Thursday 23 February 2017

All that glitters is gold!

Malfunction and disease of the pancreas almost inevitably leads to questions about pancreatic cancer.  Does a family history of pancreatic cancer increase the odds that pancreatitis may lead to cancer?  If I develop EPI, will I also develop diabetes and ultimately pancreatic cancer?  What if I already have both diabetes and EPI, am I twice as likely to develop pancreatic cancer?  Five times as likely?  The short answer: We don't really know.  Nobody can predict with perfect accuracy whether or not a cancerous state will develop from a set of symptoms or conditions.  And the problem with statistics is that 80% are made up on the spot ;)  Everybody and every body is unique and comes with a unique set of circumstances including family history, environment, diet and lifestyleFear develops from missing explanations and answers which lead to uncertainties about future prognoses and life expectency. 

What, in part, makes pancreatic cancer so terrifying and ultimately devastating is its relatively calm early stages coupled with a lack of routine testing for high risk populations.  In general, the beginning phases of pancreatic cancer do not present with any defined diagnostic characteristics.  No pain, no swelling, no palpable lumps and bumps, etc.  And again, due to the location of the pancreas (tucked nicely behind the stomach), even if there were palpable masses we would not always be able to assess them.  Imaging techniques in the form of MRI, ultrasound and CT scans have come a very long way in terms of resolution and diagnostic success.  However, early stages of pancreatic cancer (stages I and II) are often not distinguishable because of the organs and bones which envelop the pancreas and distort visualization of the fine structure (think about looking at a flower through a window full of fingerprints, you can see its a flower but can you count how many pedals it has?).  Therefore, pancreatic cancer is most commonly diagnosed in its most advanced stage (stage III), excluding options such as surgical removal or preventative care.  Stage III indicates a systemic disease, typically extending beyond the confines of this tiny gland.

The fear of pancreatic cancer, even when your 'chances' seem low, is justified and not simply misplaced anxiety.  But rest as easily as possible, because cancer research is one of the government's top funding priorities (President Obama signed the 21st Cenury Cures Act in 2015 - hopefully this will not be affected by current legislation) and a recent research report demonstrates a specific advancement in the detection of early stage pancreatic cancer using a simple blood test.  Don't run to the doctor yet, this test is still in the 'proof of concept' phase, but a few major advantages of this test include low cost (relative to similar tests), short processing time, high accuracy and small sample volume.  We are talking a sample volume comparable to having your finger pricked for a blood glucose test...just a drop!  

The components which make up our blood provide a microscopic view of our overall health.  A metabolic blood panel measures values of vitamins and minerals and our bodies absorb from food and supplements; a complete blood count measures the quantity and quality of red and white blood cells; our blood glucose level is measured by a blood test; the list goes on.  Our organs and body systems use circulating blood to send out signaling molecules (known as extracellular vessicles) which help keep all of the processes which occur in the body in sync.  If you were able to listen to the blood it would sound like a crowded stadium after the victory touchdown - loud and indecipherable.  A research group from Arizona State University has developed a method which selectively 'amplifies' the presence extracellular vessicles sent out from pancreatic cancer cells (like turning up the mic at a concert).  Using their technique, even when relatively few pancreatic cancer derived extracellular vessicles are in circulation (such as in the very early stages of disease), visualization of the signaling molecules provides support for a rapid and early diagnosis.  The visualization of the cells occurs with the help of gold nanoparticles, conveniently tagged with a targeting antibody that binds to a specific overexpressed surface protein on the cancer derived vessicle.  Think about a puzzle piece which only has one match out of millions of possibilities - that's how well designed the antibody/antigen for this test is.  With the gold nanoparticles attached (two separate nanoparticles - one nanosphere and one nanorod) each tagged cell will light up - mapping out the presence and quantity of pancreatic cancer derived cells in the blood.  This is almost like intercepting a secret message reading its contents in order to prevent further damage - think of Alan Turing breaking the enigma code 

Blood tests for cancer markers are certainly not new technology, nor is the use of gold nanoparticles as diagnostic tools.  However, this demonstrated use of gold nanoparticles allows for the possibility of a routine screening method for high risk populations, whether through family history or isolated pancreatic diseaseWith all forms of cancer and illness, early detection is key, and with pancreatic cancer, may mean the difference between 5 years and 50 years.  That's a lot of life to be lived.

