Chapter 10c
CARCINOMA OF THE
PANCREAS/MALIGNANT TUMOURS
1. DEFINITION AND OVERVIEW
Adenocarcinoma is almost exclusively the malignancy affecting the pancreas. The ICD10AM code is C25. Although it is not high on the list of human malignancies, because of its almost universal fatal outcome, it has become the fourth highest cause of death in malignancies in males (1) and fifth in females. The five year survival rate is only about 1-3% in whites and 3-5% in blacks in the U.S. Both early diagnosis and adequate early resection are most unusual. It has been increasing in frequency over the last 50 years and more, for totally unexplained reasons, in western society.
2. PREVALENCE
It kills 26000 persons annually in the U.S. and has the lowest five year
survival rate of any cancer. In women in the U.S. the age adjusted annual
incidence /10
5rose from 4.5 in the 1940s to 7.9/10
5in the 1980s and in men
from 9.2/10
5in the 1940s to 12.8/10
5in the 1960s and then stabilised.
162 2 Chapter 10c
3. GEOGRAPHIC AND RACIAL FACTORS
Here there is considerable variation; in the U.S. blacks have a higher incidence than in whites but the highest incidence recorded is in the male New Zealand Maori of Polynesian origin.
4. RISK FACTORS
These are not well understood or indeed clarified. The major ones for which the evidence seems clear are:
• Cigarette smoking
• Previous pancreatitis
• Familial / genetic
• Aromatic amines
• Hereditary pancreatitis
• Diet
• Obesity and lack of exercise
• Previous gastric surgery
• Diabetes mellitus
• Alcohol
• Coffee
• Gall stones
4.1 Cigarette Smoking
There is now convincing evidence for smoking as a risk factor with a doubling of risk which reverts to unity after a 10-15 year abstinence. It is said that cigars and pipes are benign but no data have been sighted.
4.2 Previous Pancreatitis
The most potent study is one of VA patients in the U.S. (2) of 2639
carcinoma of the pancreas patients matched to 77774 controls. The odds
ratio rose from 2.04 (1.53-2.72) in those with pancreatitis seven or more
years previously to 2.31 (1.87-2.86) where the pancreatitis was at least a
year before suggesting that some episodes of pancreatitis have carcinoma as
a basis. In a multi variate analysis, the odds ratio was 3.42 but there was no
evidence of risk with alcoholism or gall stones.
CARCINOMA OF THE PANCREAS/MALIGNANT TUMOURS 163
4.3 Familial / Genetic Factors
There is undoubtedly such a risk factor not yet fully explained. Of those with pancreatic carcinoma, 7-8% have a relative with it and it is estimated that familial / genetic factors account for as many as 10% of pancreatic carcinoma and several genes have been suggested. This is particularly in patients with hereditary pancreatitis where the risk is increased at least 10 times. The other group of genetic causes is in the genetic gut disorders such as MEN type 1, Gardner and Peutz-Jegher syndromes.
4.4 Aromatic Amines
These chemicals, present in tobacco smoke and in cooked meat, as well as in the chemical industry are probably causative but the mechanism and significance are yet to be resolved.
4.5 Hereditary Pancreatitis
As noted above, this is a potent factor but contributes only a small quantum to the total cases.
4.6 Obesity and Lack of Exercise
These have been clearly linked to the disorder (3). In those with a BMI of at least 30 the OR was significantly elevated to 1.72 compared to those with a BMI of less than 25. Physical activity was protective with the OR significantly reduced to 0.45 comparing the highest to the lowest level of activity but the protection did not extend to thin people with a BMI of less than 25kg/m
2.
4.7 Diet
There is some evidence that an elevated fat and meat intake increases the risk with a protective effect from fruit and vegetables.
4.8 Diabetes Mellitus
This has been raised as a risk factor but a large Italian study indicates that
the risk is limited to diabetes of recent onset suggesting that the diabetes was
caused by the cancer (4).
164 4 Chapter 10c
4.9 Alcohol, Coffee (5), Gall Stones
There is no firm evidence to inculpate these as causative factors.
References
1. Di Magno EP, Reber HA, Tempero HA. AGA Technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal carcinoma. Gastroenterology 117,1464- 1484 (1999)
2. Bansal P, Sonnenberg A. Pancreatitis is a risk factor for pancreatic cancer.
Gastroenterology 109,247-51 (1995).
3. Michaud DC, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS. Physical activity, obesity, height and the risk of pancreatic cancer. JAMA 286,921-9 (2001).
4. Gullo L, Pezzilli R, Morselli-Labate AM and the Italian Pancreatic Cancer Study Group.
Diabetes and the risk of pancreatic cancer. N .Engl. J.Med. 331:81-4 (1994)
5. Tavani A, LaVecchia C. Coffee and Cancer : a review of epidemiological studies. Eur. J.
Cancer Prev. 4,241-256 (2000).
