Introduction:
Pancreatic cancer(pancreatic carcinoma) is a common pancreatic tumor. It is a malignant tumor with high malignancy and difficult diagnosis and treatment. About 90% of it is ductal adenocarcinoma originating from the glandular epithelium. Its morbidity and mortality have increased significantly in recent years. The 5-year survival rate is <1%, which is one of the worst malignant tumors. The early diagnosis rate of pancreatic cancer is not high, the operative mortality rate is high, and the cure rate is very low. The incidence of this disease is higher in men than in women. The ratio of male to female is 1.5~2:1. Male patients are far more common than premenopausal women. The incidence of postmenopausal women is similar to that of males.
Cause:
(1) Causes of the disease
The cause of pancreatic cancer is not well understood. Pancreatic cancer is associated with smoking, drinking, high-fat and high-protein diets, excessive coffee consumption, environmental pollution, and genetic factors; recent surveys have found that the incidence of pancreatic cancer in diabetic populations is significantly higher than in the general population; Patients with chronic pancreatitis have a certain relationship with the incidence of pancreatic cancer. It is found that the proportion of pancreatic cancer in patients with chronic pancreatitis is significantly increased; in addition, there are many factors related to the occurrence of this disease, such as occupation, environment, geography and so on.
1. Smoking animal experiments have shown that feeding animals with tobacco acid water can cause pancreatic cancer. A large sample survey showed that smokers have a 1.5 times higher chance of developing pancreatic cancer than non-smokers. The greater the amount of smoking, the more pancreatic cancer occurs. The higher the chance, the more pancreatic cancer occurs in a pack of 4 and 2 times higher than that of non-smokers. The above information indicates that smoking in some people can induce pancreatic cancer.
2. Inappropriate diet In recent years, some scholars have attributed the increase in pancreatic cancer to improper diet. Animal experiments have shown that animals fed a high protein, high fat diet can accelerate the regeneration of pancreatic ductal cells and increase the sensitivity to carcinogens. Domestic scholar Shen Kui and other clearly stated that the diet structure is closely related to the occurrence of pancreatic cancer, and many people eating meat are prone to this disease. Japanese scholars have pointed out that the increase in the incidence of pancreatic cancer in Japan in recent years is related to the Europeanization of Japanese diet. That is, eating high protein and high fat. Some scholars believe that there is more chance of developing pancreatic cancer in coffee, but it has not been further confirmed.
3. Diabetes and pancreatic cancer Patients with diabetes are prone to pancreatic cancer. However, recent studies have indicated that people with diabetes mellitus have twice as many pancreatic cancers as non-diabetic patients, and there is an increasing trend; others believe that it is 2 to 4 times the normal population, and even reported that the incidence rate can reach 12.4% of digestive system malignancies, but the true relationship between the two is not clear.
4. Chronic pancreatitis and pancreatic cancer As early as 1950, Mikal et al. noted the relationship between chronic pancreatitis and pancreatic cancer. In 1960, Panlino-Netto pointed out that only patients with chronic pancreatitis with pancreatic calcification existed concurrently with pancreatic cancer, 1977. White further pointed out that only 3 cases of pancreatic cancer were associated with primary calcified chronic pancreatitis, accounting for 2.2%. Chronic pancreatitis and diabetes may be related to the occurrence of pancreatic cancer. Chronic pancreatitis often coincides with pancreatic cancer. According to Mikal et al. (1950), 100 cases of autopsy were reported. 49% had chronic pancreatitis under the microscope and 84% had pancreatic interstitial fibrosis. Because pancreatic cancer can cause obstruction of the pancreatic duct, which leads to the occurrence of pancreatitis, it is difficult to determine the cause and effect. Some people think that chronic pancreatitis with old calcification has a carcinogenic effect on calcification. Panlino-Netto (1960) reported that only pancreatic calcification patients, pancreatitis and pancreatic cancer. However, in White (1977) cases of pancreatitis, there are primary calcification, only 3% with cancer, in addition to calcification in pancreatic cancer. As for the relationship between pancreatic cancer and diabetes, it is not very clear. About 5% to 20% of patients with pancreatic cancer have diabetes, and 80% of them have found diabetes and pancreatic cancer in the same year. A large number of cases have also shown that 5% to 19% of cancer patients with cancer occur in the pancreas, while only 4% of non-diabetic patients develop cancer in the pancreas, indicating that diabetic patients seem to be prone to pancreatic cancer. Sommers et al (1954) reported that 28% of patients with diabetes had pancreatic duct hyperplasia, while only 9% of the control group had pancreatic duct hyperplasia. It is envisaged that cancer can occur on the basis of pancreatic duct hyperplasia. Bell (1957) reported a total of 32,508 cases of autopsy of men over 40 years old. The incidence of pancreatic cancer in diabetic patients was more than double that of non-diabetics. But there is also some evidence that the incidence of pancreatic cancer is not significantly related to diabetes. According to Lemass (1960), patients with pancreatic cancer with diabetes do not have pathological changes in islet cells that are destroyed. The glucose metabolism of some patients with pancreatic cancer can be damaged to some extent, which may be due to the fact that the release of insulin is disturbed due to the absence of pathological changes in islet cells. Others believe that pancreatic cancer combined with diabetes is not specific. The incidence of diabetes in the general population is also 10%.
5. Gene abnormal expression and pancreatic cancer are closely related to the occurrence of pancreatic cancer. The abnormal gene expression is closely related to the occurrence of pancreatic cancer. The relationship between the occurrence of various tumors and cellular genes is a hot spot for studying the causes of cancer. In each gene family, the mutation of the 12-site of the K-ras gene is closely related to the occurrence of pancreatic cancer, and the inactivation of the tumor suppressor gene P53 and the recently cloned MTS1 also has an effect. Since the occurrence of cancer is a multi-factor process, there may be activation and inactivation of various oncogenes or tumor suppressor genes, and it is not related to family inheritance.
In 1991, Tada et al. detected 12 cases of patients with pancreatic cancer and 6 patients with chronic pancreatitis. The PCR test technique was used to detect the 12 codons of c-ki-ras in 12 pancreatic patients. The author further pointed out that the change in the codon at c-ki-ras 12 is mainly a mutation in the base. Tada et al. also suggested that c-ki-ras mutations differed from carcinogenic factors in animal experiments. Smokers can induce c-ki-ras 12-site mutations, while other carcinogens such as dimethyl Benzopyrene causes a mutation in the 61-site codon of the H-ras gene. Tada's clinical analysis of patients with pancreatic cancer concluded that the c-ki-ras gene mutation had no significant relationship with the degree of tumor differentiation, but was related to the size of the tumor, suggesting that the c-ki-ras gene mutation mainly promoted tumor progression. The Lemocene study found changes in the c-ki-ras gene in pancreatic ductal epithelial cells, suggesting that changes in the c-ki-ras gene cause pancreatic ductal epithelial cells to become cancerous, and then the cancer cells infiltrate outward. There are few studies on the occurrence and genetic alteration of pancreatic cancer, and many problems need further study.
6. Endocrine Disorders Pancreatic cancer may also be associated with endocrine, which is based on the incidence of men higher than that of women before menopause, and the incidence of women after menopause increases, similar to men. The incidence of women with a history of spontaneous abortion has also increased.
7. The role of bile For many years, it has been suggested that bile contains carcinogenic factors, because bile can flow back to the pancreatic duct, and pancreatic tissue is more sensitive to carcinogenic factors than bile duct, so pancreatic cancer is more common than cholangiocarcinoma. At the same time, in pancreatic cancer, the more common part of the pancreas in contact with bile, the higher the incidence of cancer, and the cancer originates from the catheter rather than the acinus, which also indicates that this view has a certain basis.
(two) pathogenesis
1. Primary pancreatic cancer can occur in any part of the pancreas, but it is most common in the head of the pancreas. According to a large number of cases, the head of the pancreas is about twice as large as the tail of the pancreas, that is, the pancreatic head cancer accounts for 60% to 70%, and the pancreatic body tail cancer accounts for 25% to 30%. In a few cases, the cancer is scattered throughout. Gland, and it is difficult to determine its location. Bramhall et al found that 80% to 90% of the tumors in surgically treated pancreatic cancer are located in the head of the pancreas. According to recent data from the Pancreatic Cancer Professional Committee of the China Anti-Cancer Association, pancreatic head cancer accounts for 70.1%, pancreatic tail is 20.8%, and pancreatic cancer accounts for 9.1%.
2. Gross pathology The appearance of pancreatic cancer is not consistent. The general morphology of the pancreas in pancreatic cancer depends on the course of the disease and the size of the cancer. When the cancer is not large, the tumor block is deeply hidden in the pancreas and cannot be seen from the surface of the pancreas. There is only the feeling of irregular nodules at the time of percussion. When the cancer is enlarged, the shape of the pancreas changes, and there is a localized swelling of the tumor in the head or tail of the pancreas. The boundary between the tumor mass and the surrounding pancreatic tissue is not well understood. Pancreatic cancer on the cut surface is mostly gray or yellowish white irregular shape, and can also be yellowish white or grayish white. There are also bleeding spots or necrotic spots with brown or reddish brown. In the liquefied carcinoma, there are turbid brown-gray mucous fluids, some of which are small cystic cavity. The pancreas itself is often accompanied by increased fibrous tissue, which makes it firm in texture, and some have pancreatic atrophy in the pancreas. There may be localized fat necrosis, which may be due to cancer caused by pancreatic duct obstruction, pancreatic duct rupture, pancreatic juice spillover, causing local fat necrosis in the pancreas. The size of pancreatic cancer varies widely and is related to the length of the disease. Generally, the diameter of the mass is often above 5cm. Most of the cancers located in the head of the pancreas are extremely hard. There is no obvious boundary between the cancerous tissue and the normal glandular tissue. Sometimes this hard cancer can infiltrate the peripancreatic tissue extensively, and the pancreatic adhesion can not be recognized in a group of cancerous tissues; but sometimes cancer The tissue can also be located in the center of the pancreas and looks the same as the normal pancreas, with only the head of the pancreas being particularly hard. There are also many fibrous tissue hyperplasia and significant reduction of glandular tissue on the cut surface, which is difficult to distinguish from chronic pancreatitis.
Pancreatic cancer can be derived from the pancreatic duct, acinar or islet. Usually pancreatic cancer is derived from pancreatic duct epithelium, accounting for about 85% of the total cases, less from acinar and islet; the former occurs mainly in the head of the pancreas, while the latter is often in the pancreas or tail.
