Pancreatic cancer is found mostly in the later stages. However, recently Israeli studies have shown that pancreatic tumors respond to new targeted drugs. These drugs are part of targeted and biological therapy, which helps to optimize treatment and reduce side effects.
The pancreas is a part of digestive system. It is located in the upper part of the abdominal cavity, in front of the spine, above the navel, and has a length of about 15 cm. The pancreas is divided into three parts: head, body and tail. The head of the pancreas is located near the beginning of the duodenum. The central part is called the body of the pancreas. The narrow part is called the tail of the pancreas and it is located on the left side.
Professor Baruch Brenner – Head of the Department of Gastrointestinal Oncology at Medical Center Rabin (Beilinson)
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More details about pancreatic cancer and its treatment in Israel:
- 1. The pancreas functions
- 2. Types of pancreatic cancer
- 3. Causes of pancreatic cancer
- 4. The disease symptoms
- 5. Diagnostics
- 6. How to deal with pain
- 7. Treatment of pancreatic cancer in Israel
Pancreas has two main functions:
- 1. Production of pancreatic juice which helps the body to digest proteins and fats.
- 2. Production of insulin – a hormone that allows the body to use glucose and to accumulate fats.
Pancreatic juice flows through small hollow tubes inside the pancreas, and from there it reaches the wider tube – the main pancreatic duct. This duct drain to the bile duct, which transfers a bile from the liver and gallbladder before it enters the duodenum. From the pancreatic duct pancreatic juice enters into the duodenum, where it helps digestion.
Types of Pancreatic Cancer
Pancreatic cancer is classified according to its location in the pancreas and the cells type origin. Tumors can form in any part of the pancreas, but most often ones are located in the body of the pancreas (in about 80% of cases).
The most common type of tumor (about 95%) is ductal adenocarcinoma, which originates from cells lining the pancreatic ducts.
Other, less common pancreatic tumors are non-epithelial tumors:
- ♦ Neuroendocrine tumors (1-2%) – which originate from the cells responsible for hormonal secretion, including insulin and other hormones.
- ♦ Cysts are fluid sacs found in the pancreas.
- ♦ Acinar cancer – also known as ACC, it develops in the glandular cells secreting pancreatic juice.
- ♦ Lymphoma is a tumor of pancreatic lymphoid cells.
Pancreatic cancer ranks fourth among cancer deaths reasons.
Causes of Pancreatic Cancer
The causes of pancreatic cancer are unknown, but risk factors of the disease include:
The risk of pancreatic cancer is increasing with age: in most cases, it is diagnosed in the elderly aged 65 and older or about 75%. Also there are rare cases when pancreatic cancer is diagnosed in young people.
Smoking and chewing tobacco are considered significant risk factors for the disease.
Food and alcohol
There are products that regularly and often affect the risk of pancreatic cancer:
- red or processed pork
- sausages and hamburgers
- foods rich in fats and sugars
- food low in vegetables and fruits.
In addition, drinking alcohol regularly and in large quantities, especially if accompanied by smoking, increases the risk of pancreatic cancer.
Several studies have shown when being overweight it increases the risk of pancreatic cancer.
Various health conditions
Chronic pancreatitis. Patients with chronic pancreatitis have a high risk of developing pancreatic cancer. The risk is even higher in patients with hereditary pancreatitis.
Diabetes. It has been found that diabetes is associated with a risk of pancreatic cancer. However, most diabetics do not suffer from pancreatic cancer.
Infections. An increased risk of pancreatic cancer can occur from various infections, such as viral hepatitis B.
In addition, Helicobacter pylori (H. pylori) bacterium is a common cause of abdominal infections, swelling, and ulcers on the stomach wall. Over time, this infection increases the risk of cancer. There is also a link between stomach ulcer and pancreatic cancer, especially among men.
Most patients with pancreatic cancer do not have a family history of the disease, but it can be a hereditary disease in about 5–10% of patients. When more than two relatives have been diagnosed with pancreatic cancer, other family members should undergo a medical examination for inherited defective gene and a risk grade of getting sick.
