Pancreatic cancer: what are its symptoms and stages?

Pancreatic cancer is a dangerous form of cancer. It progresses rapidly and aggressively and has a very high mortality rate.

What is the pancreas and what is its function in the body?

The pancreas is located between the stomach and the spine. It is 12-20 cm long.

It is divided into three parts:

1. The head
2. Body
3. Tail

The head of the pancreas connects to the duodenum. The body and tail extend towards the spleen below the left rib arch.

The whole gland contains an exocrine and an endocrine part. The exocrine part makes up 95% of the tissue and produces the enzymes needed to digest food. The enzymes enter the pancreatic duct into the small intestine where they mix with food. The endocrine part is represented by the so-called islets of Langerhans. It produces insulin and glucagon, hormones necessary for the digestion of sugars.

Insulin lowers blood sugar and glucagon raises it.

A tumour can arise in both the exocrine and endocrine parts of the pancreas:

• Exocrine tumours are the most common. They are usually adenocarcinomas (93%).
• Endocrine tumours are less common, accounting for 7% of pancreatic tumours. They are called pancreatic neuroendocrine tumours (PNETs).

Pancreatic cancer is the tenth most common cancer in men and the ninth most common cancer in women. It is the fourth most common cause of cancer death, accounting for 8% of all cancer deaths. Approximately 75% of all pancreatic cancers occur in the head or neck region of the pancreas, 15-20% are located in the body of the pancreas and 5-10% in the tail.

Risk factors for pancreatic cancer

A risk factor is anything that increases the likelihood of getting the disease. Different cancers have different risk factors. Some risk factors, such as smoking, can be changed. Others, such as age or family history, cannot be changed.

The presence of a risk factor or even multiple risk factors may not mean you will get cancer. Conversely, some people who get cancer may have no known risk factors.

Risk factors we can control:

- Smoking - Smoking is one of the most important risk factors for pancreatic cancer. The risk of developing pancreatic cancer is about twice as high for smokers as for those who have never smoked.

It is estimated that about 25% of pancreatic cancer cases are caused by cigarette smoking. Smoking smokeless tobacco products also increases the risk. When a person stops smoking, the risk of pancreatic cancer starts to decrease.

- Being overweight - Being very overweight (obese) is a risk factor for pancreatic cancer. People who are obese (body mass index of 30 or more) are about 20% more likely to develop pancreatic cancer.

Extra pounds around the waist can be a risk factor even in people who are not very overweight.

- Diabetes - Pancreatic cancer is more common in people with diabetes. The cause of this condition is not known. People with type 2 diabetes are most at risk. This type of diabetes is increasingly common in children and adolescents, as these age groups are also becoming more obese. Type 2 diabetes in adults is also often associated with being overweight or obese.

It is not clear whether people with type 1 (juvenile) diabetes have a higher risk of developing pancreatic cancer.

- Chronic pancreatitis - Chronic pancreatitis, a long-term inflammation of the pancreas, is associated with an increased risk of pancreatic cancer. It often occurs with excessive alcohol use and smoking.

- Exposure to certain chemicals in the workplace - Extreme exposure to certain chemicals used in the chemical and metalworking industries may increase the risk of pancreatic cancer.

Risk Factors We Cannot Control:

- Age - The risk of pancreatic cancer increases with age. Almost all patients are over 45 years of age, and approximately two-thirds are at least 65 years of age. The average age at diagnosis is 70 years.

- Gender - Men are slightly more likely to get pancreatic cancer than women. This may be at least partly due to men's higher tobacco consumption, which increases their risk of developing pancreatic cancer.

- Race - African Americans are slightly more likely to get pancreatic cancer than whites. The reasons for this are not clear. It may be due to a higher prevalence of some other risk factors for pancreatic cancer, such as diabetes, smoking and being overweight.

- Family history - Pancreatic cancer runs in multiple generations in some families. In some of these families, the high risk is due to a hereditary syndrome; in other families, the gene causing the increased risk is unknown.

Although family history is a risk factor, most people with pancreatic cancer do not have a family history of pancreatic cancer.

- Inherited genetic syndromes - Inherited gene changes (mutations) can be passed from parents to children. These gene changes can cause up to 10% of pancreatic cancer cases. Sometimes these changes lead to syndromes that involve an increased risk of other cancers (or other health problems).

