Taking the mystery out of medicine
With our guest Megan Brooks RD, we explore how nutrition affects cancer.
Topics discussed include:
1) impact of red meat, sugar, dairy, processed foods, alcohol
2) value of vitamin supplementation, organic foods and non GMO
3) optimizing nutrition during chemotherapy or surgery
4) tips to caregivers
5) future directions in immunonutrition
In this inaugural episode of DISSECTING CANCER, we explore the impact of inherited genes on cancer.
With our guest host, we discuss:
1) how genetic predispositions affect cancer development
2) link between particular genes and cancer such as BRCA and breast cancer
3) big data and predictive modeling
4) testing, insurance coverage, direct to consumer
5) impact of testing on insurance premiums and life insurance
6) prenatal testing
7) future directions including CRISPR
Join me and Jennifer Siettmann (Certified Genetic Counselor) for this exciting episode.
Remember to also follow me on the Call In app to join future discussions live!
This is a topic worth diving into since there are several types of pancreatic cancers. They are very different with regards to the treatment and the prognosis.
In general, when people discuss pancreas cancer, they mean pancreatic ductal adenocarcinoma. This is a type of cancer that grows out of the glands of the duct of the pancreas.
Pancreatic adenocarcinoma, or more accurately pancreatic ductal adenocarcinoma, arises from the pancreatic duct glands. To refresh your memory, the duct is the main channel that runs through the pancreas and collects the pancreatic digestive enzymes.
The glands of the pancreatic duct can over time get injured and go through a process of precancer (PanIN) to full-blown invasive cancer cells. We still don’t know why people develop these precancer changes, or why only some people progress from PanIN to invasive cancer and others don’t. Cysts of the pancreas can also degenerate and lead to pancreatic ductal adenocarcinoma.
More of these pancreatic ductal adenocarcinomas arise in the head of the pancreas (the right side) than the body or tail (left side). Pancreatic head adenocarcinomas classically result in blockage of the bile duct leading to patients developing jaundice (yellowing of the eyes and skin). This is often a useful way to detect pancreatic cancer early, since the other signs (vague abdominal pain, back pain, weight loss) are not specific to pancreatic adenocarcinoma.
Once these lesions are found, additional CT scans or MRIs are needed to better characterize it and evaluate the other organs to look for spread. To confirm the diagnosis of pancreatic adenocarcinoma, biopsies are necessary.
Unfortunately, three quarters of the time when pancreatic adenocarcinoma is found, it has already spread. For such situations, chemotherapy is the only option available for treatment.
In patients with localized pancreas cancer that hasn’t spread outside of the pancreas or lymph nodes, the treatment is typically chemotherapy and surgery.
The second major type of pancreatic cancers are pancreatic neuroendocrine tumors (PNET). Pancreatic neuroendocrine tumors are completely different from adenocarcinomas.
Pancreatic neuroendocrine tumors arise from hormone producing cells within the pancreas. These normal neuroendocrine cells can start to over-produce leading to a tumor. For pancreatic neuroendocrine tumors, there are certain key distinguishing features such as the grade (appearance of the cells and their rate of division), size and whether they are producing hormones.
Pancreatic neuroendocrine cells produce various GI hormones, and certain tumors can over produce these. The hormones include insulin, glucagon, gastrin, somatostatin and vasoactive intestinal peptide (VIP). An insulin producing tumor, an insulinoma, can lead to severe attacks of low blood sugar that responds to glucose intake. A glucagon producing tumor, a glucagonoma, has an opposing effecting to insulin with high blood sugars and new-onset diabetes. Gastrinomas over-produce gastrin leading to stomach ulcers, diarrhea and sometimes an unexplained rash. Somatostatinomas can have vague symptoms of diabetes, diarrhea and gallstone issues. And lastly, VIPomas cause severe watery diarrhea. As you may expect, the levels of these hormones can be measured through blood tests and used for confirmation.
Generally, any pancreatic neuroendocrine tumor that secretes hormones and causes symptoms should be removed with surgery. For tumors that don’t secrete hormones (nonfunctional tumors), the management is more nuanced, but is generally based on size. Small non-functional tumors (<1 cm) rarely spread or cause problems, so are typically watched with routine imaging. As non-functional tumors grow to 2cm or more, there is a higher risk of spread and so they are generally removed. There is a special type of PET scan, called a Dotatate PET scan, that is very useful in these scenarios.
There are certain other rare types of pancreatic tumors. These include tumors such as acinar cell carcinomas and solid pseudopapillary neoplasms (SPN). These are quite rare and should be evaluated by a pancreatic specialist.
Hearing the words ‘pancreatic cancer’ is understandably frightening and worrying. However, the main purpose of this post is to ensure that you know what kind of pancreatic cancer one may be facing: adenocarcinoma or neuroendocrine tumor. The next steps for each of these are different, and the strategies for overcoming them are also different. They are both treatable, but each treatment type is unique. Please stay tuned for more posts that explore these in more detail.
