Bay Biosciences provides high-quality biopsy tissue samples, formalin fixed paraffin embedded (FFPE) tissue blocks, with matched fresh frozen sera (serum), plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids, from patients diagnosed with pancreatic cancer.
The sera (serum), plasma and peripheral blood mononuclear cells (PBMC) biofluid specimens are processed from patients peripheral whole-blood using customized collection and processing protocols from pancreatic cancer.
Fresh frozen tissue and matched biofluid samples were, collected from unique patients diagnosed with pancreatic cancer.
Bio-samples are provided to a valued pharmaceutical customer for research, diagnostics, discovery, and drug development.
Pancreatic Cancer Overview
Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas. Most pancreatic cancer begins in the cells that line the ducts of the pancreas.
The pancreas is located behind the stomach in the back of the abdomen, near the gallbladder. It contains glands that create hormones, including insulin, and enzymes. It has cells with endocrine (hormonal) and exocrine (digestive) functions; cancer cells can develop from both types of functional cells.
Pancreatic cancer is highly lethal because it grows and spreads rapidly and often is diagnosed in its late stages. This is because it often doesn’t cause symptoms until after it has spread to other organs. Most pancreatic cancers are adenocarcinomas.
Several types of growths can occur in the pancreas, including cancerous and noncancerous tumors. The most common type of cancer that forms in the pancreas begins in the cells that line the ducts that carry digestive enzymes out of the pancreas (pancreatic ductal adenocarcinoma).
Pancreatic cancer treatment options are chosen based on the extent of the cancer. Options may include surgery, chemotherapy, radiation therapy or a combination of these.
According to the American Cancer Society (ACS) about 3% of all cancers in the United States are pancreatic cancers and contribute to about 7% of all cancer deaths. In 2021, the ACS expects around 60,430 patients to receive a diagnosis of pancreatic cancer.
Chemotherapy after surgery can lower the chances of the cancer returning. For metastatic pancreatic cancer chemotherapy can extend life and improve the quality of life, but it rarely cures the patient.
Functions of the Pancreas
The pancreas is a hormone-producing organ in the abdomen that sits in front of the spine above the level of the belly button. It performs the following two main functions:
- First, it makes insulin, a hormone that regulates blood sugar levels ( which is an endocrine function); and
- Second, it makes and secretes into the intestine digestive enzymes which help break down dietary proteins, fats and carbohydrates (an exocrine function).
The enzymes help digestion by chopping proteins, fats, and carbohydrates into smaller parts so that they can be more easily absorbed by the body and used as building blocks for tissues and for energy.
Enzymes leave the pancreas via a system of tubes called “ducts” that connect the pancreas to the intestines where the enzymes mix with ingested food.
The pancreas sits deep in the abdomen and is in close proximity to many important structures such as the small intestine (the duodenum) and the bile ducts, as well as important blood vessels and nerves.
Types of Pancreatic Cancer
There are several types of pancreatic cancer, the vast majority (more than 90 percent) of all diagnoses are for adenocarcinoma of the pancreas.
Pancreatic cancer types can be divided into the following two major categories:
- Cancers of the endocrine pancreas (the part that makes insulin and other hormones) are called “islet cell” or “pancreatic neuroendocrine tumors or PNETs”.
- Cancers of the exocrine pancreas (the part that makes enzymes).
Islet cell cancers are rare and typically grow slowly compared to exocrine pancreatic cancers. Islet cell tumors often release hormones into the bloodstream and are further characterized by the hormones they produce (insulin, glucagon, gastrin, and other hormones).
Cancers of the exocrine pancreas (exocrine cancers) develop from the cells that line the system of ducts that deliver enzymes to the small intestine and are commonly referred to as pancreatic adenocarcinomas. Squamous cell pancreatic cancer is rare.
Adenocarcinoma of the pancreas comprises most all pancreatic ductal cancers.
Cells that line the ducts in the exocrine pancreas divide more rapidly than the tissues that surround them. For reasons that we do not understand, these cells can make a mistake when they copy their DNA as they are dividing to replace other dying cells.
In this manner, an abnormal cell can be made. When an abnormal ductal cell begins to divide in an unregulated way, a growth can form that is made up of abnormal looking and functioning cells.
