is injected through the fistula and the urological system can be visualized. Once a pancreatic fistula is confirmed, it should be actively treated. The key is the need for effective drainage measures. Only adequate drainage will not lead to deterioration of the disease. With effective nutritional support and anti-infection measures, most pancreatic fistulas can be controlled in 2-4 weeks and gradually heal on their own. However, improper treatment can easily lead to serious complications such as bleeding and infection, and even death. Early treatment of pancreatic fistula is appropriate to take a comprehensive treatment based on drainage of pancreatic fluid. After drainage, those who cannot heal themselves for a long time will be treated surgically. 1, supportive therapy For early pancreatic fistula patients, supportive therapy should be strengthened to maintain water, electrolyte and acid-base balance, and fasting patients should be given adequate calories and a sufficient amount of protein to maintain positive nitrogen balance and create conditions for self-healing of pancreatic fistula. It is usually believed that fasting can significantly reduce pancreatic fluid secretion, and it is also believed that diet has little effect on pancreatic secretion. In addition, the treatment of pancreatic fistula is a longer-term process, and long-term fasting is not practical if there are no measures such as perfect parenteral nutrition. For a few patients with high-flow pancreatic fistula and pancreatic fluid drainage of more than 1000 ml per day, a brief fasting and enhanced enteral and parenteral nutritional support can reduce pancreatic fluid secretion and receive temporary effects. In addition, the reasonable use of antibiotics to control infection and prevent bleeding are very important adjunctive treatment measures. This is one of the main measures to promote the healing of pancreatic fistula. (1) fasting or low protein diet: can reduce the secretion of pancreatic juice, complete parenteral nutrition is more effective in reducing the secretion of pancreatic juice; (2) drug therapy: acetylcholinergic blockers (atropine, probenecid), carbonic anhydrase inhibitors (acetazolamide), metformin, 5-Fu intravenous drip and pancreatic glucagon, growth inhibitors or sine, etc., can reduce the secretion of pancreatic juice. TPN combined with growth inhibitor releasing hormone is more effective; peptidase intravenous drip can inhibit the activity of pancreatic enzymes, reduce the destructive effect of pancreatic enzymes on tissues, and reduce the occurrence of secondary diseases. Domestic and foreign data show that the use of parenteral nutrition + growth inhibitor + growth hormone will facilitate the healing of pancreatic fistula. The purpose of applying growth hormone is to improve the general nutritional status as early as possible and accelerate the healing of fistula or wound, but the course of treatment should not be too long. (3) Radiation therapy: If the above methods are not effective, high dose radiation can be used to irradiate the pancreas, so that the pancreatic tissue is damaged by radioactivity and thus inhibit the exocrine function of the pancreas, while there is no significant effect on its endocrine function. This damage is reversible. It is usually recovered gradually in a few weeks after the cessation of irradiation. This method has been reported to be effective in the treatment of patients with pancreatic fistula complicated by postoperative pancreatic malignancy. The 4MV linear gas pedal 4.0Gy(400rad)/d can be used to irradiate the pancreas for 5d or 60Co1.5Gy(150rad)/d for 7d, which can effectively promote the closure of pancreatic fistula. 3. Adequate drainage Adequate drainage and keeping the drainage open is the most important principle in the treatment of pancreatic fistula and an important means to prevent complications. Drainage of pancreatic fluid is an important measure to prevent corrosion of adjacent tissues by pancreatic fluid, to stop the development of the disease, and to reduce serious complications such as intra-abdominal infection and bleeding. Continuous negative pressure suction with double cannula or porous silicone hose is usually used, and necrotic detached tissues blocking the drainage tube should be removed in time during the drainage process to ensure that the drainage tube is unobstructed. The common causes of poor drainage are improper drainage tube position and necrotic tissue blockage. The drainage tube should be kept in the proper position, and the blockage in the drainage tube should be removed in a timely manner, and can be dripped or flushed with saline at the same time as negative pressure suction to discharge necrotic