3. Histological changes The microscopic findings of pancreatic cancer mainly depend on the degree of differentiation of adenocarcinoma tissues. The well-differentiated people form a more mature tubular tissue of the pancreatic gland. The cells are mainly high cubes, similar in size, rich in cytoplasm, and nuclear. Similar, mostly at the bottom, showing a polarization distribution. Poorly differentiated people can form various forms or even form a glandular tubular structure, and become solid strip-like, nested, flaky, cluster-like diffuse infiltration. The cells vary in size and shape, and can be spherical, round, or polygonal. The boundaries are not clear, the positions of the nuclei are different, and the nuclei are deeply stained and have no nucleoli. The pancreatic duct-like structure of pancreatic cancer is irregularly arranged, and its epithelial cells are arranged in a stratified manner, and the positions of the nucleus are different (Fig. 1). When the pancreatic duct epithelium proliferates and has a papillary projection, it is a papillary structure called papillary pancreatic cancer. Occasionally, there is a goblet cell metaplasia, and squamous cell metaplasia can also be seen. Under electron microscopy, Mucinogen granules but no zymogen granules were seen, all from larger pancreatic duct epithelial cells. When squamous cell degeneration is obvious, it is called adenosquamous cell carcinoma or adenocanthoma. Microscopic examination showed focal hemorrhage, necrosis and steatosis of varying degrees, called cystic adenocarcinoma. If accompanied by pancreatic duct obstruction, pancreatic acinar atrophy, with papillary hyperplasia.
4. Pathological stage of pancreatic cancer The vast majority (>80%) of pancreatic cancer originates from ductal epithelial cells, and the majority of adenocarcinomas of pancreatic ductal epithelial cells from the pancreas are predominant. A small number of small pancreatic ductal epithelial cells can be derived from the pancreas. Pancreatic cancer from large, medium and small pancreatic ducts, collectively referred to as hard cancer, due to its hard texture. Pancreatic cancer originating from pancreatic vesicle cells is rare, and the cancerous tumor is soft and scented.
(1) Japanese Pancreas Association Recommended Standards (Table 1):
The Japanese Pancreas Association recommends the standard T1 to T4, that is, T1 tumor diameter ≤ 2.0 cm, T2: 2.1 to 4.0 cm; T3: 4.1 to 6.0 cm; T4 > 6.0 cm. N shows lymph node involvement; N0 is no lymph node involvement; N1 is involved in lymph nodes around the pancreas; N2 has secondary lymph node involvement; N3 has near-stage third-grade lymph node metastasis. S shows pancreatic capsule involvement: S0 means that the pancreatic capsule is not invaded, S1 refers to the pancreatic capsule infiltration, S2 means that the pancreatic capsule is infiltrated, and S3 refers to the infiltration of the surrounding organs of the pancreas. Rp showed post-peritoneal involvement: Rp0 showed no post-peritoneal involvement, Rp1 suspected retroperitoneal involvement, Rp2 must have retroperitoneal involvement, and Rp3 showed severe retroperitoneal invasion. V shows the peri-pancreatic vascular involvement, mainly refers to the portal vein, superior mesenteric vein, and splenic vein involvement: V0 means no vascular involvement, V1 suspected vascular involvement, V2 must have vascular involvement, and V3 blood vessels are seriously violated. The Japanese Pancreatic Cancer Association divided the lymph nodes around the pancreas into 18 groups, 3 stations (Fig. 2, Table 2).
(2) TNM staging: The pathological staging of pancreatic cancer contributes to the selection of treatment options and prognosis evaluation. Commonly used are TNM staging, the following is the latest revision of the 2002 International Anticancer Association (UICC) and the Japanese Pancreatic Disease Association (JPS). The American Cancer Alliance (AJCC) staging standard is roughly the same as the UICC standard. The sixth edition of the UICC staging (2002) (Table 3).
1T staging:
Tx: primary tumor cannot be determined
To: no primary tumor evidence
Tis: carcinoma in situ (including Pan In III)
T1: The tumor is confined to the pancreas ≤ 2cm
T2: Tumor is confined to the pancreas >2cm
T3: Tumor has extra-pancreatic infiltration, but does not invade celiac trunk and superior mesenteric artery
T4: Tumor invasion of the celiac trunk and superior mesenteric artery (can not remove the primary lesion)
2N staging:
Nx: Local lymph node metastasis cannot be determined
No: no local lymph node metastasis
N1: local lymph node metastasis
3M staging:
Mx: distant transfer cannot be determined
Mo: no distant transfer
M1: distant transfer
(3) JPS staging: Fifth edition (2002).
1T staging:
Tis: carcinoma in situ
T1: The tumor is confined to the pancreas ≤ 2cm
T2: Tumor is confined to the pancreas >2cm
T3: Tumor invades the biliary tract, duodenum or other peripancreatic tissues
T4: The tumor invades any of the following - adjacent to large blood vessels (such as the portal vein, arteries), nerve plexus or other organs away from the pancreas.
2N staging:
No: no lymph node metastasis
N1: first station lymph node metastasis
N2: second station lymph node metastasis
N3: third station lymph node metastasis
3M staging:
Mo: no distant transfer
M1: There is a distant transfer
5. Pancreatic cancer metastasis Because of its rapid growth, the pancreas is located in the retroperitoneum, surrounded by important organs, plus pancreatic blood vessels, lymphatic vessels are abundant, pancreas has no capsule, often early metastasis, or directly to the pancreas Weekly invasion, or lymphatic vessels and (or) blood vessels to distant and near organ tissues, the most frequently infringed parts are common bile duct, duodenum, liver, stomach, transverse colon and upper abdomen. In addition, pancreatic cancer can also be transferred outward along the nerve sheath, and the pancreas happens to be lying in front of many nerve plexuses in the upper abdomen, so that the cancer often invades these nerve tissues at an early stage, especially after the abdominal wall nerve tissue is most susceptible. It is precisely because pancreatic cancer is easily spread directly in the local area, or spreads through the lymph, blood vessels and nerves, which constitutes its diversified clinical manifestations. Therefore, clinically advanced or advanced patients, or due to organ, blood vessel, nerve infiltration, or lymph node metastasis, can not be radical resection, even if palliative resection, short-term postoperative death due to recurrence. The transfer of pancreatic cancer is mainly through the following ways:
(1) Intra-pancreatic spread: Pancreatic cancer can penetrate the wall of the pancreatic duct in the early stage and infiltrate and metastasize to the surrounding pancreatic tissue in the form of invasive ductal carcinoma. Under the microscope, the infiltration of cancer tissue is limited to 2.0 to 2.5 cm from the edge of the tumor, and rarely exceeds 3.0 cm. Due to anatomical relationship, about 70% of the carcinoma of the head of the pancreas has invaded the uncinate process.
(2) Peripancreatic tissue and organ infiltration: Pancreatic cancer can infiltrate and spread to surrounding tissues, and the oppressed infiltration at the lower end of the common bile duct is a manifestation. In addition, the duodenum, stomach, transverse colon, spleen, etc. can also be tired, but does not necessarily penetrate the gastrointestinal tract to cause mucosal ulcers. Once the pancreatic body cancer has invaded the peritoneum, extensive peritoneal transplantation can occur. According to the statistics of 62l cases of pancreatic head cancer in the Pancreatic Surgery Group of the Chinese Medical Association, the frequency of peritoneal tissue and organ invasion was 50.9% in the posterior pancreas, 39.8% in the superior mesenteric vein, 29.3% in the portal vein, and 23.8% in the superior mesenteric artery. The duodenum was 21.1%, the bile duct was 15.3%, the transverse colon was 8.9%, the stomach was 8.7%, and the splenic vein was 5.6%.
(3) Lymphatic metastasis: Lymphatic metastasis is the most important metastatic pathway in early pancreatic cancer. The lymph node metastasis rate of pancreatic head cancer is 65%-72%, which occurs in the pylorus, the back of the pancreas, the front of the pancreas, the superior mesenteric vein, the parahepatic artery, and the hepatic duodenal ligament lymph node. There is no direct relationship between lymph node metastasis rate and tumor size and peripancreatic invasion. About 30% of small pancreatic cancers have lymph node metastasis, and a few can have lymph node metastasis. Nagai et al studied 8 cadaveric specimens of early pancreatic cancer. Four of the T1 patients had lymph node metastasis and 4 had lymph node metastasis in T2. The lymph node metastasis rate of each group of pancreatic head cancer was: No. 13a, 13b was 30% to 48%, No. 17a, 17b was 20% to 30%, No. 12 was 20% to 30%, No. 8, 14a 14b, 14c, and 16 are 10% to 20%. Pancreatic body and tail cancer mainly metastasize to the pancreatic spleen lymph node group, and can also invade the stomach, liver, abdomen, mesentery, aorta, and even the mediastinum and parabronchial lymph nodes, but the supraclavicular lymph nodes are not often involved.
(4) Neurotransmission: In advanced or advanced pancreatic cancer, it is often accompanied by nerve infiltration of the extra-pancreatic plexus behind the pancreas. The spread along the plexus is a unique metastasis of pancreatic cancer. The cancer cells can directly destroy the neurotransmitter or enter The perivascular membrane is invaded into the interstitial space of the nerve bundle and spreads along the gap; or it penetrates into the outer part of the nerve bundle through the weakness of the tunica to form a new metastasis. The neurotransmission of pancreatic head cancer occurs mostly in the anterior and posterior pancreatic head, the peritoneal trunk, the common hepatic artery, the splenic artery and the superior mesenteric artery, which constitute the main way of retroperitoneal infiltration and also the main cause of residual peritoneal tumor tissue. The lymphatic vessels around the retroperitoneal nerve are infiltrated and cause persistent back pain, which is clinically important. The plexus metastasis is parallel with the infiltration of the parotid tissue and the degree of arterial infiltration, and is closely related to tumor size. According to statistics, T1 tumors do not see extra-pancreatic plexus infiltration, while T3 tumors have a 70% infiltration of extra-pancreatic plexus.
(5) blood transfer and implant metastasis: the main metastasis mode of most advanced pancreatic head cancer, and pancreatic and tail cancer can have spleen vascular erosion in the early stage. The most common blood transfer is through the portal vein to the liver. The liver passes through the veins to the lungs and then to the tissues of the adrenal gland, kidney, spleen and bone marrow. About 2/3 of the cases at the time of autopsy had liver metastases, especially in the pancreas and tail cancer. Pancreatic cancer is also often spread in the abdominal cavity and small omentum for planting metastasis.
