Every day, approximately 1,200 people worldwide receive the diagnosis of pancreatic cancer. Thus, out of the total of 18 million cancer cases registered globally in 2018, nearly 450,000* were patients with malignant tumors located in one of the most important glands in the body: the pancreas. It has two important roles in the body, besides other functions: it secretes insulin to maintain the optimum blood glucose level and secretes several enzymes required for digestion. The pancreas can develop tumors, but unfortunately, until now, there are no screening tests that can highlight the cancer at an early stage. Risk factors for pancreatic cancer include smoking, obesity, chronic pancreatitis, and genetic inheritance. Pancreatic cancer has drawn the public attention when famous patients such as Luciano Pavarotti or Patrick Swayze have been diagnosed with this type of affection. Despite the gravity of pancreatic cancer, the medicine has now some positive news: in surgeries for treating these diseases, surgeons manage to save patients and prolong their life expectancy, in cases where 10-15 years ago almost nothing could be done. These patients are the so-called borderline resectable or locally advanced pancreatic cancer patients. One of the top experts in the world who successfully tackles such cases is Prof. Dr. Güralp Ceyhan, who is currently the head of the Hepato-Pancretico-Biliary unit of the ACIBADEM team working at Acibadem Maslak and Altunizade Hospital. The modern therapy protocol includes neoadjuvant chemotherapy regimes that reduce tumor growth and progression through state-of-the-art methods and technologies. This powerful pre-treatment which is also available at the Oncology unit at the Acibadem Maslak and Altunizade Hospital enable us to resect pancreatic cancer patients which in the past were regarded as lost patients. What follows is an overall picture of pancreatic cancer and what are the treatment solutions so far.
Prof. Dr. Güralp Ceyhan: The most common and feared pancreatic tumor , is pancreatic cancer which is diagnosed as pancreatic ductal adenocarcinoma. In addition, we are diagnosing more frequently cystic pancreatic tumors like intraductal papillary mucinous neoplasms (IPMN) due to advanced imaging techniques. Now, we can diagnose these types of tumors more easily than 20 years ago where at that time we could not even see them with the imaging techniques available at the time. That’s why the number of cases with these types of tumors is increasing because we can diagnose them much easier. These tumors are not easy to treat at all. In principle, there are two major types: some can affect the main pancreatic duct, others may affect the side branches. Those that affect the main duct are associated with a higher risk of cancer than those located on side-branch ducts. In the case of tumors affecting the main duct, the treatment is similar to that for cancers, which after a certain size results in oncological resection. Side-branch IPMN tumors are not so aggressive and their malignant potential is uncertain. For these reasons, ,there is still debate on this topic: whether to monitor or resect patients with a side branch IPMN. Besides these types of tumors, there are also the neuroendocrine tumors, which can be hormone active or non-active. The most common pancreatic neuroendocrine tumors are usually hormone non-active.
Prof. Dr. Güralp Ceyhan: There is a neuroendocrine hormone-active pancreatic tumor called insulinoma, responsible for insulin production in excess. But however, regarding your question, there are times when diabetes can be a sign of pancreatic cancer: it’s the case of patients who had normal blood sugar constantly and suddenly get diabetic. If we operate these patients and remove the malignant tumor, diabetes disappears, too. Therefore, suddenly installed diabetes can be a symptom of pancreatic cancer.
Prof. Dr. Güralp Ceyhan: We could have the following situation: a patient played golf on Sunday and on Monday, his skin becomes yellowish, has jaundice, then the doctor diagnoses a pancreatic cancer, hepatic metatases, and the life expectancy of the patient is up to one year. So, we are talking about an asymptomatic patient up to the advanced stages, a situation that we encounter in almost over 50 percent of the cases. The remaining patients may develop jaundice (yellowing skin) earlier, may experience pain, lose their appetite, can weaken or may experience unexplained nausea, bloating. If the first symptom is pain, the prognosis is not very good. So as you can see we unfortunately do not have a specific symptom which is directly related to pancreatic cancer.
Prof. Dr. Güralp Ceyhan: Pain is very strong and irradiates to the back. It is also typical for patients with chronic pancreatitis but it can also be seen in those with pancreatic cancer.
Prof. Dr. Güralp Ceyhan: I would like to highlight a few things about the cystic tumors I was talking about. Regarding the pancreatic cancer, it is almost impossible to detect it early, as we can do in colon cancer by colonoscopy. Only by chance we can detect pancreatic cancer at an early stage: the patient goes to a checkup and the doctor sees something on the ultrasound and then the diagnosis is confirmed via CT. By gastroscopy, one can examine the stomach, the duodenum, but not the pancreas. For the pancreas, routine endosonography can be performed, but this is not routinely recommended so far. Therefore, we can say that there is no routine checkup to detect the tumors of the pancreas up to now. The only way of early detection is similar to liver tumors: a good doctor who can see something in a routine ultrasound. There are also tumor markers, such as CA 19-9, an antigenic determinant associated with various types of tumors. Its value may be increased in pancreas cancer, but this is not mandatory. After tumor removal operation, the value of this marker decreases. And the follow-up protocol also means evaluating this marker: if the value rises again, a recurrent tumor may have appeared. But if cancer patients do not have elevated levels of this marker before surgery, then it can not be used as a monitoring tool. Increased CA19-9 values can be associated with other problems in the body such as inflammatory processes so it can not be used extensively to detect early stage pancreatic cancer, as is the case for PSA as a solid marker for prostate cancer.
