Pancreatic Cancer (Carcinoma of the Pancreas)

What is pancreatic cancer?
The causes of pancreatic cancer remain unknown at present, but a connection with smoking is suspected in some cases. Pancreatic tumors normally develop in the head of the pancreas. This results in the tumor blocking the common bile duct which means that the secretion of bile is either greatly reduced or stopped altogether and bile is backed up until it reaches the liver. This leads to jaundice, where bile-colouring in the skin causes it to turn yellow, the urine is dark and bowel movements become pale-coloured. Jaundice can also cause serious irritation of the skin, which quickly disappears as soon as the blockage of the bile duct in the head of the pancreas is cleared. A tumor in the head of the pancreas can also block the main pancreatic duct, preventing the digestive enzymes which are normally produced in the pancreas from reaching the intestines. This leads to poor digestion, weight loss and diarrhoea. These symptoms can be relieved by taking pancreatic enzyme supplements in tablet form, or by clearing the obstruction in the main pancreatic duct. The symptoms of diabetes mellitus can appear before pancreatic cancer is diagnosed. Diabetes mellitus can however appear both after the diagnosis of cancer and after a pancreas operation. The most common form of pancreatic cancer arises in the duct cells in the head of the pancreas. Most patients are over the age of 60, but younger people may also develop the disease.

Types of Tumors
The pancreas has both endocrine and exocrine functions and consists of a large number of different cells. Endocrine relates to the production of hormones which are secreted directly into the bloodstream; exocrine relates to the production of digestive enzymes which are secreted into the intestine. Each cell type can have a tumor.

Categorization and tissue origin of tumors:

In addition to the above, there are further very rare tumor types which are not listed here.

At a rate of 80%, the pancreatic duct adenocarcinoma is the most common tumor form, which even today remains controversial. Current research has not yet fully clarified which is the cell-of-origin of this most common form of pancreatic cancer.

Not only is the categorization of tumors according to their tissue origin and tumor type, but also the tumor location within the pancreas of significance. We differentiate between the following tumor locations:
- Pancreatic head
- Pancreatic body
- Pancreatic tail

How does pancreatic cancer develop?
Pure research using methods based on molecular-biology has in recent years contributed to a significant increase in our knowledge of the causes of pancreatic cancer. Scientists have observed the increased presence of factors that stimulate the growth of cancer cells (growth factors), together with the mutation of certain genes which normally control cell growth and regulate cell death (apoptosis). Changes in the functioning of these factors allow the pancreatic cancer cells to grow more quickly than the healthy tissue and these changes are probably responsible for the resistance of the tumor to chemotherapy and radiotherapy. Further in-depth studies are necessary to investigate the precise character of these changes, as this could form a starting point for the development of new therapies. It is hoped that this research will result in the evolution of an improved form of treatment for pancreatic cancer.

What are the symptoms?
In its early stages, pancreatic cancer has no characteristic symptoms. Unfortunately there are often no symptoms in its early stage. As the disease progresses, it is commonly observed that a deterioration in one's general health takes place, with the patient suffering from loss of appetite and loss of weight. Often patients complain of a vague pain in the upper abdomen, sometimes spreading round to the back; this pain gradually increases in intensity as the disease progresses. As mentioned in the previous paragraph, tumors in the head of the pancreas can disrupt the flow of bile. This leads to jaundice, which is characterised by pale bowel movements, dark urine and irritation of the skin. Another common sign of pancreatic cancer is that the patient develops diabetes mellitus for the first time.

What are the causes?
The precise causes of pancreatic cancer remain unknown. The only known risk factor at the moment is smoking. There is no proof that certain eating habits, such as drinking a lot of coffee or eating fatty meals has any relationship with pancreatic cancer. Opinions differ at present as to whether increased alcohol consumption leads to a higher risk of developing the disease.

How can pancreatic cancer be detected at any early stage?
Even today, it often not possible to detect pancreatic cancer in its early stages. There are therefore no simple medical checks that can be carried out. Intensive research is being conducted to improve the chances of early detection, and pure research will certainly lead to new and improved diagnostic procedures in clinical practice.