6. Pancreatic cancer Advanced pancreatic cancer to the late stage Although the pancreatic tissue has been extensively destroyed, but diabetes is very rare, because islet cells can remain intact for a long time, and even more normal proliferation. Occasionally, cancers derived from pancreatic acinus can secrete large amounts of lipase, which can cause extensive necrosis of adipose tissue in the subcutaneous or intramedullary bone. Sometimes pancreatic cancer can be accompanied by extensive thrombophlebitis in the body.
Malignant tumors are multi-factorial and have undergone multiple stages of complex pathological processes. In recent years, the development of molecular biology technology has deepened the understanding of the molecular mechanisms of malignant tumors and their evolution, prompting people to explore the nature of pancreatic cancer from the molecular level. And gradually formed a molecular pathology discipline. Existing studies have found that pancreatic cancer involves the activation of proto-oncogenes and the inactivation of tumor suppressor genes. The activation of proto-oncogene K-ras is as high as 90% in pancreatic cancer, which is considered to be an independent molecular event leading to pancreatic cancer. Other genes such as inhibition The oncogenes P53, P16, PTEN, and BRCA2 are inactivated to varying degrees in pancreatic cancer tissues.
symptom:
Pancreatic cancer has no specific initial symptoms and no very specific signs. The clinical manifestations depend on the location of the cancer, the course of the disease, the presence or absence of metastasis, and the involvement of adjacent organs. Its clinical features are short duration of the disease, rapid development of the disease and rapid deterioration. The most common is the upper abdominal fullness discomfort and pain. If the middle-aged person over 40 years old complains of upper abdominal symptoms, in addition to considering hepatobiliary and gastrointestinal diseases, the possibility of pancreatic cancer should be considered. Although there is conscious pain, tenderness is not common to all patients. If there is tenderness, it is consistent with the site of conscious pain.
1. Abdominal pain Pain is the main symptom of pancreatic cancer, and whether the cancer is located in the head or tail of the pancreas. 60% to 80% of patients present with upper abdominal pain, and 85% of these patients with pain have been inoperable or have advanced. Pain is generally not related to diet. At first, most of them are mild, and persistent pain is gradually worsened. Because of the different sites of cancer and pain, abdominal pain can be diverse. The degree is from fullness discomfort, dull pain and even severe pain. There is radiation pain, pancreatic head cancer is mostly to the right side, while body tail cancer is mostly radiated to the left side. Low back pain predicts a later stage and poor prognosis. Pancreatic cancer can enlarge the pancreas due to cancer, compress the pancreatic duct, cause obstruction, dilatation, distortion and pressure increase of the pancreatic duct, causing persistent or intermittent pain in the upper abdomen. Sometimes combined with pancreatitis, causing visceral neuralgia. The nerve impulse is transmitted through the splanchnic nerve to the left and right T6～T11 sympathetic ganglia, so the early stage of the lesion often presents a wide range of mid-upper abdomen, but it is difficult to locate and the nature is vague, full of discomfort, dull pain or dull pain, and often eaten. After 1 to 2 hours, the weight is increased, so fear of eating to reduce the pain caused by eating. Less common is paroxysmal upper abdominal pain, and progressively worse, even unbearable, this is more common in early pancreatic head cancer with pancreaticobiliary obstruction, due to increased consumption of bile and pancreatic juice due to drinking or eating greasy food, Thereby, the pressure in the biliary tract and the pancreatic duct is suddenly increased. Pancreatic blood vessels and nerves are very rich, and adjacent to the retroperitoneal nerve plexus, so when the lesions expand and metastasize affect the peritoneum, pancreatic head cancer can cause right upper quadrant pain, pancreatic body tail cancer is left, and sometimes can also involve the whole abdomen. Low back pain is common, and the high-grade back pain is more severe in the advanced stage, or limited to the double-ribbed band, suggesting that the cancer is transferred along the nerve sheath to the retroperitoneal plexus. The abdominal pain of typical pancreatic cancer is often aggravated when lying on the back, especially at night, forcing the patient to sit up or bend forward and bend the knee to relieve the pain. Sometimes the patient often turns to sleep at night, possibly due to cancer infiltration and compression of the celiac plexus. Caused.
In addition to the pain in the middle or upper left abdomen and upper right abdomen, a few cases complained of left and right lower abdomen, umbilical or total abdominal pain, and even testicular pain, which is easily confused with other diseases. When a cancer involves the visceral capsule, peritoneum, or retroperitoneal tissue, there may be tenderness at the corresponding site.
2. Astragalus jaundice is an important symptom of pancreatic cancer, especially cancer of the head of the pancreas. Astragalus is obstructive, accompanied by urinary deep yellow and clay-like stools, which are caused by invasion or compression of the lower end of the common bile duct. Astragalus is progressive, although it can be slightly fluctuating, but it cannot be completely resolved. The temporary relief of jaundice is related to the regression of inflammation around the ampulla in the early stage. In the late stage, the jaundice produced by the ampullary tumor is more likely to fluctuate due to the collapse of the tumor at the lower end of the common bile duct. Pancreatic body and tail cancer appear jaundice when it affects the head of the pancreas. Some patients with pancreatic cancer have jaundice in the late stage due to liver metastasis. About 1/4 of patients with intractable skin itching are often progressive. Although it is currently believed that the occurrence of itching in obstructive jaundice may be related to the accumulation of bile acid in the skin, a small number of patients without jaundice or mild jaundice may also have symptoms of itchy skin.
Nearly half of the patients have access to the enlarged gallbladder, which may be associated with obstruction of the lower biliary tract. Clinically, obstructive jaundice with gallbladder enlargement and no tenderness is called Courvoisier sign, which has diagnostic significance for pancreatic head cancer, but the positive rate is not high. Such as the original chronic gallbladder inflammation, the gallbladder can not be swollen, laparotomy and laparoscopy often show gallbladder has been swollen, but no clinical signs. Therefore, the gallbladder can not rule out pancreatic cancer. About 50% of patients have liver enlargement due to cholestasis and cancer metastasis.
In the past, the diagnosis of pancreatic cancer often used painless jaundice as the first or necessary symptom of pancreatic cancer. The occurrence of jaundice is an important basis for the diagnosis of pancreatic cancer, so it often loses the opportunity of early diagnosis and surgery. However, painless jaundice is still the most common symptom of pancreatic cancer. About 50% of patients with this symptom have the opportunity to undergo radical surgery. The appearance of jaundice in the morning and evening is closely related to the location of cancer, and jaundice often occurs in cancer of the head of the pancreas. Astragalus may have fluctuations, manifested as complete or incomplete obstructive jaundice. Carcinomas in the tail of the body or away from the biliary pancreatic duct may cause jaundice due to lymph node metastasis to the extrahepatic bile duct or adhesion or buckling near the bile duct.
3. The most common symptoms of digestive tract are loss of appetite, followed by nausea and vomiting. There may be diarrhea or constipation or even nausea. Diarrhea is often steatorrhea. Loss of appetite and obstruction of the lower common bile duct and pancreatic duct are blocked by the tumor, and bile and pancreatic juice cannot enter the duodenum. Obstructive chronic pancreatitis of the pancreas leads to pancreatic exocrine dysfunction, which inevitably affects appetite. A small number of patients develop obstructive vomiting because of tumor invasion or compression of the duodenum and stomach. About 10% of patients have severe constipation due to frequent eating. In addition, about 15% of patients, due to pancreatic exocrine dysfunction caused by diarrhea; steatorrhea is a late manifestation, is a unique symptom of pancreatic exocrine dysfunction, but rare. Pancreatic cancer can also occur in upper gastrointestinal bleeding, which is characterized by hematemesis, melena or only fecal occult blood test, the incidence rate is about 10%. The cause of gastrointestinal bleeding is that the adjacent hollow organs such as the duodenum or the stomach are invaded and broken, and the ampullary cancer itself is more prone to bleeding. The splenic vein or portal vein is embolized by tumor invasion, followed by portal hypertension, which causes occasional rupture of esophageal and gastric varices.
4. Weight loss, fatigue, pancreatic cancer and other cancers are different, often at the beginning, there is weight loss and fatigue. This symptom has nothing to do with the tumor site. In digestive tract tumors, the weight loss caused by pancreatic cancer is the most prominent. After the onset, there is obvious weight loss in the short term, and the weight loss can reach more than 30 kg, accompanied by symptoms such as weakness and weakness. Some patients first show progressive wasting before other symptoms have emerged. The reason for the weight loss is due to loss of appetite, reduced eating, or appetite, but it is not willing to eat due to upper abdominal discomfort or abdominal pain after eating. In addition, pancreatic exocrine dysfunction or pancreatic juice is blocked by pancreatic ductal outflow, affecting digestion and absorption, and also has a certain relationship.
5. The abdominal mass of the pancreas is deep in the posterior abdomen. The abdominal mass is the result of the development of the cancer itself. It is located at the location of the lesion. If the mass has been touched, it is mostly in the advanced or advanced stage. Chronic pancreatitis can also touch the mass, which is difficult to distinguish from pancreatic cancer. Pancreatic cancer can cause dilatation of the bile duct and gallbladder in the liver and the cholestasis of the liver, so the swollen liver and gallbladder can be touched. The shape of the cancer is irregular, the size is different, the quality is firm and fixed, and there is obvious tenderness. Because the head lesions of the pancreas often have other obvious symptoms before the appearance of the mass, the abdominal mass caused by this disease is relatively more common in the tail and tail cancer. When the cancer changes to the abdominal aorta or splenic artery, a whirlpool vascular murmur can be heard in the umbilical cord or in the left upper abdomen. Sometimes the abdominal mass is swollen liver and gallbladder, and pancreatic cancer is complicated by pancreatic cyst.
6. Symptoms of diabetes A small number of patients initially manifested as symptoms of diabetes, that is, before the appearance of major symptoms of pancreatic cancer such as abdominal pain, jaundice, etc., the first diabetes, and the accompanying weight loss and weight loss were mistaken for the performance of diabetes. Instead of considering pancreatic cancer, patients with long-term diabetes may have worsened their condition recently, or the treatment measures that can control the disease for a long time become invalid, indicating that pancreatic cancer may occur on the basis of the original diabetes. Therefore, if diabetic patients have persistent abdominal pain, or sudden onset of diabetes in the elderly, or the original diabetes, and suddenly the condition suddenly worsens, you should be alert to the possibility of pancreatic cancer.
