Posts Tagged ‘pancreas’

Pancreatic Cancer

October 19, 2013

 Pancreatic Cancer 

Andrew Siegel, M.D.  Blog #124

The pancreas is a vitally important organ that serves dual roles: as an endocrine organ that produces hormones including insulin and glucagon and as an exocrine organ that secretes digestive enzymes that help the process of fat, protein and carbohydrate breakdown and digestion.  It is located deep within the upper abdomen and is divided into a head, body and tail.  The head lies within the concavity of the duodenum (the first part of the intestine).  The body runs behind the stomach and the tail touches the spleen.  The fact that it is such a deep-seated organ makes it virtually impossible to examine on a physical exam (unlike superficial organs such as the breasts or testicles) and pathological problems of the pancreas are identifiable only on sophisticated imaging studies of the abdomen.

Cancer of the pancreas is an incredibly lethal malignant tumor.  Approximately 45,000 Americans will be diagnosed with pancreatic cancer in 2013 and more than 38,000 will die from the disease, with a five-year survival rate of only about 5%.   The greatest challenge is that there are no early detection tests and, unfortunately, most patients who have early and localized disease have no recognizable symptoms such that most are not diagnosed until late in the disease—after the cancer has spread (metastasized).

In spite of the dismal prognosis, there has been recent progress in pancreatic cancer with surgery becoming safer and less invasive, the availability of new drug combinations that have been shown to improve survival, and advances in radiation that have resulted in less side effects. Significant strides forward have been made in the understanding of the genetics of pancreatic cancer, and unlocking the molecular basis of this horrific disease hopefully will translate into better treatment options.

The most common form of pancreatic cancer is invasive ductal adenocarcinoma.  The second most common type is a pancreatic neuroendocrine tumor; this is less aggressive than the ductal carcinomas, but still has a 10-year survival rate of only 45%. Some of the neuroendocrine tumors manufacture hormones such as insulin that produce clinical syndromes.

A combination of inherited and environmental factors contributes to the development of pancreatic cancer. The most common environmental risk factor is tobacco; smokers having a more than double the risk of pancreatic cancer as compared to non-smokers.  The good news is that smoking cessation will substantially reduce the risk.  Other risk factors are long-standing type II diabetes, increased body mass index, heavy alcohol consumption, and chronic pancreatitis.   A strong family history of pancreatic cancer puts an individual at significant risk.  BRCA2 gene mutations also increase the risk. Additionally, patients who have hereditary pancreatitis have a 60-fold increased risk; this is so substantial that some patients with this disease opt for a prophylactic removal of the pancreas.

Now for Molecular Biology 101:  Genes are inherited bits of information that code for proteins.  When genes become mutated, the proteins that the genes code for become dysfunctional.  One can think of genes as the written recipe for a particular meal and their product as the meal itself—when the recipe is changed (mutated) the resultant meal is defective.  In the case of the human body, the altered genes code for altered proteins that damage cellular function and replication in such a way as to alter the normal orderly process of cellular reproduction, resulting in unrestrained, disorderly cell replication, aka cancer.  Scientists have identified numerous genetic mutations responsible for cancers and they are named with bizarre combinations of letters and numbers—do not be daunted by their names as follow.

So, on a molecular level, cancer is caused by inherited and acquired mutations in genes. The sequencing of the genetic material of the pancreatic ductal adenocarcinomas has demonstrated that four specific genes are each altered in more than 50% of these cancers.  KRAS, an oncogene (a gene with the potential to cause cancer), becomes activated in 95% of pancreatic cancers—the protein coded for by this gene plays an important role in cell signaling, a complex system of communication that governs basic cellular activities and coordinates cell actions. The p16/CDKN2A gene, a tumor suppressor gene (a gene that protects a cell from cancer that, when mutated, would allow the cell to progress to cancer), becomes inactivated in 95% of pancreatic cancers.  The protein product of this gene plays an important role in the regulation of the cell cycle and its loss promotes unrestricted cell growth. The TP53 tumor suppressor gene is inactivated in 75% of pancreatic cancers. Loss of its function through mutation promotes pancreatic cancer through the loss of a number of critical cell functions.  The SMAD4 tumor suppressor gene has a protein product in the cell signaling pathway that when interfered with is associated with a very poor prognosis and widely metastatic disease. In addition to these 4 major genes, there are numerous other genes that are mutated in pancreatic cancer at lower frequencies.

