Pancreatic cystadenoma and cystadenocarcinoma

　　First, Etiology

　　The etiology of pancreatic cystadenoma is still unclear. It is estimated that its source may include the following aspects: ① invasion by ectopic intestinal rudimentary cells or Brunner gland malformation in the duodenum; ② origin from acinar cells of the duct; ③ origin from pancreatic duct epithelium; ④ residual fetal tissue. Cystadenocarcinoma may arise from the malignant transformation of mucinous cystadenoma.

　　Second, Pathogenesis

　　Cystic tumors of the pancreas can occur at any part of the pancreas, but they are more common in the body and tail of the pancreas. Cystic tumors of the pancreas are attributed to pancreatic cysts because of the covering epithelial cells of the cyst wall, and they are considered a type of true pancreatic cyst, namely, hyperplastic or accessory cysts. The benign ones are cystadenomas, and the malignant ones are cystadenocarcinomas. Cystadenomas and cystadenocarcinomas have similar gross appearances, with varying sizes, often irregularly circular, smooth surface, complete capsule, and clear demarcation from normal pancreatic tissue. There is no obvious adhesion to adjacent organs and tissues, and the thickness of the cyst wall is uneven. Cystadenocarcinomas generally do not show infiltrative growth, and in the late stage, infiltrative changes may appear, surrounded by large blood vessels, and involve surrounding tissues and organs, which may lead to local lymph node or liver metastasis.

　　According to the morphology, origin, and biological characteristics of cystadenoma, Campagno divided it into two types: serous cystadenoma and mucinous cystadenoma in 1978. Serous cystadenoma is mainly composed of small cysts, which are called pancreatic cystic or microcystic cystadenoma when composed of many small cysts. The cross-section appears honeycomb-like and porous, with connective tissue septa inside the cysts dividing them into many small cysts of 1-2 cm in size. The endothelium is composed of a single layer of flat cells or cuboidal cells. The cells and their nuclear patterns resemble those of central acinar cells, so it is also called central acinar cystadenoma. The tumor cells are without atypicality and without nuclear division. The inner wall of the cyst is smooth without papillary projections. Serous cystadenoma has no tendency to become malignant. Mucinous cystadenoma is characterized by larger cysts, mostly large unilocular or multilocular cysts, filled with mucus in the cross-section. The endothelium of the cyst wall is composed of columnar cells, and the tumor cells contain abundant mucus but no glycogen. The inner wall of the cyst is smooth or with papillary projections. Mucinous cystadenoma has a potential risk of malignant transformation, and therefore, it is considered a precancerous lesion of mucinous cystadenocarcinoma.

　　Pancreatic cystadenocarcinoma is also known as mucinous cystadenocarcinoma, originating from the epithelium of the large pancreatic duct or from the malignant transformation of a benign cystadenoma of the same origin. The cut surface is unilocular, but can also be multilocular. The fluid inside the cyst is mucinous or gelatinous, and can also be brown or bloody with necrotic tissue mixed in. The cyst wall is lined with tall columnar epithelial cells and goblet cells that produce mucus, and the cells often show atypical hyperplasia and nuclear division. Papillary or cauliflower-like projections can be seen on the inner wall of the cyst. Subepithelial hemorrhagic and necrotic areas and calcification foci can be seen, and there is a large amount of mucin in the cytoplasm and intracystic mucus without glycogen. In the same cyst, normal differentiated benign areas and undifferentiated malignant areas can be seen. In cases of malignant transformation from cystadenoma, multiple images of cystadenoma, cystadenocarcinoma, and cystadenoma with a tendency to malignant transformation can also be seen in the same cyst.

　　1. Intracystic hemorrhage and infection When cystic tumors hemorrhage and necrose, or become infected, the mass may suddenly enlarge, the pain may worsen, and fever may occur. There are also reports of peritonitis symptoms due to cyst rupture and cyst fluid flowing into the abdominal cavity.

　　2. Acute pancreatitis or diabetes due to tumor compression or invasion of the main pancreatic duct leading to poor drainage of pancreatic juice, less than 5% of patients present with acute pancreatitis attacks; tumor destruction of the pancreatic parenchyma can lead to incomplete endocrine function, causing diabetes or abnormal glucose tolerance in patients.

　　8. 10% to 25% of patients have gallstones.

　　The growth of pancreatic cystadenoma is slow, with a long history, with reports up to 30 years. Cystadenocarcinoma often originates from the malignant transformation of cystadenoma. Even the primary cystadenocarcinoma has a longer course than pancreatic cancer. Upper abdominal pain or dull pain, and a mass in the upper abdomen are the main clinical manifestations of pancreatic cystic tumors. Other symptoms include weight loss, jaundice, gastrointestinal bleeding, various gastrointestinal symptoms, and liver metastasis.