Friday 17 February 2017

A split personality

The pancreas is a small pear shaped gland which hides behind the stomach, sneakily out of view and reach for physical exams and routine imaging.  A fully functional pancreas performs an immense service to the body by aiding digestion and regulating blood glucose levels.  These two broad functions have led to two pancreatic 'personalities' ('exocrine pancreas' and the 'endocrine pancreas') based on excretion from the pancreas through a duct (exocrine) or the bloodstream (endocrine).  Pancreatic malfunction may be isolated to the exocrine pancreas or endocrine pancreas individually or may manifest as complete pancreatic disease (both endocrine and exocrine insufficiency).  Luckily, the exocrine pancreas and endocrine pancreas do not work alone - a variety of other glands and organs participate in your exocrine and endocrine systems.  Keeping everything in check can become a challenge when one or the other pancreatic functions is compromised.

The exocrine pancreas works in collaboration with the stomach, small intestine, liver and large intestine (in addition to other organs and processes occuring simultaneously) to break down the fats, carbohydrates, sugars and proteins consumed through food and drink.  The role of the pancreas in this process is twofold: to neutralize stomach acid by excreting a basic bicarbonate solution and supply your intestines with digestive enzymes used to break down components of foods.  For example, lipase produced by acinar cells in the pancreas acts by cleaving lipid bonds in triglycerides to make fatty acids.  Our bodies can more readily absorb these fatty acids and use them in a variety of metabolic pathways, most notably in the regulation of inflammation.  The exocrine pancreas also produces and excretes amylases and proteases to break down carbohydrates and proteins, respectively.  Quite a heavy burden on one single gland, making its malfunction all the more significant.  Exocrine pancreatic insufficiency (EPI) is a digestive condition in which, for a variety of reasons, the pancreas is either not able to produce or not able to excrete the bicarbonate and enzymes required for complete food digestion.  EPI is not a disease of its own, but a symptom often recognized too late for preventative treatment.  The clinical presentation of EPI (postprandial epigastric pain and steatorrhea) does not develop until over 90% of pancreatic enzyme output is lost.  In the meantime, as the acinar cells slowly succumb to damage and cease enzyme production, the remaining organs and glands in the exocrine system make up the deficit (our bodies have incredible reserve capacities!).  A few examples:  salivary amylase (made in the mouth) begins the is initial breakdown of starches as you chew and gastric lipase (made in the stomach) facilitates lipid hydrolysis.  These enzymes differ to those produced by the pancreas and offer only partial resemblance to the role pancreatic enzymes play in digestion.  Treatment regimes for EPI include a low fat diet (max. 20g of fat with no supplemental enzymes) or what is known as PERT - Pancreatic Enzyme Replacement Therapy.  Future posts will discuss the pros and cons of PERT and what products are on the market for EPI treatment.

The endocrine pancreas is a whole different ballgame, and one which enjoys attention from the media as well as the medical community.  The body's relationship with the endocrine pancreas is the key to management of types I and II diabetes (T1D and T2D, respectively).  In addition to the production of digestive enzymes (from the exocrine pancreas), the endocrine pancreas is responsible for the production and distribution of insulin.  Insulin is a hormone, made by islet cells in the pancreas, which regulates metabolism - specifically regarding blood glucose levels - every second of every minute of every hour of every day.  Even when you sleep.  Whilst the exocrine pancreas takes a break between meals, the endocrine pancreas works around the clock to keep you feeling at your best.  Malfunction of the endocrine pancreas is termed 'diabetes,' of which types I and II are the most common (gestational diabetes describes a third type, which occurs rarely during the later stages of pregnancy).  Type I diabetes is an autoimmune disorder in which the islet cells in the pancreas are attacked by the immune system and produce little to no insulin.  Those who have T1D are required to constantly monitor their blood glucose levels and dose with synthetic insulin to control hormone balance - every second of every minute of every hour of every day.  Even when they sleep.  Type II diabetes occurs when the body becomes resistent to insulin, for example, when sugar consumption prompts a constantly high blood glucose level.  The endocrine pancreas is not able to supply the correct amount of hormone to bring these levels back down and the misuse of insulin becomes systemic.  T2D is more common than T1D, and its occurence is growing at a rapid rate as we tend toward to more heavily processed and sugar filled diet.  A variety of management techniques for T2D have been reported, and the condition is reversible, meaning that diet and lifestyle modifications have significant influence on the severity of symptoms - good news!

