We often receive calls from patients stating that “I have been told that I have a mass on my pancreas, what should I do?”  or “I have been told that I have something  on my pancreas, what should I do?” There are multiple terms used to describe masses (also known as  tumors)  that can be found in the pancreas.  Masses can be described based on their physical characteristics, as defined by imaging studies, as solid (consisting of solid abnormal tissue) or cystic (filled with mucus or fluid).  Masses can also further be described based on their aggressiveness usually based on imaging and examination of their cells under the microscope as benign (no potential for turning into cancer) premalignant (some potential to turning into cancer) and malignant (cancer). Masses involving the pancreas are being recognized more frequently, in part because of the growing use of imaging.  Many lesions found on the pancreas turn out to be benign “pseudocysts,” but a variety of harmless (benign) and malignant (cancerous) neoplasms (abnormal growths) can involve the pancreas and a multidisciplinary approach including good clinical history, state of the art imaging, and careful pathology is often needed to establish the correct diagnosis. <click here for link to the Multi-D Clinic at Hopkins> 

Clinical History: The clinical history can often help establish the nature of a tumor involving the pancreas.  For example, a history of alcoholism complicated by multiple episodes of pancreatitis (inflammation of the pancreas) suggests the possibility of a pseudocyst, while patients with painless jaundice (an abnormal yellowing of the skin and eyes often caused by blockage of the bile ducts) are more likely to have a pancreatic cancer.  Blood tests can also point to the correct diagnosis.  Patients with pseudocysts often have associated pancreatitis with elevated blood levels of the enzymes amylase and lipase, while patients with pancreatic cancer may have elevated levels of the cancer marker CA19.9.

Imaging:  A number of different approaches can be used to visualize the pancreas.  The most common include CT scan (computerized axial tomography), magnetic resonance imaging (MRI), positron emission tomography (PET), endoscopic ultrasound (EUS), and endoscopic retrograde pancreatography (ERCP).  Each of these different imaging approaches has its own strengths and weaknesses.  CT scanning is a widely available and an excellent modality to image the pancreas.  MRI is a great method to visualize the pancreatic ducts, PET scanning can reveal the metabolic activity of a tumor, EUS requires slight sedation but provides excellent detail and biopsies can be performed at the same time, and ERCP can be used to visualize the duct system of the pancreas and stents (small tubes to re-establish the flow of secretions such as bile) can be placed during the ERCP procedure.  The broad questions that clinicians try to answer using these various approaches include: 1) Is a mass present? 2) Is the mass solid or is it cystic (does it form spaces or holes)? 3) Is the mass confined to the pancreas or has it spread to involve other structures or other organs?  4) What is the most likely diagnosis for this patient’s tumor?

Pathology:  Often called the “gold standard,” pathology can play a critical role in establishing the diagnosis of a mass or tumor involving the pancreas.  Pathology refers to the examination of fluids and tissues removed from the body.  This examination typically involves the examination of slides using a microscope.  The tissues to be examined by pathology are removed by biopsy (small sampling) or completely removed surgically (resection).  Individual cells in these tissues can be examined using techniques called “cytopathology” or “cytology,” or sections of the tissue can be examined using by a surgical pathologist.  In general, pathologists try to determine if the cells present can account for the lesion seen on imaging, and if the cells from the lesion are harmless (benign) or malignant (cancerous).  Pathologists have a variety of special stains, such as “immunohistochemistry” at their disposal in difficult cases.

Surgery:  All of the information obtained in the medical history, imaging and pathological analyses are considered in determining the best management of a pancreatic mass.  In general, most solid pancreatic masses are either malignant or have malignant potential.   Therefore, most solid tumors are removed surgically.  Exceptions to removal of solid tumors exist but are rare.  The management of pancreatic cyst is often much more complex since the majority of these types of tumors are benign and therefore do not require surgery.  The key in management of pancreatic cystic lesions is to avoid an operation in people who have “innocent” cysts while on the other hand not choosing to observe individuals with cysts that may harbor malignancy.  This concept may seem simple, but in practice differentiating between these two groups requires experienced physicians.  In fact, here at Johns Hopkins we have an entire clinic dedicated to the management of pancreatic cysts (the phone number of our pancreatic cyst clinic is  410-933-PANC).  Very specific criteria have been developed to guide the management of pancreatic cystic lesions and are used to predict the need for surgical resection.  These criteria rely on accurate imaging and pathological data.  If surgery  is to be performed for a mass this surgery should be done in a center with experienced pancreatic surgeons who perform many of these types of operations on a regular basis.   