The pancreas is a soft and delicate organ located in the middle of your upper abdomen against the spine. Even though the pancreas is a single organ, we describe it as having a head, neck, body and tail. The pancreas is a fascinating organ involved in digestion, hormone production and blood sugar regulation.
The pancreas has millions of little factories that produce digestive enzymes. These enzymes break down fats, some proteins, and some sugars. The pancreas collects these enzymes in a pipe (pancreatic duct) that runs through the length of the pancreas. That pipe pushes the enzymes into the first part of the intestine (duodenum) to meet with the food that comes through the stomach. These enzymes then mix with food, breaking down the fats and proteins into building blocks that can be used by your body’s cells. Not having enough of these enzymes (exocrine insufficiency) can lead to foul-smelling greasy liquid stools, vitamin deficiencies, and weight loss.
The pancreas also makes several gastrointestinal hormones. The most notable hormones are insulin, glucagon and somatostatin. Beta cells within the pancreas make the insulin and release it directly into the blood stream. The insulin in the blood stream meets the blood glucose molecules and transports the glucose molecules into the body’s organs that need energy. At a very simple level, diabetes occurs when the organs of the body aren’t able to pull the glucose molecules out of the blood into the organ. That’s why in diabetics, blood sugars are high (they can’t be taken out of the blood into the organs). The pancreas produces a constant low-level of insulin (basal insulin) to meet all the resting energy needs of the body, as well as large surges of insulin during meals or snacks (bolus insulin).
Alpha cells in the pancreas produce another hormone named glucagon. Glucagon can be thought of as the opposite of insulin. While insulin transfers glucose out of the blood stream into organs, glucagon makes more glucose available in the blood to prevent low blood sugars. Glucagon and insulin work together seamlessly to maintain blood sugars and ensure the ability of your body to use glucose when required.
Other hormones made by the pancreas include somatostatin, amylin, gastrin, and VIP. All these hormones are involved in the signaling of the gastrointestinal system and aid in food digestion and movement.
Unlike shown in the illustration above, the pancreas lays behind the stomach and in front of the spine, aorta and vena cava. On the right, the pancreas head is nestled within the turn of the duodenum (first portion of the intestine), and the tail extends towards the spleen on the left. The pancreas duct runs through the middle of the pancreas and drains into the duodenum through a door called the Ampulla of Vater. Through this same hole enters the bile duct from the liver. The common bile duct contains bile liquid full of bile salts that also help with digestion and absorption of several dietary factors. A portion of the pancreas head, called the uncinate process, wraps around one of the biggest branches of the aorta (superior mesenteric artery) and one of the main abdominal veins (superior mesenteric vein). These structures are essentials since support most of the intestines and colon. As you can see, the pancreas is truly in a very cramped and central location!
Being so centrally located, you might assume that the pancreas is a tough organ with thick skin. It is the exact opposite. The pancreas is a soft squishy organ that is hard to distinguish from the surrounding fat. It is extremely sensitive. Even minor injuries or insults can cause it to leak its corrosive digestive enzymes. A leak of these enzymes can cause unintended digestion of the surround fat causing severe abdominal pain affecting a lot of the surrounding organs. This process is called pancreatitis. Pancreatitis can be caused by alcohol abuse, gallstones, procedures performed around the pancreas (biopsies, ERCP), and some rarer causes such as high triglycerides, autoimmune conditions, and certain medications. For acute attacks of pancreatitis, the treatment is usually just hydration support and time to allow the pancreas to mend itself. Check out my upcoming video illustration of the pancreas. Now that you understand the basics of the pancreas anatomy and function, it will make it easier to grasp the types of pancreatic cancers and operations. Stay tuned for those posts.
Most of the time, we do not know why an individual develops pancreas cancers. Medically, this is referred to as ‘sporadic’ (unknown cause). To our best knowledge, a poor diet does not cause pancreas cancer, a lack of exercise does not cause pancreas cancer, and we have not identified a single environmental agent or occupational agent that causes pancreas cancer. In this post, we will discuss an overview of 1) how pancreas cancer cells develop from normal pancreas cells, 2) some known inherited genetic conditions, and 3) precancerous cysts.
There are several kinds of pancreatic cancers. The most common type is a pancreatic adenocarcinoma. These adenocarcinomas develop when the normal cells of the pancreas duct get mutations that make them cancerous. All cells eventually reach the end of their life span and must replicate to create new cells. During this replication process, errors can happen leading to mutations. These errors and mutations can stack up. Sometimes, enough mutations align just perfectly enough that the damaged offspring cells become cancerous. A cancerous cell is one that grows uncontrollably causing destruction to surrounding cells. This process typically requires multiple damages/mutations to occur for a normal cell to go from damaged to cancerous. This process happens more often in older people as the cells have undergone more wear and tear with time and thus are prone to more errors. It also may happen in situations that cause more cell damage and turnover, such as pancreatitis (inflammation of the pancreas).