There are several genetic changes that can increase risk of pancreatic cancer:
- BRCA2 gene presence associated with breast cancer, ovaries and prostate.
- Hereditary nonpolyposis colorectal cancer (HNPCC), it also called Lynch Syndrome.
- Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) – multiple moles that increase the risk of developing melanoma (skin cancer).
- Hereditary pancreatitis is a rare hereditary disease when relatives suffer from pancreatitis due to a defective gene.
- Peutz-Jeghers syndrome which causes many polyps, gastrointestinal tumors, dark spots on the face and hands.
Risk factors and risk groups for pancreatic cancer:
- Pancreatitis with a dominant autosomal hereditary defect in the trypsin gene
- Chronic pancreatitis with an inherited background
- Family history of pancreatic cancer
- Genetic mutations (BRCA, p16)
- Environmental factors – smoking, fatty foods, post-gastrointestinal status (gastrectomy).
The disease symptoms
Pancreatic cancer can develop without any symptoms for an extended period of time. Symptoms are mostly non-specific. The most common are:
Pain or discomfort
Pain or discomfort in the upper abdomen, which sometimes also extends to the dorsal region. The pain can be periodic or constant. In some cases, the pain decreases in a sitting position or leaning forward, but in a supine position intensifies.
If sudden weight loss occurs for no apparent reason, this may be due to pancreatic cancer.
Signs of Jaundice
Jaundice can occur when there is a cancerous tumor in the pancreatic head and it is blocking the bile passage duct. As a result of blockage, bile juice accumulates, causing symptoms such as:
- a change in the eye whiteness to yellow
- the body skin turns yellow and itchy
- the urine color becomes dark yellow
- the stool color is light.
- Loss of appetite
- nausea and vomiting
- swelling after eating
- diarrhea or changes in eating habits
There is a connection between the symptoms onset and the tumor location in the pancreatic parenchyma. The tumor can block the mucous membrane of the bile duct and pancreas. As a result it manifests as jaundice and chronic inflammation of the pancreatic parenchyma. Pancreatic body tumors can’t cause these symptoms anatomically, but it can locally spread to nearby blood vessels, lymph nodes, the liver and, less often, to the lungs and bones.
Pancreatic inflammation can also occur as pancreatic insufficiency due to obstruction of the pancreatic duct (oily stool (statoria), malabsorption, weight loss) or as diabetes. Severe pancreatitis may be the first sign of pancreatic cancer and should be taken into account. An increase of CA19-9 marker is a sign of a pancreatic tumor with a sensitivity and specificity in about of 80 – 90%. CA19-9 is used as an indicator of the diagnosis, prognosis and treatment monitoring.
Due to delayed symptoms, the diagnosis is usually postponed to a condition when only one fifth of the patients are cured with a therapeutic probability. For this disease, early jaundice is associated with early detection and the likelihood of successful treatment.
Pancreatic Cancer Diagnosis in Israel
Our specialist conducts a physical examination, inspects the condition of the eyes and skin, prescribes a urine test for bilirubin (protein) and a blood test. He also examines the abdominal cavity to detect swelling of the liver. Test results will help you to choose the best treatment.
Advanced diagnostics may include:
- Abdomen ultrasound
- Endoscopic ultrasound
- Endoscopic visualization of the biliary tract and pancreas
- MRI of the biliary tract and pancreas
♦ Ultrasound imaging of the abdomen. This test uses sound waves to examine the internal organs of the abdomen, such as liver, pancreas, and gall bladder.
♦ Endoscopic Ultrasound (EUS). Sometimes the pancreas needs to be examined using ultrasound endoscopy. The test helps to assess the size of the pancreatic tumor, invasion to neighboring organs and also it helps to perform a biopsy. Before the test, you will be asked to stop eating and drinking for six hours. Ultrasound endoscopic examination provides the most accurate information about a pancreatic tumor compared to other neuroimaging tests. It has additional importance for the tumor’s accessibility using FNA. The biopsy result gives important data about the pathology nature and provides a differentiated diagnosis for other signs other than adenocarcinoma, such as focal pancreatitis, lymphoma or neuroendocrine tumor.