Examples of genetic syndromes that can cause pancreatic cancer include:

• Hereditary breast and ovarian cancer syndrome caused by mutations in the BRCA1 or BRCA2 genes
• hereditary breast cancer caused by mutations in the PALB2 gene
• familial atypical multiple melanoma caused by mutations in the p16/CDKN2A gene and associated with melanomas of the skin and eyes
• familial pancreatitis, usually caused by mutations in the PRSS1 gene
• Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), most commonly caused by a defect in the MLH1 or MSH2 genes
• Peutz-Jeghers syndrome, caused by a defect in the STK11 gene. This syndrome is also associated with polyps in the gastrointestinal tract and several other cancers
• Chronic pancreatitis (due to a gene change) - Chronic pancreatitis is sometimes caused by an inherited gene mutation. People with this inherited (familial) form of pancreatitis have a high lifetime risk of developing pancreatic cancer

Factors with unclear influence on risk:

• Diet - A diet containing red and processed meats (e.g. sausages and bacon) and saturated fats may increase the risk of pancreatic cancer. Sugary drinks may also increase this risk. However, more research is needed in this area.

• Lack of physical activity - Some research suggests that lack of physical activity may increase the risk of pancreatic cancer, but not all studies have shown this. Regular physical activity may help reduce the risk of pancreatic cancer.

• Coffee - Some older studies have suggested an increased risk of pancreatic cancer when drinking coffee. However, more recent studies have not confirmed this.

• Alcohol - There are studies that have shown a link between excessive drinking and pancreatic cancer. Extreme drinking of alcohol can also lead to conditions such as chronic pancreatitis, which increases the risk of pancreatic cancer.
• Infections - Some research suggests that infection of the stomach with the bacterium Helicobacter pylori (H. pylori), which causes ulcers, or infection with hepatitis B may increase the risk of pancreatic cancer. Further studies are needed.

Initial pancreatic cancer often causes no symptoms. By the time the tumour causes symptoms, it has often already grown or spread outside the pancreas.

If you have one or more of the symptoms listed below, it does not mean that you have pancreatic cancer. In fact, it is more likely that many of these symptoms are caused by other diseases. Still, it is important to get checked by a doctor if you have any of these symptoms. That way, the cause can be found early and possibly treated.

Jaundice and related symptoms

Jaundice is a yellowing of the eyes and skin. In most people with pancreatic cancer, jaundice is the first symptom.

Jaundice is caused by a build-up of bilirubin, a dark yellow-brown substance produced in the liver. The liver normally releases a fluid called bile, which contains bilirubin. The bile passes through the common bile duct into the intestines, where it helps break down fats. Eventually, it leaves the body in the stool. When the common bile duct becomes blocked, the bile cannot get into the intestines and the amount of bilirubin in the body increases.

Tumours that start in the head of the pancreas are close to the common bile duct. These tumours can put pressure on the bile duct and cause jaundice while they are still quite small. This can sometimes lead to these tumours appearing at an early stage.

Tumours that start in the body or in the tail of the pancreas do not press on the duct until they have spread throughout the pancreas. By that time, the tumour has often already spread outside the pancreas. When pancreatic cancer spreads, it is often to the liver. This can also cause jaundice.

Other symptoms of jaundice:

• Dark urine: sometimes the first sign of jaundice is darker urine. When the bilirubin level in the blood increases, the urine takes on a brown color.
• Light or oily stools: Bilirubin usually gives stools a brown color. If the bile duct is blocked, stools may be light or gray in color. If bile and pancreatic enzymes that help break down fats do not get into the intestines, stools may be oily and float in the toilet.
• Itchy skin: when bilirubin builds up in the skin, it causes itching in addition to yellowing.

Pancreatic cancer is not the most common cause of jaundice. Other causes such as gallstones, hepatitis and other diseases of the liver and bile ducts are much more common.

Abdominal or back pain

Abdominal or backpain is common in pancreatic cancer.

Tumors that start in the body or tail of the pancreas can grow quite quickly. They begin to press on other surrounding organs, causing pain. Cancer can also spread to the nerves surrounding the pancreas. This often causes back pain. Overall abdominal or back pain is quite common. It is most often caused by something other than pancreatic cancer.

Weight loss and lack of appetite

Unintentional weight loss is very common in people with pancreatic cancer. These people often have little or no appetite.

Nausea and vomiting

If the cancer is pressing on the far end of the stomach, it can partially block it. This makes it harder for food to pass through. This can cause nausea, vomiting and pain, which are usually worse after eating.