tissue. If it still does not work, the drainage tube should be replaced. Through active and effective continuous drainage, most pancreatic fistulas can be expected to heal on their own. After the flow of drainage is significantly reduced, the tube should be gradually withdrawn, about 1 to 2 cm each time, until the drainage tube is completely removed. The first time, the pus can erode the nearby pancreatic gland and produce limited purulent pancreatitis, which can be aggravated in 12 to 24 hours and should be paid close attention to. zinner believes that the rate of self-healing of high-flow pancreatic fistula and low-flow pancreatic fistula is not much different, but the healing time of the latter is shorter than that of the former. 4, pancreatic fistula tract blocking method for abdominal infection has been controlled and limited, the pancreatic fistula tract has been formed and the open end of the pancreatic duct is open, the pancreatic fistula tract can be blocked with medical adhesives to close the duct, the effect is good. The method is to insert a 2-4 mm diameter silicon plastic tube into the pancreatic fistula tract, flush the tube with antibacterial solution, and then inject 3-6 m1 polymer adhesive (such as chloroprene emulsion) directly into the fistula tract to seal the fistula tract. Then inject 0.5 to 1.5 ml of 12.5% acetic acid, remove the catheter, and the pancreatic fistula is closed by polymer. In addition, when the pancreatic fistula tract is cleaned, the same effect of sealing the pancreatic fistula tract can be obtained by injecting about 5 m1 of TH gel from the catheter. After blocking the duct, drugs such as atropine, 5-Fu, and sennin should be used to temporarily inhibit pancreatic fluid secretion to enhance the effect of blockage. During operation, care should be taken to avoid blocking the pancreatic duct with mucolytic agents. 5.Surgical treatment Although most pancreatic fistulas can heal spontaneously after non-surgical treatment, about 10% of pancreatic fistulas still need surgical treatment. There are different views on the timing of surgical treatment. Some people believe that high-flow pancreatic fistula continuous drainage for more than 60 d can be considered for surgery; some people believe that non-operative treatment for more than 60 d and no improvement in the condition should be surgical treatment; others believe that 0.5 to 1 year should be observed, and if there is still no tendency to heal, surgical treatment should be taken. Some people believe that the timing of surgery for pancreatic fistula should be 6 to 9 months, when most of the abdominal adhesions have been absorbed and the wall of the pancreatic fistula has a certain thickness and strength, which facilitates intraoperative separation and anastomosis. In short, there is no uniform opinion on the duration of non-operative treatment, but it is not advisable to wait indefinitely. Because non-operative treatment also has certain disadvantages: (1) loss of a large amount of pancreatic fluid; (2) easy erosion and erosion of the surrounding skin; (3) the risk of serious complications such as bleeding and infection; (4) there are indeed a small number of pancreatic fistulas (such as with proximal pancreatic stenosis, etc.) that do not work with non-operative treatment. Therefore, it is generally believed that surgery should be considered for pancreatic fistulas that have not healed after 3 months of active non-surgical treatment. Prior to surgery, fistulography or ERCP is performed to understand the relationship between the main pancreatic duct and the fistula in order to decide the surgical approach. The fistula is usually first excised along the wall of the fistula up to the opening of the pancreatic duct. The next surgical step is then decided based on the site of the fistula and the relationship of the pancreatic duct. ① Pancreatic fistula tract excision: This method can be used for small fistulae and for those without stenosis or obstruction at the open end of the pancreatic duct. All fistulae are freed, cut, ligated or sutured close to the pancreas, and covered with large omental sutures. ② pancreatic fistula tract combined with distal pancreatic segment resection: it is suitable for larger fistulae in the body and tail of the pancreas without stenosis or obstruction at the open end of the fistula, with heavy adhesions around the fistula and difficulties in complete separation of the fistula. After freeing the body and tail of the pancreas concerned and transection, the pancreatic duct is first ligated, and then the pancreatic section is sutured with mattress sutures. (3) Roux-Y anastomosis of pancreatic fistula duct jejunum: It is suitable for patients with