7. Patients with advanced pancreatic cancer with thrombophlebitis have migratory thrombophlebitis or arterial thrombosis. If there is deep vein thrombosis of the lower extremity, it can cause edema of the affected lower limb. The autopsy data showed that the incidence of arterial and venous thrombosis was about 25%, which seemed to be more common in the pancreas and tail cancer. Spain believes that cancer may secrete some substance that promotes thrombosis. For example, portal vein thrombosis can cause varicose veins or ascites in the lower esophagus, and splenic vein thrombosis can cause splenomegaly. These patients are prone to acute upper gastrointestinal bleeding.
8. Psychiatric symptoms Some patients with pancreatic cancer can express mental symptoms such as anxiety, impatience, depression, and personality changes. The mechanism of its occurrence is still unclear. It may be due to the symptoms of refractory abdominal pain, inability to sleep, and inability to eat, which may easily affect the mind and mood.
9. In addition, patients often complain of fever and obvious fatigue. There may be high fever or even chills and other symptoms like cholangitis, so it is easy to be confused with cholelithiasis and cholangitis. Of course, when there is biliary obstruction and infection, there may be chills and high fever. Some patients may have small joint redness, swelling, pain, heat, subcutaneous fat necrosis around the joints and unexplained testicular pain. The supraclavicular, axillary or inguinal lymph nodes can also be enlarged and hardened by pancreatic cancer metastasis.
Ascites usually occurs in the late stage of pancreatic cancer, mostly caused by peritoneal invasion and spread of cancer. The traits of ascites may be bloody or serous, and hypoproteinemia of advanced cachexia may also cause ascites. However, one thing to note is that pancreatic cancer complicated with pancreatic cyst rupture forms pancreatic ascites. It is characterized by a rapid rise after water release, an increase in amylase in ascites, and high protein content. At this time, ascites does not mean the late stage of pancreatic cancer, so don't give up the chance of surgery.
Early detection and early diagnosis of pancreatic cancer are important factors in determining the therapeutic effect. Early patients with pancreatic cancer have no specific symptoms, and the first symptoms are easily confused with gastrointestinal and hepatobiliary diseases. Because some clinicians have insufficient understanding of the early symptoms of pancreatic cancer, or have incomplete collection of medical history and analysis of one-sided, often missed or misdiagnosed. When you have jaundice or a bump that has been touched, you may seek medical or surgical treatment. Most patients have lost the chance of surgery or radical resection.
Based on the characteristics of the onset of pancreatic cancer patients, it is currently believed that: 40 years of age or older, no induced abdominal pain, fullness discomfort, loss of appetite, weight loss, fatigue, diarrhea, back pain, recurrent pancreatitis or sudden diabetes without family history Should be considered as a high-risk group of pancreatic cancer, should be alert to the possibility of pancreatic cancer.
Those who have the following clinical manifestations should pay attention:
1. Unexplained upper abdominal discomfort or abdominal pain, the position is deep, the nature is also vague, and the relationship with the diet is different.
2. Progressive weight loss and fatigue.
3. Diabetes or diabetes that cannot be explained suddenly increases.
If there is intractable upper abdominal pain, the pain is emitted to the lower back, obvious at night, and aggravated when lying on the back, and the pain can be relieved by twisting or leaning forward, which is highly suggestive of pancreatic cancer, and further laboratory and other auxiliary examinations are needed.
B-ultrasound, CT, MRI, ERCP, PTCD, angiography, laparoscopic examination, tumor marker determination, oncogene analysis, etc., are quite helpful in determining the diagnosis and judging whether pancreatic cancer can be surgically removed. However, surgeons still cannot ignore the patient's medical history and comprehensive physical examination. To assess the safety of patients undergoing radical surgery, detailed medical history and careful physical examination are more important than single cardiac and pulmonary function tests. The choice of which test should be targeted and targeted, blindly using all diagnostic tools, is not only a waste of time and time, but also unsafe for the patient. In general, B-ultrasound, CA19-9, and CEA can be used as screening tests. Once pancreatic cancer is suspected, CT examination is necessary. The patient has jaundice and is more serious. If the diagnosis cannot be confirmed after CT examination, ERCP and PTCD can be selected. If the drainage is successful, patients with severe jaundice can be delayed for 1 to 2 weeks. The diagnostic value of MRI for pancreatic cancer is not superior to CT. The choice of angiography and/or laparoscopic examination is clinically significant in order to avoid unnecessary surgical exploration when it has been diagnosed as pancreatic cancer.
Fine needle aspiration cytology is necessary for patients with pancreatic cancer or periampullary cancer who cannot be surgically removed and who have no indications for palliative surgery. It is necessary to perform fine needle aspiration to obtain cytological examination data when chemotherapy and radiotherapy are planned. This is generally not the case for patients who have a surgical resection. Because fine needle aspiration may cause the spread of cancer cells in the abdominal cavity.
diagnosis:
Pancreatic cancer should be differentiated from stomach diseases, jaundice hepatitis, cholelithiasis, cholecystitis, primary liver cancer, acute pancreatitis, ampullary carcinoma, gallbladder cancer and other diseases.
1. A variety of chronic stomach diseases: stomach disorders can have abdominal pain, but abdominal pain is more related to diet, jaundice is rare, X-ray barium meal examination and fiber gastroscopy is not difficult to identify.
2. Scutellaria type hepatitis: It is easy to be confused at the beginning, but there is a history of contact with hepatitis. After dynamic observation, serum transaminase increases at the beginning of jaundice, and jaundice gradually subsides after 2 to 3 weeks, and serum alkaline phosphatase is not high. .
3. Cholelithiasis, cholecystitis: abdominal pain is paroxysmal cramps, fever often occurs in acute attacks and white blood cells increase, jaundice often disappears or fluctuates in the short term, no significant weight loss.
4. Primary liver cancer: often history of hepatitis or cirrhosis, serum alpha-fetoprotein positive, first hepatomegaly, jaundice appeared later, abdominal pain does not change due to body position changes, ultrasound and radionuclide scan can be found in liver Positional lesions.
5. Acute and chronic pancreatitis: acute pancreatitis has a history of overeating, rapid onset of illness, elevated white blood cells, blood urease amylase. Chronic pancreatitis can present with pancreatic masses (pseudocysts) and jaundice, which resemble pancreatic cancer, and deep pancreatic cancer that compresses the pancreatic duct can also cause chronic inflammation of the tissues surrounding the pancreas. Abdominal X-ray film found that pancreatic calcification is helpful for the diagnosis of chronic pancreatitis. However, some cases are sometimes difficult to identify after various examinations. Pancreatic biopsy can be performed with a very fine needle in laparotomy to help identify.
6. Peripheral cancer of the ampulla: The cancer around the ampulla is rarer than that of the pancreatic head cancer. The disease starts suddenly and there are symptoms such as jaundice, weight loss, itchy skin, and gastrointestinal bleeding. The ampullary carcinoma begins as a polypoid, and the cancer itself is soft and elastic, so the jaundice caused by it is often fluctuating; abdominal pain is not significant, often accompanied by cholecystitis, repeated chills, fever more common. However, the identification of the two is still difficult, combined with ultrasound and CT to improve the diagnosis rate. The resection rate of ampullary carcinoma is above 75%, and the 5-year survival rate is higher than that of pancreatic head cancer.
All of the above symptoms need to be differentiated from other diseases of the digestive tract, especially chronic pancreatitis, especially the identification of abdominal pain, because both have abdominal pain and weight loss, fatigue and so on. Chronic inflammation of the pancreas has been diagnosed and treated as a cancer, and cancer has been misdiagnosed as inflammation, so other tests should be combined to identify these symptoms.
In the differential diagnosis, the early symptoms of pancreatic cancer can be confused with common hepatobiliary and gastrointestinal diseases. If the symptoms are not relieved or gradually worsened after symptomatic treatment, further examination should be carried out for pancreatic cancer to exclude or early detection. Pancreatic cancer.
If there is abdominal pain or fullness discomfort, it should be differentiated from chronic gastritis, chronic cholecystitis, chronic pancreatitis. When jaundice occurs, the nature of jaundice should be distinguished first. If B-ultrasound does not expand the intrahepatic bile duct, the "three anti-" and liver function should be checked to rule out hepatitis. If the extrahepatic bile duct obstruction is to be differentiated from the lower common bile duct stones, benign biliary stricture, chronic pancreatitis, ampullary carcinoma, cholangiocarcinoma, CT and ERCP can be examined to determine the extent of biliary dilatation and the location and nature of the lesion. . If a pancreatic mass is present, it should be differentiated from retroperitoneal tumor, renal tumor, gastric cancer, and pancreatic lymph node enlargement.
1. Chronic pancreatitis with chronic upper pancreas full of discomfort, dyspepsia, diarrhea, anorexia, weight loss, etc. as the main clinical manifestations of chronic pancreatitis must be differentiated from pancreatic cancer. Chronic pancreatitis often presents a chronic course of disease, with a history of repeated acute attacks, diarrhea (or fat sputum), and jaundice is rare, and the condition is not progressively worsened and worsened. For example, X-ray abdominal plain film or B-mode ultrasound and CT examination found that the calcification point of the pancreas helps the diagnosis of chronic pancreatitis. Sometimes identification is still difficult, even in the surgery, the pancreas of chronic pancreatitis can be hard as a stone, or nodular changes. If there is still difficulty in identifying the laparotomy, further deep needle aspiration or pancreatic biopsy should be used for identification.
2. The anatomical location of the common bile duct, Vater's ampulla and pancreatic head of the common bile duct cancer, the clinical manifestations of the three cancers are very similar, but there are significant differences in surgical efficacy and prognosis, so the differential diagnosis is very Necessary, but it should be clearly pointed out that the incidence of cancer around the ampulla is far less common than pancreatic cancer. Table 5 shows the differential diagnosis of pancreatic head cancer, ampullary carcinoma, common bile duct cancer, and common bile duct stones.
complication:
Can be complicated by bile duct obstruction, duodenal obstruction and other symptoms. Tumor-induced splenic venous obstruction can cause splenomegaly and localized portal hypertension, causing gastric bleeding or esophageal varices.
1. Weight loss The most obvious weight loss caused by pancreatic cancer, obvious weight loss in the short term after the onset, weight loss can reach more than 30 kg, accompanied by weakness and weakness.
2. Symptomatic Diabetes A small number of patients initially develop symptoms of diabetes. Therefore, if diabetic patients have persistent abdominal pain, or sudden onset of diabetes in the elderly, or the original diabetes, and suddenly the condition suddenly worsens, you should be alert to the possibility of pancreatic cancer.
3. Patients with advanced pancreatic cancer with thrombophlebitis have migratory thrombophlebitis or arterial thrombosis.
