In pancreatic cancer where medicine has been desperate for decades, new percutaneous ablation methods have been developed recently as a result of technological advances, which can kill most of the tumor mass in the pancreas, relieve pain and provide long-term local control. The most promising of these are cryoablation and IRE therapy. In cryoablation, special needles are placed into the cancer under ultrasound and CT guidance and the mass is frozen. Cryoablation is done through tiny needle holes under local anesthesia, it takes 1-2 hours and the patient can usually go home the next day. In experienced centers, the complication rate is very low.
Pancreatic cancer is an increasingly common form of cancer, especially in developed countries. Although it is more common in alcohol consumers, smokers and diabetics, there is no significant risk factors in most patients. The incidence of pancreatic cancer increases with age; Under the age of 40 it is very rare and about half of the cases are over 70 years of age.
Pancreatic cancer often leads to complaints such as abdominal pain, nausea, vomiting, malaise, jaundice, darkening of urine. However, these symptoms generally occur at the late stages of the disease and there is usually no complaint at the early stages. Pancreatic cancers are classified in two groups as exocrine and endocrine. Exocrine tumors originate from the cells that produce digestive enzymes in the pancreas that drain into the intestine and these tumors constitute 98% of all pancreatic cancers. The most common of these is adenocarcinoma, which constitutes 85% of all pancreatic cancers. Endocrine (or neuroendocrine) tumors originate from cells that produce some hormones released from the pancreas into the blood circulation and these tumors constitute 2% of all pancreatic cancers. In general, exocrine tumors, especially adenocarcinoma, grow faster while neuroendocrine tumors (NET) show a slower course. Very rarely, metastases from the other organ in the pancreas may also occur. One of the most common metastasis to the pancreas is renal cancer (renal cell carcinoma).
How is it diagnosed?
Pancreatic cancers may be detected on imaging tests done because of complaints such as pain, jaundice and weight loss, or just by chance on ultrasound, CT, MRI or PET-CT examinations performed for other reasons. With the frequent use of these imaging modalities, the rates of early detection of pancreatic cancers have increased. However, although rare, benign tumors may be seen in the pancreas. In addition, both the course, survival and the treatment of adenocarcinomas and neuroendocrine tumors are different. For these reasons, a biopsy should be performed if a mass lesion is seen in the pancreas. The ideal biopsy method in the pancreas is ultrasound or tomography guided needle biopsy. In experienced hands, this biopsy is very safe and effective; it is carried out under local anesthesia without pain and lasts 10-15 minutes. This biopsy is done with the trucut technique that obtains cylinder-shaped tissue samples as opposed to fine needle technique used in endoscopic biopsy that obtains only clusters of cells. Tissue samples obtained in percutaneous trucut biopsy allow not only a more accurate diagnosis but also correct identification of the cancer type (adenocarcinoma vs NET) which is very important for the treatment.
It is not a suitable approach to perform surgery just for the diagnosis of pancreatic masses. This will create an unnecessary surgical risk for the patient and will delay the initiation of treatments such as chemotherapy and radiotherapy. In addition, due to the hard layer (desmoplastic reaction) around the pancreas cancers, it is not always easy to reach the tumor surgically and make a biopsy, which may sometimes cause the surgeon to get the material from the wrong place.
Staging in pancreatic cancer
Pancreatic cancer is divided into 4 stages according to the extention of the tumor. Stage 1 and 2 tumors are relatively rare; they constitute about 15-20% of pancreatic cancers and these stages are suitable for surgery since the tumor is inside the pancreas and the vessels are not involved. In stage 3, the tumor is spread out of the pancreas, to the stomach, intestine and large vessels but to distant organs (locally advanced). In such patients, that constitute about 40% of pancreatic cancers, surgical operation is useless. In stage 4, there are metastases to distant organs and surgical operation is not an option in this patient group, which constitutes another 40% of pancreatic cancers. In stage 4, only chemotherapy and supportive treatment are recommended.
How is it treated?
In pancreatic cancer, if the general condition of the patient and the structure of the tumor are appropriate, surgery is the first choice of treatment. However, only 15-20% of patients diagnosed with pancreatic cancer are eligible for surgery. In these patients, the most common operation is "Whipple" surgery. In this operation, the pancreas and the duodenum are removed, then the stomach, small intestine and liver are reconnected. Whipple surgery is a technically difficult operation; The mortality rate is 5% and the complication rate is around 40%. For this reason, it should be applied only in experienced centers who frequently perform this operation. However, even after a very well done Whipple operation performed in a suitable patient, the median survival is 18 months and the 5-year survival rate is only 10-20%.
The most common treatment for pancreatic cancer is chemotherapy. Chemotherapy can be used as a single treatment in patients who are planned to be operated (neoadjuvant), after operation (adjuvant), or in order to increase survival in patients who are not suitable for operation.
Another treatment applied in pancreatic cancer is radiotherapy. Radiotherapy is usually administered alone but not with chemotherapy. In some cases, it can be given before or after surgery. However, the benefit of radiotherapy in pancreatic cancer is controversial and is not routinely performed in many centers.
