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Pancreatic Cancer

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Patrick Swayze. Luciano Pavarotti. Michael Landon. Jack Benny. Rex Harrison. Donna Reed. Fernando Lamas. All well known people who succumbed to pancreatic cancer.

The disease is being diagnosed with increasing frequency.[1] In 2008, there were 37,700 new cases diagnosed. Compare that with 43,140 diagnosed in 2010.

Current recommendations for treatment are essentially palliative - surgery to remove the bulk of the tumor and to allow bile to flow into the intestines, medication for pain control. Chemotherapy appears to be largely ineffective, and only about 4% of patients survive for 5 years. Most die within the first one or two years. We’re not doing so well in the “war on cancer,” are we?

Pancreatic cancer ranks 4th in cancer-related deaths in the United States.[2]

pancreatic1The pancreas is an organ which lies deep in the abdomen, protected by the large and small bowel, the stomach, and the layers of fat we accumulate. This organ produces digestive enzymes so that we can break down our food so we can access the nutrients in it. It also produces insulin, the hormone required for transportation of glucose across the cell wall.

The vast majority of pancreatic cancers arise from the exocrine cells that produce digestive enzymes. A few arise from the endocrine cells which produce insulin.

Multiple genes must become abnormal in order for cancer of the pancreas to express itself.

Most pancreatic tumors give no hint of their presence until they grow large enough to block the bile ducts. The first thing a person might notice is a sudden case of jaundice - their eyes and skin turn yellow because the yellow/brown bile acids are backed up into the liver and blood stream. Poop turns clay-colored for the same reason – no bile acids can get into the intestinal tract to color the poop brown. People may feel vague, dull abdominal discomfort deep in the upper abdomen. It is rare that you will feel a severe abdominal pain. By the time you get to the doctor, you often have abnormal blood glucose, or have been diagnosed with type II diabetes within the previous two years. Most patients with significant pancreatic tumors will have weight loss, nausea, lack of appetite. Initial blood work - liver enzymes, pancreas enzymes (amylase, lipase) - may appear deceptively normal, except perhaps for abnormal blood sugar levels.

What Causes It?

The exact cause is unknown, but pancreatic cancer is more common in smokers, people who are obese, and people exposed to organophosphates.

smokingResearch shows that cigarette smokers develop cancer of the pancreas two to three times more often than nonsmokers. Cancer-causing agents (carcinogens) in tobacco smoke damage important genes that control the growth of cells, causing them to grow abnormally or to reproduce too rapidly.

About 80% of patients with pancreatic cancer have diabetes.[3] Does the diabetes cause the pancreatic carcinoma? Or is it the other way round? There is no clear-cut answer, and indeed, both may be true.[4] It’s a little like the chicken and the egg - it is rare to have one without the other, but as to which came first…

Insulin-like growth factor certainly plays some role, since the pancreas organ is so rich in insulin receptors.[5]

Genetic disposition may play a role; 5%-10% of those diagnosed with cancer of the pancreas have relatives who also suffered from the disease.

Many different genes on multiple chromosomes have been implicated in the development of pancreatic cancer.[6] These include the BRCA2 gene which has been found in about 10% of women with breast cancer, as well as at least two other tumor suppressor genes. Pancreatic cancer occurs after cells in your pancreas develop genetic mutations. These mutations cause the cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor. This is similar to what we see with cancer of the cervix, or the breast, or the colon, or most other cancers.

Insecticides may play a big role in this form of cancer. More than 90 percent of people with pancreatic cancer have mutations in the KRAS gene and abnormally high levels of organophosphates in their tissues. The organophosphate family includes some 37 insecticides, and they are the most widely used insecticides today. Do you have diazinon in your garden shed? That’s an organophosphate. Do you sweeten your iced tea with the artificial sweetener Splenda®? It is a chlorinated hydrocarbon, which makes it also a member of this insecticide family.