The abnormal changes that can be recognized under the microscope are called “dysplasia.” Often, dysplastic cells can undergo additional DNA mistakes over time and become even more abnormal.
When these dysplastic cells invade through the walls of the duct from which they arise into the surrounding tissue, the dysplasia has become a cancer.
In a recent study, researchers reported analysis of the genes in 456 pancreatic ductal adenocarcinomas. Subsequent expression analysis of these adenocarcinomas allowed them to be defined into four subtypes.
These subtypes have not been previously discerned. These subtypes include the following:
- Aberrantly differentiated endocrine exocrine (ADEX): These type of tumors display the genes (KRAS) and exocrine (NR5A2 and RBPJL) plus endocrine (NEUROD1 and NKX2-2) differentiation.
- Immunogenic: These type of tumors contain pathways that are involved in acquired immune suppression.
- Pancreatic progenitor: These type of tumors express genes involved in pancreatic development such as FOXA2/3, PDX1, and MNX1.
- Squamous: These type of tumors have enriched TP53 and KDMA mutations.
These new findings may allow future cancer patients to be treated more specifically depending on their subtype and, hopefully, more effectively. For example, the immunogenic subtype could possibly respond to therapy where the immune system is re-engineered to attack these types of cancer cells.
Exocrine (Nonendocrine) Pancreatic Cancer
Exocrine pancreatic cancer develops from exocrine cells, which make up the exocrine gland and ducts of the pancreas. The exocrine gland secretes enzymes that help break down carbohydrates, fats, proteins and acids in the duodenum.
The various types of exocrine pancreatic cancers make up more than 95 percent of all cancers of the pancreas.
These include the following:
Adenocarcinoma
Also called ductal carcinoma, adenocarcinoma, is the most common type of pancreatic cancer, accounting for more than 90 percent of pancreatic cancer diagnoses. This cancer occurs in the lining of the ducts in the pancreas.
It’s also possible for adenocarcinoma to develop from the cells that create pancreatic enzymes. When this occurs, it is called acinar cell carcinoma, which accounts for 1 percent to 2 percent of exocrine cancers.
Acinar cell carcinoma symptoms are similar to the symptoms of adenocarcinoma, which include abdominal pain, nausea and weight loss. However, jaundice is not as common. Due to an increase in enzymes, some patients may have skin rashes and joint pain.
Squamous Cell Carcinoma
This extremely rare nonendocrine cancer of the pancreas forms in the pancreatic ducts, and is made purely of squamous cells, which are not typically seen in the pancreas.
There have not been enough reported cases of this disease for its origins to be fully understood. Studies have reported that it has a very bad prognosis due to most cases being discovered after metastasis.
Adenosquamous Carcinoma
This rare type of pancreatic cancer represents 1 percent to 4 percent of exocrine pancreatic cancers. Compared with adenocarcinoma, adenosquamous carcinoma is a more aggressive tumor with a poorer prognosis. These tumors show characteristics of both ductal adenocarcinoma and squamous cell carcinoma.
Colloid Carcinoma
Another rare type, colloid carcinomas account for 1 percent to 3 percent of exocrine pancreatic cancers. These tumors tend to develop from a type of benign cyst called an intraductal papillary mucinous neoplasm (IPMN).
Because the pancreatic colloid tumor consists of malignant cells that float in a gelatinous substance called mucin, it is not as likely to spread and is easier to treat than other pancreatic cancers. It also has a much better prognosis.
Neuroendocrine Pancreatic Cancer
Pancreatic neuroendocrine tumors (NETs) develop from cells in the endocrine gland of the pancreas, which secretes the hormones insulin and glucagon into the bloodstream to regulate blood sugar.
Also known as endocrine or islet cell tumors, neuroendocrine cancers are rare, making up less than 5 percent of all pancreatic cancer cases.
Benign Precancerous Lesions
Cysts and other benign tumors can form in the pancreas, and some can be precursors to pancreatic cancers, including intraductal papillary-mucinous neoplasms (IPMNs). Often, IPMNs and other benign lesions are found when a patient is being scanned for an unrelated medical reason.
Depending on the location and type of the growth, your doctor may want to either surgically remove the lesion or continue monitoring it to ensure that it does not become malignant.
