What are the treatment methods of pancreatic cancer?

Up to now, pancreatic cancer, a refractory tumor, still puzzles oncologists and surgeons. Around this disease, various medical disciplines are looking for new treatment methods, but at present, the fundamental treatment principle is still surgery combined with radiotherapy and chemotherapy.

1. Surgical treatment of pancreatic cancer is the only possible radical cure. Surgical methods include pancreatoduodenectomy, extended pancreatoduodenectomy, pylorus-preserving pancreatoduodenectomy, total pancreatectomy and so on. However, the early diagnosis of pancreatic cancer is difficult, the surgical resection rate is low, and the five-year survival rate after operation is also low.

For unresectable obstructive jaundice pancreatic cancer, gallbladder or cholangioenterostomy can be selected to reduce jaundice and improve the quality of life of patients. Stents can also be placed under an endoscope to relieve obstruction.

(1) Preoperative preparation: Good or proper cardiopulmonary and renal function before operation is necessary. Although patients often lose weight before surgery, the nutritional status must ensure the safety of surgery. Enteral nutrition should be given when albumin is lower than 3g/dl or waiting time before operation. When the tumor occurs in the pancreatic head or there is pancreatic duct obstruction, pancreatin can be supplemented appropriately. Obstructive jaundice can damage liver, kidney and immune function. Whether to support or drain bile duct before operation is still controversial. A survey shows that preoperative routine bile duct support to reduce jaundice can not reduce complications and mortality. Therefore, it is not recommended to reduce jaundice by endoscopy or other methods before operation, as long as early surgery can be performed when early jaundice occurs, so as to strive for early treatment opportunities. However, in order to reduce the chance of biliary pressure and cholangitis, and to ensure the reduction of postoperative complications, especially renal failure, endoscopic biliary support must be properly applied. It is best to use a plastic stent of 10F or larger for this kind of stent, while a metal expansion stent is better for patients whose tumors cannot be removed, but it is not suitable for patients who are estimated to be operable. Metal stents can cause serious inflammatory reaction, and eventually penetrate into the bile duct wall, which makes the operation complicated. Advanced tumor and large tumor should not be used as contraindications for radical surgery. In fact, in major medical centers in the United States, most of the tumors removed by Whipple surgery are 3 ~ 5 cm, and there is no complete statistics in China. The patient's age should be considered in combination with the patient's specific situation and the surgeon's technical and medical conditions. It's not that you can't do radical surgery if you are not old.

(2) Surgical treatment and its management and monitoring:

① Determine the indications and timing of surgical resection: To judge whether there are indications and timing of surgical resection is not only through preoperative physical examination and imaging diagnosis, but also the final decision is often made during surgery, so certain principles are needed. Usually there is liver or retroperitoneal metastasis, or metastatic lymph nodes are not within the scope of Whipple operation, such as distant lymph node metastasis, etc., and no resection is performed. At the beginning of exploration, the abdominal cavity and its contents should be carefully examined, and any suspected metastatic area should be biopsied. When the diagnosis of frozen section is obtained, the possibility of surgical resection is determined. In the absence of distant metastasis, it is necessary to estimate whether the tumor invades major vascular structures, such as superior mesenteric artery and vein, celiac artery, hepatic artery, especially superior mesenteric vein, which often terminates the operation.

② Pancreaticoduodenectomy (Whipple operation): Pancreaticoduodenectomy is the main operation to treat pancreatic cancer. 1 Periampullary cancer resection was performed in two stages by German surgeon Kausch on 1909. Whipple performed this operation in a similar way in 1935, and improved it to one-stage resection in 1942. After resection, the anastomosis sequence was gallbladder, pancreas, stomach and jejunum, which formed today's pancreaticoduodenectomy. 1944, Child anastomosed the intestinal stump with the pancreatic stump, and then performed end-to-side anastomosis between the common bile duct and the jejunum, that is, pancreaticojejunostomy, which is called Child's method. Child method and Whipple method are commonly used surgical methods at present. At present, the minimum mortality rate of this operation at home and abroad is ≤2%. The main process of pancreaticoduodenectomy is as follows:

A. Routine exploration: Check the abdominal cavity for distant metastasis and tumor infiltration, and preliminarily judge whether it can be resected. Advanced pancreatic head cancer sometimes infiltrates the root of transverse mesocolon to form cancerous contracture (or cancerous umbilical cord), which means that superior mesenteric vein is infiltrated by cancer. If there is no preparation and conditions for vascular resection, further exploration should generally be abandoned and palliative surgery should be carried out. The sclerosing sensation when the pancreatic head is touched is differentiated from the calcification of pancreatitis. Also pay attention to the contents of the hepatoduodenal ligament, including whether there are tumors and stones in the common bile duct; When touching the duodenum, pay attention to whether there is a tumor on the nipple in the descending part. Disconnect the gastrocolon ligament, cut loose tissue between transverse mesocolon and pancreatic head, and expose the descending part of duodenum and the front of pancreatic head. At this time, fine biopsy needle can be used for multi-point puncture to extract tissue samples and send them to pathological cytology. Pay attention to the direction of needle insertion, and try to insert the needle into the anterior upper part of the pancreas to avoid damaging the main pancreatic duct. As for taking local biopsy for frozen section examination, we should be cautious, because there are often changes of chronic pancreatitis around the tumor of pancreatic cancer. If the materials are taken improperly, it will easily lead to misdiagnosis or missed diagnosis. If the cancer cannot be removed, there is still the risk of pancreatic leakage, bleeding and abscess.

B. Separation and exploration: cut the lateral peritoneum of the descending part of duodenum, cut off the hepatogastric ligament and hepatoduodenal ligament, extend to the horizontal part of duodenum and even the root of transverse mesocolon, passively separate the free tissue behind pancreas, turn the head of duodenum and pancreas up to the left, fully free the head of duodenum and pancreas from the retroperitoneum, and check whether there is invasion between cancer and vena cava, superior mesenteric artery and vein, celiac artery and hepatic artery, especially portal vein. Portal vein and superior mesenteric vein should be separated behind pancreas without obvious resistance. This step is the key to determine whether radical surgery can be performed. But sometimes, although it can be completely separated, after pancreatectomy, it is found that the tumor infiltrates part of the portal vein, such as the right posterior lateral wall. At this time, it is often necessary to prepare for partial portal vein resection and artificial vascular anastomosis.

C. Resection of the lesion and surrounding tissues: cholecystectomy, and cutting off the common hepatic duct or common bile duct. In the case of pancreatic head cancer, the bile duct must be cut off at the lower segment of the common hepatic duct; Distal gastrectomy depends on the patient's age, hyperacidity, etc. As high as 1/2 of the distal stomach, the omentum should be treated according to the requirements of radical gastrectomy. Pancreas is usually cut off at the left edge of celiac artery, while ampullary carcinoma or some benign lesions can be used as the cutting line at the neck of pancreas. When the pancreas is resected, suture at four points on the edge of the pancreas to prevent bleeding from the transverse blood vessels of the pancreas. While cutting the pancreas, peel off the pancreatic duct and protect it carefully, insert a silicone tube with the diameter suitable for the original pancreatic duct, sew 1 ~ 2 needles on the pancreatic duct with absorbable thread to fix the silicone tube, and pay attention to ligating some venous vessels on the back of the pancreas. Confirm Treitz ligament at the left root of mesentery, clearly touch the superior mesenteric artery, ligate one or two branches of jejunal artery, cut jejunum under Treitz ligament 10cm, close the proximal end, and prepare the distal end for intussusception and anastomosis with pancreas. Finally, the uncinate process of the pancreas should be treated. It is important to note that there are many small veins flowing into the superior mesenteric vein, which must be carefully ligated one by one and then cut off to avoid damaging the superior mesenteric vein and causing massive bleeding. The uncinate process of pancreatic head should be completely removed, and the lymph nodes around the superior mesenteric artery and vein should be removed.