medium or high flow pancreatic fistula with thick fistula duct. A soft catheter marker is inserted into the fistula first, and a longitudinal incision in the upper abdomen that avoids the fistula opening can be chosen. After entering the abdomen, the fistula is freed for 3-5 cm and cut at the proximal abdominal wall and set aside. A shuttle incision can also be made around the fistula opening in the abdominal wall, and the fistula can be cut 5 to 10 cm away from the pancreas. The jejunum is cut at 15-20 cm from the flexor ligament, the distal segment is closed, and the fistula jejunostomy is performed after the colon; the jejunostomy can also be performed without closing the jejunostomy, and the fistula is performed at 40 cm from the anastomosis, and the jejunostomy is performed at the proximal end and the distal segment. This procedure is suitable for patients with pancreatic fistula and pancreatic duct opening segment stenosis or obstruction in any part of the pancreas. ④Pancreatic fistula jejunostomy implantation: After freeing the fistula, the jejunum is placed 30-40 cm from the Treitz ligament in front of the colon to the fistula, the jejunum is incised, the fistula is implanted, and the surrounding tissue is sutured. Finally, a lateral anastomosis is made between the proximal and distal loops of the jejunum. This procedure is more prone to reflux and retrograde infection than the Roux-Y anastomosis of the pancreatic fistula. (5) Gastric implantation of fistula: This is suitable for fistulas close to the stomach wall with a small diameter. After freeing the fistula, the stomach wall is incised and the fistula is implanted into the gastric cavity. The surrounding tissue is then sutured. The disadvantage of this method is also that it is prone to reflux, retrograde infection or fistula blockage. (6) Coffrey’s procedure: The fistula and its surrounding tissues are completely freed and anastomosed with the digestive tract, but the wall of the separated fistula is often not strong and intact enough for successful anastomosis with the digestive tract, and postoperative anastomotic scar contraction can lead to recurrence of pancreatic fistula. The fistula is densely adherent to the surrounding organs, making resection more difficult and easily damaging the surrounding organs. Some patients may have recurrent pancreatic fistula. Therefore, surgical treatment should be extra cautious. (7) Pancreaticoduodenectomy: It is suitable for those who have multiple stenoses in the pancreatic duct or chronic pancreatitis at the same time, and it can be effective. (8) Other surgical procedures: Sphincter of Oddi: Applicable to patients with pancreatic fistula at the opening of the pancreatic duct or with stenosis of the sphincter of Oddi. For those who have a combination of internal fistula, the corresponding surgical treatment is feasible. If the opening of the pancreatic duct is open, pancreatic fistula can be removed or ligated, intestinal fistula repair or resection of the diseased intestinal duct. After the occurrence of pancreatic fistula, in addition to some patients can heal on their own within a certain period of time, most of them have a long duration of illness, some of them are more difficult to deal with, and there is a certain rate of death. Therefore, it is especially important to prevent the occurrence of pancreatic fistula. In order to prevent the occurrence of pancreatic leakage after pancreatic surgery, we must first master the local anatomical relationship of the pancreas and operate accurately, gently and carefully. When the nature of the pancreatic mass needs to be determined intraoperatively, fine needle aspiration cytology is feasible, and the mass at the head of the pancreas can be biopsied via duodenal aspiration, avoiding direct removal of the pancreatic mass for rapid pathological examination to avoid pancreatic leakage or uncontrollable bleeding. When dealing with pancreatic trauma, the extent of pancreatic injury should be correctly judged and the lifeless tissues should be completely excised, and those that cannot be sutured should not be reluctantly sutured. The pancreatic duct should be ligated when a rupture is seen. If necessary, inject dilute hydrochloric acid into the duodenum to stimulate pancreatic fluid secretion, find the rupture, and suture it properly. When dealing with pancreatic trauma or residual pancreas, tissue sutures should not be too tight and dense to avoid the formation of pancreatic fistula after necrosis and detachment of the tissue distal to the suture. Usually, the stump is cut into a V-shape and then sutured with mattress sutures so that the pancreatic tissues on both sides are aligned. The pancreatic wedge resection