What are the long-term consequences of pancreatic cancer and what form of after-care is given?
Many patients show the symptoms of diabetes mellitus before pancreatic cancer is diagnosed. After the operation, a stabilisation in this condition is normally observed, although some patients experience an improvement while for others the diabetes becomes worse. The diabetes is usually treated by following a special diet or taking medication. In a small number of cases, insulin has to be taken (by injection). In exceptional cases where the entire pancreas has been removed, insulin therapy will always be necessary.
Removal of part of the pancreas can lead to the reduced production of digestive enzymes. This results in digestive disorders, flatulence, or diarrhoea. This situation can be treated quite easily by taking tablets (or capsules) which contain pancreatic enzymes.
After a successful operation, the patient must be regularly monitored by means of physical examinations, laboratory tests and sometimes radiological examinations (ultrasound, CAT, magnetic resonance imaging). These tests are normally organised in consultation with the family physician. An additional treatment, using, for example, chemotherapy, is often carried out as part of a study and organised on a case to case basis with the patient, surgeon, oncologist (cancer specialist) and family physician.

What tests and preliminary examinations have to be carried out in the case of cancer of the pancreas?
The careful examination of patients with pancreatic tumors is carried out using the above mentioned special investigation methods, ultrasound, computerised tomography, magnet resonance imaging and ERCP. The choice of which specific method is used depends on the individual case, but a CAT scan of the abdominal cavity in combination with ERCP or MRI normally indicates whether surgery should be carried out or not. What is decisive is the quality of the test, which according to the experience of the staff and the equipment available can vary from one hospital to the next. The results of the investigations must be examined by a team of specialised doctors in order that a decision on an operation can be made.

How is pancreatic cancer treated?
Surgery, i.e. the removal of the tumor, promises the only hope of a cure. A cure is only possible if the cancer cells have not spread to other organs, such as the liver or the lungs. In addition, if the tumor has spread to surrounding vessels, it will not be possible to remove it completely. Experience has shown that in only about 15% - 20% of all pancreatic cancer patients, the disease was discovered early enough to permit a radical surgical removal. Such surgery requires that not only the tumor be removed but that also parts of the neighbouring healthy pancreas, parts of the neighboring bile duct, parts of the gallbladder, parts of the duodenum, and sometimes parts of the stomach also be removed.

If the tumor has reached an advanced stage, it will be impossible in many cases to remove it completely. The aim of the treatment is then to relieve the patient's symptoms. If the bile duct is blocked and the patient is suffering from jaundice, then the flow of bile must be restored. This can be done by inserting an endoscope into the bile duct or by a surgical procedure, known as biliodigestive anastomosis, in which a piece of the intestine is sewn on to the bile duct (Fig. 5), to ensure the flow of bile. If the tumor grows into the duodenum, it can disrupt the passage of food, i.e. food cannot pass from the stomach into the intestine or can only do so with difficulty. An operation, known as a gastroenterostomy, can be performed to join the stomach to the small intestine in order to by-pass the obstruction.

The use of radiation therapy or chemotherapy for pancreatic cancer has been intensively researched over the past few years. This has brought new, when somewhat conflicting results to light. Nowadays it can be stated that even pancreatic cancer is a disease which can be treated with appropriate chemotherapeutical remedies. There are a variety of effective substances and combination of substances, which, however, are in part, still being tested in controlled clinical studies.
Data primarily from Europe have shown radiation therapy to not be effective. It is, therefore, hardly used now in Europe. However for the sake of providing all information, it must be mentioned here that in certain cancer centers in the USA, radiation therapy in combination with chemotherapy is still used sometimes before and sometimes after surgical removal of the pancreas.