New treatment methods in pancreatic cancer
The pancreas is not considered to be an ideal organ for percutaneous ablation as it is a small and adjacent to structures that can be damaged by ablation. Likewise, since the nutrient vessels are thin and numerous, transarterial treatments are also technically difficult for the pancreas. Despite that, both percutaneous ablation and transarterial procedures are successfully applied in some centers around the world.
Heat-based ablation methods such as radiofrequency and microwave were tested in pancreas in 2000s. Although successfully applied in some centers, these methods caused some problems such as fistula, infection and neighboring organ damage in a sensitive organ like pancreas. In recent years, two new ablation techniques have become more popular in pancreas; cryoablation and IRE (nanoknife). It has been shown that both methods are safer and more successful in pancreatic tumors compared to radiofrequency and microwave. Cryoablation can be done under local anesthesia and its complication rate is lower whereas Nanoknife require general anesthesia and carries a higher complication rate. Therefore, cryoablation is currently the most preferred ablation method in pancreas at some centers including ours.
For cryoablation, two to three cryo probes are placed in the pancreas under local anesthesia plus ultrasound and tomography guidance. When the device is switched on, an iceball starts to form around the needles which then completely engulfs the mass in the pancreas. The temperature varies from -20 to -140 degrees in this iceball which can practically kill any tumor cell in this area. For a successful ablation, the tumor is frozen 2 times for 10 minutes separated by a 10 minutes thawing (melting) period. Due to the natural anesthetic effect of cold, cryoablation can be performed by local anesthesia alone. During the procedure, it is easier to protect the surrounding tissues as the ablation area can be seen as an iceball on CT and ultrasound.
Advantages of cryoablation in pancreatic cancer
1. It is done under local anesthesia, through the needle holes, the process takes only 1-2 hours.
2. Pain is very low during and after the procedure. Natural local anesthetic effect of cold prevents pain.
3. The frozen area is clearly seen on ultrasound and tomography during the procedure. Since this area can be minimized or enlarged as desired by changing the number of probes and their intensity, maximum possible ablation is achieved without damaging the surrounding tissue.
4. The patient may return to normal life after staying in hospital for a day.
5. Cryoablation is one of the most effective methods of relieving pain related to pancreatic cancer.
6. With cryoablation approximately 80-90% of the mass in the pancreas can be killed by freezing. Long-term local control can be better achieved by applying classical radiotherapy the remaining live tissue.
7. It is easier for the patient to take other treatments such as chemotherapy after decreasing the pain with cryoablation.
8. Cryoablation is known to produce the highest immunologic effect against cancer cells and for this reason, it is used in combination with immunotherapy in many centers.
Another ablation technique that is popular in pancreatic cancer in recent years is the irreversible electroporation (IRE) also known as Nanoknife. In this method, 4-5 electrodes are placed in the edges of the mass in the pancreas, under the guidance of ultrasound and CT, and electrodes are given a short but very high (3000 Volt, 50 Amperes) electric current in turn. This electric current permanently opens holes in the cell wall (electroporation) and increases the wall permeability causing cell death. The most important feature of the IRE is that it is more effective in the tumor tissue surrounding the large vessels and may cause less damage to critical tissues such as vessels, bile ducts and bowels. Therefore, it is a promising method in pancreatic cancer. However, Nanoknife is a technically more difficult process, because 4-5 needles should be placed parallel to each other with 1-2cm apart without passing through the organs such as the blood vessels, ducts and gastro-intestinal organs. Therefore, it is an ablation method that requires a high level of experience. In addition, anesthesia team should have sufficient knowledge and experience about this method because of the necessity of general anesthesia and severe hypertension and arrhythmia that may develop during anesthesia.
Our team is one of the pioneers of Nanoknife ablation procedure and received the first prize at 2 national radiology and interventional radiology congresses in 2013.
Transarterial therapies can also be applied in pancreatic cancer. The most common transarterial treatment is intraarterial chemotherapy. In this method, chemotherapy is given to the tumor from the pancreatic arteries and thus it is exposed to a higher concentration of chemotherapy drug. Other transarterial therapies like radioembolization is not used in the pancreas. Chemoembolization may sometimes be used for renal cancer metastases that are rare in the pancreas.
Recently, a type of "smart" radiotherapy called lutetium therapy has been applied in neuroendocrine tumors of the pancreas. In this method, a radioactive isotope called Lutetium (Lu177) is injected intravenously with a substance called DOTATATE which can bind to somatostatin receptors in neuroendocrine cells. Lutetium + DOTATATE compound also adheres to neuroendocrine tumor cells in the body and destroys them with radiation. This treatment is normally performed via the arm vein, but in recent years there have been some studies showing that it is more effective when given directly into the tumor-feeding arteries (intraarterial Lutetium Treatment).
Interventional oncology in cancer management
Prof Saim Yilmaz, MD