♦ CT (computed tomography). This is x-ray complex equipment that creates a three-dimensional image of the body. Scanning does not cause pain, but it lasts longer than conventional radiography and it takes 10 to 30 minutes. You will be asked to stop eating or drinking for several hours before the test. In some cases, a contrast medium is injected into a vein. This material allows to visualize better certain areas of the body. Sometimes this test is also used to perform a biopsy. After this procedure, the patient remains in the hospital overnight.
To obtain maximum information, CT should be performed according to a special protocol for the pancreas and it consists of two phases – pancreatic and portal. This information allows to decide on a treatment approach without surgery in cases where distant metastases are visible on CT, if there is pancreatic tumor infiltration into neighboring organs or obvious damage of large blood vessels. CT angiography can be performed additionally, when CT itself is uninformative. It provides data on the tumor infiltration into blood vessels.
♦ MRI (magnetic resonance imaging). During this test a magnetic field is used to build images of the body cross-section. Before patient scan doctor asks him to fill out and sign a questionnaire with special links to metal implants, such as a cardiomonitor, pacemaker, some types of metal surgical fasteners, screws or metal plates in the body. Patients with these implants cannot undergo the test due to strong magnetic fields. Any external metal part, including jewelry, must be removed before testing as well. In some cases, MRI procedure also uses a contrast medium to produce clearer images.
♦ PET-CT. The advanced test combining CT scanning and PET testing, is a imaging test in nuclear medicine. This allows to identify areas of increased metabolic activity (for example, a condition typical of a tumor) with low doses of radioactive material. The PET-CT advantage is that it scans small areas that are not visible with CT, or it shows processes in the initial stages. About an hour before the test a small amount of low-level radioactive glucose called FDG is administered to patients. This test is very sensitive and effective for detecting tumor tissue in many malignant diseases, and to determine the disease stage.
♦ Endoscopic Retrograde Cholangio-Pancreatography (ERCP). This test allows to perform a biopsy. The patient will get local anesthesia to prevent pain and discomfort. Then, a flexible tube with a tiny brush is used to collect cell samples through the esophagus or to treat jaundice symptoms and eliminate bile duct obstruction. If there is a blockage, doctor will inject iodine into the bile duct to see this clearly. A stent expands this area when it is inserted through an endoscope. A stent will keep the bile duct open for drainage.
Endoscopic Retrograde Cholangio-Pancreatography (ERCP) is very useful in diagnosing cancer of the pancreatic head and usually it shows a sign of a double duct – the distal bile duct and the pancreatic duct. Today, ERCP are used less for diagnostic purposes and more for drainage purposes. If patient is undergoing surgery, drainage is not advisable, because it increases the infections frequency after surgery. Drainage, preferably metal, is performed for patients undergoing non-surgical treatment.
♦ Magnetic Resonance Cholangiopancreatography (MRCP). This type of MRI scan is performed to obtain a detailed images of the pancreas, gall bladder and liver.
♦ Biopsy. This is a procedure where a tissue sample or tumor cells is taken to examine under a microscope. The patient get a local anesthetic injection, and then a needle FNA will be inserted into the proposed area. Endoscopic ultrasound is used to take tissue samples and to navigate the FNA precisely in combination with computed tomography, when it is necessary.
The treatment method depends on a number of factors: health condition, age, localization of the cancerous tumor, spread to other organs. Our doctor will take into account all the information about the patient, as well as the results of the diagnosis, and he will prescribe the appropriate treatment.
Depending on treatment option the following specialists may be involved into the process:
- GI oncologist-radiologist
- supportive care specialist.
If necessary, an oncological nurse, nutritionist, physiotherapist, social worker and psychologist can be connected as well.
The most effective treatment for cancer at an early stage is to remove part or all the pancreas. This is a complex operation, which is suitable for patients in good physical condition, without serious background diseases. The operation can be performed when the tumor does not develop rapidly and does not spread to other organs.
After surgery chemotherapy will be given to reduce the risk of relapse. In some cases, combination therapy with radiation will be provided.