　　1. Abdominal pain:It is an early symptom that can be a dull pain, bloating, or discomfort. The cause of abdominal pain may be the gradual enlargement of the tumor, increased intracystic tension. As the tumor gradually enlarges, it can compress the stomach, duodenum, transverse colon, etc., causing displacement and symptoms of incomplete gastrointestinal obstruction. In addition to abdominal pain, symptoms and signs such as decreased appetite, nausea, vomiting, indigestion, and weight loss may also be present.

　　2. Abdominal mass:It is the main symptom and sign, often the main reason for patients to seek medical attention. It can be the patient's main complaint or discovered during physical examination. The mass is often located in the upper central abdomen or the upper left abdomen, with a large difference in size. The small ones can only be felt, while the large ones can occupy the entire abdominal cavity. The mass is deep and presents as circular or elliptical, with tough texture. Large masses may have a sac-like sensation when touched, generally without tenderness. A few cases of cystic tumors located in the head of the pancreas may cause jaundice due to compression of the common bile duct. When the tumor compresses or invades the splenic vein, it can cause thrombosis, manifested as splenic enlargement, and may also cause varices in the fundus of the stomach and the lower segment of the esophagus, even leading to hematemesis. In some cases, the tumor can invade the stomach, duodenum, transverse colon, and rupture into the gastrointestinal tract, causing rare symptoms of gastrointestinal bleeding.

　　3. Liver metastasis:Some patients may develop intrahepatic metastatic lesions on the basis of pancreatic cysts, manifested as the coexistence of single or multiple cystic lesions in the liver.

　　Patients with unexplained, long-term epigastric distension, pain, and discomfort, which occur multiple times, should undergo ultrasound examination. If there is any suspicion from the ultrasound examination, a CT scan should be performed. Early detection and early surgery are crucial to strive for the resection of the lesion, and active treatment can improve the cure rate of the disease. Choose healthy foods and beverages instead of high-fat, high-sugar, and high-calorie foods. Eat a variety of vegetables and fruits, whole grains, and legumes. Reduce the intake of red meat (beef, pork, and lamb), avoid processed meats, and limit the intake of high-salt foods. To prevent tumors, try not to drink alcohol. If alcohol is consumed, the daily drinking amount should be limited, with men not exceeding 2 glasses a day and women not exceeding 1 glass.

　　Firstly, serum tumor markers

　　The serum CA19-9 level in patients with cystadenocarcinoma of the pancreas may be significantly elevated, which decreases after surgical resection and may increase again with tumor recurrence or metastasis. CA19-9 can be used as an indicator for detecting recurrence after cystadenocarcinoma surgery. In patients with cystadenoma, blood CEA and CA19-9 levels are generally normal.

　　Secondly, cyst fluid analysis

　　Enzymatic, tumor marker, and cytological examinations before or during surgery have differential diagnostic value. The methods for obtaining cyst fluid include percutaneous needle aspiration guided by ultrasound, needle aspiration during surgery, aspiration through the duodenum during ERCP, and laparoscopic examination with needle aspiration.

　　1. Cytological examination:This method is of great value for diagnosing mucinous tumors. If the cyst fluid smear shows the presence of mucin containing glycogen or mucinous cells, it is diagnosed as a mucinous cystic tumor. The sensitivity for diagnosing mucinous cystadenoma is 54% to 87%, and for mucinous cystadenocarcinoma, it is 50% to 75%. The presence of malignant tumor cells confirms the diagnosis. Since the tumor may only locally become malignant, the absence of positive findings does not exclude cystadenocarcinoma. About 60% of serous cystadenomas and cystic tumors with degenerative changes may have no shed epithelial cells in the cyst fluid. Therefore, when the cyst fluid shows an inflammatory appearance without epithelial cells, it cannot differentiate pseudocysts from cystic tumors.

　　2. Amylase:The amylase levels in pseudocysts are generally elevated, while cystic tumors usually do not communicate with the main pancreatic duct. The amylase in the cyst fluid does not increase, which has a certain differential diagnostic significance. However, when the cyst cavity of the tumor communicates with the pancreatic duct, the amylase in the cyst fluid can increase. Lewandrowski et al. reported that the amylase in the cyst fluid was 543-36610 U/L for pseudocysts and 44-34400 U/L for cystic tumors, with 43% of the amylase levels overlapping with pseudocysts. It is only when the amylase levels are very low that it may suggest a cystic tumor. Therefore, it is not reliable to differentiate pseudocysts from cystic tumors based on the amylase levels in the cyst fluid.