The KRAS gene makes a protein involved in cell signaling pathways, cell growth, and apoptosis. Mutations of the KRAS gene make the cells more active in signaling. It is now known that KRAS mutations occur long before the formation of the actual cancer, within lesions called Pancreatic Intraepithelial Neoplasia.

The Diagnosis

The Cancer Antigen19-9 test is typically ordered when trying to diagnose pancreatic cancer. It is a blood test that measures proteins shed by pancreatic cancer cells. It is helpful to differentiate between cancer of the pancreas and other conditions, such as pancreatitis (inflammation of the pancreas). It is not always able to accurately detect cancer. If the results are positive and high, then yes, that is indicative of cancer. But if not positive, that doesn’t mean that you don’t have pancreatic cancer. It just means that if you do have pancreatic cancer, it’s not producing a lot of CA 19-9.

Getting an image of the organ is the first step to a solid diagnosis. An abdominal CT scan with contrast material (barium) is the best way to diagnose a pancreatic mass.[7] Endoscopic ultrasound is a relatively new procedure that can be used to probe the pancreas for cancers by inserting a long tube down the throat. microscopeBecause the ultrasound probe is close to the pancreas, it is possible to identify small cancers within the pancreas. The cancers also can be biopsied through the endoscope.

As with any suspected cancer, the formal diagnosis requires that a piece of tissue be evaluated under a microscope.

This may have to wait until the time of surgery, if there is obstruction to the bile ducts, or if there are signs of large tumor or apparent metastatic disease, and surgery is clearly needed. There is concern about spreading the tumor if needle biopsy is attempted.

How Is Pancreatic Cancer Treated In Conventional Medicine?

Surgical excision of the tumor is the only currently known “curative” modality - although even with so-called curative surgery, fewer than 5% of patients are alive after 5 years. Because pancreatic cancer is often advanced when it is first found, few pancreatic tumors can be removed by surgery.

Current recommendations include either pre-operative or post-operative treatment with chemotherapeutic agents - mainly gemcitabine and/or fluorouracil/leucovorin. This combination does appear to improve disease-free progression and overall survival by a relatively small amount. More recently erlotinib, an epidermal growth factor receptor inhibitor, has been shown to benefit a certain number of patients. The toxicity is high, and the benefit accrues only to those small numbers of patients who do not have the KRAS2 mutation, perhaps 10% of the total.

Pancreatic cancer is notoriously resistant to standard chemotherapy and radiation. Chemotherapy works best when it makes contact with cells at the time they are dividing because that is when they are weakest, most vulnerable to the drug. With pancreatic cancer, however, the cancer cells don’t divide often. Emerging evidence suggests that a tumor’s ability to grow and propagate is dependent on a small subset of cells within a tumor, called cancer stem cells. Pancreatic cancer stem cells[8] are very slow growing, and therefore not particularly affected by the chemotherapeutic agents currently in use.

Treatment of Cancer of the Pancreas at the Arizona Center for Advanced Medicine

If the body does not survive, then the rest becomes a moot point. So first, we treat the body.

We begin with what is going in to the body. Is nutrition adequate? And healthy? Is it mostly sugars and starches? Hormone-fed meats? Pesticide-free fruits and vegetables? Is the patient still able to eat enough of the right kind of calories to sustain life? If not, then we immediately start intravenous nutrition with vitamins, minerals, and other immune stimulating substances, so that the body can begin to deal with this cancerous growth that is out of control.

We have nutritional counselors on staff who help you figure out what is most healthy for you to eat and what you are capable of eating, so that you can begin to restore the health of your digestive system - of which the pancreas is an important part.[9,10]

We move on to dealing with the cancer cells. It is important to know what they may be sensitive to, and so immediately we test for chemosensitivity - which drugs will work best for you. If we are seeing you early in the course of your disease, we may wait for the results of those tests before deciding which chemotherapeutic agents to use with our Insulin Potentiation Therapy - low dose™ (IPT-LD) method of treatment. If it is later in the course of the disease and you are very ill, then we will follow the conventional standard of care recommendations, using IPT-LD treatment with gemcitabine and fluorouracil/leucovorin - until the results of the chemosensitivity tests come back. At that time, we can switch to something which would be more effective with your particular circulating tumor cells.