Multi-Disciplinary Approach:   It should be clear that a multi-disciplinary team approach, involving the coordinated efforts of clinicians, radiologists and pathologists is often the best way to evaluate a tumor involving the pancreas.  For more information on the Multi-Disciplinary Pancreas Team at Johns Hopkins <click here>.

Pancreatic Cancers often grow into the tissues adjacent to the pancreas.  The location of the pancreas deep within the abdomen places the pancreas close to major blood vessels (see “Where is the pancreas?” post).  Pancreatic cancers that invade into these blood vessels pose a significant surgical problem and in some cases may even preclude surgery.  Pancreatic cancers that invade these nearby vessels (called the celiac artery, the portal vein, and the superior mesenteric artery and vein) are referred to as either “border-line resectable” or “locally advanced”.  Pancreatic cancers in these categories are challenging to treat.  Despite this aggressive feature, some patients in this situation will be able to undergo surgery and have their cancer removed, while others will be treated with chemotherapy or chemoradiotherapy (”radiation therapy”).  To complicate matters, other patients will have surgery, but only after undergoing chemoradiotherapy first.  The bottom line is that in order to deliver the most effective treatment for these patients with pancreatic cancer a cooperative effort of a team of cancer experts is required.  We have found that this is best accomplished through a multidisciplinary clinic where patients are evaluated by all of the specialists in a single day.  As a result, the first-ever and most successful Pancreatic Cancer Multidisciplinary Clinic was developed at Johns Hopkins.  If you would like to learn more about this clinic please feel free to contact us at 410-933-PANC.  We will be able to answer your questions and schedule a clinic appointment for you at your request.

One of the most important steps in determining the best treatment for someone with locally invasive pancreatic cancer is a high quality imaging study.  At Johns Hopkins we perform a computerized tomography scan (aka “CT scan”) using a cutting edge 64 or 128 slice CT scanner. Information obtained from this CT scanner allows us to view the cancer and its relationship to nearby blood vessels from numerous angles and even in three-dimensions.  These images are reviewed in our multidisciplinary conference.  This portion of the discussion is lead by the world’s leading expert on pancreatic CT imaging, Dr. Elliot Fishman.

The CT images are reviewed by the team in order to determine if surgery is possible.  In the absence of metastatic disease this is determined by assessing the relationship of the tumor to vessels as follows. There are two main arteries and one main venous system near the head, neck and body of the pancreas.  The main arteries are called the celiac artery and the superior mesenteric artery.  The venous system is the portal vein and its tributaries (superior mesenteric vein, splenic vein).  Cancer invasion into arteries and veins is handled differently.  Cancers that are found to significantly involve the artery on CT scan (”encasement”) are typically not operable.  Although it may be technically possible to remove these cancers, the complications of doing so and the side effects of this procedure outweigh any potential benefits.  Moreover, removal of such cancers under these circumstances often leaves a portion of the cancer behind (R2 resection) and thus the surgery may confer no survival benefit while potentially subjecting the person to debilitating side effects.

Unlike arteries, isolated involvement of the portal and/or superior mesenteric vein does not rule out tumor removal – although it does make the operation more complex.  If the cancer involves the vein but not the artery, and it is technically possible to reconstruct the vein, these cancers can be surgically removed with long-term survival similar to pancreatic cancer not involving vessels.  There are numerous exceptions to this general algorithm based on the individual patient and their cancer.  In addition, select patients may benefit from chemoradiotherapy (”radiation therapy”) prior to surgery.  The complexity of the many treatment options underscores the need to be evaluated by an experienced team of specialists.

