Pancreatic Cancer UK

A paper from the West Midlands looked at incidence and related this to socioeconomic status. Overall there was a slight decrease in the incidence of pancreatic cancer between 1985 and 2000. However the socioeconomic evaluation showed an increase in the more affluent groups with a reduction in deprived groups. The reason for these changes is not clear. The study also pointed out the potential for improving results because there were differences in survival between affluent and deprived groups, although the challenge remains now to ensure that all groups achieve equally good outcomes.

Pancreatic cancer remains a difficult condition to diagnose. Often the tumour grows without causing symptoms, and the early symptoms may be very non-specific. This was confirmed in a study of 75 patients with pancreatic cancer. The first recorded symptom was indigestion in ⅓ of patients, pain in ⅓ and jaundice in almost all the remainder. The mean time between the onset of symptoms and investigation in hospital was over 1 month, and many patients had experienced symptoms for much longer.

These figures suggest that improvements in diagnostic techniques will have little effect on early diagnosis because many patients do not seek advice when they first get symptoms.

Two new techniques are currently being evaluated to help diagnose and stage pancreatic cancer.

Endoscopic ultrasound is a technique in which an ultrasound probe placed at the end of an endoscope can be manipulated close to the tumour to give better images. In a study of 43 patients endoscopic ultrasound accurately predicted tumour size in patients having tumour resection but this accuracy was reduced if they had previously been treated by chemotherapy and radiotherapy. In another study of 15 patients endoscopic ultrasound showed better accuracy than CT scanning for staging the disease.

Positron emission tomography (FDP-PET) is a new technique which relies on metabolic differences between cancer cells and normal tissues. Theoretically it should be very specific for detection of malignant tumours, but unfortunately it is not very sensitive for very small tumours, which limits its use for early diagnosis. Experience so far suggests that FDP-PET is better for detection of metastases than for diagnosis of the primary tumour. Further work presented at the meeting confirmed that at the moment CT scanning gives better results than this new technique. However this may change in the years to come.

Preoperative chemoradiotherapy was tested in 61 patients with resectable pancreatic cancer. In patients who responded, the treatment seemed to be associated with better long-term outcome, but the major disadvantage was that over ⅓ of patients who had an apparently resectable tumour before the chemoradiation, did not have the tumour removed because of disease progression. Although the concept of adjuvant treatment before surgical removal is attractive, the failure rate in such a high proportion of patients makes it difficult to recommend this treatment. Most surgeons continue to prefer to operate as soon as possible and then use chemotherapy to follow up after surgery.

Although laparoscopic surgery is applied increasingly often to the treatment of benign disorders such as pseudocysts, pancreatic necrosis and neuroendocrine tumours, the role of surgical treatment for pancreatic malignancy by laparoscopic (keyhole) surgery appears very limited. The main problem is that the surgery has to be extensive, in order to clear the tumour and surrounding tissue. This is difficult to achieve by the laparoscopic approach, and if a large piece of tumour and pancreas tissue needs to be removed, the surgeon must make an incision in order to do so.

The results of standard surgery for pancreatic cancer continue to improve slowly. Most surgeons now expect their mortality rate to be less than 5% although the rate of complications remains stubbornly high at around 1 in 3. Surgeons appreciate that extensive resection, for example to remove lymph nodes that might be involved, is associated with a greater risk of complications. However this has to be balanced against the need to ensure that the tissue removed extends beyond the limits of the tumour to give the best chance of longer survival.

Cachexia is the wasting of body tissues with loss of weight, that sometimes accompanies advanced pancreatic (and other) cancers. In part the weight loss is due to loss of appetite, but it is also partly due to increased breakdown of body tissues.

Doctor S Wyke, from Professor Tisdale’s laboratory in Birmingham, explained their research which has shown that the mechanisms involved include normal signalling processes for inflammation which appear to be over stimulated in this condition. Urine from cachexia patients contains a factor which can induce cachexia (proteolysis-inducing factor, PIF).

The catabolic action of PIF can be reduced by polyunsaturated fatty acids, particularly EPA which is found in fish oil. Doctor Wyke described a series of animal experiments which suggested possible clinical application for EPA. In clinical studies large doses of EPA blocked protein breakdown and weight loss in patients with advanced pancreatic cancer. Weight gain could be achieved if the patients were also given a high energy high protein nutritional supplement.

This topic was reviewed by Professor Uomo from Naples. Chemotherapy for pancreatic cancer has a long history of disappointments, but there are now some encouraging treatments emerging.

In addition to single agent treatment with 5FU and now gemcitabine, investigators have looked at combinations of several drugs, including these two drugs which are active alone. However the current clinical standard is gemcitabine therapy and it is likely that other combinations will only be offered to patients enrolled into clinical trials. This is because it is necessary to establish whether the potential benefit in terms of survival can outweigh the disadvantages in terms of side effects from the more aggressive treatment.

It seems that we are now on the threshold of a new era in the treatment of pancreatic cancer, although none of the treatments described below has yet been adopted as routine clinical practice. Further clinical trials are necessary to ensure that these early results are maintained on wider application.

All pancreatic cancers have mutations which lead to changes in their immune profile. Mutations of the K-ras gene and telomerase have been investigated as targets for immune therapy. This involves stimulating the patients own immune system by combination of the mutant protein with a highly stimulating antigen.

This approach has produced some promising early results with no side effects and prolonged survival of patients who have shown a response. However it must be borne in mind that those patients who can produce a good response are likely to be those with more natural immunity who might have survived longer in any case. Nevertheless work continues in Oslo, with combinations of vaccines that achieve a response to the vaccine in a large majority of patients. Time will tell whether this will be reflected in improved survival.

Gene therapy involves introduction of genes that lead either to changes in the body’s response to cancer cells, or which enable administration of prodrugs which are then activated by the therapeutically altered cells. Many laboratories are working on these different approaches, and at present the results are very much at the early experimental stage. Several different approaches are being tested, and it is very much a case of "watch this space" to see which approach will deliver the most promising results.

One really encouraging piece of news for chemotherapy in pancreatic cancer is the success of the ESPAC studies, coordinated by Professor Neoptolemos from Liverpool. The ESPAC-1 study showed that chemotherapy given after surgical removal of pancreatic cancer can improve survival. This approach should now be considered standard treatment. The ESPAC organisation has moved on to a new trial, designed to determine whether 5FU or gemcitabine gives better results in this situation. The results will not be available for some time, but patients in the trial all receive chemotherapy, as this should now be standard treatment.