What makes IPT-LD fundamentally different from conventional chemotherapy is its ability to prompt the cells to divide; slowly dividing cancer stem cells are an issue with pancreatic cancer. Insulin stimulates cells to grow, which they do by dividing. So when insulin is administered a few minutes prior to administering the drugs, we are prompting the cells to divide which makes the chemotherapy more effective for pancreatic cancer.

Insulin also makes possible a more effective delivery of chemotherapy. All cancer cells are endowed with extra insulin receptors - you could call them doors into the cells. Insulin opens the “doors” to the cancer cells and efficiently shuttles the drugs inside where they can kill the cells. Healthy cells, which don’t have nearly as many insulin receptors, are largely bypassed. This targeted approach allows us to use about one-tenth the conventional amount of drugs. The body’s immune system is not heavily damaged with IPT-LD as it is with conventional chemotherapy.

In addition to IPT-LD treatments, we also use multiple forms of complementary and alternative therapies - orthomolecular and herbal therapies to stimulate the immune system, so the body can begin to distinguish normal tissue from tumor tissue, and encourage the tumor tissue to self-destruct (apoptosis). We use high-dose vitamin C infusions[11], as well as other forms of immune system modulation, both oral and injectable, to restore your immune system to a more functional state. In this way, we enable your own immune system to fight this abnormal growth which, for its own survival, hijacked your body’s normal mechanisms.

Other Messages Which This Cancer Giving Us

When we get out of balance, our own bodies make every effort to let us know something is not right. We all develop illness in our own particularly vulnerable organs - some in the heart, some in the lungs, some in the breasts or testes, some in the pancreas... Our body is always trying to communicate with us. The messages generally start in the areas easiest to feel and work with - muscle tension, tendonitis, runny nose - and then progress to more systemic manifestations - high blood pressure, diabetes, anxiety - before they settle in to the most extreme cry for help - heart attack, irritable bowel, autoimmune disease, cancer.

It may seem overwhelming, when faced with a diagnosis of cancer, to think that the body is actually trying to help us figure out something important, some significant imbalance, or some life-shattering event that we have been unable to deal with. But this may indeed be the time to examine whether there are any issues that we should consider.

The pancreas lies deep in the abdomen, between the intestines and the spine, in the most protected place of the body. It is the physical location of the third chakra, the power chakra. When this chakra is out of balance, we experience a feeling of helplessness and hopelessness, and utter lack of power. Is it a real lack of power? Or just a perception of lack? The brain really does not know the difference, and puts out the same “victim” messages, whether the situation is real or simply perceived. So... this might be a good time to consider whether there are things in your life over which you feel you have no control, and how to deal with them in a way where you do not accept the role of the victim. We have professionals on staff who can help you explore those issues, should you care to travel that road.

Why the pancreas? Why not the bone marrow (in the form of leukemia) or the stomach or any other organ of the body? This is where genetics plays a part. If you have a KRAS mutation, you may not be able to deal as well with pollution caused by organic solvents or insecticides. So in the context of the above “hopeless and helpless” scenario, you manifest these “we need to deal with this issue” messages in the pancreas.

Does healing come through chemotherapy? Nutritional modification? Spiritual experience? Does it really matter? All the levels are connected. The physical level takes longer to manifest, being more dense material than the other levels. But healing will occur on all levels, as long as the root cause is examined and dealt with.

Looking to the Future

The Hedgehog gene was identified in genetic screens used to understand body segmentation of fruit flies of the genus Drosophila (Nusslein-Volhard et al; 1980). Loss of the secreted Hedgehog sign aling protein was found to cause Drosophila embryos to develop as spiny balls reminiscent of hedgehogs.