D. Reconstruction of digestive tract: there are mainly Child's pancreaticojejunostomy, biliary-enterostomy and gastrointestinal anastomosis, Whipple's pancreaticojejunostomy and gastrointestinal anastomosis. At present, the Child method is popular, and its pancreaticojejunostomy adopts end-to-end embedded anastomosis between pancreas and jejunum, and both of them adopt seromuscular suture. Sometimes the cross section of the pancreas is wider than the jejunal cavity. In order to prevent the obstruction of blood circulation in intestinal wall caused by hard insertion and affect the healing of anastomosis, it is necessary to remove the upper and lower edges of pancreas or only the lower edge of pancreas and wedge the pancreas into it. Routine cholangioenterostomy still needs to place T tube, and its size should be appropriate; Not too big, not too small. Others use catheters to support them. Finally, gastrojejunostomy was performed, generally 40 ~ 50 cm below the pancreaticojejunostomy, and anastomosed with the stump jejunum before colon. If enteral nutrition is needed, enterostomy is needed, and the feeding tube is sent to the jejunum in the output section under the anastomosis, and the gastric tube should also go deep into the input section. Whipple method is to close the distal jejunum and pull it to the colon before cholangioenterostomy. Pancreaticojejunostomy can be divided into two types: one is end-to-side pancreaticojejunostomy, which is suitable for patients with obvious dilatation of pancreatic duct; The other is that the pancreatic duct is transplanted into the jejunum, and a silicone tube needs to be inserted into the pancreatic duct for fixation. In order to prevent pancreatic fistula, it is advocated to place a catheter in the main pancreatic duct to drain pancreatic juice, regardless of Child method or Whipple method.

③ Modified pancreaticoduodenectomy:

A. Pancreatoduodenectomy with preservation of pylorus: Because of the problems of weight loss and malnutrition in standard pancreatoduodenectomy, many surgeons seek to improve it, such as pancreatoduodenectomy with preservation of pylorus. This kind of operation preserves the stomach's function of storing stomach and digesting, promotes digestion, prevents dumping syndrome, and is beneficial to improving postoperative nutrition. Although the degree of operation has been reduced, it has not reduced the postoperative survival rate and adapted to the requirements of improving the quality of life after operation in the near future, so it has been popularized since the 1970s. But people are most concerned about whether this improvement will affect the radical cure degree and long-term survival rate of malignant tumors. Compared with standard pancreaticoduodenectomy, there are many literature reports about the nutritional status and radical degree of postoperative patients, but there is still no convincing data to draw a conclusion on this issue. Because one of the key problems of these two kinds of operations is that patients can't be randomly selected, the operation method is often decided according to the specific situation of patients. It is generally believed that this operation can be used for benign lesions around the pancreatic head, ampullary cancer, pancreatic head tumor with low malignancy and cancer that has not infiltrated pylorus and duodenum. Malignant lesions need to cut off the right gastric artery for lymph node dissection, which may affect the blood supply of pylorus and duodenal bulb. Some patients have delayed gastric emptying after operation, and gastrostomy should be added during operation to alleviate the pain caused by long-term indwelling nasal feeding tube after operation.

B. Extended pancreaticoduodenectomy: Pancreatic cancer is mostly pancreatic duct epithelial adenocarcinoma, and lymph node metastasis is an important way of pancreatic cancer metastasis. The metastasis and spread of pancreatic cancer, besides lymph node metastasis and infiltration of cancer into surrounding tissues, is another way of pancreatic cancer metastasis. Therefore, the so-called extended radical operation should not only remove lymph nodes, but also remove the celiac artery, superior mesenteric artery and nerve plexus next to abdominal aorta. Complete resection of superior mesenteric plexus can lead to intractable diarrhea. In addition, it is necessary to remove the soft tissue around the pancreas, so all operations include removing all or most of the pancreas and its surrounding soft tissue and lymph nodes, biliary tract below the hilum, duodenum, part of jejunum, stomach and the whole transverse mesocolon. Because of the high incidence of early complications, high mortality and unsatisfactory long-term survival rate, extended surgery has not been widely used in Europe, America and China. Even in Japan, where most scholars advocate this kind of expanded surgery, there are still many scholars who disagree.

④ Postoperative complications and their prevention and treatment:

A. Pancreatic fistula: This is usually the most fatal and common complication after pancreatectomy. Most of them occurred 5 ~ 7 days after operation. Patients with abdominal distension, abdominal pain, high fever and increased abdominal drainage, such as increased amylase in abdominal drainage, can be identified as pancreatic fistula. Non-surgical treatment is generally used because surgery is difficult to repair. Different digestive tract reconstruction methods are of great significance to prevent pancreatic fistula. The Affiliated Hospital of China Medical University summarized 1 18 cases of pancreaticoduodenectomy. Of the 42 patients treated with Whipple, 10 had pancreatic fistula, and 6 of them died. Among 75 cases of Child method, pancreatic fistula occurred in 2 cases and died 1 case. The incidence of pancreatic fistula in Child method was significantly lower than that in Whipple method. At present, Whipple method is rarely used for digestive tract reconstruction in China. Pay attention to the strict pancreaticojejunostomy during the operation, especially the placement and drainage of the catheter in the main pancreatic duct, and the abdominal drainage should be sufficient. It is best to use a pan drainage tube, and if necessary, add a double-cavity drainage tube. Early continuous use of drugs that inhibit pancreatic juice secretion, such as somatostatin and its derivatives.

