PANCREATIC CANCER OVERVIEW 

The pancreas is an organ which is located at the back of the stomach. It lies horizontally at the lower part of the stomach. It is divided into head, body, and tail. This is an accessory digestive organ with both exogenous and endogenous functions.

Pancreatic amylase, pancreatic lipase, and trypsin which are exogenous enzymes facilitate the breaking down of carbohydrates, lipids, and proteins respectively for absorption by the body. On the other; insulin and glucagon endogenous hormones regulate blood sugar.
Cancer of the pancreas are neoplasms of either exocrine or endocrine components of the pancreas with the former commonly encountered. A large percentage of pancreatic function has to be impaired before its deficient symptoms manifest, because of this reason and its location behind the stomach pancreatic cancer is diagnosed late in its advanced stage.

Hence, curative management is mostly impossible because of metastasis. In the United States, pancreatic cancer is the fourth in ranking based on deaths caused by cancers.

WHAT IS PANCREATIC CANCER?

In very simple terms pancreatic cancer refers to the abnormal growth of the cells and tissues of the pancreas. This abnormal cells invade nearby tissues and spread to other parts of the body.

The cells that produce digestive enzymes are the ones that are most affected by cancers. Though hormone-producing islet cells are also cancer originating cells, they are rarely diagnosed.

TYPES OF PANCREATIC CANCER

Pancreatic cancers are grouped under two main categories based on the cell type of abnormal proliferation. Under this category we have;

1. PANCREATIC EXOCRINE CANCERS;

These kind of cancers are the most common types of pancreatic cancers known. They affect the cells that produce digestive enzymes. Exocrine cancers of the pancreas are further classified below;

A. Pancreatic Adenocarcinoma of the ducts;

It is the most common type of all exocrine cancers of the pancreas. It ranks as 95% of all pancreatic cancers diagnosed. This kind of cancers begins in the main duct, interlobular ducts, and ductules of the pancreas. It affects the columnar and cuboidal epithelial cells of the duct.

Ductal adenocarcinoma affects the epithelial cells in the body and tail of the pancreas but it affects the cells in the head of the organ the most. Because of its ability to puncture into nearby tissues and organs, it is also known as Invasive Ductal adenocarcinoma of the pancreas.

B. Acinar Cell Carcinoma;

This type begins in the epithelial cells of the digestive enzymes producing cells of the pancreas called the Acinar cells. This kind of pancreatic cancer is rare and mostly affect men. It constitutes less than a percentage of all pancreatic cancers.

C. Adenosquamous Carcinoma of the pancreas;

This type of pancreatic cancer begins in the duct of the pancreas. As the name states, these cancerous cells are a mixture of squamous cell carcinoma and adenocarcinoma. This is a very rare form of exocrine cancer of the pancreas.

Because the ducts of the pancreas do not have squamous cells, it is assumed that the squamous cells that are found in this cancer are due to squamous metaplasia. This refers to a change of the glandular epithelial cells in the pancreatic duct into squamous epithelial cells. This change normally happens due to chronic inflammation of the pancreas.

D. Undifferentiated pancreatic carcinoma;

This is a very rare form of pancreatic cancer which affects elderly people. It affects both genders equally and has a very poor prognosis. Under a microscope, the actual origin of these cancerous cells is not easily detected. This is because the cells look so abnormal and different from the normal cells in the pancreas. For this reason, it is also known as anaplastic carcinoma of the pancreas.

E. Carcinoma of the Ampulla of Vater;

This kind of cancer begins from the hepatopancreatic duct called the ampulla of Vater. This means that the cancerous cells originate from the cells of the pancreatic duct and the cells of the common bile duct. This cancer normally blocks the transfer of bile from the gall bladder to the liver and consequently cause (jaundice) yellowing of the skin and sclera of the eye.

F. Pancreatoblastoma;

This kind of cancer affects children mostly and it is very rare in the elderly. It normally forms a large solid mass in the pancreas. Histologically cells from this cancer resemble acinus cells which fit together in a squamous pattern.

G. Solid pseudopapillary tumors;

This kind of neoplasm affects young women around age 30. It is a rare kind of tumor and it is mostly benign. It can sometimes become cancerous as well. It is characterized by a well-demarcated encapsulation around the abnormal cell. It is most often located in the tail of the pancreas.