Enlargement of the gallbladder or liver

If cancer blocks the bile duct, bile can build up in the gallbladder and cause it to enlarge. The doctor can sometimes palpate this (as a large lump under the right side of the rib cage) when examining the abdomen.

Pancreatic cancer can sometimes also enlarge the liver, especially if the cancer has spread to the liver by metastasis. The doctor can palpate the edge of the liver under the right side of the rib cage on examination. An enlarged liver can be seen on imaging tests (ultrasound).

Blood clots

Sometimes the first sign of the disease is a blood clot in a large vein, often in the leg. This is called a deep vein thrombosis. Symptoms may include pain, swelling, redness and warmth in the affected leg. Sometimes the clot can break off and get into the lungs. This can make breathing difficult or cause chest pain. A blood clot in the lungs is called a pulmonary embolism.

However, a blood clot does not mean you have cancer. Most blood clots are caused by other causes.

Diabetes

Rarely, pancreatic cancer causes diabetes (high blood sugar). It destroys the cells that make insulin. Symptoms may include feeling thirsty and hungry and frequent urination. More often, cancer can lead to small changes in blood sugar that do not cause symptoms of diabetes. These can be detected with blood tests.

In the early stages, pancreatic cancer is difficult to detect. This is because the doctor cannot feel the pancreas during a routine abdominal examination.

Laboratory parameters

Laboratory tests are relatively unimportant for the diagnosis of pancreatic cancer.

The doctor finds anaemia if the tumour has grown into the surrounding area (duodenum or stomach).

Sedimentation of red blood cells is regularly elevated.

If the tumor is pressing on the bile ducts, we find jaundice and elevated bilirubin and alkaline phosphatase (ALP). If the patient develops acute pancreatitis, we may find elevated amylase levels in the blood and urine.

Tumour markers are of little diagnostic value. They are useful for monitoring the stage of the disease and monitoring the effectiveness of treatment. Many publications show a good correlation between the finding of an elevated carcinoembryonic antigen (CEA) concentration in the blood and the diagnosis of pancreatic cancer. The test is positive in 85% of patients.

CA 19-9 is the most frequently studied oncogenic marker in the diagnosis and follow-up of patients with pancreatic cancer.

Non-invasive testing methods

• Abdominal ultrasonography (USG) is the first examination performed when pancreatic cancer is suspected. USG reliably shows the pancreas with the pancreatic duct, liver, gallbladder and bile ducts. Under ultrasound guidance, it is possible to perform a targeted fine-needle puncture of the pancreas and obtain a sample of the pancreas for histological examination.

• Computed tomography (CT) has the most important position in the diagnosis of pancreatic cancer. Compared to ultrasound, it has a better spatial orientation of the organs and a better view of the organs themselves.

• Magnetic resonance imaging (MRI) and magnetic resonance cholagiopancreatography (MRCP) can be more accurate than CT in the diagnosis of pancreatic cancer. It is used in cases where CT scan is inconclusive. MRCP shows the biliary and pancreatic ducts in the MR image.

• Endoscopic ultrasonography (EUS) is an ultrasound examination of the pancreas performed with a probe inserted into the stomach and duodenum. It is an indispensable examination method in the preoperative care of patients with pancreatic cancer. For tumors larger than 2 cm, the diagnostic yield is 100%, while for smaller tumors the diagnostic accuracy decreases.

Invasive imaging methods

• Endoscopic retrograde cholangiopancreatography (ERCP) is an examination in which a probe is inserted into the duodenum. The biliary and pancreatic ducts are filled with a contrast agent, which is then imaged under X-rays. This is one of the most reliable methods for diagnosing pancreatic cancer. Pancreatic cancer causes changes in the pancreas and bile ducts. During the examination, in some cases, a sample can be taken for histological examination.

• Endoscopic ultrasonography and fine-needle aspiration biopsy is another type of examination. During the ultrasound examination described above, it is possible to take a sample of pancreatic tissue for histological examination. The advantage is the possibility of taking samples from small tumours (a few mm).

Stages of pancreatic cancer: from stage 0 (carcinoma in situ) to stage IV - from local to extensive carcinoma with distant metastases.

Prognosis of the disease

Pancreatic cancer is one of the worst cancers ever. Only about 1% of patients survive 5 years after diagnosis. After radical surgery, the average survival time is between 12 and 18 months.

Any advances in early diagnosis and treatment of this tumour can bring great relief to the patient.