4. Psychiatric symptoms Some patients with pancreatic cancer can express mental symptoms such as anxiety, impatience, depression, and personality changes.
treatment:
(a) treatment
To date, this refractory tumor of pancreatic cancer still plagues oncologists and foreign scientists. Around this disease, various disciplines in medicine are looking for new treatments, but the current principle of treatment is still surgical treatment. The main combination of radiotherapy and chemotherapy and other comprehensive treatment.
1. Surgical treatment of pancreatic cancer is the only possible cure. Surgical methods include pancreaticoduodenectomy, enlarged pancreaticoduodenectomy, pyloric pancreaticoduodenectomy, and total pancreatectomy. However, due to the early diagnosis of pancreatic cancer, the surgical resection rate is low, and the five-year survival rate is also low.
For pancreatic cancer with obstructive jaundice and can not be removed, gallbladder or bile duct jejunostomy can be used to reduce jaundice and improve the quality of life of patients. The stent can also be placed under the endoscope to relieve obstruction.
(1) Preparation before surgery: Good or proper cardiopulmonary and renal function before surgery is required. Although patients often have weight loss before surgery, their nutritional status must ensure the safety of surgery. Enteral nutrition should be given when albumin is less than 3 g/dl or during waiting time before surgery. When the tumor occurs in the head of the pancreas or has a pancreatic duct obstruction, trypsin may be appropriately supplemented. Obstructive jaundice can impair liver, kidney and immune function. There is still debate about whether to support or drain the bile duct before surgery. Some investigations have shown that routine bile duct support before surgery to reduce jaundice does not reduce complications and mortality. Therefore, endoscopic or other methods of reducing the yellowness before surgery are not recommended, as long as early jaundice can be treated as early as possible. Surgery to fight for early treatment opportunities. However, in order to reduce biliary pressure and reduce the chance of cholangitis, and to ensure the reduction of postoperative complications, especially renal failure, proper application of endoscopic biliary support is necessary. This support is best to use a plastic stent of 10F or larger, and the expanded metal stent is better for the treatment of patients with unresectable tumors, but should not be used for patients who are estimated to be operable. Metal stents can cause serious problems. The inflammatory response eventually eventually penetrates into the bile duct wall, creating a complex procedure. Progressive tumors and larger tumors should not be used as contraindications for radical surgery. In fact, in the main medical centers in the United States, most of the tumors removed by Whipple surgery are in the range of 3 to 5 cm. The situation in China has not yet been fully verified. The age factor of the patient should be considered in combination with the patient's specific conditions and the surgeon's technical and medical conditions. It is not possible to perform radical surgery at an advanced age.
(2) Surgical treatment and its management and monitoring:
1 to determine the indications and timing of surgical resection: to determine whether there are indications and timing of resection, not only through physical examination and imaging diagnosis before surgery, many times in the final decision in the surgery, so need to have a certain in principle. Usually liver or retroperitoneal metastases, or metastatic lymph nodes are not included in the scope of the Whipple surgical resection, such as distant lymph node metastasis, etc., no resection is performed. At the beginning of the investigation, the abdominal cavity and its contents should be carefully examined for biopsy of any suspicious metastatic area. When the diagnosis of frozen sections is obtained, the possibility of surgical resection has been determined. In the absence of distant metastases, it is also necessary to estimate whether the tumor invades major macrovascular structures, such as the superior mesenteric artery and vein, the celiac artery, and the hepatic artery, especially the superior mesenteric vein, often ending the surgery.
2 pancreaticoduodenectomy (Whipple surgery): pancreaticoduodenectomy is the main surgical treatment of pancreatic cancer. The first case of periampullary cancer resection was performed by German surgeon Kausch in two separate phases in 1909. In 1935, Whipple performed the procedure in a similar manner and improved to a one-stage resection in 1942. After resection, the anastomotic sequence was bile, pancreas, stomach and jejunum anastomosis, which formed today's pancreaticoduodenectomy. . In 1944, Child anastomosis of the jejunal stump and the end of the pancreas. Then, the jejunal end-to-side anastomosis and the end-to-side anastomosis of the jejunum were performed. The pancreas, gallbladder, stomach and jejunum were anastomosed. The Child method and the Whipple method are currently more common surgical methods. At present, the lowest mortality rate of this operation at home and abroad is ≤ 2%. The main processes of pancreaticoduodenectomy are as follows:
A. Routine exploration: Check the abdominal cavity for distant metastasis and cancer invasion, and initially determine whether it can be removed. Progressive pancreatic head cancer sometimes infiltrates the transverse mesenteric root to form a cancerous contracture (or cancer umbilical), which means that the superior mesenteric vein is infiltrated by cancer. If there is no preparation and condition for vascular resection, general exploration should be abandoned and palliative should be given. Sexual surgery. The feeling of hardening when the head of the pancreas is touched needs to be differentiated from the calcification of pancreatitis. Also need to pay attention to the contents of the hepatoduodenal ligament, including the presence or absence of tumors and stones in the common bile duct; when touching the duodenum, pay attention to the medial nipple of the lower part of the lower nipple. Disconnect the gastric collateral ligament, cut the loose tissue between the transverse mesenteric and the head of the pancreas, reveal the descending part of the duodenum and the front of the pancreatic head. At this time, a biopsy fine needle can be used for multi-point puncture to extract tissue specimens for pathological cytology. It is necessary to pay attention to the direction of the needle and try to insert the needle into the front of the pancreas to avoid damage to the main pancreatic duct. As for the removal of local living tissue for frozen section examination, should be cautious, because there are often changes in chronic pancreatitis around the mass of pancreatic cancer, such as improper access to misdiagnosis or missed diagnosis, such as cancer can not be removed, there is still pancreatic leakage , the risk of bleeding and abscesses.
B. Separation and exploration: cut the lateral peritoneum of the descending duodenum, cut the liver and stomach ligament and the duodenal ligament, extend to the level of the duodenum and even the root of the transverse mesenteric, and bluntly separate the loose tissue after the pancreas. The duodenum and pancreatic head are turned to the left side, and the duodenum and pancreatic head are fully released from the retroperitoneum. The cancer and the vena cava, the superior mesenteric artery and the vein, the celiac artery and the hepatic artery are examined. There is no violation, especially the invasion of the portal vein. The portal vein and superior mesenteric vein should be separated without significant resistance behind the pancreas. This step is the key to the final decision whether or not to perform radical surgery. However, although it can be completely separated, the cancer is infiltrated and part of the portal vein is found, such as the right posterior side. Wall, at this time, it is often necessary to prepare partial portal vein resection and artificial vascular anastomosis.
C. Resection of the lesion and surrounding tissue: removal of the gallbladder, cutting off the common hepatic duct or common bile duct, such as pancreatic head cancer, the bile duct must be removed in the lower part of the common hepatic duct; the distal stomach is removed, the scope depends on the age of the patient and the presence or absence of gastric acid More than, up to 1/2 of the distal end of the stomach, the greater omentum should be treated according to the requirements of radical gastrectomy; the pancreas is cut, the range is generally in the left edge of the celiac artery, while the ampullary carcinoma or some benign lesions can be in the pancreatic neck As a cut line. When cutting the pancreas, suture at the edge of the pancreas at four points to prevent hemorrhage of the pancreatic transverse blood vessels. The pancreas should be cut open, the pancreatic duct should be removed and carefully protected, and a silicone tube suitable for the diameter of the original pancreatic duct should be inserted and used. The absorption line is sutured in the pancreatic duct for 1 to 2 needles to fix the silicone tube, and attention is paid to ligating some veins on the back of the pancreas. The Treitz ligament was confirmed at the left side of the mesentery, the superior mesenteric artery was touched, the first and second branches of the jejunal artery were ligated, the jejunum was cut 10 cm below the Treitz ligament, the proximal end was closed, and the distal end was fitted with the pancreas. . Finally, the pancreatic uncinate process is mainly treated. Here, a number of small veins are introduced into the superior mesenteric vein. They must be carefully cut one by one and then cut off to avoid damage to the superior mesenteric vein and massive bleeding. The pancreatic head uncinate process should be completely removed, and the lymph nodes around the mesenteric arteries and veins should be cleared.
D. Reconstruction of the digestive tract: There are mainly Child method in the order of pancreatic intestine, biliary intestine and gastrointestinal anastomosis and Whipple method in the anastomosis of the biliary, pancreatic and intestinal. At present, the Child method is more popular. The pancreaticojejunostomy is performed by embedding the end of the pancreas and the jejunum, and the whole layer is sutured with the muscle layer. Sometimes the pancreatic section is wider than the jejunal cavity. In order to prevent the blood circulation disorder of the intestinal wall caused by hard insertion, affecting the healing of the anastomosis, the upper and lower margins of the pancreas should be removed or the lower edge wedge should be removed to remove the pancreas. In. Conventional methods for biliary anastomosis still require the placement of a T-tube, the size of which should be appropriate; not too large or too small. Others use a catheter to support it. At the end of the stomach jejunum anastomosis, generally 40 ~ 50cm below the anastomosis of the pancreatic intestine, in the anterior stomach of the colon and the jejunum anastomosis. For enteral nutrition, it is also necessary to make intestinal fistula. The nutrient tube should be fed into the jejunum under the anastomosis outlet, and the stomach tube should also go deep into the input section. The Whipple method is to perform the biliary anastomosis after the distal end of the jejunum is closed and pulled to the colon. There are two types of pancreaticojejunostomy: one is the end-to-side anastomosis of the pancreatic duct, which is suitable for the obvious enlargement of the pancreatic duct; the other is the intra-jejunal transplantation of the pancreatic duct. This method involves inserting a pancreatic duct into the pancreatic duct and the pancreas. The tube is fixed. Regardless of the Child method or the Whipple method, in order to prevent the occurrence of pancreatic fistula, it is advocated that a catheter drainage pancreatic juice is placed in the main pancreatic duct.
3 modified pancreaticoduodenectomy:
A. Preserving the pyloric pancreaticoduodenectomy: Because standard pancreaticoduodenectomy often has weight loss and nutritional disorders, many surgeons seek to improve the pyloric pancreaticoduodenium This is the case with resection. This procedure preserves the function of gastric storage and digestion, promotes digestion, prevents dumping syndrome, and helps improve nutrition after surgery. Although the degree of surgery has been reduced, it has not reduced the survival rate after surgery, and has been adapted to the recent improvement in the quality of life of the opponents. Therefore, it has been promoted since the 1970s. However, people are most concerned about whether this improvement affects the degree of radical cure and long-term survival of malignant tumors. Compared with standard pancreaticoduodenectomy, the nutritional status and degree of radical resection of patients after surgery, although there are many reports in the literature, there is still no convincing information to draw conclusions on this issue. Because there is a key problem that patients cannot be randomly selected to perform these two operations, it is often determined according to the specific circumstances of the patient. It is generally believed that benign lesions around the head of the pancreas, ampullary carcinoma, tumors of the head of the pancreas with a low degree of malignancy, and cancer have not yet infiltrated the pylorus and the duodenum. Malignant lesions need to cut off the right gastric artery to facilitate lymph node clearance, which may affect the blood supply of the gastric pylorus and duodenal bulb. Some patients have delayed gastric emptying after surgery, so gastric fistula should be added during surgery. To alleviate the pain caused by the patient's long-term intestine retention after surgery.
