Pancreatic Cancer

What is pancreatic cancer?

Pancreatic cancer is a serious disease that develops as a result of the uncontrolled multiplication of cells in the pancreas.

The pancreas is an organ lying behind the stomach, which produces the enzymes needed for digestion and also secretes hormones such as insulin that regulate the blood sugar.

The great majority of pancreatic cancers are pancreatic ductal adenocarcinoma, which develops from the cells lining the pancreatic ducts.

The neuroendocrine tumours and certain rarer tumours that can develop in the pancreas have different characteristics, and their treatments may differ too.

Why does pancreatic cancer matter?

One of the most important characteristics of pancreatic cancer is that it may not give rise to marked complaints in its early stages.

Because the pancreas lies deep within the abdomen, small tumours cannot be noticed from outside. Some of the complaints that do appear early can also be seen in other digestive diseases.

For this reason the disease may in some people give symptoms only once it has advanced.

But pancreatic cancer should no longer be seen as “a disease about which nothing can be done”. Thanks to early diagnosis, modern surgical methods and improving drug treatments, there are important treatment possibilities in suitable patients.

What are the symptoms of pancreatic cancer?

The symptoms can vary with which part of the pancreas the tumour is in and how far the disease has spread.

The most important symptoms include:

• Jaundice,
• Unexplained weight loss,
• Loss of appetite,
• Upper abdominal pain,
• Pain going through to the back,
• Nausea and indigestion,
• Weakness,
• Newly begun diabetes, or diabetes whose control suddenly deteriorates,
• Pale-coloured stools,
• Darkening of the urine.

The presence of these symptoms does not mean the person definitely has pancreatic cancer. Far commoner conditions can cause the same complaints.

Why does jaundice matter?

Tumours developing in the head of the pancreas in particular can press on the main bile duct and prevent bile from flowing into the bowel.

The result may be:

yellowing of the eyes and skin → darkening of the urine → paling of the stool → sometimes itching.

Jaundice that develops without pain in particular is an important finding that should be assessed without delay.

But jaundice has many other causes too, such as gallstones, hepatitis and other diseases of the liver or bile ducts.

Does pancreatic cancer cause pain?

Some patients may have pain that begins in the upper part of the abdomen and spreads through to the back.

The pain may be constant or intermittent.

But in the early stage of pancreatic cancer there may be no pain at all. The absence of pain therefore does not exclude the disease.

Why does weight loss occur?

Unexplained weight loss is one of the important symptoms that may be seen in pancreatic cancer.

It may have several causes:

• A reduction in appetite,
• Metabolic changes the body develops in response to the tumour,
• Disturbance of digestion and absorption,
• A fall in pancreatic enzymes,
• The development of diabetes

can all contribute to weight loss.

Where there is marked, unexplained weight loss in a short time in particular, the cause should be investigated.

Can newly begun diabetes be a sign of pancreatic cancer?

It can sometimes. But the great majority of people who develop new diabetes do not have pancreatic cancer.

Because the pancreas is the organ that produces insulin, certain diseases of the pancreas can affect the control of the blood sugar.

In later life in particular, in situations such as:

• Newly begun diabetes,
• Diabetes together with unexplained weight loss,
• The sudden deterioration of previously well-controlled diabetes,
• Accompanying abdominal or back pain,

the pancreas may need to be assessed, taking the patient’s other characteristics into account as well.

Screening for pancreatic cancer is not needed in every patient with new diabetes.

What are the risk factors for pancreatic cancer?

There is no single cause of pancreatic cancer.

The factors that may increase the risk include:

• Smoking,
• Advancing age,
• Obesity,
• Long-standing chronic pancreatitis,
• Certain hereditary or genetic diseases,
• Pancreatic cancer in the family,
• Certain pancreatic cysts,
• Diabetes.

Even so, many people who develop pancreatic cancer may have no clear risk factor.

Does smoking matter?

Yes. Smoking is one of the most important modifiable risk factors for pancreatic cancer.

Stopping smoking matters not only for pancreatic cancer but for reducing the risk of a great many cancers and of heart and vascular disease.

Do pancreatic cysts turn into cancer?

