Breakthrough Diagnostic: Detects 95% Stage 1 Pancreatic Cancer

Pancreatic Cancer (iStock Credit: libre de droit)

Is there potential to reduce the mortality rate from this deadly disease?

Pancreatic cancer is the third leading cause of cancer death as of 2022 and is forecasted to become the second by 2030. In general, pancreatic cancer is less common than many other large cancer groups, however due to the rising incidence in an aging population, and the high fatality rate, it is rapidly becoming one of the most frequent causes of cancer deaths.

In this article, we will explore the signs, stages, risk factors, and a potential new screening tool for pancreatic cancer.

Pancreatic cancer is a disease in which malignant (cancer) cells form in the tissues of the pancreas. The pancreas is a dual-functioning organ located in the abdomen behind the stomach. It functions as both an exocrine and endocrine gland. The exocrine component produces and secretes digestive enzymes into a network of ducts. These enzymes help to break down carbohydrates, fats, and proteins into smaller fragments for absorption.

The endocrine portion of the pancreas is made up of islet cells called the islets of Langerhans, which produce and release insulin and glucagon. Insulin lowers blood sugar while glucagon raises blood sugar. Keeping blood sugar levels in balance is important for the functioning of different organs, such as the brain, liver, and kidneys.

Pancreatic tumors originate from two different types of cells. About 95% are exocrine tumors, with the most common type being pancreatic adenocarcinoma or PDAC. This type starts in the cells that line the pancreatic duct. The remaining 5% are neuroendocrine tumors, which are also called islet cell tumors. Knowing the type of tumor is important because each type acts differently and responds to specific treatments.

Stage is a term used in cancer treatment to describe the extent of the cancer’s spread. The stages of pancreatic cancer are used to guide treatment and to classify patients:

Stage 0: No spread. The pancreatic cancer is not visible on imaging tests.

Stage 1: Local growth. Pancreatic cancer is limited to the pancreas, but has grown greater than 2 cm but no more than 4 cm.

Stage 2: Local spread. Growth is over 4 cm and is either limited to the pancreas, or the cancer has grown outside of the pancreas, or has spread to nearby lymph nodes.

Stage 3: Wider spread. The tumor may have expanded into nearby major blood vessels or nerves.

Stage 4: Confirmed Spread. Pancreatic cancer has spread to distant organs.

Signs and symptoms of pancreatic cancer may be absent or subtle in the early stages, but as the disease progresses, individuals may experience:

· Jaundice (yellowing of the skin and eyes)

· Dark brown urine

· Light-colored or greasy stools

· Pain in the abdomen or back

· Digestive difficulties including indigestion, nausea, vomiting, and diarrhea

· Unintended weight loss often accompanied by a general loss of appetite and fatigue

· Abdominal swelling

· Sudden onset diabetes (or when well-controlled diabetes suddenly becomes uncontrolled)

While having one or more of the symptoms does not guarantee pancreatic cancer, the symptoms are initially attributed to other less serious and more common conditions. It is recommended to visit a doctor to be sure of the cause and receive proper treatment.

Pancreatic cancer is multifactorial and has various risk factors. The risk increases after age 45. Most patients are between the ages of 65–70 at the time of diagnosis. Men are more likely to develop pancreatic cancer due to higher tobacco use.There is also a higher incidence among African Americans than other ethnic groups.

Cigarette smoking increases the risk of pancreatic cancer by twofold, and 25% of pancreatic cancers are thought to be a direct result of smoking. Workplace exposure to certain chemicals in the dry cleaning and metal working industries poses an environmental risk factor.

Obesity, particularly during early adulthood, increases the risk of pancreatic cancer in addition to having excessive abdominal fat. Pancreatic cancer is more common in people who have had type 2 diabetes for more than five years. It is common for individuals to develop diabetes before pancreatic cancer is detected.

Chronic pancreatitis, long term inflammation of the pancreas, is a risk factor usually linked to excessive alcohol use and smoking or due to an inherited gene mutation.

