Early Pancreatic Cancer detection kit

Currently, there is no reliable diagnostic tool or established early detection method for pancreatic cancer, precluding a cure for the patient. In the United States, pancreatic cancer is the fourth most common cause of deaths due to cancer.The disease occurs most often in the developed world, where about 70% of the new cases in 2012 originated. Pancreatic adenocarcinoma, which accounts for 95% of pancreactic cancershave a very poor prognosis: after diagnosis, 25% of people survive one year and 5% live for five years, because most are diagnosed in the late stages. For cancers diagnosed early, thefive-year survival raterises to about 20%.Neuroendocrine cancers have better outcomes; at fiveyears from diagnosis, 65% of those diagnosed are living, though survival varies considerably depending on the type of tumor.

The pancreas has multiple functions, served by endocrine cells in the islets of Langerhans and the exocrine acinar cells. The exocrine group of cells are dominated by the most common cancer - pancreaticadenocarcinoma(variations of this name may add "invasive" and "ductal"), representing about 85% of all pancreatic cancers. The next most common type,acinar cell carcinoma of the pancreas, arises in theclusters of cellsthat produce these enzymes, and represents 5% of exocrine pancreas cancers.Cystadenocarcinomasaccount for 1% of pancreatic cancers, and they have a better prognosis than the other exocrine cancers. There are also a small minority of tumors that arise elsewhere in the pancreas that are mainly pancreaticneuroendocrine tumors(PanNETs). Pancreatic Cancer has the lowest five-year survival rate of any common cancer and, sadly one that has barely improved in 40 years. More than 80% of people with the disease are diagnosed when it has already spread, so they are not eligible for surgery to remove the tumor –which is currently the only potential cure. Those at higher risk include people with a family history of the cancer, heavy smokers, obese people and people over 50 who are newly diagnosed with diabetes.

Diagnosingand Treating Pancreatic Cancer

The pancreas is deep within the body, so early tumors cannot be seen or felt, and 4 of 5 patients are diagnosed only after it has spread. Patients usually have no symptoms until the cancer has spread to other organs. While surgery to remove the tumor or the organ can cure up to 50 percent of early-stage pancreatic cancer, doctors see few patients at this stage.When diagnosed early, surgical resection offers the best chance for long term control of pancreatic cancer, therefore, tests sensitive enough to detect pancreatic cancer in the earliest stages are urgently needed. Until a reliable early detection test is developed, screening protocols for high-risk individuals are presently used. Doctors agree that having two or more close family members with pancreatic cancer puts a person at high risk for the disease.Two types of research programs for high-risk individuals are surveillance programs and family registries. The goal of surveillance programs is to detect early pancreatic cancer and pre-cancerous lesions in patients who are at high risk for developing pancreatic cancer. These programs involve regular monitoring of high-risk persons using tests such as EUS, CT scan and/or ERCP. Participants may also undergo novel imaging procedures, be tested for genes associated with hereditary pancreatic cancer, and have biological fluids, such as blood and pancreatic juice, collected and analyzed. Using Bloodtests doctors can monitor certain substances, such ascarcinoembryonic antigen(CEA) and CA 19-9,which are sometimes elevated in people with pancreatic cancer. However,bloodtests don't allow for early detection of pancreatic cancer, because these levels may not rise until pancreatic cancer is advanced, if at all.

Diagnosing pancreaticcancerusually happens when someone comes to the doctor after experiencing weeks or months of symptoms.Pancreatic cancer symptomsfrequently includeabdominal pain,weight loss,itching, orjaundice(yellowskin). A doctor then embarks on a search for the cause, using the tools of the trade and patient history: Pancreatic cancer often can be challenging to diagnose. Symptoms usually do not appear in the early stages, and if they do they may be mistaken for signs of another condition. Also, the pancreas is deep inside the body, behind several other organs. This makes it difficult to feel or see without proper equipment.

Treating pancreatic cancer is challenging when it's discovered at an advanced stage. Accurate diagnosis and staging are important because they help choose the best type of treatment.Treatment includes highly invasive surgery for removal of cancer or pancreatic organ for which hormones would need to be taken to replace those lost. The alternative is also invasive; long treatments of chemotherapy which may extend life briefly as this is typically the only treatment for patients who are too advanced for surgery. Several medical tests usually are required to find and stage pancreatic cancer including the following:

  • CBC count
  • Hepatobiliary tests: Patients with obstructive jaundice show significant elevations in bilirubin (conjugated and total), ALP, GGT, and, to a lesser extent, AST and ALT.
  • Serum amylase and/or lipase levels: Elevated in less than 50% of patients with resectable pancreatic cancers and in only 25% of patients with unresectable tumors
  • Tumor markers such as CA 19-9 antigen and CEA: 75-85% have elevated CA 19-9 levels; 40-45% have elevated CEA levels

Imaging studies that aid in the diagnosis of pancreatic cancer include the following:

  • Computed Tomography (CT) scanning
  • Transcutaneous ultrasonography
  • Endoscopic ultrasonography (EUS)
  • Magnetic resonance imaging
  • Endoscopic retrograde cholangiopancreatography (MRCP)
  • Positron emission tomography scanning
  • Ultrasound
  • MR angiography (MRA)
  • Percutaneous transhepatic cholangiography (PC)

Neuroendocrine tumors tests:

  • Somatostatin receptor scintigraphy (SRS) or OctreoScan

Blood tests for exocrine pancreatic cancers are often not helpful for diagnosis

Liver function tests:Jaundice (yellowing of the skin and eyes) is often one of the first signs of pancreatic cancer, but it can have many causes other than cancer. Doctors often get blood tests to assess liver function in people with jaundice to help determine its cause.