Ever heard of the “sonic hedgehog pathways?” Your cells have. Hedgehog molecules are signaling proteins that can switch genes on or off. These molecules can also affect genes by increasing their concentration. The body uses them any place where it is measuring out, partitioning, and organizing a pattern of cells.

The hedgehog signaling pathway gives cells information to the embryo to develop differentiated body parts - like digits on fingers and toes. Developmental pathways in the immune system are also regulated by the Sonic hedgehog pathway.[12] In the embryo, when this gene is abnormal, we see midline defects - cleft lip or palate, Cyclops, etc.

hedgehogIn adults, this signaling pathway controls cell division of adult stem cells. When the pathway malfunctions, it can result in erectile dysfunction and cancer. The sonic hedgehog messenger system is abnormally active in pancreatic cancer.

However, in the lab, when this signaling is blocked, the growth of pancreatic cancer cells is slowed.

This work is still in the very early stages, and not yet developed to the point where it can be used. We have no idea what other pathways are affected when we block this one. But therein lies the promise that someday, we may be able to block the signaling pathway and slow pancreatic cancer long enough to get on top of it and work with the body to eradicate it.


[1] NCI website, http://www.cancer.gov/cancertopics/types/pancreatic downloaded July 11, 2010.[2] NEJM 362:17 1605-1617(April 29,2010).[3] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4.[4] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4. [5] Bergmann U, Funatomi H et al. Insulin-like Growth Factor I Overexpression in Human Pancreatic Cancer: Evidence for Autocrine and Paracrine Roles. Cancer Res May 15, 1995 55; 2007. [6] Li DH, Xie KP et al. Pancreatic cancer. The Lancet 363:1049-1057 (March 27, 2004). [7] Hidalgo M. Pancreatic Cancer. N Engl J Med 2010;362:1605-17. doi 10.1056/NEJMra0901557 [8] Li CW, Heidt DG et al. Identification of Pancreatic Cancer Stem Cells. Cancer Res February 1, 2007 67; 1030. [9] Mouria M, Gukovskava AS et al. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. IJC 98;5:761-69. [10] Chan JM, Wang F et al. Vegetable and Fruit Intake and Pancreatic Cancer in a Population-Based Case-Control Study in the San Francisco Bay Area. Cancer Epidemiology, Biomarkers & Prevention September 2005 14; 2093; doi: 10.1158/1055-9965.EPI-05-0226 [11] Härtel C, Strunk T et al. Immunomodulatory Effect of Vitamin C on Intracytoplasmic Cytokine Production in Neonatal Cord Blood Cells. Neonatology 2007;91:54-60. DOI: 10.1159/000096972. [12] Downloaded from http://scienceblogs.com/pharyngula/2008/08/basics_sonic_hedgehog.php July 17, 2010.
Pancreatic Cancer

pancreatic1The pancreas is an organ which lies deep in the abdomen, protected by the large and small bowel, the stomach, and the layers of fat we accumulate. This organ produces digestive enzymes so that we can break down our food so we can access the nutrients in it. It also produces insulin, the hormone required for transportation of glucose across the cell wall.

The vast majority of pancreatic cancers arise from the exocrine cells that produce digestive enzymes. A few arise from the endocrine cells which produce insulin.

Multiple genes must become abnormal in order for cancer of the pancreas to express itself.

Most pancreatic tumors give no hint of their presence until they grow large enough to block the bile ducts. The first thing a person might notice is a sudden case of jaundice - their eyes and skin turn yellow because the yellow/brown bile acids are backed up into the liver and blood stream. Poop turns clay-colored for the same reason – no bile acids can get into the intestinal tract to color the poop brown. People may feel vague, dull abdominal discomfort deep in the upper abdomen. It is rare that you will feel a severe abdominal pain. By the time you get to the doctor, you often have abnormal blood glucose, or have been diagnosed with type II diabetes within the previous two years. Most patients with significant pancreatic tumors will have weight loss, nausea, lack of appetite. Initial blood work - liver enzymes, pancreas enzymes (amylase, lipase) - may appear deceptively normal, except perhaps for abnormal blood sugar levels.

