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Pancreatic cysts, advances in imaging methods have led to the removal of cysts (pancreatic cysts) with an increasing frequency. Cystic tumors of the pancreas constitute 10% of all pancreatic tumors. They can be benign (benign) or malignant (malignant).
Pancreatic cyst is found in 5 out of every 100,000 people who undergo abdominal imaging with US (Ultrasoundography), CT (computerized tomography) or MRI (Magnetic resonance examination).
Cysts of the pancreas with malignant potential are called cystic neoplasms of the pancreas (PKN). PCNs constitute 50% of all pancreatic cysts. This distinction is important in treatment selection. While surgical treatment is usually required in neoplastic cysts, symptomatic treatment may be sufficient in non-neoplastic cysts.
The vast majority of PCNs do not show pancreatic cysts and are detected incidentally after examination for another purpose. Some of the patients may experience symptoms such as pancreatitis, jaundice, abdominal pain, bloating and early satiety.
Cystic diseases of the pancreas can be classified as follows;
Serous cystadenomas are cystic structures that are well circumscribed and contain many honeycomb-shaped cystic cavities of various sizes. The inner surface of the cysts is lined with glycogen-rich epithelial cells. The cyst contains a serous fluid.
Since it is not associated with the pancreatic duct, pancreatic enzyme (amylase) is not detected in the cyst fluid. In 1/5 of the cases, the glowing sun appearance, which is a characteristic finding due to calcification (calcification) of the cyst, can be observed on direct abdominal X-ray. Small cysts in serous cystadenomas may be very small (microcystic) or larger in volume (Oligocystic serous cystadenomas). Oligocystic serous cysts can be confused with other cysts of the pancreas.
Microcystic serous cystadenomas may appear as a solid mass on tomographic examination. Serous cystadenomas can be diagnosed using one or more of the US, CT, MRI and endoscopic ultrasonography (EUS) methods.
In EUS, the honeycomb-like structure of the cyst is quite typical. EUS can also be examined by taking fluid from the cyst (fluid aspiration) (see Endoscopy and endoscopic ultrasonography). During aspiration, serous fluid, which can sometimes be slightly bloody, is taken. In some of the cases (<50%), glycogen-rich epithelial cells are seen in the histopathological examination of the cyst fluid taken. The CEA (Carcinoembryonic antibody) level in the cyst fluid is typically below 5ng/ml.
When serous cystic tumors reach a size of more than 4-5 cm, they may cause pain and may be palpable during body examination. In serous cystadenomas, it is important whether there are clinical signs of the disease in the selection of the treatment method.
Malignant degeneration (cancerous, serous cystadenocarcinoma) is extremely rare. Serous cystadenomas, which do not cause any complaints and do not develop any complications, are sufficient to follow up at regular intervals. In symptomatic cases, treatment is planned according to the part where the cyst is located in the pancreas.
They are cysts consisting of single or multiple large cystic spaces, located mostly in the tail part of the pancreas. The cyst contains a fluid with a consistency close to egg white. Since it is not associated with the pancreatic duct, pancreatic enzyme (amylase) is not detected in the cyst fluid.
The inner surface of the cyst is covered with mucinous epithelial cells that may show varying degrees of atypia. CEA concentration is high in the fluid taken from the cyst. CEA level > A value of 192ng/ml suggests that the cyst is mucinous.
In the case of malignant transformation, the CEA level reaches much higher levels, but there may not always be a direct relationship between the CEA level and malignancy.
Mucinous cystic neoplasms are usually seen on US, CT, MRI, and EUS as a single large cyst or a large cystic structure with large chambers.
It can be examined by taking a fluid sample from the cyst with EUS, and the cyst volume can be reduced by draining the fluid in possible cases. Examination of the cyst fluid can reveal the presence of malignant transformation in 1/3 of the patients. Clear cyst fluid does not definitively rule out the presence of malignancy.
The presence of the following findings in a mucinous cystic neoplasm should suggest malignant transformation;
Mucinous cystic neoplasms should be surgically removed because of the risk of malignancy (10-40%). Close follow-up of the patient is important in cases where surgical pancreatic cyst treatment is not considered.
Since mucinous cystic neoplasms are usually located in the tail portion of the pancreas, surgical removal of a portion of the pancreas is usually sufficient.
In some cases, the spleen may also need to be removed. In cases with malignancy, the pancreas and surrounding tissues are completely removed.
As with other cystic lesions of the pancreas, most patients with IPMN do not have any complaints. Some patients may have chronic pancreatitis, vague abdominal pains, back pain, jaundice, loss of appetite, weight loss and diabetes.
IPMNs may arise from the main pancreatic duct (60%) or its branches (30%), or both (10%). Since the cyst is associated with the pancreatic duct, pancreatic enzymes (amylase and lipase) are present in high amounts in the fluid inside the cyst. US, CT, MRI and EUS are the diagnostic methods. Unlike other cysts, ERCP is more frequently needed in the evaluation of IPMNs (See Endoscopy-ERCP). In EUS, fluid is taken from the cyst and examined for malignancy by histopathological and biochemical methods.