There is another factor that determines the possibility of an operation. It can be performed only in the case when large blood vessels are not involved in the tumor area. Due to the delayed onset of symptoms of a pancreatic tumor, surgery can be prescribed only to a small number of patients. Preoperative examination does not always provide accurate information about the tumor, therefore, laparoscopic examination can be used to determine the options for surgical treatment.
Types of Pancreatic Cancer Surgery
♦ Whipple pancreatodeodontectomy. During this operation head of the pancreas, gall bladder, duodenum and a small part of the stomach are removed. Digestive system is restored by connecting the small intestine to the stomach, biliary tract and pancreas.
♦ Pancreatectomy (Total Pancreatectomy). During this operation the entire pancreas is removed.
♦ Distal resection of the pancreas. Usually combined with splenectomy. In cases where the tumor cannot be completely removed, the surgeon will “bypass” the cancerous tumor to help reduce the symptoms of the disease (such as jaundice). After splenectomy, postoperative vaccines will be needed.
♦ Gastroejunostomy – elimination of intestinal obstruction. In cases when the tumor blocks the first part of the small intestine, food and fluids cannot flow from the stomach to the intestines. It accumulates in the stomach and causes nausea and vomiting, therefore, a bypass operation is necessary, at it opens an obstacle and ensures proper passage from the stomach to the intestines.
♦ Laparoscopic resection. In some cases, especially in the case of pancreatic surgery, laparoscopy may be offered. During this operation, several small punctures are performed in the abdomen instead of one large incision. The surgeon uses a special device called a laparoscope to perform the surgery. The advantage of this type of surgery is a relatively quick recovery time compared to a large sectional operation.
Alternative insulin therapy and enzymes
If part of the pancreas is removed during surgery, the left part may not produce insulin, a substance that balances blood sugar.
Immediately after surgery you will be given an intravenous infusion of insulin. Thus, insulin will be administered until the remaining pancreas is restored, then insulin will be produced naturally. You may also need tablets containing digestive enzymes that are produced by the pancreas.
Digestive enzymes help the digestive process and break down fats and proteins. The lack of these enzymes makes difficult to maintain weight, as the main food ingredients are poorly absorbed.
After surgery the patient remains for observation for some time. During this time, patients will be advised to get up and start walking as soon as possible. Even if you are forced to stay in bed, it is important to move your legs and perform regular breathing exercises under the guidance of a physiotherapist or nurse.
After surgery the patient is briefly connected to a catheter for intravenous fluid infusion, until he can eat and drink on his own. This method is also used for pain relief. A thin tube connected to the dorsal region (epidural) is used for neural anesthesia and analgesia. The tube for feeding is connected to the abdominal wall and it is used to transport food until patient can eat properly. A thin tube (probe) is inserted into the stomach and intestines through the nose and allows fluid to stand out from the stomach, that prevents nausea or food from entering the body. This tube will be removed from the body a few days after surgery. A small tube (catheter) will also divert urine into the external bag. This tube is usually removed from the body.
To help cope with the pain the patient is prescribed painkillers for several days. There are many painkillers available, depending on pain experienced by the patient.
Treatment at the local stage (cancer is inoperable)
Patients with localized blood vessel infiltration and without distant metastases are recommended to undergo radiation therapy in combination with chemotherapy to control the progression of the disease and alleviate its symptoms. If the tumor blocks the bile duct or intestines, a shunt or stent may be inserted to remove the obstruction. There are cases when doctors are also still trying to operate the tumor at this stage. Chemotherapy can reduce the swelling, allowing surgery.
Treatment at advanced pancreatic cancer in Israel
Surgery is not recommended for patients with signs of distant metastasis. As a rule, they are prescribed chemotherapy treatment (usually gemcitabine, alone or in combination with another drug).
In this situation, the main goal is to alleviate the symptoms, provide the patient with the highest possible quality of life and extend his life as much as possible. This treatment is called “maintenance therapy” or “palliative therapy.” In this context, chemotherapy can be used to reduce the impact of the disease. Installing a stent helps to reduce jaundice symptoms. Radiation therapy, analgesics, blockades, and more are used to relieve pain.
