Perusing the Pancreas
I recently got the opportunity to spend a pair of summers working on a research project at a hospital just outside of Boston. The goal was to investigate diabetes and pancreatic cancer, and see how new-onset, or previously undiagnosed, diabetes might be an indication of pancreatic cancer. The study is not yet published and the data is being analyzed as this essay is written. Nonetheless, the science behind diabetes and pancreatic cancer is fascinating, and the topic is one that will be of increasing importance as lifespans increase and cancer becomes increasingly common. While I started this job almost entirely ignorant of the science behind what I would be studying, I found the topic fascinating, and I thought others would too. With that in mind, I thought a discussion of the science and literature I studied might be of interest to the population at large.
To start, let’s consider the pancreas. The pancreas is a small, six-inch organ that sits slight behind and below the stomach. It’s part of the endocrine system, which essentially means it produces hormones which circulate in the blood. For our purposes here, the most important hormone produced is called insulin. Insulin is, essentially, a gatekeeper which allows glucose, or sugar, to be transferred from the bloodstream into cells. Cells all over the body, including those in the liver, lungs, and fat, use the glucose to store energy and do the tasks they need to do to keep the body healthy.
Next, let’s discuss diabetes. Diabetes is a condition where too much glucose is present in the blood. Especially in extremities, excess glucose, or hyperglycemia, can cause nerve, eye, or liver damage. There are two main types of diabetes. The first is Type I, where human immune cells falsely identify pancreatic cells as foreign. They then attack those cells, which, once destroyed, are unable to produce insulin. Type I diabetes is generally diagnosed in childhood, and while serious, is treatable with injections of insulin. Type II diabetes, on the other hand, occurs when cells are unable to use insulin as effectively as normal. Type II diabetes ranges in severity, and can frequently can be controlled with diet changes or a fitness regimen. Unlike Type I diabetes, Type II diabetes can occur later in life. Diabetes can be diagnosed through a variety of means, but for this study we used a criteria of >6.5% HbA1c. Essentially, this number measures how much glucose blood cells come in contact with over the course of about a month. If the number is higher, more glucose is present in the blood, which is a sign of diabetes (1).
Finally, we turn to pancreatic cancer. Cancers occur when the normal life cycle of a cell is disrupted. Normally cells divide only as needed for growth or to replace dead cells. Additionally, cells will undergo apoptosis, or a programmed cell death, if they are compromised. Events that might lead to programmed cell death include infection by a virus or other pathogens, or dividing too rapidly. However, in cancer cells, mutations in DNA disrupt both processes. Thus, cancer cells will not only divide rapidly, they become very hard to kill through ways the body can mediate. Pancreatic cancers tend to be particularly nasty forms of cancer, simply because they are very hard to detect early on. The pancreas is hidden deep inside the body, and symptoms, such as jaundice and abdominal pain, normally do not appear until the disease is significantly advanced. Because of this, the 5 year survival rate for newly-diagnosed pancreatic cancer patients is one of the lowest, around 5.5% (2). Fortunately, when pancreatic cancer is detected early, as is the case for 1 in 5 patients, survival rates significantly improve, to between 20 and 25% percent (2).
Thus, it is essential to improve early diagnosis rates of pancreatic cancer. Notably, a combined 65% of pancreatic cancer patients have either diabetes or pre-diabetes when they are diagnosed, almost always Type II (2). The exact relationship between pancreatic cancer and diabetes is unknown, particularly if one causes the other. However, many people with diabetes never develop pancreatic cancer, so preemptive testing based solely on a diabetes diagnosis is unnecessary and likely to cause undue stress to the patient. It would be ideal to have a system of criteria which could be used to assess how necessary pancreatic cancer screening would be for specific patients.
This was essentially the goal of the project I worked on. By using several medical record search mechanisms to highlight patients who had been diagnosed with diabetes, and then later diagnosed with pancreatic cancer, or simply diagnosed with diabetes, we could construct a database of a variety of physical characteristics that are commonly associated with increased risk of pancreatic cancer, including BMI, smoking status, and alcohol use (3). This data was collected from several medical databases. To do this, I was specifically responsible for combing through patient records and extracting data. I also coordinated a couple medical record sources, and worked directly with a physician on study design.
Once this data was collected, it was handed over to a statistician, who will examine the data for so called “statistically significant” differences, differences in the data unlikely to be due to variation or random chance. For example, we hypothesize if individuals develop sudden-onset diabetes despite not being at risk (for example people who are young, or active), this may be a sign that pancreatic cancer is causing the disease. Once potential points of interest are detected and an article is (hopefully) published, more clinical research and laboratory work will begin, to further assess the criteria. In an ideal situation, a doctor may eventually be able to use the results of this study and ones like it to assess a patient’s risk for developing pancreatic cancer. As mentioned above, any potential for early diagnosis greatly increases a patient’s long-term outlook.
I’m so grateful I got the chance to work on this study. Before starting, I had no research experience, and little understanding of how medical research. I know feel like I understand a lot more about the research process. This project informed my work at school and when doing research projects at school I’ve often chosen to examine topics related to diabetes or pancreatic cancer. While I wanted to be a doctor before, this experience only cemented that desire.
Author Bio: Luke Scheuer is a member of the Class of 2017 at Bowdoin College, majoring in Biochemistry and Mathematics. His other interests and hobbies include acting, cooking, and working with children at Harriet Beecher Stowe Elementary School in Brunswick, ME. Luke hopes to eventually attend medical school. He would like to thank Dr. Thomas Schnelldorfer and the Lahey Clinic for allowing him to work there on the project described in this article.
- Peters, A. L., et al. (1996). “A clinical approach for the diagnosis of diabetes mellitus: An analysis using glycosylated hemoglobin levels.” JAMA 276(15): 1246-1252.
- “Special Section: Pancreatic Cancer.” American Cancer Society, Inc. N.p., 2013. Web. 2 Feb. 2017. https://old.cancer.org/4/groups/content/@research/documents/document/4pc-038828.pdf
- Lowenfels, A. B. and P. Maisonneuve (2006). “Epidemiology and risk factors for pancreatic cancer.” Best Practice & Research Clinical Gastroenterology 20(2): 197-209.
- Everhart J, Wright D. Diabetes Mellitus as a Risk Factor for Pancreatic Cancer A Meta-analysis. 1995;273(20):1605-1609. doi:10.1001/jama.1995.03520440059037
- Chari, Suresh T. (01/2008). “Pancreatic Cancer–Associated Diabetes Mellitus: Prevalence and Temporal Association With Diagnosis of Cancer”. Gastroenterology (New York, N.Y. 1943)(0016-5085), 134 (1), p. 95.
- Berrino, F., et al. (2007). “Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study.” Lancet Oncol 8(9): 773-78
- Chari, S. T., et al. (2008). “Pancreatic Cancer–Associated Diabetes Mellitus: Prevalence and Temporal Association With Diagnosis of Cancer.” Gastroenterology 134(1): 95-101.
- Pannala, R., et al. (2009). “New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer.” The Lancet Oncology 10(1): 88-95.
- Li, D., et al. (2004). “Pancreatic cancer.” The Lancet 363(9414): 1049-1057.
- Schnelldorfer, T., et al. (2008). “Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible?” Ann Surg 247(3): 456-462.
- Sener, S. F., et al. (1999). “Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database1.” Journal of the American College of Surgeons 189(1): 1-7.