What are the chances of a cure?
Surgery on the pancreas has in recent years become a very safe procedure. Nevertheless, very few patients who have had a tumor removed survive the first 5 years after the operation. In cases where the tumor cannot be removed, patients seldom survive for more than a year. The enormous efforts that are being put into research give us hope that this situation will improve significantly in the coming years. In relation to this, genetic therapies are worthy of special mention. In recent years, knowledge of the complex factors which cause pancreatic cancer has improved considerably. This knowledge can be combined with genetic therapies to offer the hope of a new start. However, a realistic assessment of the present situation shows that with the exception of a small number of selected patients who are undergoing genetic therapy as part of clinical studies, the research and development of genetic therapies is still taking place in the laboratory alone. Further examination of the molecular-biological changes in pancreatic cancer should lead to a clearer understanding of how tumors develop, and provide new starting points for the gene-based treatment of pancreatic cancer.

After-care
After the operation has been carried out, the patient has to be given regular checks, including physical examinations, laboratory tests and possibly also radiological tests (ultrasound, computerised tomography, magnetic resonance imaging). These follow-up examinations are normally organised in consultation with the patient's family doctor. An additional form of treatment, e.g. chemotherapy, is often carried out as part of studies into the disease, and this is organised on an individual basis between patients and their surgeons, oncologists (cancer specialists) and family doctors.

Part of my pancreas has been removed - what happens now?
Patients who have had a part or the whole of their pancreas removed may experience a reduction in the functioning of their pancreas, dependent on how much of the organ has been lost. This leads to two problems, above all: - Too few pancreatic enzymes (leading to digestion problems) - Too little insulin (leading to high blood-sugar levels)
These deficiencies can be treated by taking suitable medication.

Pancreatic Enzyme Substitution
Nowadays there are excellent, modern preparations on the market which contain substances that replace the pancreatic enzymes (e.g. Creon, Fig. 7). These preparations must be taken with all meals, including fat- or protein-rich snacks. The required dosage varies from patient to patient and is determined by the nature of the food and the symptoms of the patient. It is essential that the therapy eliminates the patient's bloated feeling and the foul-smelling diarrhoea with the fatty deposits. Typically, 2-3 capsules have to be taken with main meals and 1-2 capsules with snacks. It is important that the pancreatic enzymes reach the food so that they can fulfil their function. For this to happen, from 6-12 capsules need to be taken every day. These numbers may be significantly higher or lower, dependent on how well the remaining part of the pancreas functions. These enzyme preparations are normally easily digestible and have virtually no side-effects. In very rare cases, they can cause an allergic reaction.

Insulin Substitution
If the pancreatic disorder or operation lead to high blood sugar levels being recorded, the patient will require an appropriate form of blood sugar therapy. To start with, and where the blood sugar levels are not particularly high, the situation can be controlled by following a suitable diet and taking tablets which influence the sugar level. However, where extensive resectioning of the pancreas has been carried out, direct insulin replacement treatment is sometimes required. Various forms of insulin are now available for this treatment. These either come from animals or are manufactured using gene technology. For the most part, these are identical to human insulin and are therefore described as human insulin. All forms of insulin must be injected. The large variety of insulin types allow the therapy to be tailored to the needs of the patient and special attention can be paid to eating habits. The aim of any therapy is to ensure that the patient feels well and the blood sugar levels are kept under control. By doing this, serious damage to the health can be avoided, both in the short and the long term. It is particularly important in the initial phase of treatment that the patient is closely monitored by his family doctor or specialists in the field.

My spleen has been removed - what happens now?
Sometimes the spleen is also removed as part of an operation on the pancreas. It is quite possible to live without a spleen. The spleen plays a certain role in the human immune system. If it is removed, a person is more susceptible to certain bacterial infections. To provide protection against infection after removal of the spleen, the patient should be given certain inoculations after the operation. According to current guidelines, these inoculations should be repeated every 3 to 5 years. In addition, the patient should always seek medical help if he contracts a serious infection, and tell the doctor that he or she no longer has a spleen. The doctor can then decide whether treatment with antibiotics is required. The removal of the spleen can also lead to a build-up of blood platelets (thrombocytes). In the first week following the removal of the spleen, it is especially important to have this situation regularly monitored. If the number of platelets is too high, this can lead to the thickening of the blood and a possible thrombosis. If the level is too high, your doctor will prescribe a temporary course of medication to thin the blood, in order to reduce the risk of thrombosis.