B. Expanded pancreaticoduodenectomy: Pancreatic cancer is mostly adenocarcinoma of the pancreatic duct epithelium, and lymph node metastasis is an important pathway for pancreatic cancer metastasis. Metastasis and spread of pancreatic cancer In addition to lymph node metastasis and infiltration of cancer into surrounding tissues, diffusion along the nerve bundle is another way of metastasis of pancreatic cancer. Therefore, the so-called enlarged radical resection should clear the celiac artery in addition to clear lymph nodes. The superior mesenteric artery and the nerve plexus next to the abdominal aorta. Complete resection of the peripheral nerve plexus on the mesentery can lead to intractable diarrhea. In addition, the soft tissue around the pancreas needs to be removed, so all the operations include removal of all or most of the pancreas, the hepatic artery and the superior mesenteric artery, and the soft tissues and lymph nodes around it, the biliary tract, the duodenum, and the part of the jejunum. , stomach and whole transverse mesenteric membrane. Due to the high incidence of early complications, high operative mortality, and unsatisfactory long-term survival rate, it has not been widely used in Europe, America, and China. Even in Japan, where most scholars advocate this expansion, there are still many scholars. This holds an objection.
4 postoperative complications and prevention:
A. Pancreatic fistula: often fatal and the most common complication after pancreatectomy. It usually occurs 5 to 7 days after surgery. The patient has abdominal distension, abdominal pain, high fever, and increased peritoneal drainage fluid. For example, the amylase in the peritoneal drainage fluid can be determined as pancreatic fistula. Non-surgical treatment is generally used, which is difficult to repair due to surgery. Different methods of digestive tract reconstruction are important for preventing the occurrence of pancreatic fistula. Affiliated Hospital of China Medical University summarized 118 cases of pancreaticoduodenectomy, and 10 of 42 cases with Whipple method developed pancreatic fistula, of which 6 died. In the case of Child method, 2 cases of pancreatic fistula occurred in 2 cases, 1 case death. The incidence of Child's pancreatic fistula is significantly lower than the Whipple method. At present, the Whipple method is rarely used in the country to reconstruct the digestive tract. During the operation, attention should be paid to the strictness of pancreaticojejunostomy, especially the placement and drainage of the main pancreatic duct. The drainage of the abdominal cavity should be sufficient. It is best to use a pan-type drainage tube and, if necessary, a double-chamber drainage tube. Early use of drugs that inhibit the secretion of pancreatic juice, such as somatostatin and its derivatives.
B. Abdominal hemorrhage: divided into primary and secondary. Primary hemorrhage is often in the early stage of surgery, mostly blood flow from the drainage tube, mostly due to incomplete hemostasis or coagulation dysfunction during surgery; should be closely observed, immediate infusion and blood transfusion, application of hemostatic drugs, if the condition does not improve, should Immediate open exploration. Secondary hemorrhage usually occurs 1 to 2 weeks after surgery, mostly due to the infiltration of pancreatic pancreatic juice into the abdominal cavity, digesting and corroding surrounding tissues, and should be actively treated with non-surgical treatment; if there is active bleeding, angiography may be considered, but sometimes It is still difficult to find the bleeding site, and it is often difficult to succeed in hemostasis. It should be cautious. Primary bleeding can also occur in the margin of the pancreas or jejunum, mainly in the operation of hemostasis, resulting in local bleeding and hematoma after surgery, hematoma compression further makes the anastomotic blood flow poor, resulting in anastomotic or pancreatic Hey, so local bleeding is often associated with various sputum. Close observation of the drainage tube should be performed. If there is persistent bleeding, surgery should be performed immediately. Prevention is mainly to stop bleeding in surgery. In addition, bio-protein glue can be applied around the end of the pancreas and around the anastomosis. On the one hand, hemostasis can be used. On the other hand, there is a suitable adhesion.
C. Gastrointestinal bleeding: Early postoperative bleeding may consider incomplete gastric hemorrhage or coagulopathy. Hemorrhage around 1 week after surgery is considered to be stress ulcer bleeding, which can be treated according to stress ulcer bleeding, and antacids are routinely applied early after surgery.
D. Intra-abdominal infection: It is a serious complication, which is caused by infection of pancreatic fistula, biliary tract or abdominal effusion. Can have abdominal pain and high fever, body consumption, anemia, hypoproteinemia. Strengthen systemic supportive therapy and apply high-efficiency broad-spectrum antibiotics.
E. biliary sputum: less common, once it occurs mainly by smooth drainage, it can generally be cured, poor drainage and peritoneal irritation should be surgically explored.
2. Palliative treatment of pancreatic cancer
(1) indications for surgical palliative surgery: important for palliative care of pancreatic cancer. Because approximately 88% of patients cannot perform radical surgery due to local tumor spread and metastasis, the surgeon must decide which palliative measures to reduce biliary or duodenal obstruction when the primary tumor cannot be removed. In addition, internal surgery is needed to treat jaundice, pain, weight loss, pancreatic insufficiency, and even depression and failure. There is also a medical treatment of biliary stent or drainage failure, or re-obstruction or even cholangitis after placement in the stent. Choosing palliative and yellowing surgery not only requires judgment before surgery, but also the abdominal cavity should be explored in detail after laparotomy. The method and sequence of exploration are the same as pancreaticoduodenectomy. Usually, if the tumor invades the mesenteric root or the portal vein, it is considered unsuitable for radical resection, and palliative surgery is performed. If necessary, fine needle aspiration cytology or biopsy should be performed to confirm that it can be performed.
(2) surgical palliative surgery: for cases that are not suitable for radical surgery, it is often necessary to remove obstructive jaundice, generally using gallbladder jejunostomy, unconditional can do external hemorrhoids (cholesterol fistula or extra-biliary drainage) to reduce yellow Surgery, most patients can relieve symptoms and improve the state of the body in a short period of time. The general survival time is about half a year. There are several main types of palliative and yellowing surgery:
1 gallbladder jejunum anastomosis: gallbladder jejunum anastomosis is to adhere the gallbladder to the jejunum, in order to prevent biliary ascending infection, 15cm under the Treitz ligament routine lateral collateral side anastomosis (Braun anastomosis). This kind of gallbladder jejunostomy has the advantages of easy exposure, convenient anastomosis, short operation time and less complications, and can be used as the preferred surgical procedure.
2 Gallbladder jejunum Roux-en-Y anastomosis: Gallbladder and jejunum Roux-en-Y anastomosis is to cut the jejunum 15 cm below the Treitz ligament, and the distal jejunum is pulled to the gallbladder before or after the colon. The anastomosis between the jejunum and the gallbladder is to suture the jejunal stump, and the end of the gallbladder jejunum can be anastomosis. End-to-end anastomosis can also be used. Although this method is slightly more complicated, there is less chance of a postoperative biliary infection.
If the gallbladder does not expand during surgery, it indicates that bile can not enter the gallbladder. At this time, the jejunum and the common hepatic duct or the jejunum and common bile duct anastomosis should be selected. If the gallbladder jejunostomy is indeed performed, the lateral side of the cystic duct and the common hepatic duct or common bile duct should be added to ensure the bile drainage. If combined with biliary tract infection, gallbladder inflammation and edema is serious, it is advisable to perform gallbladder ostomy.
3 common bile duct jejunostomy: Although the gallbladder jejunal anastomosis is simple, the curative effect is not as good as the common bile duct jejunostomy. The average survival time after biliary jejunostomy was 4.7 to 6.7 months, recurrent jaundice and cholangitis were 1.5% to 64.0%, with an average of 20%. The average survival time after biliary jejunostomy was 5.7 to 9.2 months. Astragalus and cholangitis ranged from 7.3% to 16.6% with an average of 8%. The above situation indicates that the bile duct jejunostomy is better than the gallbladder jejunum. The bile duct (the common bile duct or the common hepatic duct) can be anastomosed with the Roux-en-Y side or end-to-side anastomosis. If the bile duct is dilated (generally greater than 2 cm), the end-to-side anastomosis is preferred. The biliary drainage should be routinely placed to reduce the biliary tract and anastomosis.
4 gastrointestinal, double intestinal anastomosis: pancreatic head cancer often leads to the second segment of the duodenum obstruction, body cancer is easy to cause the fourth segment of obstruction. Pancreatic cancer with obstructive jaundice and duodenal obstruction is suitable for gastrointestinal and biliary double anastomosis. Endoscopy or gastrointestinal X-ray examination should be performed before surgery to determine whether there is any obstruction. This double anastomosis is used when the patient has symptoms or signs of obstruction, or obstruction seen by endoscopy, or when the duodenum is narrowed or compressed during surgery. It is generally not advisable to have a preventive gastrointestinal anastomosis in the absence of obvious signs. Sometimes pancreatic cancer invades the gastrointestinal motility of the retroperitoneum, which will lead to gastrointestinal motility. The clinical manifestation of obstructive symptoms is functional obstruction. If the gastrointestinal anastomosis is performed, it is not only unnecessary, but also ineffective. The surgical method is based on the biliary anastomosis plus the gastric jejunum or Roux-en-Y anastomosis. In other cases, a second-stage gastrointestinal anastomosis is performed after the biliary anastomosis to solve the patient's eating problem.
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 primary treatment, pancreatic cancer is often found late, and the chance of radical cure is lost, so comprehensive treatment of pancreatic cancer is needed. To date, like most tumors, there is no comprehensive treatment plan that is efficient and fully applicable. The current comprehensive treatment is still based on surgical treatment, supplemented by radiotherapy and chemotherapy, and is exploring new ways to combine biological treatment with immunity and molecules.