B. Abdominal hemorrhage: divided into primary and secondary. Primary bleeding mostly occurs in the early stage of operation, mostly due to blood flowing out of drainage tube, mostly due to incomplete hemostasis or coagulation dysfunction during operation; Close observation, immediate infusion and blood transfusion, application of hemostatic drugs, if the condition does not improve, should immediately open exploration. Secondary bleeding mostly occurs in 1 ~ 2 weeks after operation, which is mostly caused by pancreatic fistula and pancreatic juice flowing into abdominal cavity, digesting and corroding surrounding tissues, so non-surgical treatment should be actively taken; If there is active bleeding, angiography can be considered, but sometimes it is still difficult to find the bleeding site, and it is often difficult to stop bleeding by surgery, so be careful. Primary bleeding can also occur at the cutting edge of pancreas or jejunum, mainly due to incomplete hemostasis during operation, which leads to local bleeding and hematoma after operation. Hematoma compression further aggravates anastomotic leakage or pancreatic leakage, so local bleeding is often accompanied by various fistulas, so it is necessary to closely observe the drainage tube. If the bleeding persists, the operation should be performed again immediately. Prevention is mainly to stop bleeding completely during operation. In addition, fibrin glue can be coated around the pancreatic stump and anastomosis to stop bleeding on the one hand and have proper adhesion on the other.

C. Gastrointestinal bleeding: Early postoperative bleeding can be considered as incomplete hemostasis under gastric mucosa or coagulation dysfunction. Postoperative bleeding around 1 week is mostly considered as stress ulcer bleeding, which can be treated as stress ulcer bleeding, and antacids should be used routinely in the early postoperative period.

D. Intra-abdominal infection: It is a serious complication, which is mostly caused by pancreatic fistula, biliary fistula or peritoneal effusion with infection. There may be abdominal pain, high fever, physical failure, anemia and hypoproteinemia. Strengthen systemic support therapy and apply high-efficiency broad-spectrum antibiotics.

E. biliary fistula: rare. Once it happens, it can be cured mainly by unobstructed drainage. Patients with poor drainage and peritoneal irritation should be explored surgically.

2. Palliative treatment of pancreatic cancer

(1) indications for palliative surgery: it is of great significance for palliative treatment of pancreatic cancer. Because about 88% patients can't undergo radical surgery because of the local spread and metastasis of the tumor, when the primary tumor can't be resected, the surgeon must decide what palliative measures to take to alleviate the obstruction of biliary tract or duodenum. In addition, the cooperation of internal medicine and surgery is needed to deal with jaundice, pain, weight loss, pancreatic insufficiency, and even depression and failure. There is also the failure of biliary stent placement or drainage, or obstruction or even cholangitis after stent placement, which also requires surgical treatment. The choice of palliative jaundice reduction surgery should not only be judged before operation, but also be explored in detail after laparotomy. The method and sequence of exploration are the same as pancreatoduodenectomy. Usually, if the tumor invades the mesenteric root or portal vein, it is considered that radical resection is not suitable, but palliative surgery should be performed, and fine needle aspiration cytology or biopsy should be performed if necessary.

(2) Palliative surgery: For cases that are not suitable for radical surgery, it is often necessary to relieve obstructive jaundice. Cholecystostomy is generally used, and external fistula (cholecystostomy or external drainage of bile duct) can be done unconditionally. Most patients can relieve symptoms and improve their general condition in a short time, and the average survival time is about half a year. Palliative yellowing surgery mainly includes the following types:

① Bow-loop Anastomosis of Gallbladder and Jejunum: Bow-loop Anastomosis of Gallbladder and Jejunum is a routine bilateral jejunum anastomosis (Braun anastomosis) under Treize ligament 15cm to prevent upward infection of biliary tract. This cholangioenterostomy has the advantages of easy exposure, convenient anastomosis, short operation time and few complications, and can be used as the first choice.