Tumor markers:Tumor markers are substances that can sometimes be found in the blood when cancer is present. Two tumor markers may be helpful in pancreatic cancer:

CA 19-9:is a substance often released into the blood by exocrine pancreatic cancer cells, although it often can’t be detected until the cancer is already advanced.

Carcinoembryonic antigen(CEA): is another tumor marker that might help find advanced pancreatic cancer in some people, but it is not used as often as CA 19-9.

Molecular testing of the tumor (other markers).Laboratory tests on a tumor sample to identify specific genes, proteins, and other factors unique to the tumor. Biomarkers for pancreatic cancer includeRAS,SPARC,hENT1, andDPC4.

Blood tests for pancreatic neuroendocrine tumors are more helpful for diagnosis

Blood tests looking at the levels of certain pancreatic hormones can often help diagnose pancreatic neuroendocrine tumors (NETs).

For insulinomas, insulin, glucose, and C-peptide levels are measured. The diagnosis of an insulinoma is made when there is low blood glucose with high levels of insulin and C-peptide.

Other pancreatic hormones, such as gastrin, glucagon, somatostatin, pancreatic polypeptide, and VIP (vasoactive intestinal peptide) can be measured in blood to help diagnose pancreatic NETs. Measuring the level of a substance calledchromogranin A(CgA) can be very helpful. This level goes up in most cases of pancreatic NETs — even tumors that don’t make excess hormones (non-functioning tumors).

Carcinoid tumors:For carcinoids, a blood test may be done to look for serotonin, which is made by many of these tumors. This test can help diagnose many (but not all) carcinoid tumors.Other common tests to look for carcinoids include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin.

Biopsy

A person’s medical history, physical exam, and imaging test results may strongly suggest pancreatic cancer, but usually the only way to be sure is to remove a small sample of tumor and look at it under the microscope.

Percutaneous (through the skin) biopsy:Endoscopic biopsy is used to attain the tissue

Stages of Pancreatic Cancer

The stage of the cancer is a measure of the extent to which the tumor has grown in the pancreas and has spread to other sites in the body. Pancreatic cancer can be assigned one of the following four stages:

Stage I– The tumor is less than 2 cm in diameter and is completely contained within the pancreas.

Stage II– The tumor has begun to grow outside of the pancreas, but has not invaded a major blood vessel. Stage II pancreatic cancer may have spread to nearby lymph nodes, but not to distant sites.

Stage III– The tumor is growing outside of the pancreas, and has moved into nearby large blood vessels or major nerves.

Stage IV– The cancer has spread to other parts of the body, such as the liver or the peritoneum (inner lining of the abdomen).

Current Research and the future
The American Cancer Society says that up to 10% of pancreatic cancers may be caused by inherited DNA changes. Studies are ongoing to see if aggressive screening with endoscopic ultrasound works for early detection of pancreatic cancer in healthy family members. Early results are promising. However, endoscopy is an invasive procedure, so its use is only justified in people already at high risk for pancreatic cancer.

Using genetic analysis, scientists are also looking for specific genes and changes within genes that are associated with pancreatic cancer. Preliminary studies have revealed that a significant number of genes are abnormally active in pancreatic cancer cells. Scientists are also analyzing biological fluids, such as saliva and blood, for biomarkers that are present in patients with pancreatic cancer that may be used in diagnosing early stages.There are also new imaging techniques that are showing promise in detecting pancreatic cancer in its early stages.

However, a diagnostic test involving any biomarker must be able to distinguish between a person with pancreatic cancer and an unaffected individual with near 100% accuracy and possibly detect low levels. Several markers, including the ones mentioned previously (CA-19-9and CEA), have been tested as diagnostic tools with promising results but not at 100% accuracy. It is doubtful that one marker alone will be specific enough to reliably diagnose all types of pancreatic cancer. It is more likely that a group, or panel, of many markers will need to be combined to create an accurate test.As far as other tests, imaging tests can be expensive and uncomfortable as well as not effective in viewing small changes such as those that may occur in early stages. What is needed is a robust and accurate diagnostic test using either blood, urine, saliva or other fluid that can be attained noninvasively.

The Challenge

The seeker specifically wishes to identify a robust method that:

  1. Uses blood, saliva or urine samples preferably, but other fluids will be considered if it is minimally invasive.
  2. Minimizes the time for diagnosis to hours.
  3. Easy to use and cost effective and can be done at point of care or reference lab.
  4. Freedom to practice: no IP, however licensing opportunities will be considered.

In Scope

  1. Protocols that describe assays that include procedural steps with reagents and instruments.
  2. Scientific explanations and reasons for the recommended techniques.
  3. Reference to papers or clinical trials supporting the techniques.

Out of Scope
The Seeker is not interested in a solution that:
• Consists of a literature survey
• Requires excessively expensive reagents or supplies
• Has many or time-consuming steps
• Is primarily theoretical and would be difficult to assess efficacy in a practical manner
• Has negative health and safety issues or environmental impact
Criteria that must be met:
1. Level of detail provided for the proposed protocol such as reagents, solution formulations, consumables, equipment
2. Accessibility and cost of the technological solution, i.e., does not require development of an entirely new technology.
3. Ease of method for use at the point of care

Project Deliverables
Challenge solutions should provide:
1. A detailed description and explanation of the proposed solution or solutions;
2. Persuasive scientific rationale and, ideally, experimental data, to justify the solution; and,
3. Full disclosure of any third party intellectual property used in the solution.

References

American Cancer Society,

en.wikipedia.org/ pancreatic cancer

Pancreatic cancer action network.ww.pancan.org

Memorial sloankittering cancer center