With regard to family history and genetic susceptibility, inherited gene changes may cause as many as 10% of pancreatic cancers. The risk of developing pancreatic cancer multiplies 2–3 times if one or more first-degree relatives (parent, sibling, or child) are diagnosed with pancreatic cancer.

There are several inherited gene mutations that have been linked to an increased risk of pancreatic cancer including: Hereditary breast and ovarian cancer syndrome caused by mutations in the BRCA1 or BRCA2 genes, hereditary Lynch syndrome (colorectal cancer), hereditary melanoma and hereditary pancreatitis.

Pancreatic cancer has been known as a “silent disease” because most patients present with non-specific symptoms and are at an advanced stage when diagnosed. At this time, cancer cells have broken away from where they first formed (the primary tumor), travelled through the blood or lymph system and formed new tumors (metastatic tumors) in other parts of the body. Conventional therapies such as surgery, chemotherapy, and radiation therapy have limited success at this stage.

Additionally, the pancreas is located deep within the abdomen and imaging tests may be inconclusive, causing the disease to go unrecognized even as it progresses rapidly from stage 1 to stage 4. Furthermore, there are no biomarkers detectable in the blood or other bodily fluids to indicate the presence of the tumor. Consequently, over 50% of pancreatic cancer cases are diagnosed when the disease has already metastasized (stage 4).

Screening for pancreatic cancer is not a widely accepted practice as this type of cancer is uncommon in the general population resulting in unnecessary costly tests. Yet most doctors do recommend annual screening for individuals who are known to be at a higher risk due to family history or the presence of associated conditions. This would involve one of the following tests: An MRI scan, a CT scan, or endoscopic ultrasound.

Early detection of cancer before symptoms arise is essential for improving patient survival. For the small number of individuals (~15%) diagnosed with localized cancer, the 5-year survival rate is approximately 25%. If pancreatic ductal adenocarcinoma (PDAC) is identified at Stage 1, survival rates can be as high as 80%.

Over the last couple of decades, cancer researchers have developed multi-cancer early detection (MCED) tests designed to detect various cancer types from multiple organs simultaneously. Similar to other screening tests, MCED tests do not diagnose cancer but rather detect it in those with no symptoms. MCED tests analyze blood plasma for changes in DNA, RNA, and proteins, in addition to antibodies that a person may produce against parts of cancer cells. Several MCED tests based on these approaches show potential in finding advanced (stage 3 and 4) cancers and are useful for predicting the outcome of the illness.

Research scientists are exploring new technology that could detect signs of stage 1 and 2 cancers. Early stages of cancer have very few cancer-related biomarkers, so current MCED tests are not sensitive enough to detect them.

Fortunately, Dr. Andrew Lowy, a clinical director for Cancer Surgery at UC San Diego School of Medicine, and his colleagues have identified a promising new method involving extracellular vesicles (EVs) for detecting cancer-related biomarkers from blood in the early stages. EVs are released by tumors into the bloodstream and carry functional protein biomarkers that represent the tumor proteins.

By using an ACE platform, scientists were able to separate and measure the concentrations of proteins in EVs from the blood of people with early-stage pancreatic, ovarian, and bladder cancers, as well as from healthy individuals. With this information, a machine-learning algorithm was created to identify a small set of EVs biomarkers which, together with age, successfully detected early-stage pancreatic (95.5%), ovarian (73.1%), and bladder (43.8%) cancers with more than 99% specificity. This demonstrates the potential value of this technology for early cancer detection.

Current liquid biopsy tests — a blood test that detects signs of cancerous tumors- for early-stage cancer detection have a high chance of producing false-positive results — a result that indicates a given condition exists when it does not. This can lead to expensive and dangerous diagnostic tests for people who are actually healthy.

However, the results of this new test are five times more accurate making it a much more viable option for early-stage cancer detection.

At present, only 5% of pancreatic cancers are diagnosed during stage 1, and only 10% are found in time for surgery. Pancreatic cancer has the lowest 5-year relative survival rate of all major cancers, and is the only one for which the incidence and death rates are both increasing.

With more advanced testing, this method could prove to be a useful screening tool for medical professionals to detect cancer in its early stages, and potentially reduce mortality from this deadly disease.













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