When necessary, the cyst is emptied and its volume is reduced. Since IPMNs can show malignant transformation, close follow-up of patients and surgical treatment should be recommended in necessary cases. The larger the cyst, the greater the risk of malignancy. Malignant degeneration (transformation into cancer) is seen in 1/3 of cysts larger than 5 cm. It was understood that 5-25% of IPMNs whose pancreatic cancer was removed with surgical treatment had early stage cancer and 15-40% had advanced stage cancer.
Malignancy develops in 45% of pancreatic cysts that are larger than 3 cm and the cyst wall is irregular (nodular). The limit of surgical treatment is determined according to the results of the pathological examination to be performed during the operation. There are publications reporting that good results are obtained with alcohol injection into the cyst with the endosonographic method in IPMNs.
Cysts in the pancreas may occur in 15% of patients after acute pancreatitis (See Acute pancreatitis). In some cases, there may be no history of acute pancreatitis or trauma. Pseudocysts can also develop in the course of chronic pancreatitis. It is accepted that they are formed as a result of the accumulation of pancreatic fluid leaking into the pancreatic tissue as a result of damage to the pancreatic duct by being limited in a capsule. Cells in the capsule wall are composed of non-epithelial cells.
A period of at least 4 weeks is required for the capsule to strengthen with the connective tissue and form a pseudocyst. Since pseudocysts are associated with the pancreatic duct, pancreatic enzymes (amylase and lipase) are detected at high levels in the cyst fluid. Although sometimes they can reach the size to cover the entire pancreas, they are usually 2-8 cm in diameter. When serum amylase levels do not decrease to normal levels in patients with pancreatitis and abdominal pain continues, necessary investigations should be done considering that a pseudocyst may have developed.
Pseudocysts formed after acute pancreatitis regress spontaneously in the majority of patients (85%), usually within 6 weeks. In some cases, this improvement may take up to 2 years. Spontaneous resolution is very rare in cysts that do not disappear after 8 weeks. Pancreatic pseudocysts smaller than 4 cm usually disappear spontaneously. This probability is lower in cysts larger than 6 cm and those with chronic pancreatitis. In 40% of pseudocysts smaller than 6 cm, the cyst needs to be drained. Cases that develop pseudocysts after pancreatitis are followed up at regular intervals. In principle, it is recommended to monitor pseudocysts that do not cause pain, are not infected, and do not show signs of compression on adjacent organs.
Pseudocysts that do not regress spontaneously, cause complaints such as pain and swelling, or develop complications such as bleeding and infection, can be treated by evacuation (cyst drainage) by endoscopic, radiological and surgical methods. Pseudocysts can also cause other symptoms by pressing on organs adjacent to the pancreas. At least 4-6 weeks should be waited for the cyst wall to mature before drainage.
Endoscopic methods should be preferred because they are less invasive and have a low complication rate. In endoscopic methods, the cyst is mouthed to the stomach (transmural route, cystogastrostomy) or a catheter is inserted into the cyst through the pancreatic duct (transpapillary route), allowing the cyst fluid to drain into the stomach or intestine.
Surgical treatment is applied in cysts that cannot be drained by endoscopic method. In surgical evacuation, the cyst is emptied by mouthing it into the stomach or small intestine. In some cases, the liquid inside the pseudocysts can become infected and create a life-threatening picture. In this case, the cyst should be drained as soon as possible.
Necrotic areas formed in the pancreas after acute pancreatitis may turn into irregular cystic structures after a while. It is usually seen when necrosis occurs in more than half of the pancreas.
Patients may have symptoms such as recurrent abdominal pain, loss of appetite, weight loss, nausea and vomiting. This situation may resolve spontaneously, or it may be necessary to evacuate by endoscopic or surgical methods in patients with severe complaints.
Molecular analysis of cyst fluid can be helpful in classifying cysts. For this purpose, the DNA structure of the cells obtained from the cells in the cyst fluid is examined.
DNA concentration, K-ras mutation and loss of heterogeneity (allelic imbalance) can be investigated with commercially available assays. The DNA concentration in the cyst fluid gives information about the division and proliferation of the cells lining the cyst surface. High DNA density indicates the presence of rapidly proliferating malignant cells. Similar findings can be seen in cyst bleeding or acute pancreatitis.
K-ras is a gene that prevents transformation into cancer during the proliferation and development of normal pancreatic cells (tumor growth inhibitory gene, tumor suppressor gene). In pancreatic cancer, this gene is frequently mutated and cannot do its job. The presence of a K-ras mutation in the cyst fluid suggests a malignant potential in that cyst.
The loss of heterogeneity (allelic imbalance) is important in terms of inactivating tumor suppressor genes. The presence of the above-mentioned findings in the cyst fluid suggests that the cyst may be mucinous and malignant.