The pancreas, although hidden deep in the abdominal cavity, has huge influences on our daily lives.  Its dual personality dictates what we are able to eat, which can be challenging in a society which is very food-centric.  But being food driven is not bad.  We find commonality, culture and enjoyment out of food - as we should!  Taking care of your pancreas involves knowing your limits, specifically with respect to alcohol and fast foods, and giving your system a break when requested.  The next time you enjoy a burger, savor the moment and thank your pancreas for the help!

Thursday 9 February 2017

The 'angry organ'


The recent explosion of interest in our gut microbiomes has prompted renewed interest in digestive diseases by both academic and pharmaceutical research communities.  However, for every unique individual there is a unique digestive system and a unique microbiome and therefore the possibility for unique disease or combination of disorders.  Despite high incidence, however, some of the most well understood yet severely under-researched and clinically ignored digestive maladies remain low priority for research funding allocation.  Several of these diseases and disorders include malfunction and mis-regulation of critical components of our digestive system - the liver, colon, intestines and (my favorite) the pancreas.

Increased hospitalizations due to acute and chronic pancreatitis alone constitute a heavy burden on the US healthcare system.  Chances are, you know at least one individual hospitalized from pancreatitis - annual admissions have risen to nearly half a million Americans. Too much to eat or drink around the holidays?  The resulting abdominal pain may be from the stomach as most people suspect, but there is a good chance it is from the pancreas (which hides just behind the stomach and is often neglected in Emergency Room settings).  Other diseases and disorders which have a pancreatic component are types I and II diabetes (T1D and T2D, respectively), cystic fibrosis and Shwachman-Diamond syndrome (the later two being extremely rare).  Both endocrine and exocrine pancreatic insufficiencies are a symptom of some form of pancreatic malfunction, and it is well established that pancreatic cancer comes with a higher mortality rate than most (although recently published research may improve detection of early stage (I and II) pancreatic cancer).

Describing and treating diseases of the pancreas proves challenging due to the highly sensitive and often extremely reactive nature of this gland.  Physicians avoid palpating or working anywhere near the 'angry organ' due to the likelyhood of induced pancreatitis. Due to the increased volume of reported pancreatic disorders and comparative inexperience in dealing with the pancreas (as opposed to the liver or stomach, for example) both in the lab and on the operating table, a promising research arena exists and is in desperate need of attentionPancreatitis (inflammation of the pancreas), which is a component of most pancreatic diseases and disorders, may be broadly classified into three categories - acute (short lived, often related to an isolated incident), chronic (persistent, often related to alcohol consumption or gall stones) and idiopathic (a fancy term for 'unknown cause').  The mechanisms of action through which acute and chronic pancreatitis occur are more thoroughly documented (click here for a recent review about acute pancreatitis), but an increasing number of individuals present with idiopathic pancreatitis.  Much like a diagnosis of fibromyalgia, the diagnosis of idiopathic pancreatitis is often one of elimination when no other obvious cause for symptoms is discovered.  The root cause of discomfort and additional symptoms may remain elusive for years or never fully resolve.  

An understanding of the many personalities of the pancreas, and how each persona interacts with the rest of our digestive system, may explain points of malfunction and misdiagnosis - and hopefully provide relief for those of us still asking 'what is going on and why is this happening?'