　　3. Carbohydrate antigen:The tumor markers in the cyst fluid are different from those in the serum, with the characteristic of significantly increased specificity. Polysaccharide antigens, such as CEA, CA15.3-CA72-4-CA125, were studied more in the mid-1980s. Pinto et al. reported that the CEA level in cyst fluid was 22ng/ml for mucinous cystadenoma, 141ng/ml for mucinous cystadenocarcinoma, significantly higher than 3.2ng/ml for pseudocyst and 8.2ng/ml for serous cystadenoma. Lewandrowski believes that when CEA〉26ng/ml, it suggests a mucinous tumor, but cannot differentiate between benign and malignant. This is not important because both mucinous cystadenoma and cystadenocarcinoma require resection. CA15.3-CA72-4 is superior to CEA in differentiating mucinous cystadenocarcinoma. CA15.3〉70U/L can achieve a specificity of 100％ in diagnosing cystadenocarcinoma. CA72-4〉70U/L can differentiate cystadenocarcinoma from cystadenoma and pseudocyst. When CA72-4〉150U/L, the specificity and sensitivity in diagnosing cystadenocarcinoma can reach 100％.

　　4. Relative viscosity (RV):Lewandrowski used a quantitative viscometer (Ostwald viscometer) to measure the relative viscosity (RV) of the cyst fluid, and compared it with the normal plasma RV (1.4～1.8). The results show that when RV〉1.63, the sensitivity for diagnosing mucinous cysts is 89％, and the specificity is 100％; if RV〈1.63, it strongly suggests a non-mucinous cyst. The greatest advantage of this method is that it is rapid, suitable for use during surgery.

　　Three. Pancreatic juice K-ras gene mutation analysis

　　The semi-quantitative PCR method for detecting K-ras gene mutation in pancreatic juice shows positivity in 43％ of cystic tumors.

　　Four. Abdominal flat film

　　10％～18％ of such diseases have fine calcification, and abdominal X-ray flat film scanning often finds calcification in the tumor wall. It is estimated that about 10％ of patients with serous cystadenoma of the pancreas have tumor calcification on X-ray films. The calcification rate of serous cystadenoma is higher than that of mucinous cystadenoma, and serous cystadenoma often shows linear or bow-shaped calcification located centrally. Among them, 10％ of calcification located in the central star-shaped scar often shows a sunbeam-like pattern. Once this characteristic manifestation appears, it can basically be diagnosed. Mucinous cystadenoma often shows peripheral calcification.

　　Five. Ultrasound

　　It is superior to CT in displaying the internal structure of the tumor, the situation of septa, and the presence of exudates.

　　1. Serous cystadenoma:Cysts and solid components are commonly displayed on sonograms. When the tumor is composed of a large number of extremely small cysts (〈2mm), it still shows a homogeneous solid appearance; if the cysts are larger (5～20mm), they exhibit a multicystic appearance, with each chamber closely connected in a honeycomb-like structure. Fugazzola et al. believe that when a honeycomb-like pattern is observed on ultrasound or CT, it can be diagnosed as serous cystadenoma; central strong echo with shadowing suggests calcification.

　　2、黏液性囊腺瘤和囊腺癌：It can be single-chamber or multi-chamber, but the diameter of each chamber in the multi-chamber type is relatively large, and there is often a posterior wall enhancement effect. Sometimes large, irregular papillary赘生物 can be seen protruding into the cyst from the cyst wall.

　　六、CT

　　It is superior to ultrasound in showing the calcification, location, wall thickness, and blood circulation of pancreatic cysts. On unenhanced CT, the density is between water and muscle tissue according to the content of tumor connective tissue. However, mucinous cystadenomas often appear as homogeneous low-density masses, with CT values of 10-16 Hu, which can be lobulated. Sometimes calcification spots and starry-rayed calcification can be seen. Due to the rich capillary network in mucinous cystadenomas, they often show diffuse and homogeneous or locally relatively enhanced masses after enhancement scanning, with clear boundaries and showing honeycomb-like or radiating interwoven septa. Warshaw found that only 50% of mucinous cystadenomas appear as multiple small cysts on CT, while starry-rayed calcification accounts for only 11% of patients. Mucinous cystadenomas often show large single-chamber thick-walled cysts on CT scans, with densities close to water and clear boundaries. Sometimes straight or curved thin septa can be seen inside the cyst, and it can also appear in the form of multiple cysts. Low-density pedunculated赘生物 can be seen growing from the cyst wall to the lumen, and daughter cysts can be seen growing along the larger cyst wall. During dynamic large-dose contrast enhancement scanning, the cyst wall, pedunculated赘生物, and intracystic septa all show enhancement. Mucinous cystadenocarcinoma is similar to mucinous cystadenoma, but with tumor infiltration and distant metastasis.

