Pancreatic cancer is a relatively common malignant tumor of the digestive system, and its incidence and mortality have been on the rise worldwide in recent years. Most patients with pancreatic cancer are already in the middle or late stage at the time of diagnosis, losing the chance of radical resection. The 5-year survival rate of pancreatic cancer has long been the lowest among all types of cancers, and therefore it is called the “king of cancers”. Pancreatic malignant tumors are far more common than benign tumors, and pancreatic cancer accounts for about 8-10% of all malignant tumors of the digestive tract. Pancreatic cancer is a highly malignant tumor, the cause of which is not yet clear, but is generally associated with smoking, abnormal glucose tolerance or diabetes, chronic pancreatitis, and alcohol consumption. In addition, the disease is associated with increasing age, mostly between 40 and 70 years old; animal experiments have shown that a diet rich in fat and protein increases pancreatic cell renewal and the sensitivity of the pancreas to carcinogens. In terms of incidence, cancer of the head of the pancreas accounts for 60-70%, followed by 20-30% of the body of the pancreas, and at least 5-10 of the tail of the pancreas, and about 5% of the whole pancreas. The volume of pancreatic head cancer is mostly smaller while the body or tail is larger, and the rare pancreatic follicular cell carcinoma or mucinous adenocarcinoma are larger in size. Microscopically, pancreatic cancer can be divided into ductal cell adenocarcinoma (i.e. ductal adenocarcinoma or pancreatic adenocarcinoma), ductal cell carcinoma (including mucinous adenocarcinoma, adenosquamous carcinoma, and pleomorphic carcinoma), and alveolar cell carcinoma.
I. Diagnostic status
(I) Biomarkers
(1) Pancreatic cancer-associated antigen (PCAA) and pancreatic-specific antigen: the positive rate of the former for pancreatic cancer swelling is about 53%, but chronic pancreatitis and cholelithiasis also have a positive rate of about 1/3 to 50%. For the latter, the positive rate is as high as 60% in stage I pancreatic cancer, and the positive rate is lower in benign pancreatic disorders and biliary diseases. We can combine these two antigens for testing.
(2) Pancreatic embryonic antigen (POA): In 1974, Banwo extracted an antigen as pancreatic embryonic antigen from fetal pancreas and pancreatic cancer tissue swelling. In patients with pancreatic cancer, POA is increased up to 73%, but its specificity is not high, and the positive rate is around 50% and 40% for gastric and colon cancer, respectively. POA decreases significantly after tumor resection, decreases to normal 1~2 months after surgery, and rises in case of recurrence.
(3) Glycoantigen CA19-9: an antigen associated with gastrointestinal cancer discovered by Krowski in 1979. The antigenic determinant cluster is a sialic acid-containing ganglioside, which has acquired monoclonal antibodies. The positive rates were 86.2%, 33.7%, 28.5% and 73.5% in pancreatic cancer, colon cancer, gastric cancer and bile duct cancer, respectively. CA19-9 serum values were not significantly related to the site of pancreatic cancer, main pancreatic duct dilatation, presence of metastasis and stage of disease, but decreased after tumor resection.
(4) Determination of serum carcinoembryonic antigen (CEA) and glycoantigen CA50 by ELISA: the sensitivity, specificity and accuracy of CEA in pancreatic cancer were 36.4%, 94.7% and 54%, respectively; the above values of CA50 were 74.6%, 82.2% and 76.7%, respectively. In addition, observation of dynamic changes of CEA can help to assess the prognosis of pancreatic cancer.
(II) Ultrasound endoscopy
It has been widely used in the diagnosis of pancreatic diseases and can detect small pancreatic cancer, which is superior to CT and ultrasound. Its correct diagnosis rate is about 90-95%. It can clearly show the site of cancer, main pancreatic duct and its dilatation. When other tests cannot be distinguished from chronic pancreatitis, and the diagnosis can be clarified by puncture under ultrasound endoscopy. This new technique can be used for precise staging of patients with peripancreatic cancer that is not suitable for surgery.
