The vast majority of pancreatic cancers are adenocarcinomas (cancers arising from glandular linings). Given that the role of the pancreas is to secrete digestive juices/enzymes into the gut, it is not surprising that this is the type of cancer that arises here. There is no useful subtyping of the pancreatic adenocarcinoma into better outlook and worse.
The pancreas is also a hormone gland, secreting insulin and glucagon. Tumours of these cell types give rise to malignant apudomas.
Symptoms of cancer of the pancreas
The main symptoms of pancreatic cancer are pain, weight loss and jaundice.
Most patients have pain at some point in the diagnosis. It is usually in the upper part of the abdomen and may be felt in the back at the same time. Pain is not always present at the time of diagnosis and there are many ways of controlling the pain if it occurs
Weight loss can be substantial; often more than 10% of the original body weight. There may also be a loss of appetite.
Jaundice, when the skin turns yellow, happens if the tumour blocks the thin tube that runs from the liver to the small bowel. This leads to a build up for bilirubin in the blood stream which accounts for the yellowness. The jaundice may also cause itching. As well as jaundice, the urine may turn very dark and the stools very pale.
The symptoms can vary according to where in the pancreas the tumour is.
By the time the tumour causes symptoms, it is not removable by an operation in half of cases.
Treatment of cancer of the pancreas
Once the staging tests have been done, the first decision to be made is whether treatment is aimed at cure or at controlling the disease and symptoms for as long as possible.
If the tumour is only in the pancreas, and the scan looks as though the tumour can be removed surgically without leaving any visible disease behind, then the standard operation is offered. The usual procedure is called a 'pancreas preserving pancreatico duoedenectomy', also known as a Whipple's operation. It is a major procedure, and patients need to be fit enough for the surgery and the recovery afterwards. The surgery should be done by a specialist surgeon in a unit that specialises in such operations.
There is now evidence that giving chemotherapy after a Whipple’s operation improves the probability of cure. The chemotherapy that is used is usually gemcitabine, given week for 3 weeks via a drip, followed by a week off, then again weekly for 3 weeks. Most oncologists aim for 6 months of treatment.
If, after the operation, it turns out that the tumour is close to the edge of what has been removed, a combination of chemotherapy and radiotherapy may improve the chance of cure. The radiotherapy is usually given daily, Monday to Friday, for 5 weeks. Simultaneously, a continuous intravenous delivery of chemotherapy is given throughout the 5 weeks of treatment. So the treatment can be given as an outpatient, a long lasting tube is place into one of the veins in the arm, and a small portable pump containing the chemotherapy is attached. This delivers the chemotherapy continuously and can be carried around, similar to carrying a portable music player. The portable pump is changed every week, and the tube is removed at the end of the treatment.
Where the patient has disease localised to the pancreas on scanning, then consideration to radical pancreatectomy should be given. Only radical surgical resection has a chance of cure and therefore this large operation must be therefore considered. In the operation called Whipple’s operation, the pancreas, duodenum and far end of stomach are removed, leaving a patients biliary tree draining into bowel. If the patient is an insulin requiring diabetic, then following the removal of the pancreas will require a pancreatic enzymal replacement. The operation is a major undertaking and undoubtedly one for which results are better when the operator specialises in the procedure and performs a large number of these operations. Before the operation, the patient must be in the best possible condition and any jaundice may be best alleviated by a stent placed at endoscopic examination through the obstructed segment of the bile duct. The jaundice is then allowed to settle before the operation itself.
Even under these circumstances there is an operative mortality of up to 7% and the ultimate cure rate only 20-25% and this in this carefully selected, perceived better outlook, and localised cases. Unfortunately, the majority of patients (75% of the total) are not suitable for radical surgery as this disease often presents in too advanced a stage. Where the disease is still localised in the pancreatic region and has not yet invaded the liver on CT scanning, then there are some useful chemo-radiotherapy protocols which stand a reasonable chance of holding the disease at least for some time (the timing of the development of liver metastases being an unpredictable event that may not happen for some time in a significant minority of patients; it is for these that a chemo-radiotherapy programme will be of most use).
The term chemo-radiotherapy is used for a course of therapy during which both chemotherapy drug treatment of cancer is delivered at the same time as a course of conventionally fractionated radiotherapy. Let us discuss each in turn; the chemotherapy drugs for this disease are not highly effective but can cause some worthwhile regressions and can delay the occurrence of liver disease, which, as implied before, is the potentially most lethal development in the natural history of this disease. The chemotherapy is usually given by intravenous injection once three weekly, although there are some interesting protocols with longer infusions of drugs during the radiotherapy course. The radiotherapy is the usual external beam therapy with high energy x-rays; the patient lies on the treatment couch and the beam is concentrated onto the pre-mapped area using a combination of approaches. Usually, the course of radiation therapy lasts several weeks; either the patient receives chemotherapy in the first and last weeks of the radiation, or, as stated above, there may be a continuous infusion during the course. The side effects of this therapy are nausea and languor which are difficult to fully control, but standard best anti-sickness drugs certainly help.
The results of this therapy can be well worthwhile in the group of patients who will not develop rapidly progressive liver metastases, but the overall outlook for life (prognosis in medical speak) remains suboptimal.
For patients presenting with metastatic disease, the use of combination chemotherapy may provide partial regressions for some time and are reasonably well tolerated in patients without severe jaundice at the time of presentation and not too wasted by the disease.
Sometimes an aggressive approach in patients with jaundice, by first stenting an obstructed biliary tree by the cancer can improve the patient's liver function and allow chemotherapy to be later instigated.
Recently, it has been demonstrated that the tyrosine kinase inhibitor: erlotinib (tarceva) adds to the benefit of chemotherapy in advanced disease.
Other forms of attack on liver metastases include thermo-ablation, a technique which seems effective at eliminating a small number liver metastases which are less than a couple of centimetres in diameter.