Pancreatic Cancer – Risk Factors, Causes, Symptoms And Treatment
Pancreatic cancer is a condition with a fairly high frequency, accounting about 2% of all visceral cancers. Although its frequency is lower than colon or esophageal cancer, increasing number of patients are diagnosed with this terrible disease, especially after the age of 50. Unfortunately, most patients become symptomatic when it is already too late. Due to aggressive features (survival after diagnosis, even with treatment, is about 6 months up to 1 year in the majority of cases) and resistance to treatment, mortality is very high.
Most epidemiological studies recorded show that women have a two times higher risk than man for pancreatic cancer. Among the causes of cancer death, the pancreas ranks fourth in men, after lung, colon and prostate and fifth in women after breast, lung, colon and uterine cancer. Although tumors of this type can be found at any age, their frequency increase gradually after 40 years and has a maximum in the decades 7 and 8.
- Exocrine pancreas cancer is more common in urban areas than in rural areas and globally is twice as common in developed countries than in developing countries. These data seem to be explained by differential exposure to risk factors and longer life expectancy, possibly with different degree of screening.
- Smoking is a significant risk factor due to the presence of carcinogens in the cigarettes smoke like nitrosamines which have a carcinogenic specific effect to pancreatic cancer as well as other substances that may act indirectly by increasing blood lipids.
- Chronic pancreatitis, regardless of its cause with over 10 years of evolution
- Oncology loaded family history, especially on the pancreatic line can be considered a risk factors, as well as the the existence of the relatives with pernicious anemia, multiple endocrine adenomatosis syndrome and Gardner syndrome (colorectal polyposis).
- Exogenous risk factors can be found in persons working in the chemical industry and who are exoposed to nitrosamines and their metabolites.
- Alcohol and coffee are not considered to be specific pancreatic cancer risk factors.
A diet rich in fat and protein is often correlated with pancreatic cancer (especially in those who underwent gastrectomy surgery). The same relationship was found in those who consume bakery products rich in highly refined flour.
Diets rich in fats effect can be explained by excessive stimulation of production of pancreatic enzymes, whose role in contributing to pancreatic acinar cell proliferation has been proven experimentally. Pancreatic cell proliferation is stimulated both by endogenous and exogenous colecistokinin and as well as glucocorticoids. Changes in digestive hormone metabolism may explain the greater frequency of pancreatic cancer in patients with pancreatic and biliary derivations and colectomies.
Diabetes mellitus, particularly with juvenile-onset, is appreciated as a significant risk factor for pancreatic cancer because the frequency is two times higher in diabetics than in the general population. On the other hand, about 15% of patients with cancer of the exocrine pancreas develop diabetes, whose manifestations usually precede shorlty the clinical onset of the pancreatic cancer.
For acute pancreatitis and chronic pancreatitis a statistically significant relationship with pancreatic cancer has not been prooved.
In the development of pancreatic cancer four stages of evolution are described :
- Asymptomatic or latent period. In this period the diagnosis can be established only incidentally by fine imaging, motivated by another condition or disease.The tumor is small and has no clinical manifestations, general signs, neoplastic impregnation, and symptoms and signs of tumor location are missing.
- The period of clinical onset characterized by general symptoms and digestive symptoms. Pancreatic cancer symptoms are generally mild initially, but evolve gradually and sometimes seem inexplicable and the patient may encounter: physical fatigue, mental fatigue and depression, tendency to weight loss, sometimes migratory superficial thrombophlebitis (Trousseau sign). To the general state of decline digestive symptoms can be added: loss of appetite, epigastric discomfort and a discrete dyspepsia, difficult digestion with capricious changes in bowel habits. Correct diagnosis and appropriate surgical indication is rarely established during clinical onset stage of the pancreatic cancer, when surgery could have a radical intent, with significant opportunities for a good and lasting result.
- The specific clinical picture can be observed in the last stage and the clinical diagnosis and laboratory diagnosis are especially easy to achieve, but the chances of successful surgery with radical intent, even associated with complex oncological treatments are low.