Not every pancreatic cyst is cancer, and most pancreatic cysts never turn into pancreatic cancer.

But some kinds of cyst — particular IPMNs and mucinous cystic neoplasms especially — may have the potential to become cancer over time.

The kind of cyst, its size, its relationship to the pancreatic duct, any nodules within it and its change over time are therefore assessed.

Does chronic pancreatitis increase the risk of cancer?

Yes. The risk of pancreatic cancer is increased in people with long-standing chronic pancreatitis compared with the general population.

But not everyone with chronic pancreatitis develops pancreatic cancer.

In certain hereditary forms of pancreatitis the risk may be higher.

How is pancreatic cancer diagnosed?

The diagnosis is generally not made with a single test.

After the patient’s history and examination, blood tests and imaging methods are used.

The chief methods are:

• Computed tomography (CT) with a pancreas protocol,
• Magnetic resonance (MR) and MRCP,
• Endoscopic ultrasound (EUS),
• Biopsy where needed.

What is a pancreas-protocol CT?

Where pancreatic cancer is suspected, contrast CT with a pancreas protocol, carried out with a special technique, is one of the most important imaging methods.

CT helps to assess:

• The site and size of the tumour,
• Its relationship to the important blood vessels around it,
• The lymph nodes,
• Whether there is spread to the liver or other organs.

This information is also important in establishing whether the tumour can be operated on.

When are MR and MRCP used?

MR can be useful in the detailed assessment of the pancreatic tissue, the bile ducts and the pancreatic ducts.

MRCP helps in particular with imaging the bile and pancreatic ducts.

They may be used in patients where CT has not given enough information, or where certain situations need more detailed assessment.

What is the place of EUS in pancreatic cancer?

Endoscopic ultrasound (EUS) allows the pancreas to be examined at high resolution from immediately alongside the stomach and duodenum.

It can be very useful particularly in assessing small pancreatic lesions.

One of the important advantages of EUS is that, where necessary, a tissue sample can be taken from a suspicious mass with a fine needle.

Pathological examination can then be carried out.

Does every patient need a biopsy?

No.

Whether a biopsy is needed is decided according to the patient’s situation and the treatment planned.

Before starting systemic treatments such as chemotherapy or radiotherapy in particular, the diagnosis usually has to be confirmed on tissue.

In some patients whose tumour is operable and whose imaging features are quite typical, whether a biopsy is needed before surgery can be decided by multidisciplinary assessment.

What is CA 19-9?

CA 19-9 is a tumour marker whose level in the blood may be raised in some pancreatic cancers.

But there is an important point:

CA 19-9 does not on its own establish a diagnosis of pancreatic cancer.

It can also be raised in obstruction of the bile duct and in certain benign conditions. And in some people who do have pancreatic cancer, CA 19-9 may be normal.

For this reason it is not used on its own as a screening test to look for pancreatic cancer in the population.

In patients already diagnosed, it may help — together with the other findings — in following the course of the disease and the response to treatment.

Why does staging matter in pancreatic cancer?

One of the most important things determining the treatment plan is the assessment of how far the disease has spread.

What is investigated is:

• Whether the tumour is confined to the pancreas,
• Its relationship to the large blood vessels around it,
• Whether it has spread to the lymph nodes,
• Whether there is distant spread to the liver, the lungs or the lining of the abdomen.

Treatment is planned accordingly.

What does “operable” pancreatic cancer mean?

In pancreatic cancer it is not only the size of the tumour but particularly its relationship to the important blood vessels, and whether it has spread to distant organs, that matter in the decision to operate.

Patients can broadly be assessed in groups such as:

• resectable (operable),
• borderline resectable,
• locally advanced,
• metastatic.

This distinction directly affects the treatment given.

Is an operation possible in pancreatic cancer?

Yes. Where the disease is caught at a suitable stage, surgical treatment is possible and is one of the most important treatment options for long-term control of the disease.

But not every patient diagnosed with pancreatic cancer is suitable for an operation.

If the tumour has spread to distant organs, or has involved certain important blood vessels in a way that cannot be removed surgically, different treatment methods are preferred.

What is the Whipple operation?