Surgery for the removal of cancers that involve main vessels should only be attempted by surgeons experienced in pancreatic resections.  The team of surgeons at Johns Hopkins perform more pancreatic resections than any other group in the country.  Our team has extensive experience in performing vein resection and reconstruction for the removal of locally aggressive pancreatic cancers.  We are confident in our ability to perform these operations and have recently published our results (PMID: 19394156).  We reported that patients undergoing vein resection and reconstruction for the removal of locally aggressive pancreatic cancers here at Johns Hopkins had a very low risk of operative-related death and a similar rate of complications to a pancreatic operation without a vein resection.  Most importantly the long-term survival of patients undergoing a portal vein or superior mesenteric vein resection with reconstruction was no different than those who did not require this procedure and underwent a standard operation.

Our team has four surgeons with expertise in pancreatic surgery for patients in whom their cancer involves the portal veins and/or superior mesenteric vein: John L. Cameron, MD, FACS, Barish H. Edil, MD, FACS, Richard D. Schulick, MD, FACS and Christopher L. Wolfgang, MD, PhD, FACS.  If you have been told you have a pancreatic cancer that involves blood vessels and would like to be evaluated by the Johns Hopkins Multidisciplinary Team please call our schedulers at 410-933-PANC.

Ask the Expert:  Pancreatic Surgeon Barish H. Edil, MD, FACS

The Whipple Operation is called a pancreaticoduodenectomy in medical terms.  It takes the name “Whipple” from the New York surgeon Allen O. Whipple who was the first in the United States to describe the procedure.  It is performed very differently today than it was back in the time of Dr. Whipple.  There are two general variations of the procedure called the Classic Whipple (standard pancreaticoduodenectomy) or the Pylorus Preserving Whipple (pylorus preserving pancreaticoduodenectomy) also known as the “Mini-Whipple”. Both variations of the Whipple Operation involve the removal of the gallbladder, common bile duct, duodenum and the head of the pancreas. The operation is done for tumors of the pancreas (pancreatic cancer), ampulla of Vater, duodenum and distal bile duct. This operation is complex and requires extensive experience by the surgeons performing the operation.  In addition the surgeon must work in an environment with experienced surgical nurses, ICU and anesthesia team, pathologists and ancillary hospital staff. A landmark study conducted in 2002 by John D. Birkmeyer and his co-investigators published in the New England Journal of Medicine shows that the lowest mortality and best outcomes are obtained for the Whipple operation when it is performed at high volume centers.  The pancreatic surgeons at Johns Hopkins do more Whipple operations (both Classic Whipples and Pylorus Preserving Whipples  aka Mini-Whipple) than any other institution in the United States.  Last year the team at Johns Hopkins performed over 240 Whipple operations, of these, approximately 160 were pylorous preserving Whipples (Mini-Whipples).

What is the difference between the Classic Whipple and the Pylorus Preserving Whipple (Mini-Whipple)?

Both operations involve a similar dissection, postoperative stay and recovery. The resection is identical except for the proximal gastrointestinal tract. In the Classic Whipple a 30-40% distal gastrectomy or stomach resection is preformed. In the pylorus preserving Whipple (Mini-Whipple) the stomach is preserved and the GI tract is transected 1 inch past the stomach leaving a small segment of duodenum (the first portion of intestine leaving the stomach).

Why do one over the other?

We are often asked by our patients if they can have a “Mini-Whipple” instead of a Classic Whipple.  This question is often prompted by confusing and misleading information on the internet.  It should be clear that there is nothing “mini” about either a pylorus preserving or classic Whipple.  The operation to remove a tumor from the head of the pancreas is a big one no matter what variation is used.  This will likely be the case for all other variations of the Whipple Operation that will be developed in the near future – including the laparoscopic Whipple.  The Classic Whipple and Pylorus Preserving Whipple (mini whipple)  are similar with regards to potential complications, rate of complications, return to a regular diet, size of incision, postoperative pain control issues, length of hospital stay and recovery time.  In fact, from the patient’s perspective no difference would be noted between the two operations.  Most importantly, there is no difference in the long-term survival between the two operations.  The main advantage of the pylorus preserving Whipple (Mini-Whipple) is that it involves a slightly less complicated operative reconstruction.  In certain instances of pancreatic cancer, such as tumors of the proximal neck of the pancreas, the pylorus may be involved with tumor and a classic Whipple must be performed to achieve complete removal.  Thus the choice between a Classic Whipple and Pylorus Preserving Whipple is based on the technical aspects of removing the tumor at the time of operation and not a preoperative “choice” made by surgeon and patient to minimize the extent of the operation.