General signs of neoplastic impregnation and some digestive disorders are common to all cancers regardless of their location but here are a number of clinical manifestations that vary depending on the topography of pancreatic tumor.
General manifestations more severe than in the onset period that note a severe biological decline:
- Marked physical fatigue
- Decreased exercise capacity
- Marked mental fatigue
- Decreased intellectual ability
- Psychotic disorders, especially depressive syndromes;
- Dramatic weight loss – emaciation, cachexia
- Superficial thrombophlebitis (Trousseau sign)
- Skin and blood paraneoplastic syndromes
Common digestive disorders :
- Anorexia sometimes disgust or intolerance to certain foods
- Sometimes fatty diarrhea and other dyspeptic suggestive symptoms of exocrine pancreas secretory failure, with consequent reduction of intestinal digestion and absorption capacity
- Deep epigastric pain with with radiation to the left upper quadrant ,resistant to common analgesic drugs.
Diagnosis is difficult in the initial stage, when dyspepsia and overall health status can be attributed to other diseases. It is less difficult when the tumor can be felt or jaundice is present, radiology and laboratory examinations greatly ease the diagnosis. Weight loss, loss of appetite, epigastric pain and obstructive jaundice are suggestive for pancreatic cancer. Other explorations specify the diagnosis. Differential diagnosis should be made with all diseases which are accompanied by jaundice and especially the following conditions: cholestatic hepatitis, liver cirrhosis and particularly cholelithiasis. The most difficult diagnosis is exclusion of chronic pancreatitis. The prognosis is severe.
Laboratory tests can reveal : hypochromic anemia, hyperleukocytosis, increased erythrocyte sedimentation rate, changes in pancreatic ferments in the blood, urine and duodenal juice (increased serum amylase and decreased amylase levels in the duodenal juice). For more accurate diagnosis, sometimes more tests are necessary : selective arteriography,ultrasound, scintigraphy.
The ideal objective in treating exocrine pancreatic cancer has two components:
- Oncological – the disappearance of the tumor and absence of recurrence and / or metastasis after 5 years of treatment with radical intent;
- Functional – dealing with complications caused by the expansive tumor: biliary retention, pancreatic retention, possible duodenal stenosis.
This can only be fully achieved surgically by wide excision of the tumor (or sometimes the entire pancreas) and the locoregional lymphatic stations, according to general principles of oncological surgery. In most statistics, when surgery indication is present the proportion of cases with resectable tumors is between 10 and 20%. Of those about 4% are surviving 5 years after syrgery. Recent statistics highlight the improvement of these parameters mainly for intraductal papillary tumors.
The relatively long evolution without significant clinical manifestations delays the diagnosis and radical surgery intervention is impossible. This can be caused by:
- Advanced tumor evolution with massive invasion of neighboring structures (especially large vessels);
- Advanced evolution by lymphatic dissemination with regional neoplastic lymph nodes and / or distant metastases (liver, peritoneum)
- Advanced age and associated diseases (wakened body that does not allow a laborious and long intervention).
In these circumstances, the fundamental component the oncological goal is impossible. Therefore, treatment aims only to improve the patient’s quality of life by addressing complications caused by the evolution of the expansive pancreatic tumor:
- Biliary retention
- Pancreatic retention
- Duodenal stenosis
- Pancreatic pain syndrome
Palliative surgery can be performed (conventional or laparoscopic) or by imaging and / or interventional endoscopic techniques.
The symptomatic treatment usually uses analgesics and is the only attempt to ease the suffering of the patient when the evolution and dissemination to locoregional lymph nodes makes impossible or ineffective any palliative measure. Life expectancy is minimal.
Therapeutic means that can be implemented to achieve the therapeutic goals, in relation to the particular situation of each patient are:
- Laparoscopic surgery or classic surgery
- Interventional endoscopy
- Interventional imaging
- Radiation therapy
- Hormone therapy