② Roux-en-Y cholecystojejunostomy: Roux-en-Y cholecystojejunostomy is to cut off the jejunum under Treize ligament 15cm, and pull the distal jejunum near the gallbladder through the front or back of colon. The method of anastomosis between jejunum and gallbladder is to close the broken end of the empty intestine, perform end-to-side anastomosis between gallbladder and jejunum, or adopt end-to-end anastomosis. Although the operation of this method is slightly complicated, there is less chance of ascending biliary tract infection after operation.

If the gallbladder does not expand during the operation, it means that bile cannot enter the gallbladder. At this time, jejunum and common hepatic duct or jejunum and common bile duct should be anastomosed. If cholangioenterostomy is really used, the cystic duct should be anastomosed with the side of the common hepatic duct or common bile duct at the same time to ensure smooth bile drainage. If complicated with biliary tract infection and serious gallbladder inflammation and edema, cholecystostomy should be performed.

③ Common bile duct jejunostomy: Common bile duct jejunostomy is simple, but its curative effect is not as good as common bile duct jejunostomy. The average survival time after cholangioenterostomy was 4.7 ~ 6.7 months, and the recurrent jaundice and cholangitis were 65438 0.5% ~ 64.0%, with an average of 20%. The average survival time after cholangioenterostomy was 5.7 ~ 9.2 months, and the recurrent jaundice and cholangitis were 7.3% ~ 16.6%, with an average of 8%. The above situation shows that cholangioenterostomy is better than cholangioenterostomy. Roux-en-Y-shaped lateral or end-to-side anastomosis can be used for the anastomosis of bile duct (common bile duct or common hepatic duct) and jejunum. If the bile duct is dilated (generally more than 2cm), it is best to choose end-to-side anastomosis. Biliary drainage should be placed routinely to reduce the pressure of biliary tract and anastomosis.

④ Gastrointestinal cholecystojejunostomy: Pancreatic head cancer often leads to the obstruction of the second segment of duodenum, while body cancer easily leads to the obstruction of the fourth segment. Pancreatic cancer complicated with obstructive jaundice and duodenal obstruction is suitable for gastrointestinal and biliary-intestinal double anastomosis. Endoscopy or gastrointestinal X-ray examination should be performed before operation to determine whether there is obstruction. This double anastomosis should be used only when the patient has symptoms or signs of obstruction, or when endoscopic examination finds obstruction, or when the duodenum is narrow or compressed during operation. Preventive gastrointestinal anastomosis is generally not advocated when there are no obvious signs. Sometimes pancreatic cancer invades the retroperitoneal gastrointestinal motor nerve, which will lead to gastrointestinal peristalsis paralysis. The clinical manifestation of obstruction is functional obstruction. Gastrointestinal anastomosis is not only unnecessary, but also ineffective. Surgical methods include adding gastrojejunal loop anastomosis or Roux-en-Y anastomosis on the basis of cholangioenterostomy. In other cases, the second stage of gastrointestinal anastomosis was performed after choledochojejunostomy to solve the feeding problem of patients.

3. Comprehensive treatment of pancreatic cancer Pancreatic cancer has a high degree of malignancy, low surgical resection rate and poor prognosis. Although surgery is still the main treatment, pancreatic cancer is often found late, losing the chance of radical cure and needing comprehensive treatment. So far, like most tumors, there is not an efficient, complete and applicable comprehensive treatment scheme. At present, the comprehensive treatment is still mainly surgical treatment, supplemented by radiotherapy and chemotherapy, and a new method of combining immunotherapy with molecular biotherapy is being explored.

(1) Radiotherapy: Pancreatic cancer is a tumor with low sensitivity to radiotherapy. Because of the deep position of the pancreas, the surrounding gastrointestinal tract, liver and kidney, spinal cord and so on have low tolerance to radiation, which is not conducive to radiotherapy of pancreatic cancer. However, in recent years, with the development of intraoperative radiotherapy and multi-field external radiotherapy under CT precise positioning, radiotherapy has become one of the main methods for the treatment of pancreatic cancer. Radiotherapy alone has no significant effect on the survival of patients with unresectable advanced pancreatic cancer. The combination of radiotherapy and chemotherapy can effectively relieve symptoms, relieve pain, improve the quality of life and prolong the survival time. Intraoperative radiotherapy can determine the target area under direct vision, make the irradiation site more accurate, and thus protect the surrounding normal tissues to the maximum extent, but it requires special equipment and can only be irradiated once. In recent years, preoperative radiotherapy and chemotherapy have been advocated to control tumor metastasis.