At Johns Hopkins approximately two-thirds of the Whipple Operation’s are the Pylorus Preserving or Mini-Whipple variation and the remaining one third are the Classic Whipple.  This distribution results from the need to perform the classic Whipple based on the operative findings and underscores the importance of having an experienced pancreatic surgeon.
If you would to become a patient at Johns Hopkins please call our schedulers at: 410-933-PANC (7262).  We would be delighted to assist you.

Autoimmune pancreatits is pretty darn rare.  A hospital survey from Japan, estimated that less than one person per 100,000 has autoimmune pancreatitis.  Most patients are elderly, with an average age of 68, but teenagers have been diagnosed with the disease as well as octogenarians.  Unlike most other autoimmune diseases, men develop autoimmune pancreatitis more commonly than do women (the male to female ratio is 4 to 1).  Most patients do not present with signs and symptoms of pancreatitis, instead most patients develop signs and symptoms that are more suggestive of pancreatic cancer.  These would include jaundice (an abnormal yellowing of the white part of the eyes), and diabetes mellitus (sugar diabetes).  A CT scan is often taken and it can reveal a localized “sausage-like” enlargement of the pancreas, a finding suggestive of pancreatic cancer.  As a result, many patients with autoimmune pancreatitis are often felt to have pancreatic cancer.  A blood test can be helpful as many, although certainly not all, patients with autoimmune pancreatitis have elevated serum “IgG4 levels.” 

Autoimmune pancreatitis can be associated with immune injury to other organs, and some patients also develop a swelling of their salivary glands, kidney problems, and a scarring of the internal abdomen (called retroperitoneal fibrosis). 

Because autoimmune pancreatits so closely mimics pancreatic cancer, many patients with autoimmune pancreatits are taken to surgery and have the abnormal portion of their pancreas removed.  In these cases the pathology of the pancreas can be diagnostic.  It shows three features- 1) a mixed inflammatory cell infiltrate composed of plasma cells and lymphocytes, 2) inflammation centered  on the pancreatic ducts, and 3) inflammation involving the veins of the pancreas (“venulitis”).  In questionable cases a special stain for IgG4 can be performed and it will label the inflammatory cell infiltrate in the pancreas helping to establish the diagnosis.

Autoimmune pancreatits is important to recognize because some patients respond to steroid therapy (30–40 mg/day of prednisolone).  As clinicians become familiar with this rare disease it is hoped that more and more patients will be diagnosed without the need for surgery.

 For more information visit: http://www.springerlink.com/content/258070050r37ht55/

We are often asked about the causes of pancreatic cancer.  While it is virtually impossible to tell what caused a specific person to develop pancreatic cancer, there are some important principles of cancer biology that can help us understand why pancreatic cancer develops, and large population-based studies help us understand the many risk factors for this disease.

Pancreatic cancer is fundamentally a disease caused by damage to the DNA (mutations).  These mutations can be inherited from mom or dad, or they can be acquired as we age.  First, let us look at the inherited mutations.  Remember that we have two copies of each gene – one copy we inherit from mom, the other copy we inherit from dad.  Most individuals with an inherited cancer syndrome inherit one mutant copy (let us say from dad) and one intact (normal) copy (let us say from mom) of a cancer associated gene.  As they age, some of these people will damage the good copy of the gene (the copy they got from mom) in a cell in their pancreas.  That cell will have two bad copies of the gene, and, as a result, that cell in the pancreas will grow into a cancer.  It doesn’t mean that everyone with an inherited predisposition will get cancer, it means that since they only have one copy of the gene, they are more likely to get cancer.  I like to think of it using the analogy of the space shuttle, with the shuttle standing in for a person, and computers on the space shuttle standing in for genes.  Normally the shuttle goes into space with a computer and a back-up for that computer.  Only  if both computers break is there a problem.  For people with a genetic predisposition to pancreatic cancer, it is like going up into space with one good computer and one bad computer.  If something goes wrong with the one good computer, they are in trouble.