The exact cause is unknown, but pancreatic cancer is more common in smokers, people who are obese, and people exposed to organophosphates.

smokingResearch shows that cigarette smokers develop cancer of the pancreas two to three times more often than nonsmokers. Cancer-causing agents (carcinogens) in tobacco smoke damage important genes that control the growth of cells, causing them to grow abnormally or to reproduce too rapidly.

About 80% of patients with pancreatic cancer have diabetes.[3] Does the diabetes cause the pancreatic carcinoma? Or is it the other way round? There is no clear-cut answer, and indeed, both may be true.[4] It’s a little like the chicken and the egg - it is rare to have one without the other, but as to which came first…

Insulin-like growth factor certainly plays some role, since the pancreas organ is so rich in insulin receptors.[5]

Genetic disposition may play a role; 5%-10% of those diagnosed with cancer of the pancreas have relatives who also suffered from the disease.

Many different genes on multiple chromosomes have been implicated in the development of pancreatic cancer.[6] These include the BRCA2 gene which has been found in about 10% of women with breast cancer, as well as at least two other tumor suppressor genes. Pancreatic cancer occurs after cells in your pancreas develop genetic mutations. These mutations cause the cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor. This is similar to what we see with cancer of the cervix, or the breast, or the colon, or most other cancers.

Insecticides may play a big role in this form of cancer. More than 90 percent of people with pancreatic cancer have mutations in the KRAS gene and abnormally high levels of organophosphates in their tissues. The organophosphate family includes some 37 insecticides, and they are the most widely used insecticides today. Do you have diazinon in your garden shed? That’s an organophosphate. Do you sweeten your iced tea with the artificial sweetener Splenda®? It is a chlorinated hydrocarbon, which makes it also a member of this insecticide family.

The KRAS gene makes a protein involved in cell signaling pathways, cell growth, and apoptosis. Mutations of the KRAS gene make the cells more active in signaling. It is now known that KRAS mutations occur long before the formation of the actual cancer, within lesions called Pancreatic Intraepithelial Neoplasia.

The Diagnosis

The Cancer Antigen19-9 test is typically ordered when trying to diagnose pancreatic cancer. It is a blood test that measures proteins shed by pancreatic cancer cells. It is helpful to differentiate between cancer of the pancreas and other conditions, such as pancreatitis (inflammation of the pancreas). It is not always able to accurately detect cancer. If the results are positive and high, then yes, that is indicative of cancer. But if not positive, that doesn’t mean that you don’t have pancreatic cancer. It just means that if you do have pancreatic cancer, it’s not producing a lot of CA 19-9.

Getting an image of the organ is the first step to a solid diagnosis. An abdominal CT scan with contrast material (barium) is the best way to diagnose a pancreatic mass.[7] Endoscopic ultrasound is a relatively new procedure that can be used to probe the pancreas for cancers by inserting a long tube down the throat. microscopeBecause the ultrasound probe is close to the pancreas, it is possible to identify small cancers within the pancreas. The cancers also can be biopsied through the endoscope.

As with any suspected cancer, the formal diagnosis requires that a piece of tissue be evaluated under a microscope.

This may have to wait until the time of surgery, if there is obstruction to the bile ducts, or if there are signs of large tumor or apparent metastatic disease, and surgery is clearly needed. There is concern about spreading the tumor if needle biopsy is attempted.

How Is Pancreatic Cancer Treated In Conventional Medicine?

Surgical excision of the tumor is the only currently known “curative” modality - although even with so-called curative surgery, fewer than 5% of patients are alive after 5 years. Because pancreatic cancer is often advanced when it is first found, few pancreatic tumors can be removed by surgery.