① Intraoperative radiotherapy: during the operation, high-energy electron beam of 10 ~ 20 MeV was used to fully expose the tumor tissue, cut off the normal tissues such as the surrounding gastrointestinal tract, and accurately aim the light limiting tube at the tumor bed. High dose 15 ~ 25 Gy for 4 ~ 6 min was used during the operation. Intraoperative radiotherapy should include abdominal aorta, paraperitoneal artery and superior mesenteric artery. According to domestic and foreign reports, the analgesic effect of intraoperative radiotherapy is 60% ~ 98%, and the median survival time is 3 ~ 1 1 month.

② postoperative external irradiation: external irradiation was started 2 weeks after operation, 10MeVX-ray, multi-center irradiation before and on both sides of abdomen, 180 ~ 200 cgy each time, 3 times a week, with a dose of 40 ~ 60 Gy for 4 ~ 6 weeks, which can be treated continuously or by stages. Intraoperative and postoperative radiotherapy can relieve patients' pain and shrink tumors. The median survival time of patients was 4 ~ 16 months.

③ Precise radiotherapy: In recent years, with the rapid development of computer technology and CT imaging technology, the tumor can be accurately located in three dimensions, and the computer-controlled rays can accurately irradiate the target tissue without causing obvious damage to the surrounding tissues. This stereotactic radiation technique (SRS) was originally applied to brain surgery, and now it is also applied to pancreatic tissue. In SRS technology, three-dimensional conformal radiotherapy (3D-CRT) is developed, which can make the dose of high dose area distributed in three-dimensional space and conform to the actual shape of target area. The latest development is intensity modulated radiation therapy (IPMT). By changing the radiation intensity of the target area, IPMT can achieve an ideal dose at any point in the target area. In fact, it is uneven illumination. The steps are: patient selection → patient fixation →CT/MRI scanning → target area and sensitive tissue determination → reverse calculation system → database → treatment plan verification → radiation dose verification → treatment implementation → summary follow-up. Because the pancreas is located behind the peritoneum, its position is relatively fixed, which is suitable for this precise radiotherapy. Because IPMT only acts on the tumor tissue to be irradiated, but not on the surrounding gastrointestinal tissues, it greatly improves the gastrointestinal inflammation caused by the original radiotherapy, and its adverse reactions after radiotherapy are far less than those of traditional radiotherapy, and the treatment scheme can be adjusted at any time according to the CT situation. Since this technology was developed in the late 1990s, there is no complete clinical analysis report on the survival rate of patients, but its application has made a good start and will be the development direction of radiotherapy in the future. Its disadvantage is that the cost is more expensive than general radiotherapy and the equipment requirements are higher. But with the further development of technology, it will become more and more popular. In order to obtain the good effect of this treatment, certain premise support is needed. In particular, patients with jaundice should be treated by internal medicine or surgery, and appropriate nutritional support should be given before this treatment.

Radiotherapy alone can't achieve good results, so it's better to combine chemotherapy with radiotherapy. A random survey recently published by the European Organization for Research and Treatment of Cancer (EORTC) shows that when the total radiation dose after resection is 4000cGy, fluorouracil is given 500mg/m2, three times a day, and used for two years after radiotherapy, the 2-year survival rate of the treatment group is 43%, while that of the control group is 65438 08%. It shows that radiotherapy combined with chemotherapy has obvious curative effect.

(2) Chemotherapy: Chemotherapy can be given to pancreatic cancer that cannot be surgically removed or to prevent postoperative recurrence. Chemotherapy for pancreatic cancer is expected to reduce the incidence of postoperative recurrence and metastasis.

(1) The common monotherapy is:

A. fluorouracil (5-Fu): 10 ~ 12 mg/kg, intravenous drip, 1 time /d, changed to 5 ~ 10 mg/kg and 8 ~ 12 g after 3 ~ 5 days. Because the half-life (T 1/2) of fluorouracil (5-FU) is short, it is considered that using a lower dose and prolonging the drip time can improve the curative effect and reduce the side effects.