The second way we can damage our DNA is with our behavior.  The carcinogens in cigarette smoke can damage our DNA.  If the carcinogens damage a key cancer-associated gene in a cell in the pancreas, then that cell may grow into a cancer.  Simply put, don’t smoke!

The third way our DNA gets damaged is by chance.  This is probably the least satisfying explanation, but it is true.  Every cell in our body (and there are trillions of them!) contains a 23 chromosomes and these 23 chromosomes contain 3 billion base-pairs of DNA.  Every time a cell divides it has to copy all of that DNA (so that it can make a daughter cell with a full complement of DNA).  The DNA copying machinery in cells is pretty darn good, but it is not perfect.  Occasionally mistakes are made.  On one hand, this is good from a population or species perspective, because these mistakes allow for evolution to occur (if we copied our DNA perfectly we would not evolve!).  If one of these chance errors in copying (DNA mutations)  damage a key cancer-associated gene in a cell in the pancreas, then that cell may grow into a cancer.

To summarize, pancreatic cancer is caused by DNA mutations, and there are three ways that we can damage our DNA.  We can be born with a DNA mutation inherited from mom or dad, we can do something, like smoke, that damages our DNA, or our DNA can be damaged by chance.

The second way to answer the question about what causes pancreatic cancer is to ask what are the risk factors for pancreatic cancer?    Some of the risk factors include:

1. Cigarette smoking: Smoking doubles the risk of pancreatic cancer. Smoking is also associated with early age at diagnosis, and, very importantly, the risk of pancreatic cancer drops close to normal in people who quit smoking.  Simply put, cigarette smoking is the leading preventable cause of pancreatic cancer.  In fact, some scientists have estimated that one in four, or one in five cases of pancreatic cancer are caused by smoking cigarettes.
2. Age: The risk of developing pancreatic cancer increases with age. Over 80% of the cases develop between the ages of 60 and 80.
3. Race: Studies in the United States have shown that pancreatic cancer is more common in the African  American population than it is in the white population.  Some of this increased risk may be due to socioeconomic factors and to cigarette smoking.
4. Gender: Cancer of the pancreas is more common in men than in women.  Men are more likely to smoke than women.
5. Religious background: Pancreatic cancer is proportionally more common in Ashkenazi Jews than the rest of the population. This may be because of a particular inherited mutation in the breast cancer gene (BRCA2) which runs in some Ashkenazi Jewish families.
6. Chronic pancreatitis: Long-term inflammation of the pancreas (pancreatitis) has been linked to cancer of the pancreas.
7. Diabetes: Diabetes is both a symptom of pancreatic cancer, and long-standing adult-onset diabetes also increases the risk of pancreatic cancer.
8. Obesity: Obesity significantly increases the risk of pancreatic cancer.
9. Diet: Diets high in meats, cholesterol fried foods and nitrosamines may increase risk, while diets high in fruits and vegetables reduce risk. Folate may be protective.
10. Genetics:  As mentioned earlier, a  number of inherited cancer syndromes increase the risk of pancreatic cancer.  These include inherited mutations in the BRCA2, FAMMM, or Peutz-Jeghers genes.  To learn more about familial pancreatic cancer visit the web site of the National Familial Pancreas Tumor Registry (http://pathology.jhu.edu/pancreas/NFPTR/).

Dr. Ralph H. Hruban

Located directly behind the stomach, the pancreas lies deep in the center of the abdomen. Its position corresponds to an area 3-6 inches above the “belly button”, straight back on the back wall of the abdominal cavity. In fact, the bones of the spine are just a few inches behind the pancreas. And the major vessels of the abdomen (the portal vein, mesenteric vessels, aorta, and vena cava) all course through or next to the pancreas, making it a treacherous area for a surgeon inexperienced in pancreas surgery.

The pancreas is an integral part of the digestive system. The flow of the digestive system is often altered during the surgical treatment of pancreatic cancer. Therefore it is helpful to understand the normal flow of food before reading about surgical treatment. Food is carried from the mouth to the stomach by the esophagus. This tube descends from the mouth and through an opening in the diaphragm. (The diaphragm is a dome shaped muscle that separates the lungs and heart from the abdomen and assists in breathing.)