H. Cystic Tumors of the pancreas;

These are mostly benign or precancerous cell growth in the pancreas know by fluid-filled sacs called cysts. These are mostly called cystadenomas. Some types of these cystic neoplastic growths are explained below;

• Mucinous Cystic tumors;

This is the most common type of fluid-filled neoplasm in the pancreas. It normally forms in the body and tail of the pancreas. It affects women around the age of 40 to 50 years. The fluid-filled cells are thickly walled and produce a translucent and viscous fluid called mucinous fluid. These cysts can become malignant transforming from its precancerous cystadenoma into cystadenocarcinoma.

• Serous cystic tumors;

These neoplasms mostly affect elderly women around age 60 to 70 years. They are mostly benign tumors which do not spread. But they can grow bigger on a few occasions and cause pain and discomfort. The fluid-filled cells have thick walls. The cysts contain transparent glycogen based serious fluid.

• Intraductal papillary Mucinous tumors;

This kind of neoplasm is the most common precancerous cyst in both women and men around age 70. The fluid-filled cells grow in the main duct where they cause distention of the duct. They can also be found in the interlobular ducts. This fluid cells can be localized or malignant. The fluid contained in the cyst is the unclear and viscous protein based mucinous fluid.

2. PANCREATIC ENDOCRINE(NEUROENDOCRINE )CANCERS;

This type of cancer originates from the hormone-producing cells of the pancreas known as the Islet cells. These are very rare cancers and comprise about 5% of all pancreatic cancers. These cancers are grouped according to the particular type of islet cells they originate from. On a wider picture, neuroendocrine pancreatic cancers are categorized into two main groups, based on the amounts of hormones produced and the resulting effects of the hormones in the body. These types are;

A. FUNCTIONAL PANCREATIC NEUROENDOCRINE CANCERS.

This kind of neuroendocrine tumors affect cells that produce a lot of hormones which have a significant effect on the body.

Examples of this type are;

• INSULINOMA;

This is a kind of neuroendocrine tumor which affects the beta cells of the pancreas. The tumor of this cell causes high levels of insulin which as a result lead to hypoglycemia in the patients. It is characterized medically by the Whipple’s triad. Most people with insulinoma are known by these criteria; symptoms of low blood sugar, blood glucose level lower than 2.78mmol/L, recovery from hypoglycemic symptoms after glucose intake. These three form the Whipple’s triad. These tumors are mostly benign and they do not spread to distant tissues.

• GLUCAGONOMA;

This type affects the glucagon hormone-producing cells of the pancreas known as the alpha cells. This kind of tumor cause over secretion of glucagon which causes an effect on the body. The main effects caused by the increased glucagon levels due to this tumor is grouped into a syndrome called glucagonoma syndrome.

This syndrome is made up of;

1. Red itchy rashes on the buttocks, perineum, armpit, in-between the thighs, and lower abdomen (NECROLYTIC MIGRATORY ERYTHEMA),
2. Sudden diabetic mellitus (persistent high blood sugar),
3. A low number of normal-sized red blood cells(normocytic anemia),
4. Weight loss.

• GASTRINOMAS;

This kind of tumor affects the cells that produce the hormone gastrin. These cells are called G cells of the pancreatic islets of Langerhans. This overproduction of gastrin leads to overstimulation of the parietal cells of the stomach. This overstimulation leads to excess production of hydrochloric acid (hyperchlorhydria) in the stomach, leading to peptic ulcer disease. This type of tumors is mostly cancerous.

• VIPoma;

This type of tumors come from the Delta 2 cells in the pancreas that produce the hormone vasoactive intestinal peptide(VIP). This hormone causes relaxation of gastric smooth muscles. It causes the release of sodium, chloride, potassium, water, and inhibit the secretion of hydrochloric acid. It also inhibits reabsorption of the electrolytes and it causes increased gastrointestinal motility. This consequently causes; secretory (Watery )diarrhea, low levels of potassium due to diarrhea, dehydration, and low levels of gastric acid (Achlorhydria). This type of tumor is mostly cancerous. It is sometimes called Pancreatic diarrhea.

• SOMATOSTATINOMA;

In this type of tumor there is an increased secretion of the hormone somatostatin. These tumors occur in the delta cells of the pancreas. The increased amounts of somatostatin cause the following, inhibition of insulin production (mild form of diabetes), inhibition of gastrin release and resultant low levels of gastric acid (achlorhydria), and inhibition of cholecystokinin production which prevents digestion of fats causing (excess fat in feces) and accumulation of bile and cholesterol in the gall bladder (gallstones). They are mostly cancerous in nature.