Prof. Dr. Güralp Ceyhan: If patients are refered to a specialized center for pancreatic and liver surgery, the success of the treatment is provided by a multidisciplinary team. Obviously, the presence of an experienced surgeon in this team is important, but equally important is the presence of a specialist in interventional gastroenterology, oncology, radiotherapy and in interventional radiology. These medical disciplines form a team that successfully is able to treat patients with both chronic pancreatitis and, pancreatic cancers and advanced hepatic tumors. Currently, the importance and the value of minimal invasive gastrointestinal oncologic surgery is steadily increasing. This is also the case for oncological pancreatic and liver surgery. Some resections in pancreatic tumors are already well established for laparoscopic approach but now more and more also robotic surgery takes its valid place in these scenarios. With the help of the robot it seems that we can remove especially lymph nodes in a more radical way and hoping with this to enable a better prognosis for our patients. Additionally, the use of the robot or the laparoscopic approach seem ,to recover the patient much faster with less scars.
Prof. Dr. Güralp Ceyhan: This is an extremely exciting subject today, because things are changing in the approach to pancreatic cancer. First, let’s look at the patients: 20% of pancreatic cancer patients at primary diagnosis have a , tumor which is distinctively located at the head, body, or tail of the gland, there are no metastasis and no , infiltrations to the vessels. In these patients, we can easily perform an oncological resection, we can apply an adjuvant chemotherapy after the operation, and the 5 year survival rate in this setting with an R0 Resection (no visible and no microscopic tumor left) can be up to 40% at our own series, which we have recently published in Annals of Surgery. This is a great achievement since usually the 5 year survival rates are reported internationally up to 20% only. . Then, another patient category, representing 20-25% of all patients at initial diagnosis, the cancer is locally advanced: there are vascular infiltrations in the portal or mesenteric veins or there are tumor infiltrations around the arteries, the super mesenteric artery or, the celiac trunk. A few years ago, this second category of patients was similar to the third group and unfortunately, representing between 50 – 55% with pancreatic cancer and distant metastasis. Over 15 years ago, these two categories were treated in the same way, with palliative chemotherapy. Now, things have changed dramatically: if the second group with locally advanced cancer receives neoadjuvant chemotherapy regimes like FOLFIRINOX or Gemcitabine Abraxane, two combinations which have proven to be effective, then these locally advanced cancer become more and more resectable in more than 50% of the patients. To underline once again, these patients ,were no candidates for resection in the past and we could not give them a chance for cure. With the help of these powerful neoadjuvant therapy regimes, tumors can decrease in size or stay stabile but with no active cancer cells left, and surgery can be performed. How do we treat those who do not objectively regarding CT or MRI analysis respond to the treatment and do not change their size and shape? In this situation we cannot judge objectively whether the neoadjuvant therapy has worked or not. In these situations, radiology does not help us, and many medical publications have proven this that CT scans are not able to sensitively and specifically predict whether we have a response to the neoadjuvant therapy or not. CT scans, it appears as if we have a tumor with no response at all, but as published in a large series we often have a tumor which keeps its size and shape but is an empty mask. This answer can only be given when the patients after neoadjuvant therapy are surgically explored and intraoperatively tissue is harvested send to histopathology lab and finally often showing no remnant tumor. So, we have to give these special types of patients the chance of resection and do not give up early. Radiological imaging can not tell us whether neoadjuvant -chemotherapy has helped the patient or not. These are real challenges for us ,surgeons. We can now operate and resect a large number of patients with serious infiltrations to the arteries that in the past we would have thought not to be able to resect, but we can do NOW. Today, with the improvement of neoadjuvant therapy regimes we must fight for each individual patient and do not give up to early, it is really worth fighting. Surgery after neoadjuvant therapy is not something which we have to fear. The complications after neoadjuvant therapy and surgery compared to upfront surgery are comparable. It is even the case that patients receiving neoadjuvant treatments reveal an dramatically decreased risk of pancreatic fistula, which is the most feared complication after pancreatic surgery. It seems that the neoadjuvant regimes modify the pancreatic tissue in such a positive way, that the risk of postoperative fistula decreases and also with this the risk of death after surgery. Pancreatic fistula is characterized by enzyme leakage , into the abdominal cavity. These enzymes can effect neighboring organs like arteries which can result in severe life-threatening bleeding. Thus, these pancreatic fistulas and enzymatic leaks should be avoided at all costs. Therefore, the pancreatic surgeon’s experience in resecting the pancreas and performing the pancreatic anastomosis is very important and crucial. Usually pancreatic fistula and mortality rates mirror whether a pancreatic center is excellent or not.
Prof. Dr. Güralp Ceyhan: Pancreatic cancer is still a dangerous disease, but we can now help patients we would not have thought to be able to help in the past. We are getting better and better but pancreatic cancer is still unfortunately a very aggressive ant lethal tumor but we gained now hope for our patients!