Immediately after passing through the diaphragm’s opening, the esophagus empties into the stomach where acids that break down the food are produced. From the stomach, the food flows directly into the first part of the small intestine, called the duodenum. It is here in the duodenum that bile and pancreatic fluids enter the digestive system.

At the time of surgery, exposing the pancreas requires retracting the liver, stomach, omentum, small bowel, and colon. The liver, stomach, and omentum are retracted up towards the head and the small bowel and transverse colon is retracted down towards the feet. The kidneys do not need to be retracted because the pancreas sits between the 2 kidneys. The center of the back wall of the abdominal cavity, or the retroperitoneum, is pancreas bed, a space the pancreas shares with the first part of the small intestine (a.k.a. the duodenum). In fact, the head of the pancreas is intimately in contact with most of the duodenum.

The Whipple operation for tumors of the pancreas head removes both the pancreas head and duodenum as a unit due to their close proximity and shared blood supply. In addition, the Whipple operation removes part of the bile duct (which carries bile from the liver to the duodenum) because the bile duct courses through pancreas head. Thus after the pancreas tumor is removed in a Whipple operation, the intestine, bile duct, and remnant pancreas are meticulously reconstructed, making the operation long and tedious.

Conversely, tumors of the pancreas body or tail may not require removal of a segment of intestine and these tumors can sometimes be removed laparoscopically, even sparing the spleen in select cases. These minimally-invasive options are determined by the location of the tumor, the tumor size, the proximity to the portal vein, and the surgeon’s experience with laparoscopy.

The deep and central location of the pancreas in the abdomen, coupled with its “wet sponge” texture, make it a unique organ for surgeons to conquer. Adding to the complexity of pancreas surgery, the pancreas lacks a capsule, or covering, and is thus prone to bleed or leak juices with even a small degree of rough handling. For these reasons, we recommend that pancreas surgery be performed by a specialist who is familiar with standard tissue handling techniques for the pancreas.

When performed open, pancreas surgery often involves an incision directly over the organ. This incision begins at the lower aspect of the central sternal bone (the xyphoid), and extends to a point a few inches below the “belly button”. Laparoscopic pancreas surgery usually involves 3-4 one-inch incisions for instrumentation and a camera.

Every week, newly diagnosed patients call to ask if a their CAT scan findings indicate that surgery open, or laparoscopic, is feasible. For most patients, a quick assessment of the CAT scan findings can yield a rough estimate of surgical candidacy, and allow for planning for the next steps in assessment leading to the appropriate care in a rapid and timely fashion.

Marty Makary M.D., M.P.H.
Pancreas and Advanced Laparoscopic Surgery
Johns Hopkins Hospital

The team sequenced more than 20,000 genes in a series of 24 well-characterized pancreatic cancers and discovered over 1,500 DNA mutations in these cancers. An average of 63 mutations was found in each cancer, supporting the growing body of evidence that cancer is fundamentally a disease caused by alterations in the DNA. The complex picture presented by these mutations was simplified by the finding that many of them acted in concert through a set of well-defined signaling pathways and processes. The scientists identified 12 core signaling pathways and processes that were each altered in more than two-thirds of the cancers. These 12 core pathways provide the basis for novel diagnostic and therapeutic approaches in pancreatic cancer.

As a part of the study the team also discovered over 500 genes that were made at abnormally high levels in the 24 cancers. Fifty-four of these over expressed genes were predicted to be secreted or made on the surface of the cancer cells, suggesting that these genes may be useful therapeutic targets or may form the basis for new tests for the early detection of pancreatic cancer.

The landmark study characterizes the fundamental genetic components of pancreatic cancer and will guide research on this disease for the next decade. The improved understanding realized from these studies, and their follow-up work will hopefully lead to dramatic improvements in the prevention, detection, or treatment of pancreatic cancer.

The project is also a great example of the power of private giving. The major funding The Pancreatic Cancer Genome Project came from the Sol and Lillian Goldman Charitable Trusts. Significant funding also came from The Lustgarten Foundation for Pancreatic Cancer Research. Additional funding came from the Virginia and D. K. Ludwig Fund, Susan G. Komen Foundation, Michael Rolfe Pancreatic Cancer Foundation, Joseph C. Monastra Foundation, the family and friends of George Rubis, Viragh Family Foundation, Broad Foundation, Emerald Foundation, and National Institutes of Health.

by Michael A. Erdek, M.D.