• PPmomas;

This refers to tumors of the cells that produce the hormone pancreatic polypeptide(PP). This is the F cells of the pancreas. This tumors are mostly silent and do not produce a lot of symptoms. On the contrary, they can also be malignant. High levels of the pancreatic polypeptide can prevent the release of bile and secretion of pancreatic enzymes.

B. NON FUNCTIONAL PANCREATIC NEUROENDOCRINE CANCERS.

These tumors are mostly of cells that contain small secretory granules that can produce very small amounts of hormones. The hormones produced by these tumors are not enough to cause any metabolic alterations. An example is a Carcinoid tumor of the pancreas. A carcinoid tumor of the pancreas is rare and it grows slowly but produces just a hand full of hormone which has no recognizable effect in the patient.

EPIDEMIOLOGY

Pancreatic cancer is ranked as the seventh most common cause of cancer deaths in the world. This is because statistically, it causes over 331,000 deaths per year based on information produced by GLOBOCAN in the year 2012. This makes up to about 4% of all deaths recorded in the world. In the same 2012, an estimated number of over 337,000 people were diagnosed with pancreatic cancer. The frequency of occurrence and rate of death of pancreatic cancer is higher in men than in women.

Pancreatic cancer is the fourth highest cause of cancer fatalities in the United States and ranks as the sixth leading a cause of cancer deaths in the United Kingdom. It affects elderly people around the age of 60 to 70 years. Most pancreatic cancers are found in their advanced stages which make them impossible or difficult to manage.

Statistically, cancers of the pancreas are common among African Americans. The highest frequencies of occurrences were found in Northern America, Western part of Europe.

On the other hand, the lowest incidences of pancreatic cancer were found in the Middle part of Africa and Southern Part of Asia (mostly the south-central areas of Asia ). Globally a lot of factors are linked to pancreatic cancer, and some of these factors are; tobacco smoking, alcoholism, obesity, genetic factors, and others.

CANCER RESEARCH BUDGET PER YEAR

The world has never rested on research into reduction of the incidence and mortality of all cancerous conditions in the world. Research continues, in order to find better treatment procedures and develop potent drugs which can help increase the survival rate of cancer diagnosed patients.

Pancreatic cancer just like all other cancers is a huge problem in the world. The National Institute of Health(NIH) from the American government allocated an amount of about 4,900million dollars in 2015, about 5,200million dollars in 2016, and about 5,900 million dollars 2017 for research by the National Cancer Institute.

In addition to this, the budget made particularly for research into pancreatic cancer from the years 2012 to 2017 is about 790million dollars. The average amount of money over this period per year is about 120 million dollars. It is well noted that the American government spends a lot of money on cancer researches.

CAUSES

The cause of pancreatic cancer is not that clear but just like all other kinds of cancers, it is due to Genetics mutations.

These mutations can be;

1. Inherited Genetic;

Mutations which occur before birth (spontaneous mutations ) or may be acquired during intrauterine life.

2. Acquired mutations;

Induced mutations caused after birth due to environmental factors like smoking of tobacco and exposure to other carcinogens.

 

PATHOPHYSIOLOGY

The effects of genetic mutation on cell cycle lead to uncontrolled cell division and proliferation. These cells refuse to die, hence accumulate and form tumors.

These tumors continue to grow and invade nearby tissues and finally, some of them spread to distant organs through blood and lymph nodes.

RISK FACTORS

1. Smoking of tobacco products.
2. Eating foods with too much fat.
3. Obesity.
4. Chronic pancreatitis.
5. A family history of pancreatic cancer.
6. Increased age over 65 years.
7. A family history of mutations on the P53 gene, and higher levels of Epidermal growth factor receptors on pancreatic cells.
8. Being a diabetic patient.
9. Being a Chronic alcoholic.
10. Having liver damage.
11. Race (African American).
12. Not eating or eating too little amounts of vegetables and fruits.

CLINICAL MANIFESTATIONS 

Symptoms are mostly not manifest in the early stage of this disease but present mostly at the advanced stage.

1. Weight loss.
2. Loss of appetite.
3. Abdominal Pain that radiates to the back.
4. Yellowing of skin and sclera of the eye.
5. Blood clots.
6. Depression.
7. Skin itchiness.
8. Sudden onset of diabetes mellitus.

COMPLICATIONS

1. Enlarged liver.
2. Total body weakness.
3. Altered mental status; severe depression.
4. Intestinal obstruction; constipation.
5. Diarrhea.
6. Nausea and vomiting.
7. Peptic ulcer formation.
8. Dark urine.
9. Fatty stools.
10. Intestinal obstruction and/Gastric obstruction.