(C) Transduodenoscopic retrograde cholangiopancreatography (ERCP)
ERCP can directly observe the situation of the jugular abdomen, such as whether there is any occupancy, the infiltration status of the duodenal papilla, the pancreatic duct or bile duct, and the cytological examination of pancreatic fluid or pathological observation by taking biopsy. The diagnosis rate is higher than 90%. Of course, the examination is more painful and reflects mainly the pancreatic ducts but not the infiltration of the pancreas as a whole, and sometimes it is not easy to differentiate from focal chronic pancreatitis. The ERCP of pancreatic cancer is characterized by a cut-off of the pancreatic duct or common bile duct, with blunt ends and a cupped or rat-tailed shape. The duct wall may be stiff and irregular. If both the pancreatic duct and common bile duct are obstructed and interrupted at the same time, it becomes a double duct sign.
(IV) MRCP
The positivity and sensitivity of MRCP for pancreatic cancer is about 90%. Because of its sensitivity to show fluid-filled structures, it does not require contrast.
(v) CT examination
Local enlargement, deformation or dilation of the pancreatic duct can be seen, and there is some difference in CT density between tumor tissue and peripheral pancreatic tissue. In the case of pancreatic head cancer, round or elliptical low-density enlarged bile duct images can be seen in the pancreatic head tissue, showing the “ring shadow” sign. CT examination using oral and intravenous contrast agents is a good way to evaluate pancreatic tumors. Modern techniques allow dynamic scanning with rapid intravenous contrast administration, which provides more detailed information and allows for the reconstruction of three-dimensional images. The dynamic scan image is more suitable for assessing the relationship between the pancreas and the surrounding vessels, allowing a better understanding of the local invasion of the tumor into the adjacent PV and superior mesenteric vessels. the correct diagnosis of pancreatic cancer by CT is about 80%. The disadvantage is that there are false positives and difficulty in differentiating from chronic pancreatitis.
(vi) Histocytopathological examination
The main tests include pancreatic ductal cannulation via duodenoscopy to collect pancreatic fluid for cytological analysis, CT or ultrasound-guided aspiration of cancer cells from the pancreas with a fine needle, etc. The positivity rate is 80%. Recently, it has been reported that laparoscopic examination and clamping of pancreatic tissues or nearby lymph nodes can lead to a clear diagnosis with a high positive rate. However, all of them require certain facilities and techniques.
In conclusion, when the diagnosis of pancreatic cancer is suspected, ultrasound examination should be performed first, and ERCP or CT examination or even abdominal dissection should be performed when suspicious points are found.
II. Treatment progress
(A) Surgical treatment
The treatment of pancreatic cancer is still mainly surgical treatment. The resection rate of pancreatic head cancer is low, only 5-25%, and the prognosis is poor.
1. Preoperative preparation: If there is severe jaundice, biliary drainage should be done first to reduce jaundice and restore liver function. It usually takes about 2~3 weeks. In the past, cholecystostomy was mostly followed by second-stage surgery. Nowadays, percutaneous hepatic bile duct placement can be performed first, followed by radical surgery. When the patient is malnourished due to impaired digestion and absorption, improving nutrition is the first priority. Often nasal gastrointestinal nutrition and parenteral nutrition some elements of diet, amino acids and glucose, etc. are used.
2.Surgical modalities.
(1) Pancreaticoduodenectomy (Whipple procedure) is the preferred way of pancreatic cancer surgery. Now many enlargements are evolved on the basis of this procedure. Because of its high local recurrence rate of 50-75%, recurrence rate and mortality can be reduced by extensive lymph node dissection (whole resection of pylorus, common bile duct, para-aortic lymph nodes, etc.).
Progressive pancreatic cancer is often associated with superior mesenteric vein-portal vein (SMPV) invasion, and tumor involvement of the SMPV may be due to chronic inflammation of the surrounding pancreatic tissue, not tumor infiltration. fortner et al [3] confirmed pathologically that the few cases of what appeared to be vascular wall invasion to the naked eye did not have cancer cell infiltration microscopically, but rather inflammatory adhesions to the tumor. Resection and reconstruction of the portal vein has been performed for many years, and local excision with contralateral anastomosis is practical in many settings. If the length of resection of the portal vein is within 4-5 cm, the vascular tension can be significantly released after adequate freeing of the entire portal vein, and a direct contralateral anastomosis between the portal vein and the superior mesenteric vein can be performed. However, in cases where the tumor involves nearly the entire portal vein and the defect is large after resection, reconstruction is quite difficult. Especially when the pancreatic adenocarcinoma invades the beginning of the mesenteric vessels, surgical resection will result in a large segment of vascular defect that cannot be reconstructed, and interposition of vessels is required.