Pain due to pancreatic cancer most commonly manifests itself as abdominal pain which may radiate through to the back, and may be associated with the patient assuming a forward-leaning position in order to maximize his or her comfort.

Traditionally, a continuum has been followed with regard to managing pain due to pancreatic cancer. Intermittently dosed opioid medications (such as morphine or oxycodone) may be given every few hours to help control a patient’s pain. If and when the pain becomes refractory to this strategy, a long-acting or sustained release opioid (narcotic) preparation may be started.

For patients whose pain is either poorly controlled by the above modalities, or who develop dose-limiting side effects from these medications (often sleepiness or tiredness), a celiac plexus block may be employed. The celiac plexus is a group of nerve fibers in a bundle that sits just in front of the spine and the aorta at a take-off point for various blood vessels that supply the upper abdominal organs (the celiac trunk, hence its name). This celiac plexus serves most of the abdominal organs, and is an important structure in the pain associated with pancreatic cancer.

The procedure is done as an outpatient and may last up to about an hour. Sedation may be provided if necessary. The patient lies face down on an x-ray table. The physician uses radiographic guidance to help place one or two needles through the back to the area of the celiac plexus. The first step is the diagnostic block, which is done with local anesthetic to determine if this block will take away a significant amount of the patient’s pain. If so, a neurolytic block is the next step, which may or may not be done immediately following the diagnostic block. Alcohol or phenol is used to do the neurolytic block, which can interrupt this nerve transmission for on the order of 3-6 months. The block can be repeated if deemed necessary.

Many patients are able to significantly decrease their opioid intake after a successful celiac plexus neurolysis. The following article from JAMA is one of the best known on the subject and looks at celiac plexus block and neurolysis versus standard analgesic therapy.

By Dr. Joseph Herman

There have been a number of questions on the Johns Hopkins pancreatic website regarding stereotactic radiosurgery for pancreatic cancer. Therefore, we thought it is important to review the literature on stereotactic radiosurgery and help patients better understand the risks and benefits of this treatment and clarify some of the misconceptions. Stereotactic radiosurgery (SRS) can also be called stereotactic body radiotherapy (SBRT) or CyberKnife. It is important to stress that all of these modalities use radiation and that there is no actual surgery done.

The theory is that the radiation doses are high enough to cause ablation of the pancreatic tumor. While the data suggests that SBRT and/or CyberKnife can ablate certain tumors (brain metastasis and lung tumors) there is no prospective data showing that SBRT and/or CyberKnife can effectively ablate pancreatic tumors or shrink them to the point where they can be resectable. As you can see by the two prospective trials posted on this blog, SBRT and CyberKnife appear to prevent pancreatic tumors from progressing (grow) but there is no evidence that it causes pancreatic tumors to shrink or improve survival. Further, the data suggests that high doses of radiation given by SBRT or CyberKnife can cause some unacceptable acute (within 2-3 months of treatment) and chronic side effects from treatment when compared to conventional radiation treatment delivered over 2-6 weeks of treatment. Specifically, approximately 30-40% of all patients treated with SBRT/CyberKnife develop gastrointestinal side effects including a small number of patients who developed ulcers which required surgical repair. The authors suggest that this may be because the duodenum and small bowel is adjacent to the pancreatic tumors and it is hard to treat the pancreatic tumor and avoid irradiating these areas.

It is important that almost all patients in these studies developed metastatic disease, clearly demonstrating a need for better drugs to control pancreatic tumor spread. Finally, the survival in both of these studies unfortunately were very similar to conventional radiation and chemotherapy. While SBRT and CyberKnife are more convenient for patients (1-5 days of treatment) compared with 25 treatments (conventional), the increased risk of side effects with shorter course radiation with no improved survival make us question whether these treatments in their CURRENT FORM are clearly benefiting patients with pancreatic cancer.