Pancreatic Cancer Subtypes
Genetic analysis has identified the following four pancreatic cancer subtypes:
- Aberrantly differentiated endocrine exocrine (ADEX)squamous
- Immunogenic
- Pancreatic progenitor
- Squamous
Signs and Symptoms of Pancreatic Cancer
The symptoms of pancreatic cancer often do not appear until the later stages. They can also resemble the symptoms of other conditions, which can make diagnosis more challenging. If the cancer spreads, new symptoms can appear elsewhere in the body.
Following are some of the common symptoms of pancreatic cancer:
- Abdominal Pain
- Back Pain
- Blood clots in the legs, (deep vein thrombosis or pulmonary embolism)
- Dark colored urine
- Diarrhea or constipation
- Diabetes
- Fever and chills
- Jaundice, which is present in around 70% of people with this type of cancer
- Itchy skin
- Indigestion
- Loss of appetite and weight loss
- Nausea
- Overall weakness
- Pale gray or fatty stool
- Swelling of the gallbladder or liver
- Rash due to jaundice
- Vomiting
Causes of Pancreatic Cancer
The cause of pancreatic cancer is unknown. Pancreatic cancer occurs when abnormal cells begin to grow within the pancreas and form tumors, but it’s unclear why this happens.
Usually, healthy cells grow and die in moderate numbers. In the case of cancer, there’s an increase in the production of abnormal cells. These cells eventually take over healthy cells.
While the underlying cause of pancreatic cancer is unknown, certain factors may increase your risk of developing it.
Risk Factors of Pancreatic Cancer
Following are some of the factors which increase the risk of developing pancreatic cancer:
Genetic Factors
There is some evidence to suggest that the pancreatic cancer may run in families.
Certain genetic conditions that may have links to pancreatic cancer include the following:
- Von Hippel-Lindau syndrome
- Peutz-Jeghers syndrome
- Lynch syndrome
Sex and Age
Pancreatic cancer affects more males than females. According to the American Cancer Society (ACS) estimates this year about 62,210 people (32,970 men and 29,240 women) will be diagnosed with pancreatic cancer.
Although pancreatic cancer can occur at any age, including during childhood it is more likely to appear after the age of 55 years.
Exposure to Environmental Toxins
Exposure to chemicals used in dry cleaning or metalworking may increase the risk of pancreatic cancer.
Other Medical Factors
Patients with the following health conditions may have a higher risk of pancreatic cancer:
- Cirrhosis or scarring of the liver
- Diabetes
- Infection of the stomach with the ulcer-causing bacterium Helicobacter pylori
- Obesity
- Chronic pancreatitis or inflammation of the pancreas
Lifestyle Factors
Some lifestyle factors may also contribute to the development of pancreatic cancer, such as:
- Consuming two or more soft drinks per day
- Eating a diet that is high in red meat and fat and low in fruits and vegetables
- Drinking a lot of alcohol over time
- Having excess weight
- Getting low levels of exercise
- Smoking
Pancreatic Cancer Racial Inequalities
Statistics show that black Americans are more likely to develop pancreatic cancer than any other group in the United States.
A recent study notes that the most likely explanation for this is social inequality. This impacts outcomes in various ways, including the availability of effective treatment options. This inequity affects both Black and Hispanic Americans.
The Pancreatic Cancer Action Network urges Black Americans to participate in clinical trials. This not only gives them access to treatment that might otherwise be unavailable, but it also increases the likelihood of research taking Black people’s needs into account.
Pancreatic Cancer Stages and outlook
The outlook for pancreatic cancer depends partly on which stage it is at when a doctor diagnoses it. A cancer’s stage refers to how far it has spread.
For pancreatic cancer, the stages are:
- Stage 1: The cancer is in the pancreas. It is localized.
- Stage 2: The cancer has reached the bile duct and other structures but not the lymph nodes. It is regional.
- Stage 3: The cancer affects the lymph nodes but is still regional.
- Stage 4: The cancer has reached other organs and parts of the body. It is distant.
According to the ACS a patient who receives a diagnosis of pancreatic cancer has the following chances of surviving for another 5 years or longer compared with someone who does not have the condition:
- 39% when it is localized
- 13% when it is regional
- 3% when it is distant
In the early stages, treatment may be able to remove the cancer from the pancreas. As the cancer progresses, however, this becomes more challenging.