Although most pancreas cancers are sporadic, there are a small number of pancreas cancers that are related to inherited genes. There is no single ‘pancreas cancer gene’, however certain genes that increase the risk of pancreas cancer above normal risk. For those with one of those genes, early screening is recommended. (On a related note – everyone diagnosed with pancreatic cancer should also undergo genetic screening to look for these inheritable genetic mutations)
As shown below, based on the gene mutation, the risk of pancreas cancer varies and so does the recommendation for screening. Screening for pancreas cancer is usually done with the use of an MRI, and sometimes with an endoscopic ultrasound. MRIs provide great images of the pancreas making it a useful test to pick up early pancreas cancers. It’s important to remember that even in the setting of a high-risk genetic condition, the risk of pancreatic cancer is only nominally greater than average risk.
Most major centers will have a pancreas screening program if you have one of these high-risk mutations. Your primary care doctor should be able to tie you into a pancreas screening program or connect you to an oncologist who would have access to the guidelines that guide screening. Below is an example of a reasonable screening strategy.
| Gene | Precondition | Screening Strategy | Age of Onset | Frequency |
| ATM BRCA1 BRCA2 MLH1 MSH2 MSH6 EPCAM PALB2 TP53 | At least >1 first or second-degree relatives with pancreatic cancer | MRI/MRCP | Age 50 (or 10 years prior to earliest age of onset in the family) | Annual |
| STK11 | None | Initial EUS & MRI/MRCP Annual MRI/MRCP | Age 30-35 (or 10 years prior to earliest age of onset in the family) | Annual |
| CDKN2A | None | Initial EUS & MRI/MRCP Annual MRI/MRCP | Age 40 (or 10 years prior to earliest age of onset in the family) | Annual |
| PRSS1 SPINK1 | None | Initial EUS & MRI/MRCP Annual MRI/MRCP | At onset of pancreatitis, or beginning at age 40 | Annual |
Cysts are liquid filled growths on the pancreas. While most cysts are either benign (non-cancerous), or unlikely to ever develop into a cancer, there are some that are precancerous. These concerning cysts ought to be removed or watched closely.
Symptoms, blood work, MRIs and endoscopic ultrasound results can help identify the type of cyst and provide information regarding the risk of that cyst progressing into a cancer. There are very well-developed international guidelines that can guide a physician in figuring out how to manage these cysts. The factors that go into the guidelines include size, the way it looks on MRI, can sometimes analysis of the cyst fluid after a biopsy. If these cysts are found, check with a pancreatic surgeon or a gastroenterologist for follow-up and management.
For most pancreas cancers, a specific cause cannot be identified. As a result, there are few actions that can be taken to prevent the development of pancreas cancer. Related to that is the fact that there isn’t much that a person does that leads to the development of pancreas cancer.
Exceptions are certain genetic mutations and pancreatic cysts. If you have one of these conditions, early screening can help identify a potential pancreas cancer in the pre-cancerous stage or at a very early stage. Reach out to your doctors to learn about whether you qualify for screening.
Hello!
Welcome to this blog.
I am a practicing surgical oncologist and I work with patients who have gastrointestinal and abdominal cancers.
One of my greatest joys in medicine is the conversations I get to have with patients and families who have been newly diagnosed with cancer. Educating patients about their new diagnosis, discussing various treatment options, and then arriving at a joint decision on the best treatment course is my passion and calling.
From a cancer biology standpoint, I am deeply interested in liver, pancreas and metastatic cancers. We are in the middle of a revolution in targeted therapy and immunotherapy, and this is changing nearly everything we know about life with cancer.
In my clinical practice, I use a lot of visual aids and analogies to demystify the anatomy, physiology and biology of cancers. These efforts are rooted in my conviction that taking the mystery out of medicine will allow physicians and their patients to be more equal partners in their care, and provide patients with increased ownership and command of their disease.
For a person with cancer, I believe that success in cancer care is not based on ‘beating a cancer’, and sometimes is not even based on being ‘cured’. Rather, I see success when that person asserts their life values, retains the gift of making decisions, and truly lives with dignity till the end of their life.
In these series of blog posts, I hope to provide you with some useful information about certain gastrointestinal and liver/pancreas cancers. I also hope to dive into other challenging topics that many people and many doctors are uncomfortable discussing, such as end of life decision making and when to say ‘enough’.
I would love feedback and any suggestions on topics you want to hear about, and I look forward to this journey together.
Yours truly,
Rajesh Ramanathan MD
Scalpel On Paper