Chemotherapy uses anticancer drugs that destroy cancer cells. This is one of the most common treatment options available for patients with pancreatic cancer. Chemotherapy is carried out in the following cases:
- ♦ After surgery to reduce the risk of relapse. This is called adjuvant chemotherapy.
- ♦ To reduce the size of the cancer tumor before surgery. It is called “neoadjuvant chemotherapy” (preliminary treatment).
- ♦ To relieve symptoms.
Chemotherapy is given as tablets, intravenous injection or infusion. Most drugs are absorbed into the bloodstream and distributed throughout the body. Chemotherapy drugs destroy cancer cells throughout the body and are usually done in several treatment cycles. The number of treatment cycles depends on the drug used and its effect on the patient. The attending physician will monitor the effectiveness of the treatment and according to the test results he will determine the number of procedures.
After surgery to remove pancreatic cancer, chemotherapy is usually performed for six months. The most common drug is gemcitabine (gemzar), administered once every three weeks by intravenous infusion for about 30 minutes. Another medicine used after surgery is fluorouracil, which is administered in tablets or intravenously.
Chemotherapy for patients with advanced cancer
At this stage chemotherapy is given as a single drug or as a combination of two to three drugs. A decision on the pharmaceutical composition will be discussed between you and your healthcare provider. The usual options are:
- ♦ Gamcitabine – The drug can also be administered in combination with another chemical, such as capititabin or nab-paclitaxel (Abraxan), as directed by your doctor.
- ♦ Folfirinox – Occasionally “This medicine consists of folic acid (Leucovorin) and three chemicals: fluorouracil; irinotecan (Irinotecan); oxaliplatin (aloxetine, eloxatin). Recent studies have shown that this step helps control progression of the disease, but it is accompanied by more serious side effects, and therefore is not suitable for all patients.
Depending on the patient’s functional condition, stage of disease, liver function and treatment goals, the oncologist will decide on the protocol that is most suitable for the patient. There are other drug combinations that can be used to treat the disease, sometimes in clinical trials.
Radiation therapy uses high-intensity X-rays that destroy cancer cells, causing as little damage to the healthy cells around them. Radiation therapy is painless, but you need to remain motionless for several minutes. Treatment does not require isolation, after it you can be surrounded by loved ones.
Treatment varies depending on the individual needs of each patient. Sometimes only one treatment is required, but in most cases, treatment is carried out every day (each procedure lasts 15-10 minutes), with the exception of a two-day weekend break, for several weeks. Before starting treatment, the patient will receive an explanation of the possible side effects. ⇒ More about radiation therapy.
It is important to note that this treatment is not common among patients with pancreatic cancer.
Targeted Therapy (personalized)
Pembrolizumab (Keytruda) is an immunostimulating drug that activates the immune system to fight cancer. The drug works by blocking the PD-1 protein found in T cells of the immune system, thereby restoring the ability of T cells to identify and destroy cancer cells. This treatment is only suitable for patients with an MMR-D or MSI-H tumor. The drug is administered every three weeks by intravenous infusion for 30 minutes.
⇒ More about pancreatic immunotherapy
How to deal with pain
Pancreatic cancer pain can usually be treated. If you suffer from pain, it is important to tell your doctor so that he can help you. Today, there are many effective treatments that help relieve pain, as well as procedures such as chemo and radiation therapy.
Patients with pancreatic cancer may suffer from chronic pain in the abdomen and back as a result of the tumor’s pressure on the “plexus” (neural network in the back of the abdomen). These pains can be treated with nerve blockade of the area. A nerve block will prevent pain signals from entering the brain, so you won’t feel pain. There are two ways to perform nerve blockade:
- ♦ Injection of anesthetics directly into the nerve – the procedure is performed under local anesthesia. This blocking is performed using computed tomography, which helps the doctor to inject accurately the material into the nerve through the back.
- ♦ Nerve resection – performed under general anesthesia, usually when the patient undergoes additional surgery, such as bypass surgery.
♦ Genetic tests for cancer heredity.
⇒ More details
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