Unfortunately, most pancreatic cancers do not cause specific symptoms and are not diagnosed in a timely manner. Typical non-specific symptoms include upper abdominal pain radiating to the back; unexplained weight loss; nausea; jaundice; clay colored stools; and in a small percentage of people, migratory thrombophlebitis (multiple blood clots appearing in a variety of veins). At times, it can present with diabetes, symptoms of pancreatitis, or depression. Diagnosis is predicated upon imaging tests including CT, MRI, and endoscopic ultrasound.  Standard cancer staging is stage I through stage IV, with stages I an II being localized, III being locally advanced, and IV being metastatic. In the absence of metastatic disease, the ability to surgically remove the cancer is predicated on the relationship of the tumor to the adjacent major blood vessels.

Pancreatic cancer is a complex disease and is best treated by a multidisciplinary team including a surgeon, medical oncologist, and radiation oncologist. In general, patients with stage I/II disease should undergo surgery followed by adjuvant therapy (chemotherapy and/or radiation).  Patients with stage III locally advanced disease should be treated with chemotherapy and/or chemo-radiation.  Patients with stage IV and good performance status may receive systemic therapy and those with poor health should be given supportive therapy.

The best chance of long-term survival of a patient with localized pancreatic cancer is surgical removal. However, because pancreatic cancer is often beyond the confines of the pancreas at presentation and due to the potentially negative impact of surgery on quality of life as well as the low chance of long-term survival, surgery is often non-curative. Certainly, the risk of local and systemic recurrence after surgery is very high.

Bottom Line: Pancreatic cancer is a wickedly lethal cancer.  In terms of minimizing one’s risk, avoid tobacco, obesity and heavy alcohol consumption. So, don’t smoke, eat a healthy diet, maintain a good weight, and be moderate with alcohol.  Despite the dismal prognosis, there have been recent advances on many fronts, particularly in terms of the genetics of the cancer, wherein the key to treating this miserable cancer most likely lies.

“Sometimes life hits you in the head with a brick. Don’t lose faith. I’m convinced that the only thing that kept me going was that I loved what I did. You’ve got to find what you love. And that is as true for your work as it is for your lovers. Your work is going to fill a large part of your life, and the only way to be truly satisfied is to do what you believe is great work. And the only way to do great work is to love what you do. If you haven’t found it yet, keep looking. Don’t settle. As with all matters of the heart, you’ll know when you find it. And, like any great relationship, it just gets better and better as the years roll on. So keep looking until you find it. Don’t settle.” 

Steve Jobs, who died of neuroendocrine cancer of the pancreas

Reference: Recent Progress in Pancreatic Cancer, Wolfgang, Herman, Laheru, Klein, Erdek, Fishman and Hruban

CA CANCER J CLIN 2013;63:318-348 September/October 2013

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in Kindle edition

Author of: Male Pelvic Fitness: Optimizing Sexual and Urinary Health; in press and available in e-book and paperback formats in January 2014.

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Organ Donation: America Can Do Better

November 30, 2012

Andrew Siegel, MD    Blog #84

photo (3) copy 2

This past Monday marked the death of Dr. Joseph E Murray at the age 93, the surgeon who performed the first successful human organ transplant.  In 1954, he removed a healthy kidney from a 23-year-old man and implanted it into the man’s identical twin.  This heralded the beginning of the transplant era that has saved the lives of thousands of patients who have received new kidneys, heart, lungs, livers and other organs after their own had failed.  In 1990, Dr. Murray was awarded the Nobel Prize in medicine.

Currently, there are over 100,000 Americans on the waiting list for organ transplantation, 75% of whom are awaiting a kidney.  The situation is literally at a crisis level insofar as there are only about 30,000 transplants performed annually. Twenty or so Americans die EVERY day for want of an organ donor. The bottom line is that people are literally dying while on the wait list for organs; this is a huge public health issue that becomes a very private one if it becomes you, a family member or friend who is the one in need of that organ. What makes this particularly tragic is that this is a readily remediable problem!