According to an article, in around 23% of people with pancreatic cancer, the tumor is localized at the time of diagnosis. However, about 52% of people receive a diagnosis when it has already spread to other parts of the body.
Diagnosis of Pancreatic Cancer
Your doctor will ask about symptoms, take a family and medical history, and carry out a physical examination. They may also recommend some tests.
Some of the following diagnostic tests may be recommend by your doctor to diagnose pancreatic cancer :
- A biopsy to confirm a diagnosis
- Blood tests, including a liver function tests (LFT)
- Urine and stool tests
- Imaging tests, such as X-rays, ultrasound scans, or MRI scans
Treatment of Pancreatic Cancer
The treatment options for pancreatic cancer will depend on:
- Type of pancreatic cancer a patient has
- Cancer stage
- Patient’s age, overall health, and other characteristics
- Personal choices
Treatment aims to:
- Remove the cancer
- Delay or stop its progress
- Relieve the symptoms
Surgery
If the cancer is localized at the time of diagnosis, it may be possible to eliminate the cancer cells by removing all or part of the pancreas.
The three main surgical procedures for pancreatic cancer are:
Whipple Procedure
In a Whipple procedure, a surgeon removes the pancreas head and sometimes the whole pancreas, along with a portion of the stomach, duodenum, lymph nodes, and other tissue.
Complications include leaking, infections, bleeding, and stomach problems.
Distal Pancreatectomy
In distal pancreatectomy, the surgeon removes part of the pancreas and usually the spleen as well.
The spleen supports the immune system, so there may be a higher risk of infection after its removal.
Total pancreatectomy
In total pancreatectomy, the surgeon removes the entire pancreas and spleen.
A person can live without a pancreas, but diabetes may develop because the body no longer produces insulin cells.
Palliative Surgery
Palliative surgery can help relieve symptoms such as obstructions in the bile duct or duodenum.
A surgeon can create a bypass so that bile can continue to flow from the liver. This can minimize pain and digestive problems.
Another option is to insert a small stent in the bile duct to keep it open. This is a less invasive procedure using an endoscope.
Embolization
In embolization, a doctor will into an artery a substance that stops blood from reaching the cancer cells. Without the blood supply, these cells will die.
Side effects of embolization include abdominal pain, nausea, fever, infections, and a risk of blood clots in the area of the injection.
Ablation
Ablation uses heat or cold to destroy a tumor. It may help with tumors that are smaller than one inch across. A surgeon will insert a needle or a probe to apply the treatment. Possible side effects include pain, infections, and internal bleeding.
Targeted Therapy
This is a newer approach than chemotherapy. It stops cancer cells from developing by targeting substances they need to grow.
There are different types of targeted therapy, such as:
- EGFR inhibitors, which block the EGFR protein
- PARP inhibitors, which block PARP enzymes
- NTRK inhibitors
Unlike chemotherapy, these drugs have specific targets, so their impact on the whole body is lessened. However, they can still have adverse effects, which will depend on the type of treatment a person receives.
Immunotherapy
Immunotherapy works by helping the body’s immune system recognize and destroy cancer cells.
PD-1 inhibitors are one type of immunotherapy that may help treat pancreatic cancer. People receive this treatment as an infusion once every 2–3 weeks.
Possible side effects include fatigue, a cough, a rash, and joint pain.
Radiation Therapy
Radiation Therapy destroys cancer by focusing high energy rays on the cancer cells. It can shrink or remove a tumor. In the later stages, it can help relieve symptoms by removing or reducing a blockage.
Like chemotherapy, it can cause some side effects, such as skin changes, gastrointestinal disturbances, and fatigue. However, these usually pass after completing treatment.
A person may receive radiation therapy either alone or with other treatments, usually on five days per week for several weeks.
Before making a diagnosis, a doctor will need to rule out other possible causes of the symptoms.
These could include:
- Acute pancreatitis
- Chronic pancreatitis
- Cholangitis
- Cholecystitis
- Peptic ulcer disease
- Stomach cancer
Prevention of Pancreatic Cancer
No specific measure can prevent pancreatic cancer, but some lifestyle choices can help reduce the risk.
These include:
- Eating fresh fruits and vegetables
- Maintaining a moderate weight
- Exercising often
- Limiting one’s intake of red meat
- Quitting smoking
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