biopsy has the possibility of damaging the large pancreatic duct, so it should not be cut too deeply. The pancreatic duct can be easily damaged by coarse needle puncture, while fine needle puncture is safer. The prevention of pancreatic fistula after pancreatic head and duodenectomy should first be considered from the perspective of surgical approach (especially the pancreatic-intestinal anastomosis) and surgical technique. At present, the commonly used pancreatic-intestinal anastomoses include end-to-end pancreatic dissection jejunostomy, pancreatic duct jejunal mucosal anastomosis, end-to-end pancreatic dissection jejunal sleeve anastomosis, and pancreatic dissection jejunal bundle anastomosis. These anastomoses have advantages and disadvantages, but regardless of the anastomosis method, as long as the pancreatic-enteric anastomosis is reliable, the occurrence of pancreatic fistula can be avoided. Peng Shuji et al. used pancreatic dissection with jejunal bundle anastomosis in more than 150 consecutive cases without pancreatic fistula. However, regardless of the procedure, there is a possibility of pancreatic fistula unless total pancreatectomy is performed. The surgical technique of the surgeon is also very important, and skilled operation of the same surgical approach can significantly reduce the occurrence of postoperative pancreatic fistula. If the caudal pancreatectomy is performed, the main pancreatic duct is carefully searched and reliably ligated in the center of the pancreatic section, and then a “U” shaped suture is made 1 cm inward of the pancreatic cut edge to reliably ligate the main pancreatic duct, and the pancreatic section is tightly hemostatic and then sparsely sutured with several stitches. After the pancreatic head and duodenum resection, the residual section should be mattress sutured and the main pancreatic duct should be exposed, and a thin silicone tube of matching diameter should be inserted into the lumen to support the drainage and fixed with sutures, and the silicone tube should be drained out of the body from the jejunostomy, and the drainage tube should not be dislodged, and most of the pancreatic fluid should be drained out of the body in 2-3 weeks after the operation. The scope of pancreatic stump free during surgery should be appropriate, with the stump set into the jejunum about 2 cm, so as to avoid ischemic necrosis of the pancreatic stump and pancreatic leakage. In cases where the pancreatic stump is congested and edematous, thick, hypertrophic, brittle or adherent to the superior mesenteric vein or splenic vein, resulting in difficulty in freeing the pancreatic stump and snapping it into the jejunum, pancreatic duct embolization can be considered. The stump of the pancreas can also be wedge-shaped resected and snapped into the jejunostomy in the shape of a fish mouth. The pancreatic and bile intestinal anastomosis should be kept at a proper distance and the tension should be moderate, with a distance of 10 cm being more appropriate, and a lateral anastomosis of the proximal and distal jejunum should be made under the Childs’ gastrojejunal anastomosis, so that bile and pancreatic juice can flow smoothly into the distal jejunum to reduce the pressure of the pancreatic and bile intestinal anastomosis and prevent the occurrence of anastomotic leakage. In addition to surgical approach and surgical technique, it has been suggested that long duration of preoperative jaundice, poor nutritional status and liver function, decreased creatinine clearance and high intraoperative bleeding are risk factors for pancreatic fistula after pancreatic head and duodenectomy. The chance of pancreatic fistula after surgery is higher in malignant diseases than in benign ones. Therefore, intraoperative placement of appropriate abdominal drains is essential to drain the exudate and blood out of the body, avoid local fluid accumulation and infection, and facilitate the healing of the pancreatic-intestinal anastomosis. After surgery, the amount and nature of drainage fluid should be observed at all times to keep the abdominal drainage tube open to prevent blockage. Once pancreatic leakage occurs, it should be fully drained and actively treated, and the site of the drainage tube should be adjusted in time for those with poor drainage. If necessary, re-surgical drainage should be performed. In addition, the use of acid-suppressing drugs, growth inhibitors or octreotide and 5-Fu to inhibit the exocrine function of the pancreas after pancreatic surgery can help reduce the occurrence of pancreatic fistula. Postoperative intensive supportive therapy Improving the nutritional status of patients is beneficial to the repair of trauma and wound healing.