I am signed up to be an organ donor.  This was a decision that I opted in for when I received my New Jersey driver’s license.  I figured that this is the least I can do for my fellow man.  If I get hit by a bus or suffer an injury that renders me in a permanent vegetative state, why not recycle my organs for the benefit of the living? I will happily donate my corneas, kidneys, heart, liver, lungs, pancreas or any other organ that will help improve the quality and quantity of the life of my fellow man or woman, particularly as these organs will do me no good at all where I am going.
Charitable acts that are of benefit to another living human being are essential, particularly insofar as in the USA we have a tremendous shortage of available organs, as demand far exceeds supply. With advances in dialysis, patients with kidney disease are surviving longer than ever. This, coupled with the rise in prevalence of kidney failure due to greater longevity, as well as an increase in the prevalence of hypertension and diabetes related primarily to the growing obesity epidemic, has resulted in a major demand for kidneys.

In the USA, consent for organ donation is an opt-in system, usually authorized by the person designated as medical power of attorney.  So those persons who give explicit consent become potential donors. However, alternatively, a number of European countries, including Spain, Austria and Belgium, have laws that provide an opt-out system.  In these countries, one must petition to be excluded from being an organ donor after death, presumptive consent existing in the absence of specifying a preference.

In general, the opt-out system will dramatically increase consent rates for organ donation. For example, Germany, a country that utilizes an opt-in system, has an organ donation consent rate of 12%; this is as opposed to Austria, a nation that utilizes an opt-out system, which has a consent rate nearing 100%.   It would seem that in general, people do not like having to make a decision and check off a box, and if a system is set up such that the default mode results in an action, then meaningful change can result.

Israel has developed an interesting alternative to the aforementioned opt in or opt out approaches.  They have enacted a system that prioritizes organ allocation based upon willingness to be a donor.  A donor card is issued to willing donors and a registry of donors is maintained.  Highest priority (3.5 points) for organ allocation goes to donors and first-degree relatives of those individuals who are non-directed donors (those not donating to a specific individual).   Whereas a donor of a live, non-directed organ gets 3.5 points, a directed living donor (those donating to a specific individual) gets no prioritized organ allocation.  Anybody with a donor card gets 2 points.  If a family member has a donor card, 1 point is given to any first-degree relative of that individual.  Even though this approach seems somewhat arbitrary, consent rates for donation have increased, resulting in a significant increase in the number of organ transplants since this system was enacted.

In the late 1980s, Iran adopted a system of paying kidney donors and within a decade or so became the only country in the world to have no waitlists for transplants.  Now, by no means am I suggesting that people “sell” their organs for transplantation; however, how sad that monetary incentive compels individuals to act to save lives.

Thanksgiving, the day that we give thanks for the bounty of fortune that we have, has recently passed. The holiday season fast approaches, the time of giving gifts to our loved ones.  I’m not certain if the United States will ever develop an opt-out system for organ donors, but in the meantime, the simple act of opting in can provide the ultimate gift to a person in dire need.  The DMV has made opting in extremely easy: one need not wait to renew one’s license to check the little opt-in box—simply log onto www.dmv.org to learn how to acquire a form to change your donor status to “yes.” Many states have downloadable forms that, once completed, are mailed or faxed in.  And some more progressive states, like California and Pennsylvania, actually allow you to register as a donor on-line.

It was less than 60 years ago that Dr. Murray performed the first transplant—a courageous and heroic moment that many at the time deemed ludicrous—ushering in an era such that transplants have become commonplace.  Let us celebrate the holiday season and commemorate the death of Dr. Murray by trying to increase the ranks of organ donors by simply checking the little opt-in box, a painless and altruistic act that, instead of wasting valuable organs, will recycle them, and in so doing, recycle someone’s life.  That someone, some day, might just be you, your loved one or your friend.

 

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

Available on Amazon in paperback or Kindle edition

Blog subscription: A new blog is posted every Saturday morning.   On the lower right margin you can enter your email address to subscribe to the blog and receive notifications of new posts by email. Please avail yourself of these educational materials and share them with your friends and family.