B mitomycin (MMC):4 ~ 6mg/ time, intravenous injection, 1 time/week. The curative effect is similar to that of fluorouracil (5-FU). Bone marrow suppression is its main side effect.

C. streptozotocin: nitrosourea. Daily 15mg/kg, intravenous injection for 5 days, every 2 ~ 4 weeks for 1 course of treatment. The effective rate was 1 1%.

D. Adriamycin (adriamycin) and epirubicin (epirubicin): 30 ~ 50mg/m2, intravenous injection, repeated for 3 ~ 4 weeks 1 time. The main side effects are myocardial toxicity and bone marrow suppression, and heart failure may occur in severe cases. Epirubicin (Epirubicin) is less toxic to myocardium.

E.paclitacel: It is a new type of anti-microtubule agent, which acts on M phase and G2 phase cells. Recently, I tried to use it to treat pancreatic cancer. 175mg/m2 intravenous drip was completed within 3 hours, repeated every 3 weeks, ***5 cycles. To prevent allergic reaction, dexamethasone 10 ~ 20 mg was taken orally/2 h and 6h before medication, and diphenhydramine 50mg was injected intravenously 30min before medication. Taxotere is a semi-synthetic product, and its efficacy is about 2 times higher than that of paclitaxel.

Gemcitabine: It's a difluoro deoxycytidine. After it is activated in the cell, it inhibits nucleotide reductase by mixing it into DNA chain, preventing its elongation and leading to cell apoptosis. It mainly acts on S-phase cells. The dosage was 1000mg/m2 (body surface area), and it was given intravenously within 30min minutes, 1 time/week for 3 weeks. Repeat every 4 weeks. The preliminary results show that it can improve symptoms and prolong survival time, which is worth further study.

② Combined chemotherapy: Pancreatic cancer is not sensitive to chemotherapy, and the effect of single drug treatment is not good. Combined chemotherapy can reduce the drug resistance of tumor and improve the curative effect. But it is still not ideal for prolonging the survival time.

A.FAM regimen: fluorouracil 600 mg/m2, intravenous injection1at the 2nd, 5th and 6th weeks; Mitomycin 10mg/m2, injected intravenously at 1 week; Adriamycin 20mg/m2, 1, intravenous injection 1 time within 5 weeks.

B.SMF regimen: STZ 1.0mg/m2, 1, 8, 29 and 36 days, 1 time, intravenous injection; Mitomycin was injected intravenously on 1 day; Fluorouracil (5-Fu)600mg/m2 was given intravenously on days 1, 8, 29 and 36. Repeat after 8 weeks.

C.FAD regimen: epirubicin (EADM)40mg/m2, intravenous drip every day/kloc-0; Cisplatin 20mg/m2, intravenous drip on day 1 ~ 5; 5- fluorouracil 500mg/m2, intravenous drip on day 1 ~ 5.

③ Interventional chemotherapy: Intra-arterial infusion chemotherapy can greatly increase the drug concentration in tumor tissues and reduce the side effects of systemic medication. The catheter can be kept in the body for a long time, connected with the subcutaneous implanted perfusion pump, and administered repeatedly through the perfusion pump to improve the curative effect.

(3) biotherapy: biotherapy includes immunization and molecular therapy. With the rapid development of immunology and molecular biology research, it will be the most challenging research, because some new methods must be developed to treat refractory tumors such as pancreatic cancer.

① Gene therapy: Gene therapy is in the ascendant, but most of it still stays in the early clinical stage, and few of them have entered clinical phase I or II trials. With the rapid development of molecular biotechnology and genetic engineering, gene therapy has become an important research field of tumor treatment. Gene therapy for pancreatic cancer is still in the experimental stage. There are many targets of gene therapy, and newer methods are aimed at the process of cell circulation, such as using P2 1WAF- 1 gene and adenovirus vector. P2 1WAF- 1 protein is an important cell cycle inhibitor. In vitro experiments showed that the cultured cells were infected with P2 1WAF- 1 gene (rAD-P2 1) constructed by adenovirus vector, and the cell proliferation could stay at G0/G 1 phase. However, the transduction rate of this virus vector into cells is low, and the host reaction is serious. Restrictive replication virus, such as G207, can transform this adenovirus or retrovirus vector to replicate only in specific cell types, such as cancer cells. G207 is a mutant of herpes virus. This specific mutation ensures the replication of the virus in the target cell, thus playing the role of specific gene therapy. On the one hand, this vector has the same inhibitory effect on cell proliferation as P2 1; On the other hand, it can carry suicide genes like Hs-tK.

