Download Managing Pancreatic Cancer, Part 1: Introduction to Pancreatic

Managing Pancreatic Cancer, Part 1: Introduction to Pancreatic Cancer
by Dr. Matthew Katz, Surgeon, MD Anderson Cancer Center, Houston, TX
I’m Matthew Katz; I’m Assistant Professor of Medical Oncology at the University of Texas, M.D.
Anderson Cancer Center. I’m a fulltime pancreas cancer clinician and researcher and I’m pleased
to present this talk today where I hope to give some general overview of pancreas cancer and
particularly resectable pancreas cancer, which is in my purview as a surgical oncologist.
I have three primary objectives with this talk. The first will be to provide a brief overview of both
the pancreas and pancreas cancer; second, to describe the system that clinicians use to stage
this disease; and then finally to discuss the treatment of resectable pancreas cancer with
particular attention paid to surgical therapy as well as adjuvant or non-operative therapy, I’ll
describe what those are later in the talk.
The pancreas is a soft organ that lies underneath the stomach in the upper abdomen. The
pancreas is actually a gland, which means that it’s an organ that secretes chemicals. In this case
the chemicals that the pancreas produces both help the body digest food and regulate the
glucose metabolism.
The pancreas lies deep within the back or what’s called the retroperitoneum. This deep location
within the abdomen is in part responsible for the delay that is characteristically associated with the
diagnosis of diseases of the pancreas.
In the left diagram you can see the pancreas itself. It’s a strange looking organ that is surrounded
on its left side by the first part of the small intestine and is also intimately approximated to the
vessels that supply the liver, small intestine and large intestine.
The pancreas has a single major pancreatic duct which is used to bring digestive juices from the
pancreas into the small intestine to help digest food, and then there are scattered cells throughout
the pancreas which produce certain chemicals that aid in the metabolism of glucose.
On the right you can see a general schematic of the organs of the abdomen. In the upper aspect
of the abdomen you can see in red the liver and underneath that the stomach which is yellow. You
can’t actually see the pancreas because it is in the back, behind the stomach.
Again, the pancreas has two primary functions. The first is an exocrine function i.e. to digest food
and the second is an endocrine function to help with glucose metabolism. The pancreas secretes
digestive enzymes into the first part of the small intestine which then mix with food as the food
comes down from the stomach. These chemicals, digestive enzymes, help break down the food
so that nutrients can be absorbed in the small intestine.
The endocrine cells which can be seen in the lower right aspect of the diagram in multiple colors
are cells that produce chemicals such as insulin, which most people have heard of, and other
cells such as glucagon and somatostatin, which fewer people have heard of but are as important
in regulating glucose metabolism and the metabolism of other aspects of body function.
Failure to perform these exocrine and endocrine functions can occur when the gland is taken over
by cancer cells. This failure can produce some other characteristic symptoms and comorbid
conditions, such as diabetes, that are associated with pancreas cancer.
I want to discuss a little bit about cancer in general before I discuss pancreas cancer. Cancer
develops at the single cell level. Essentially it involves dysregulation of cell growth in which a
single cell becomes mutated and starts dividing faster than normal. Unlike normal cell division,
this division is both fast as well as unregulated, and it’s essentially unstoppable. The growth of
these cells develops into the primary tumor. For pancreas cancer the primary tumor develops
secondary to unregulated growth of a certain type of cell that lies within the normal pancreas.
Once the tumor has gotten to a small size it’s supplied with blood vessels from the body, as seen
in Part B. once the tumor becomes big enough, cells from the primary tumor can invade into the
vasculature of the pancreas in this case, and then circulate throughout the body pumped by the
heart. These cells can lodge, take up residence in distant organs, such as the liver or the lungs,
and these new tumors are what are called metastases, as opposed to the primary tumor, which
again in this case is in the pancreas.
So, for pancreas cancer we’re often dealing with multiple tumors or multiple nodules. The primary
cancer or tumor being located in the pancreas itself, as seen here on the left and a metastatic
deposit, such as the lung depicted here on the right, which has developed in the liver.
In this case, while the tumor in the liver is cancer, it’s actually not liver cancer, it’s pancreas
cancer that has traveled from the primary tumor in the pancreas to develop within the liver.
There are multiple types of pancreas cancer, and they are determined by the initial cell that
becomes mutated and starts all this unregulated growth and expansion. The pancreas again, as
you can see in the figure on the right, is composed of ducts and acini, which produce these
exocrine digestive enzymes on the top. And then at the bottom it is also composed of cells which
are responsible for the production of hormones involved in glucose metabolism.
When the cells of the pancreatic ducts become cancerous they develop into a cancer called
ductal adenocarcinoma and this type of cancer is “true pancreas cancer” or the type that people
think of when they think of pancreas cancer, and this particular type is responsible for about 90%
of cases of pancreas cancer. But there are other types such as neuroendocrine carcinomas which
can occur when the hormone producing cells become malignant or acinar cell cancers which
occur when the acini become malignant or even other types of cancers which begin in other less
frequent cells scattered throughout the pancreas such as squamous cell cancer or embryonic
cancers that occur primarily in children.
So, there are a number of different types of pancreas cancer but what I’m going to limit my talk to
you today is essentially pancreatic ductal carcinoma which accounts for 90% of cases. Pancreas
cancer is a notoriously deadly disease. This slide is from the American Cancer Society, which
shows the leading sites of new cancer cases and deaths in the United States in 2011. On the left
aspect of the table are the estimated number of new cases of various types of cancers in both
men and women in 2011 and on the right aspect of the table are the estimated number of deaths
in 2011 in both men and women by the most common cancers.
Pancreas cancer is outlined in red, and what you can see is that it’s the tenth most common
cancer among both men and women each year, but it is the fourth most common cause of cancer
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related death. Equally as important is that the number of new pancreas cancer cases is about
equal to the number of pancreatic cancer deaths per year.
Clearly this is a disease that is very difficult to manage, but for a distinct group of patients proper
timely therapy can be curative. I’ll explain more about who these patients are and how they can
be treated in the remainder of the talk.
This is another slide from the American Cancer Society, showing trends in five year survival.
These are five year survival rates of patients with a variety of different cancers. The table depicts
the five year survival rates of patients who were treated in each of three time groups – the first
group between 1975-77, the second group between 1987-89, and the last group in the more
recent era of 2001-07. The numbers below each of those time periods indicate the percent of
patients diagnosed with each type of cancer who lived for five years or more following diagnosis.
What you can see is that pancreas cancer survival rates are quite low, and in fact the lowest the
cancers reported here. I think even more alarming than the numbers themselves is the fact that
the numbers have not increased or improved over the past forty years. So whereas the five-year
survival rate in the 1970s for patients with pancreas cancer was 2%, we’re still forty years later at
a five-year survival rate of 6%. So, there’s clearly a lot of work to be done in this area, and I can
assure you that as clinicians and researchers we are hard at work trying to change these numbers.
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