PROGNOSIS

Pancreatic carcinomas generally have a poor prognosis. The exocrine carcinomas (adenocarcinoma) of the pancreas normally have the worst prognosis. This is because most adenocarcinomas are detected in their advanced stages where they are not surgically removable. They are mostly not responsive enough to chemotherapy. The survival duration of people whose advanced adenocarcinomas respond to combination chemotherapy is about only a year.

About 80% of all pancreatic cancers are diagnosed in advanced stages. This makes the 5-year survival rate for pancreatic cancer patients very low at about 2 %to 5%. On the other hand pancreatic neuroendocrine cancers normally can be surgically removed because most of them stay localized in the pancreatic tissues.

The patients diagnosed with endocrine carcinomas normally have an increased survival rate of not less than 15%.
Undifferentiated pancreatic carcinomas have a very poor prognosis of less than a year in most cases. When adenocarcinomas of the pancreas are detected early or are found to be localized tumors, surgical treatment is most successful. This increases the five years survival rate of about 20%.

ROUTES OF METASTASIS OF PANCREATIC CANCER

1. Local invasion; cancerous cells invade nearby structures like portal vein, duodenum, and other structures.
2. Lymphatic spread; Cancerous cells move through lymphatic vessels to celiac, sub-pyloric lymph nodes.
3. Blood; Cancerous Cells spread to liver mostly and sometimes to other organs like the bones, brain, lungs etc through the bloodstream.

STAGES OF PANCREATIC CANCER

The staging of pancreatic cancer just like all other cancers is very important for the management procedures and it also determines the outcome of treatments. The staging is made by; the size of the tumor, a number of lymph nodes invasions, and metastasis. This is known as the TNM classification. Based on this we have;

1. Stage 0(T0, N0, M0); This type of tumor is found only in the upper parts of the pancreatic duct. It is called Carcinoma In situ meaning cancer in its original place.

2. Stage 1A(T1, N0, M0); The tumor is localized in the pancreas and has a smaller size which is less or equal to 2cm. It has not invaded any lymph node. It has not moved to any distant organ.
Stage 1B(T2, N0, M0); The tumor is larger than 2cm and it’s localized in the pancreas. There is no lymph node invasion nor distant spread.

3. Stage 2A(T3, N0, M0); The tumor has grown bigger and outside of the pancreas. But it hasn’t invaded lymph nodes nor moved to distant organs.
Stage 2B(T1 to T3, N1, M0); The tumor is grown locally in the pancreas or it has grown out of the pancreas. But it has not grown into major blood vessels or compressed nerves. Tumor cells are in neighboring lymph nodes but there is no distant spread to other organs.

4. Stage 3(T4, N1, M0); The cancer cells have grown out of the pancreas into close major blood vessels and compressed nearby nerves. Cancer is in nearby lymph nodes. But cancer has not spread to distant organs.

5. Stage 4(T4, N1, M1); Cancer has spread to distant organs like liver, lung, bones, and brain.

DIAGNOSIS OF PANCREATIC CANCER

1. Imaging techniques; Magnetic Resonance Imaging (MRI), Computed Tomography (CT ); This gives you a clear picture of the pancreas and help to determine structural alterations or cancer growth.
2. Endoscopic Ultrasounds.
3. Contrast media X-ray(Barium swallow).
4. Tissue biopsy.
5. Blood tests to determine tumor markers.
6. Endoscopic Retrograde Cholangiopancreatography (ERCP); A dye is injected into the pancreas to observe the bile ducts in the pancreas. X-ray images are taken after the dye has been injected.

PREVENTION

1. Stop Smoking.
2. Eat a diet full of vegetables and fruits.
3. Exercise regularly.
4. Avoid alcohol abuse.
5. Reduce intake of high fatty diets.

MANAGEMENT OF PANCREATIC CANCER

1. Surgery;

a) Pancreatoduodenectomy;

In this procedure part of the pancreas, part of the small intestine, and part of the gall bladder are removed. It is done for cancers affecting the head of the pancreas.

b) Distal pancreatectomy;

The removal of the lower parts of the pancreas. It is normally done for cancers that affect the tail of the pancreas.

2. Chemotherapy;

Use of drugs to kill cancer cells.

3. Targeted biological therapy;

Drugs are designed to kill only cancerous cells but not normal cells. These drugs target; new blood supply of cancer cells, intoxicate abnormal cells, cause immune cells to destroy cancer cells, inhibit cancer cells proliferating pathways.

4. Radiation therapy;

High energy light rays are directed towards cancerous cells to kill them.