Another therapeutic method based on the expression gene of pancreatic cancer is to use the characteristics of RAS oncogene. In the past 10 years, RAS gene and its encoded protein have been fully studied. RAS protein is a membrane-bound protein of GDP, which acts as a molecular switch of mitotic signal transduction. The mutation of RAS gene can continuously activate this function, which occurs in about 90% pancreatic cancer and leads to the continuous proliferation of cells. RAS protein needs a farneski group of 15 carbon after translation to bind to cell membrane. If this group is blocked, the mutant RAS protein will not bind to the cell membrane and remain inactive. Farnesyl transfeRASe inhibitors can inactivate farnesyl, an organic group, thus inactivating ras protein. Various farnesyl transferase inhibitors have been synthesized and have activities in vivo and in vitro. The drug 1998 has entered the clinic and can be taken orally continuously with less toxicity. Pancreatic cancer is the first choice because of the high expression and mutation of RAS gene.

Mainly includes the following aspects:

A. metastasis of wild-type tumor suppressor genes p53, p 16, retinoblastoma (Rb), etc. By transferring the above tumor suppressor genes into pancreatic cancer cells, apoptosis is induced and the growth of cancer cells is inhibited.

B. Introducing suicide genes: introducing some drug metabolism genes possessed by viruses or bacteria into pancreatic cancer cells, so that some compounds can be transformed into metabolites with cytotoxic effects, thereby killing tumor cells. For example, the adenosine kinase encoded by herpes simplex virus tk gene can phosphorylate ganciclovir (GCV) in cells and further metabolize it into triphosphate compounds. The production of DNA can be stopped by inhibiting fluorocytosine polymerase or competitively doping DNA. Escherichia coli cytosine deaminase (Ec-CD) gene can transform 5- fluorocytosine into 5- fluorouracil, and inhibit the synthesis of KNA and DNA. Nitrobenzene, aziridine and propyl compounds (CB 1954) can be reduced to G- hydroxylamine with cytotoxic effect by the nitro reductase (Ec-witroreducase) gene of Escherichia coli.

C antisense nucleic acid technology: artificially synthesize DNA or RNA fragments complementary to the oncogene sequence expressed in tumor cells and transfer them into cells to reduce or stop their expression. Anti-ak-ras can inhibit the proliferation of pancreatic cancer cells.

D. Immune gene transduction: transfer genes of cytokines such as interleukin -2, interleukin-12(IL-2, IL- 12) and tumor proliferation factor (TNF), modify tumor cells, and enhance the anti-tumor immune response of the body.

Because the occurrence of tumor cells is the result of multi-gene and complex action, simply introducing a certain gene is not enough to achieve satisfactory therapeutic effect.

② Immunotherapy: It is a part of comprehensive therapy to use immune preparations to enhance the immune function of the body. At present, the commonly used non-specific immune preparations are OK-432, thymosin, interferon, ADI interleukin -2 and so on. As a potential therapeutic system, it may be superior to radiotherapy and chemotherapy because it can produce specific anti-tumor effects without damaging normal tissues. Antitumor immunity can be divided into active immunity and passive immunity. Tumor vaccine is a kind of immunotherapy, which can amplify active immunity and immune response and continuously enhance immune memory. Because the occurrence of tumor is mainly due to low immunity, the purpose of anti-tumor immunity is to improve the body's own immune function.

In the tumor vaccine, the whole tumor cell vaccine is used first, that is, the whole tumor cell is used as the antigen. Because it is not completely clear which protein in pancreatic cancer cells can be recognized by the immune system, the whole cell can only be used as the antigen source. There are two ways: one is to modify tumor cells to express cytokines, so as to attract antigen presenting cells (APC) such as macrophages and dendritic cells to reach tumor cells, and these APC can also activate T helper lymphocytes and T killer lymphocytes; The second way is to modify tumor cells to express * * * stimulating factors and directly activate killer T lymphocytes. Both methods have been pre-clinical tested. However, they have some limitations and technical difficulties. First, it is difficult to isolate and amplify vaccines in vitro.