(1) Radiation therapy: Pancreatic cancer is a tumor that is less sensitive to radiotherapy. Due to the deep position of the pancreas, the surrounding gastrointestinal, liver, kidney, spinal cord and the like are less tolerant to radiation, which is not conducive to radiation therapy of pancreatic cancer. However, in recent years, with intraoperative radiotherapy and the development of treatment plans and multi-field in vitro radiotherapy under the precise positioning of CT, radiotherapy has become one of the main methods in the treatment of pancreatic cancer. Postoperative and inoperable advanced pancreatic cancer, radiotherapy alone had no significant effect on patient survival. Combined radiotherapy and chemotherapy can effectively relieve symptoms, relieve pain, improve quality of life, and prolong survival. Intraoperative radiotherapy can determine the target area under direct vision, making the irradiation site more precise, thus maximally protecting the surrounding normal tissue, but requires special equipment and can only be used for a single irradiation. In recent years, there have been advocates of radiotherapy and chemotherapy before surgery to control the metastasis of tumors.
1 intraoperative radiotherapy: intraoperative radiotherapy with 10 ~ 20 MeV high-energy electron line, fully reveal the tumor tissue, remove the normal tissues such as the surrounding gastrointestinal, accurately align the light-limiting tube to the tumor bed, a large dose of 15 ~ 25Gy, irradiation time 4 to 6min. Intraoperative radiotherapy should include the abdominal aorta, the celiac artery, and the superior mesenteric artery. According to reports at home and abroad, the intraoperative radiotherapy analgesic effect is 60% to 98%, and the median survival time is 3 to 11 months.
2 postoperative external radiotherapy: external radiotherapy started 2 weeks after surgery, 10 MeV X-ray, multi-center irradiation before the abdomen plus abdomen, 180 ~ 200 cGy each time, 3 times a week, dose 4 ~ 6 weeks 40 ~ 60 Gy, can be treated continuously or in stages. Intraoperative and postoperative radiotherapy can reduce the pain of the patient and shrink the tumor. The median survival of patients was 4 to 16 months.
3 precise radiotherapy: In recent years, with the rapid development of computer technology and CT and other imaging technologies, accurate three-dimensional positioning of tumors can be performed. Computer-controlled radiation can accurately illuminate the target tissue without significant damage to surrounding tissues. This stereotactic radiosurgery (SRS), which was first applied to brain surgery, was also applied to pancreatic tissue. In the SRS technique, three-dimensional adaptive radiotherapy (3D-CRT) was first developed. The 3D-CRT enables the dose distribution in the high-dose region to be distributed in three dimensions and consistent with the actual shape of the target region. The latest development is intensity modulated radiation therapy (IPMT). IPMT is to achieve the desired dose at any point in the target zone by changing the intensity of the radiation in the target zone. In fact, it is uneven illumination. The steps are: patient selection→patient fixation→CT/MRI scan→target area and sensitive tissue determination→reverse calculation system→database→treatment plan verification→irradiation dose verification→treatment implementation→summary follow-up. Since the pancreas is located in the retroperitoneum and is relatively fixed in position, it is suitable for such precise radiotherapy. Because IPMT only acts on the tumor tissue to be irradiated, but does not irradiate the surrounding gastrointestinal tissue, it greatly improves the gastrointestinal inflammation caused by the original radiotherapy, and the adverse reactions after radiotherapy are also smaller than the conventional radiotherapy. Much more, and at any time adjust the treatment plan according to CT conditions. Since this is only the technology carried out in the late 1990s, there is no complete clinical analysis report on patient survival rate, but the application has achieved a good start and will be the future development direction of radiotherapy. The disadvantage is that the cost is more expensive than general radiotherapy and the equipment requirements are high. However, with the further development of technology, it will become more and more popular. In order to achieve good results in this treatment, there must be certain prerequisite support. In particular, patients with jaundice should be treated with internal medicine or surgical yellowing, and appropriate nutritional support.
Simple radiotherapy still can not achieve better results, it is best to combine chemotherapy after radiotherapy. The European Organization for Research and Treatment of Cancer (EORTC) recently published a randomized survey showing that fluorouracil was administered at a dose of 4000 cGy for 500 mg/m2, 3 times/d, and after the end of radiotherapy, 2 In the year, the 2-year survival rate was 43% in the treatment group and 18% in the control group. It shows that radiotherapy combined with chemotherapy has obvious curative effect.
(2) Chemotherapy: Chemotherapy can be performed on pancreatic cancer that cannot be surgically removed, or to prevent postoperative recurrence. Chemotherapy for pancreatic cancer is expected to reduce the incidence of postoperative cancer recurrence and metastasis.
1 single-agent chemotherapy commonly used are:
A. Fluorouracil (5-FU): 10～12mg/kg, intravenous drip, once/d, changed to 5～10mg/kg after 3~5 days, the total dose is 8～12g for one course of treatment. Due to the short half-life (T1/2) of fluorouracil (5-FU), it is considered that the use of lower doses and prolonged infusion time can improve the efficacy and reduce side effects.
B. Mitomycin (MMC): 4-6 mg/time, intravenous injection, 1 time/week. The efficacy is similar to that of fluorouracil (5-FU). Myelosuppression is its main side effect.
C. Streptozocin (streptomycin): nitrosourea. 15mg/kg per day, intravenous injection, for 5 consecutive days, every 2 to 4 weeks for a course of treatment. The effective rate is 11%.
D. Doxorubicin (doxorubicin) and epirubicin (epimycin): 30-50 mg/m2, intravenously, repeated once every 3 to 4 weeks. The main side effects are myocardial toxicity and myelosuppression, and severe heart failure can occur. Epirubicin (epimycin) is less toxic to the myocardium.
E. paclitaxel: a novel anti-microtubule agent that acts on M and G2 cells. Recently tried to treat pancreatic cancer. 175mg/m2, intravenous infusion within 3h, repeated every 3 weeks for a total of 5 cycles. In order to prevent allergic reactions, oral dexamethasone 10-20 mg should be taken 12 h and 6 h before administration, and diphenhydramine 50 mg should be given intravenously 30 min before. Taxotere is an artificial semi-synthetic product that is about twice as effective as paclitaxel.
F. gemcitabine: is a difluorodeoxycytidine that, after activation in cells, prevents apoptosis by inhibiting nucleotide reductase and incorporation into the DNA strand. Mainly used in S phase cells. The dose was 1000 mg/m 2 (body surface area), and intravenously instilled within 30 min, once a week for 3 weeks. Repeat every 4 weeks. Preliminary results show that the symptoms can be improved and the survival time is prolonged, which deserves further study.
2 combined chemotherapy: pancreatic cancer is not sensitive to chemotherapy, single drug treatment is not effective. Combined chemotherapy can reduce tumor resistance and improve efficacy. However, it is still not ideal for prolonging the survival period.
A.FAM regimen: fluorouracil (5-Fu) 600 mg/m2, one intravenous injection at 2, 5, and 6 weeks; mitomycin (MMC) 10 mg/m2, intravenous injection at week 1; doxorubicin ( ADM) 20 mg/m2, intravenously once every 1st, 5th week.
B.SMF protocol: STZ 1.0mg/m2, 1st, 8th, 29th, 36th day, intravenous injection; mitomycin (MMC) 1 day intravenous injection; fluorouracil (5-Fu) 600mg/m2, Intravenous infusion on days 1, 8, 29, and 36. Repeat after 8 weeks.
C.FAD regimen: epirubicin (EADM) 40mg/m2, intravenous infusion on day 1; cisplatin (DDP) 20 mg/m2, intravenous infusion on days 1 to 5; fluorouracil (5-Fu) 500mg/m2, intravenous infusion on days 1 to 5.
3 interventional chemotherapy: arterial intubation chemotherapy can greatly increase the concentration of drugs in tumor tissue, reduce the toxicity of systemic medication. The catheter can be left in the body for a long period of time, connected to a perfusion pump implanted under the skin, and repeatedly administered by a perfusion pump to improve the therapeutic effect.
(3) Biological therapy: Biological therapy includes immune and molecular therapy. With the rapid development of immunology and molecular biology research, this will be the most challenging research, because refractory tumors such as pancreatic cancer must develop some new methods to treat.
1 gene therapy: gene therapy is in the ascendant, but most of them remain in the preclinical stage, and few enter clinical phase I or phase II trials. With the rapid development of related disciplines such as molecular biotechnology and genetic engineering, gene therapy has become an important research field in cancer therapy. Gene therapy for pancreatic cancer is currently in the experimental stage. There are many targets for gene therapy, and a newer method is to target the process of cell cycle, such as the application of P21WAF-1 gene and adenoviral vector. P21WAF-1 protein is an important cell cycle inhibitor. In vitro experiments showed that P21WAF-1 gene (rAD-P21) constructed by adenovirus vector infects cultured cells, which can keep cell proliferation in G0/G1 phase. The growth inhibition effect is also dose dependent. However, this viral vector has a low transduction rate into the cell and a severe host response. Restrictive replication viruses, such as G207, can transform such adenovirus or retroviral vectors into replication only in specific cell types such as cancer cells. G207 is a mutant of herpesvirus, and this specific mutation ensures that the virus replicates in target cells, thereby exerting a specific gene therapy effect. In one aspect, the vector is used to carry a cell proliferation inhibitory effect like P21; on the other hand, it can carry a suicide gene such as Hs-tK.
Another treatment based on pancreatic cancer-expressing genes is the use of RAS oncogenes. Over the past 10 years, the RAS gene and its encoded proteins have been well studied. The RAS protein is a GDP membrane-bound protein that acts as a molecular switch for mitotic signal transduction. The mutation of the RAS gene can continue to activate this effect, and this mutation occurs in about 90% of pancreatic cancer, causing cellular Continue to proliferate. The RAS protein requires a 15 carbon farnesyl group after translation so that it binds to the cell membrane, and if the group is blocked, the mutated RAS protein will not bind to the cell membrane and Stay inactive. The farnesyl transferase inhibitor can inactivate the organic group of farnesyl, thereby inactivating the RAS protein. Various farnesyl transferase inhibitors have been artificially synthesized and active in vitro and in vivo. It has been made into a drug in 1998 and is safely orally administered with less toxicity. Pancreatic cancer is the preferred target of this drug because of its high RAS gene expression and mutation.
It mainly includes the following aspects:
A. Transfer of wild-type tumor suppressor gene p53, p16, retinoblastoma (Rb) gene, etc.: By transducing the above tumor suppressor gene into pancreatic cancer cells, apoptosis is induced and cancer cell growth is inhibited.