For operable tumours in the head of the pancreas, the surgical method used most often is pancreatoduodenectomy (the Whipple operation).

In this operation, according to where the disease lies, the head of the pancreas is removed together with the duodenum, part of the bile duct, the gallbladder and some of the surrounding tissues, and the digestive system is reconstructed.

For tumours in the body or the tail of the pancreas, different pancreatic operations may be used.

Pancreatic surgery is an important surgical field and one that requires experience.

Why is chemotherapy used?

Chemotherapy forms an important part of the treatment of pancreatic cancer.

According to the stage of the disease it may be used:

• Before an operation,
• After an operation,
• As the main treatment in patients for whom an operation is not possible.

There are today different chemotherapy programmes in which more than one drug is used together.

The choice of treatment is made according to the stage of the disease, the person’s age, their general state of health and the characteristics of the tumour.

Is radiotherapy used?

Radiotherapy may be of use in some selected patients.

It may come into consideration particularly in certain locally advanced or borderline operable tumours, together with chemotherapy or at different stages of treatment.

Radiotherapy is not used routinely in every patient with pancreatic cancer.

Is genetic testing needed in pancreatic cancer?

The importance of genetic and molecular assessment in the treatment of pancreatic cancer has grown.

Certain inherited gene changes can affect both the patient’s treatment options and the risk assessment of members of their family.

In advanced disease, establishing certain molecular characteristics of the tumour can also open up targeted treatment or immunotherapy options in a small number of patients.

Genetic counselling and molecular tests may therefore come into consideration in suitable patients.

Should everyone be screened for pancreatic cancer?

No.

Routine screening for pancreatic cancer is not recommended for the whole population of people without symptoms and at average risk.

Screening is considered particularly in people at high risk.

For instance:

• Those with a strong family history,
• Those carrying certain inherited gene changes,
• People with certain genetic syndromes that markedly increase the risk of pancreatic cancer

may be taken into follow-up programmes at specialist centres.

Methods such as MR/MRCP and EUS are often used in these programmes.

Who is followed up, from what age and how often, is decided according to the person’s risk.

Is it possible to prevent pancreatic cancer?

It is not possible to prevent all pancreatic cancers.

But it is possible to reduce some of the risks.

The following are useful for general health in particular:

• Not smoking, or stopping,
• Keeping to a healthy body weight,
• Taking regular physical activity,
• Avoiding excessive alcohol,
• Keeping to regular follow-up of chronic pancreatitis and metabolic diseases.

What is the course of pancreatic cancer?

The course of the disease can differ greatly from person to person.

One of the most important determinants is the stage at which the diagnosis is made.

Detecting the disease while it is confined to the pancreas and can be removed completely improves the chance of treatment considerably.

But because pancreatic cancer may give no symptoms early on, the diagnosis is made at a more advanced stage in some patients.

Treatments are steadily improving, and more individualised approaches are being used according to the characteristics of the patient’s tumour.

For which symptoms should a doctor be consulted?

Assessment should not be delayed particularly where there is:

• Newly developed jaundice,
• Unexplained marked weight loss,
• Constant or increasing upper abdominal pain,
• Unexplained pain going through to the back,
• Loss of appetite,
• Newly begun diabetes together with weight loss in later life,
• Darkening of the urine and marked paling of the stool.

It should not be forgotten that most of these symptoms can arise from diseases other than pancreatic cancer.

Remember

Pancreatic cancer may give no symptoms early on; but not every abdominal pain, weight loss, case of diabetes or pancreatic cyst means pancreatic cancer.

Painless jaundice, unexplained weight loss and certain newly developed symptoms in particular should be assessed properly.

In diagnosis, pancreas-protocol CT, MR/MRCP and EUS are methods that complement one another. Where needed, a biopsy can be taken under EUS guidance.

CA 19-9 is not a test that can be used on its own to diagnose cancer or to screen a population.

The decision on treatment depends on many factors, chief among them the stage of the disease and whether it can be operated on. It matters that the treatment of pancreatic cancer is planned by a multidisciplinary team in which gastroenterology, pancreatic surgery, medical oncology, radiology, pathology and, where needed, radiation oncology work together.