　　七、MRI

　　Mucinous cystadenomas are uniformly displayed on MRI with nodular boundaries surrounding the tumor, especially in the T2-weighted image. This phenomenon may be due to the large contrast between normal pancreas and intracystic fluid in the T2-weighted image (the T2 relaxation time of the fluid is longer than that of normal pancreas). There are visible septa within the tumor. On the T1-weighted image, the tumor appears as a uniform low density, while on the T2-weighted image, it appears as a uniform high density. Mucinous cystadenomas or cystadenocarcinomas appear as round or irregularly elliptical masses, with visible internal septa; and their clarity is higher than that of CT. The density between the compartments of the tumor is different on both T1 and T2-weighted images. Large papillary赘生物 can also be seen protruding into the cyst, and the reason for the different density between the compartments may be related to factors such as intracystic hemorrhage, protein content in the cyst fluid, and the proportion of solid and cystic components within the tumor. Although not a specific manifestation, it is helpful for differentiation.

　　Vascular造影

　　Mucinous cystadenomas have a rich vascular network, therefore, they can be represented on the imaging film as large feeding vessels supplied by abdominal or mesenteric vessels, draining veins, homogeneous tumor staining, and occasional arteriovenous shunts. Mucinous cystadenomas often appear as an avascular area surrounded by vessels, which is mainly related to the fact that such tumors are mainly composed of cystic components. There is mild tumor staining and small areas of new blood vessels inside the cyst wall or papillae. The presence of an artery sheath is considered to be a sign of malignant tumor. Both mucinous cystadenomas and mucinous cystadenocarcinomas can cause displacement, compression, and obstruction of the splenic vein.

　　1. It is recommended to eat less or limit the intake of foods that are difficult to digest, such as fatty meat, fish roe, brain, greasy, fried foods, and avoid spicy and stimulating foods such as scallions, ginger, garlic, and chili peppers. Avoid smoking and drinking.

　　1. Diet after pancreatic cancer surgery should commonly use tonifying Qi and blood, invigorating the spleen and stomach crystals, such as glutinous rice, red beans, broad beans, yam, goji, conpoy, figs, hazelnuts, milk, and chestnut flour, etc.

　　1. Treatment

　　Cystic tumors of the pancreas are insensitive to chemotherapy and radiotherapy, and surgery is the only treatment method. Cystadenomas often have complete capsules and are commonly found in the body and tail of the pancreas. Small cystadenomas can be removed, and most patients require resection of the body and tail of the pancreas, including the spleen. Cystadenocarcinoma has a lower degree of malignancy, develops slowly, and the lesions are relatively clear in early and middle stages. Even if there is adhesion and infiltration with adjacent organs, radical resection should be actively performed. Cystic tumors of the pancreatic head can be treated with pancreatectomy and duodenectomy. When the lesion involves the entire pancreas, radical pancreatectomy can be performed. For cases with liver metastasis, if the primary tumor can be completely resected, liver metastasis resection can be performed simultaneously to extend survival. For cystadenocarcinoma that cannot be resected after exploratory laparotomy and pathological confirmation, palliative internal and external drainage can be performed to relieve symptoms.

　　2. Prognosis

　　Surgical resection of serous cystadenoma and benign mucinous cystadenoma can achieve long-term survival. Malignant mucinous cystadenoma has low malignancy and a low recurrence rate. Chang hai Hospital reported that 12 cases of cystadenocarcinoma (including 8 cases of mucinous cystadenoma with malignant transformation) showed no signs of recurrence after 6 months to 8 years of follow-up after surgical resection. The longest one survived for 8 years after surgery. None of the 16 patients with completely resected benign cystadenomas (9 cases of serous cystadenoma, 7 cases of mucinous cystadenoma) had recurrence after surgery. Cystadenocarcinoma also has low malignancy, grows slowly, and metastasizes late, and the surgical effect is significantly better than that of solid pancreatic duct adenocarcinoma. Mayo Hospital's 20 cases of cystadenocarcinoma had a 5-year survival rate of 68% in complete resection, 14% in palliative resection, and a 56% 5-year survival rate reported by Ridder in 1996, which was much higher than that of solid cancer.