(2) Total pancreatectomy (standard resection): It is suitable for stage I and II pancreatic cancer with multiple lesions in the pancreas that can be radically treated. A median or bilateral subcostal incision can be chosen. Kocher maneuver is taken on the head of the pancreas to increase the mobility of the tumor, duodenum and head of the pancreas to separate the head of the pancreas from the inferior vena cava and aorta in the retroperitoneum. For more advanced tumors, resection can be extended to hemigastrectomy. This procedure is less frequently performed in recent years because of the decreased quality of life or the development of uncontrollable brittle diabetes mellitus after this procedure.
(3) Regional pancreatectomy: Removal of all pancreatic tissue and surrounding soft tissues and lymph nodes, the bile duct below the hepatic hilum or part of the adjacent organs.
(4) Palliative surgery: In advanced pancreatic cancer with multiple lymph node metastases or poor systemic condition that makes radical surgery difficult to tolerate, diversion surgery, choledochoduodenal anastomosis, common bile duct jejunostomy, gastrointestinal anastomosis, biliary-intestinal anastomosis plus gastrointestinal anastomosis (double bypass surgery), etc. are performed.
(II) Chemotherapy
In order to facilitate surgical treatment and chemotherapy, the clinical classification method based on imaging findings is mostly used: stage I is pancreatic cancer that can be surgically resected, stage II is locally progressive pancreatic cancer and stage III is pancreatic cancer with distant metastases. More than 80% of them are stage II and III patients in clinical practice. For stage I, surgery is the best and only curable method; for stage II, radiotherapy and chemotherapy can be given first, and some (about 10%) can regain the chance of surgery. stage III patients are suitable for systemic chemotherapy.
With the development of arterial cannulation angiography, some scholars configure permanent arterial cannula for postoperative chemotherapy by descending a catheter with a pump inserted until the root of the gastroduodenal artery and pumping out to inject methylene blue 2~4ml, which can reduce pain and prolong the patient’s life. Watch out for complications that occur with local pump placement such as catheter obstruction, vascular obstruction, catheter displacement, and infection.
Gemcitabine is a nucleoside analogue with an objective response rate of 11% and good clinical efficacy in phase II clinical trials. Patients showed physical and mental improvement and pain relief. Trospium is also recognized for its targeted therapeutic effects. Others are hormone analogues such as CCK, growth inhibitors and their analogues and some farnesyltransferase inhibitors targeting ras proteins, which are only in the laboratory research and application stage and have not yet been applied in the clinic. As for ultrasound-guided intracancerous injection of 5-Fu or anhydrous alcohol, etc., they are in the stage of expanding clinical cases and revalidation.
(C) Radiotherapy
There are radical and palliative treatments. The former can be used as preoperative adjuvant treatment to shrink the mass to facilitate resection, and is suitable for stage I and II patients. The latter is suitable for those who cannot be resected and have severe back pain that can be relieved or eliminated after radiotherapy. Specific methods include external irradiation method, inter-tissue irradiation method and intraoperative irradiation method. The use of external irradiation is limited because damage to the surrounding normal tissues can lead to the development of complications such as upper gastrointestinal bleeding and biliary obstruction. Intraoperative radiotherapy (IORT) can be used to reduce the local recurrence rate, but the latter does not improve the survival rate.
Concurrent postoperative radiotherapy and chemotherapy significantly improve the treatment outcome. For the first 3 days of each phase of radiotherapy, 5-Fu is given daily, and the total dose of radiotherapy is 40 cGy of stomach in 2 doses. Each time is 2 weeks apart.
(iv) Biological therapy
Trials and clinical studies of cytokines and oncogenes for the treatment of pancreatic cancer are mainly reported. Cytokines include interleukin-2, interferon and tumor necrosis factor. Immunoreactive cells include LAK cells and TIL cells, etc.