It is important to note that the doses of radiation used in these studies are high. In the Stanford CyberKnife study (Koong et al.) the dose was 25 Gy given in one fraction and in the SBRT (Denmark) trial the total dose was 45 Gy. It is possible that lower doses (15-25) delivered over 3-5 fractions may be better tolerated than the doses given in these two studies, however this data has not been published in a prospective controlled fashion. In summary, SBRT/CyberKnife does appear to result in good local control of pancreatic tumors, however it is unlikely that it will shrink a majority of pancreatic tumors enough for surgical resection and patients are likely to have increased chronic (long term) side effects when compared to conventional treatment.

Additional prospective (patients treated on a clinical trial and followed for side effects) studies are needed to test the true benefit and safety of SBRT and Cyberknife treatment for patients with unresectable pancreatic cancer. While SBRT and CyberKnife therapy does hold promise we have to be careful not to tell patients that it is likely to cure them of their cancer….the data simply isn’t there.

Commonly asked questions:

1) What is CyberKnife and how does it differ from stereotactic body radiation therapy (SBRT)? How does it differ from standard conventional radiation?

a. Cyberknife and SBRT are both radiation. No surgery is actually done. The theory is that high doses of radiation (15-45 Gy) given over a shorter period of time (1-5 days) can more effectively kill pancreatic cancer cells when compared to conventional radiation (50 Gy) given over a 5 week period. CyberKnife and SBRT are both attractive because they limit the amount of time a patient needs to undergo radiation (1 week vs. 5 weeks). While higher doses of radiation may more effectively kill pancreatic cancer cells, it can also cause more damage to normal tissues which are directly adjacent to the pancreas tumor such as the duodenum or bowel.

b. CyberKnife can deliver beams from 1200 or more different directions, a capability that allows it to target lesions precisely. Often 100 beams of radiation are used in each treatment plan. Using multiple beams of radiation can limit the dose to adjacent structures. The treatment is also non-isocentric which means it does not rely on one point in the tumor and can deliver beams of radiation to any area of the tumor. It relies on a robotic arm to track gold seed markers in the tumor which can move during breathing. Treatment time can be 1-2 hours. One limitation is the beams of radiation are not able to treat the patient from all directions (360 degrees) and sometimes the patient needs to be turned over during radiation treatment.

c. SBRT uses 10-25 beams of radiation. It also can limit adjacent structures. The treatment is isocentric meaning it relies on a central spot in the tumor to focus the radiation. Often gold seed markers are used to track the tumor. The machine can deliver radiation all around the body (360 degrees). Rather than using a robotic arm to track the tumor, SBRT tries to control or limit breathing motion with specific body molds or breathing devices (airway, breathing, control devices-ABC). The treatment time is typically 20-40 mintues. There have been no real head-to-head comparisons of CyberKnife and SBRT in the treatment of pancreatic cancer. However, in other sites they have been shown to have comparable results (lung cancer).

2) Does SBRT/CyberKnife cure patients of pancreatic cancer and/or improve survival? Although there may be anecdotal evidence of this, there is no published data showing that SBRT/CyberKnife cures patients of pancreatic cancer. There is no evidence to show that CyberKnife clearly improves survival compared to conventional chemotherapy and radiation.

3) Does SBRT/CyberKnife improve local control? Based on CT and PET/CT imaging, higher doses of radiation does appear to improve local control compared to conventional radiation however in its current form (15-45 Gy delivered in 1-5 fractions) it does appear to cause more chronic side effects (gastrointestinal) when compared to conventional treatment.

4) Should I be treated with CyberKnife? While SBRT/CyberKnife is promising, additional prospective studies are needed to determine the optimal daily and total dose of radiation needed to improve local control while limiting treatment related side effects. Patients should be consulted by a radiation oncologists who has ample experience in the treatment of patients with CyberKnife and SBRT.

5) Does Johns Hopkins have SBRT/CyberKnife? Johns Hopkins does not have CyberKnife, however we do have SBRT. We are currently writing a protocol to determine the optimal dose for SBRT with several other institutions and we hope to be enrolling patients on this trial in the next year. Currently we use a short course (2 weeks) of radiation or conventional radiation (5 weeks) with chemotherapy which does downstage a small proportion of patients with limited side effects (10-15%).

For more information on the studies discussed in this blog please click below:

Cyberknife Pancreas PDF (Koong et al.)

Stereotactic Radiation Pancreas PDF (Hoyer et al.)

Please feel free to email me with any questions or comments.