B. Introduction of suicide genes: The introduction of certain drug metabolism genes possessed by viruses or bacteria into pancreatic cancer cells, thereby converting some compounds into cytotoxic metabolites to kill tumor cells. The adenosine kinase encoded by the herpes simplex virus (HSV) TK gene can phosphorylate the adenosine analog ganciclovir (GCV) and further metabolize into a triphosphate compound in the cell by inhibiting fluorocytosine polymerase or Competitively incorporated into DNA to terminate DNA production; E. coli cytosine deaminase (Ec-CD) gene, which converts 5-fluorocytosine to 5-fluorouracil, inhibits the synthesis of KNA and DNA. The E. coli nitroreductase gene can reduce the nitroaniline-based compound (CB1954) to a cytotoxic G-hydroxylamine organism.
C. Antisense nucleic acid technology: For the oncogene sequence expressed by tumor cells, artificially synthesize DNA or RNA fragments complementary thereto, and transfer into cells to reduce or stop their expression. Anti-ak-ras inhibits the proliferation of pancreatic cancer cells.
D. Immune gene transduction: gene transfer of cytokines such as adiponectin (interleukin-2), interleukin-12 (IL-2, IL-12), tumor growth factor (TNF), and modification of tumor cells Enhance the body's anti-tumor immune response.
Since the occurrence of tumor cells is caused by a variety of genes, the result of complex effects, the simple introduction of a certain gene is not enough to achieve a satisfactory therapeutic effect.
2 immunotherapy: the application of immune preparations to enhance the body's immune function, is part of a comprehensive treatment. Currently, non-specific immunological preparations commonly used include OK-432, thymosin, interferon, and aldesleukin white (interleukin-2). As a potential treatment system, it may be superior to radiotherapy and chemotherapy because it produces specific anti-tumor effects without damaging normal tissues. Anti-tumor immunity can be divided into active immunization and passive immunization. Tumor vaccine is a kind of immunotherapy, which produces amplification of active immunity and immune response, and continuously enhances immune memory. Because the occurrence of tumors is mainly low immunity, the purpose of anti-tumor immunity is to improve the body's own immune function.
In the tumor vaccine, the first complete tumor cell vaccine is used, that is, the intact tumor cells are used as antigens, because it is not completely clear which protein in pancreatic cancer cells can be recognized by the immune system, so only intact cells can be used. Source of antigen. There are two ways to do this: First, the tumor cells are modified to express cytokines to attract antigen-presenting cells (APCs) such as macrophages and dendritic cells to reach tumor cells. These APCs also have the ability to activate T-assisted lymphocytes. Cells and T killer lymphocytes; the second way is to modify the tumor cells to express co-stimulatory factors and directly activate killer T lymphocytes. Both methods have been preclinical trials. However, they have some limitations and technical difficulties. One is that it is difficult to separate and amplify autologous tumor cells that can be used for vaccines in vitro; the second is that autologous tumor vaccines can only be used for each patient and cannot be widely used for the same cancer. Different patients, and therefore the cost is very expensive, can not be mass-produced, so the above two methods are not fully used in the clinic. In order to overcome this deficiency, an allogeneic vaccine has been developed, which is to modify tumor cells to express granulocyte colony stimulating factor (GM-CSF). Since GM-CSF can attract and mediate APC to activate T-killing and T-helper lymphocytes, it can activate the immune system.
(4) Other therapies: Thermotherapy is based on the fact that tumor cells are more sensitive to heat in an acidic environment, and the tumor tends to be acidic due to anaerobic metabolism. Pancreatic cancer is a hypoxic tumor with low sensitivity to radiotherapy and chemotherapy, but is highly sensitive to heat. In recent years, due to technical improvements, thermotherapy has been applied. The usual temperature is 44 °C. However, the heating and temperature measurement methods need to be improved.
4. Symptomatic support for the treatment of advanced pancreatic cancer, due to pancreatic exocrine insufficiency, the emergence of steatorrhea, can take pancreatic enzyme preparations in the meal to help digestion. For refractory abdominal pain, analgesics, including opioid analgesics; if necessary, 50% to 75% ethanol for celiac plexus injection or sympathectomy. Radiotherapy can relieve pain in some patients. Nutritional support should also be strengthened to improve nutritional status.
(two) prognosis
Pancreatic cancer is a highly malignant tumor with a very poor prognosis. Although it has made great efforts in the past 50 years, it has not made much progress in improving the survival rate of pancreatic cancer. Patients with untreated pancreatic cancer have a survival period of about 4 months. Patients who underwent bypass surgery have a survival period of about 7 months. After the operation, the patient can survive for 16 months. The National Institutes of Health reports that the overall 1-year survival rate for pancreatic cancer is 8%, the 5-year survival rate is 3%, and the median survival time is only 2 to 3 months. According to the statistics of our surgery, the 5-year survival rate is only about 5%. Early diagnosis and early treatment are the key to improve and improve the prognosis of pancreatic cancer. There are data showing that the tumor can be completely cured in the early stage, and the 5-year survival rate can be >20%. If the tumor is confined to the head of the pancreas (≤ 2 cm), a pancreatic total resection or Whipple surgery may have a 5-year survival rate of 15% to 20%. Surgery with adjuvant chemotherapy, such as radiotherapy and chemotherapy, can improve survival. For patients undergoing surgery-assisted chemotherapy plus radiation therapy, the 2-year survival rate can reach 40%.
Although the imaging diagnostic techniques and molecular biological detection methods for pancreatic cancer have made some progress in recent years, the early diagnosis problems are far from solved. 85% of patients have advanced treatment at the time of treatment. Only 10% to 15% of clinically diagnosed patients have the chance of surgical resection, of which only 5% to 7.5% can be cured. Therefore, the treatment of advanced pancreatic cancer is clinical. A real problem that must be addressed at work. According to statistics from the United States, the total surgical resection rate and 5-year survival rate of pancreatic cancer have not changed significantly in the past 20 years. Faced with such a severe reality, we must admit that in the 21st century, human beings Medical workers still face enormous challenges in the diagnosis and treatment of pancreatic cancer. How to improve the early diagnosis rate of pancreatic cancer under existing conditions, strengthen comprehensive treatment, and improve the prognosis, we need to pay more attention and further efforts.
prevention:
The early detection and early diagnosis of pancreatic cancer has always been a problem that people have been trying to solve. The following aspects should be done.
(1) Doctors find suspected objects in the general population, that is, high-risk groups. This is a very difficult problem because the patient has neither specific symptoms nor specific signs. The doctor is highly vigilant and the doctor has to be "hearted." Only the upper abdominal pain can be provided by the patient, sometimes the sensation of swelling exceeds the pain, and the others only have indigestion, weight loss, and "sudden diabetes". These non-specific symptoms, clinicians should be boldly suspected if the clinician cannot find other symptoms that can explain these symptoms, and then after symptomatic treatment, these symptoms fail to improve and then worsen.
(2) Popularize anti-cancer knowledge, conduct regular routine physical examinations, and carry out secondary prevention.
(3) Conducting modern high-tech investigations on high-risk subjects, such as comprehensive application of B-ultrasound, ERCP, MRI selective celiac angiography and newly developed oncogene detection.
1. Primary prevention Currently, there is no specific preventive measure for the prevention of pancreatic cancer. Therefore, the primary prevention focuses on the prevention of possible causes and risk factors and the improvement of the health of the body.
Epidemiological survey data suggest that the incidence of pancreatic cancer is closely related to smoking, excessive intake of fat and protein in the diet, alcoholism and other unhealthy lifestyles and irrational nutrition. Therefore, in order to avoid or reduce the occurrence of pancreatic cancer, it should be done:
(1) Alcohol withdrawal: Although there is no final conclusion on whether drinking alcohol can cause pancreatic cancer, reducing alcohol consumption, especially drinking less alcohol and not drinking high alcohol content can avoid pancreatitis, and may also avoid or reduce the possibility of pancreatic cancer. Sex. In addition, avoid the combined effects of smoking, drinking and eating a high-fat, high-protein diet.
(2) Quit smoking: In particular, educate young people not to smoke. The amount of cigarettes smoked per day and the length of the smoke are positively correlated with the occurrence of pancreatic cancer. Those who smoke from adolescence are more likely to develop pancreatic cancer.
(3) Promote low-fat, low-protein, high-fiber and high-vitamin diets: Gold and other found fresh fruits and vegetables can prevent pancreatic cancer. A survey by Correa et al. in Los Angeles also showed that fruit or orange juice (containing vitamin C) can significantly reduce the incidence of pancreatic cancer. Farrow and Davis's research suggests that fruits, vegetables, and vitamins A and C have nothing to do with the incidence of pancreatic cancer, and that increased calcium intake reduces the risk of developing pancreatic cancer, especially for men over 65 years of age. . Some data indicate that the high calorie diet caused by the increase in the proportion of sugar in the diet is positively correlated with the occurrence of pancreatic cancer, while the long-term high-fiber diet is negatively correlated with the occurrence of pancreatic cancer.
In addition, to reduce the consumption of coffee, especially to avoid decaffeinated coffee.
(4) Reduce environmental pathogenic factors: Good environmental factors play an important role in preventing pancreatic cancer. Radioactive materials should be reduced or avoided, and good protective measures should be taken for personnel engaged in radioactive work. Opportunities for viral infections should be reduced, especially for epidemic viral infections. Avoid prolonged exposure to substances associated with pancreatic cancer, such as certain metals, coke, gas, asbestos, elixir, beta-naphtholamine, benzidine, methylcholine, N-nitrosomethylamine, acetamido Deuterium and hydrocarbons, etc., and take good protective measures as much as possible.
(5) reduce or prevent the occurrence of related diseases: in order to reduce the incidence of pancreatic cancer, appropriate measures should be taken to prevent diabetes, chronic pancreatitis and cholelithiasis. Improve women's health care and avoid multiple abortions, oophorectomy and endometrial hyperplasia. Correct all kinds of endocrine disorders in time.
2. Secondary prevention
(1) Early diagnosis: Pancreatic cancer can be detected early in the general population over 40 years old. The census means can rely on CA19-9 monoclonal antibody, which is characterized by high sensitivity and positive rate of pancreatic cancer of more than 90%. Therefore, patients with positive CA19-9 monoclonal antibody should be reviewed regularly. First, B-ultrasound diagnosis, if necessary, ERCP, EUS and other in-depth examination, found that pancreatic mass can be used for B-ultrasound guided percutaneous fine needle aspiration biopsy, routine examination of the negative EUS often found small pancreatic cancer. For those with a family history of pancreatic cancer, CA19-9 and B-ultrasound should be checked regularly.
(2) Early treatment: Early surgery is currently the main method for the treatment of pancreatic cancer. At the same time, comprehensive treatment of traditional Chinese and Western medicine should be actively adopted.
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