Current recommendations include either pre-operative or post-operative treatment with chemotherapeutic agents - mainly gemcitabine and/or fluorouracil/leucovorin. This combination does appear to improve disease-free progression and overall survival by a relatively small amount. More recently erlotinib, an epidermal growth factor receptor inhibitor, has been shown to benefit a certain number of patients. The toxicity is high, and the benefit accrues only to those small numbers of patients who do not have the KRAS2 mutation, perhaps 10% of the total.

Pancreatic cancer is notoriously resistant to standard chemotherapy and radiation. Chemotherapy works best when it makes contact with cells at the time they are dividing because that is when they are weakest, most vulnerable to the drug. With pancreatic cancer, however, the cancer cells don’t divide often. Emerging evidence suggests that a tumor’s ability to grow and propagate is dependent on a small subset of cells within a tumor, called cancer stem cells. Pancreatic cancer stem cells[8] are very slow growing, and therefore not particularly affected by the chemotherapeutic agents currently in use.

Treatment of Cancer of the Pancreas at the Arizona Center for Advanced Medicine

If the body does not survive, then the rest becomes a moot point. So first, we treat the body.

We begin with what is going in to the body. Is nutrition adequate? And healthy? Is it mostly sugars and starches? Hormone-fed meats? Pesticide-free fruits and vegetables? Is the patient still able to eat enough of the right kind of calories to sustain life? If not, then we immediately start intravenous nutrition with vitamins, minerals, and other immune stimulating substances, so that the body can begin to deal with this cancerous growth that is out of control.

We have nutritional counselors on staff who help you figure out what is most healthy for you to eat and what you are capable of eating, so that you can begin to restore the health of your digestive system - of which the pancreas is an important part.[9,10]

We move on to dealing with the cancer cells. It is important to know what they may be sensitive to, and so immediately we test for chemosensitivity - which drugs will work best for you. If we are seeing you early in the course of your disease, we may wait for the results of those tests before deciding which chemotherapeutic agents to use with our Insulin Potentiation Therapy - low dose™ (IPT-LD) method of treatment. If it is later in the course of the disease and you are very ill, then we will follow the conventional standard of care recommendations, using IPT-LD treatment with gemcitabine and fluorouracil/leucovorin - until the results of the chemosensitivity tests come back. At that time, we can switch to something which would be more effective with your particular circulating tumor cells.

What makes IPT-LD fundamentally different from conventional chemotherapy is its ability to prompt the cells to divide; slowly dividing cancer stem cells are an issue with pancreatic cancer. Insulin stimulates cells to grow, which they do by dividing. So when insulin is administered a few minutes prior to administering the drugs, we are prompting the cells to divide which makes the chemotherapy more effective for pancreatic cancer.

Insulin also makes possible a more effective delivery of chemotherapy. All cancer cells are endowed with extra insulin receptors - you could call them doors into the cells. Insulin opens the “doors” to the cancer cells and efficiently shuttles the drugs inside where they can kill the cells. Healthy cells, which don’t have nearly as many insulin receptors, are largely bypassed. This targeted approach allows us to use about one-tenth the conventional amount of drugs. The body’s immune system is not heavily damaged with IPT-LD as it is with conventional chemotherapy.

In addition to IPT-LD treatments, we also use multiple forms of complementary and alternative therapies - orthomolecular and herbal therapies to stimulate the immune system, so the body can begin to distinguish normal tissue from tumor tissue, and encourage the tumor tissue to self-destruct (apoptosis). We use high-dose vitamin C infusions[11], as well as other forms of immune system modulation, both oral and injectable, to restore your immune system to a more functional state. In this way, we enable your own immune system to fight this abnormal growth which, for its own survival, hijacked your body’s normal mechanisms.

Other Messages Which This Cancer Giving Us

When we get out of balance, our own bodies make every effort to let us know something is not right. We all develop illness in our own particularly vulnerable organs - some in the heart, some in the lungs, some in the breasts or testes, some in the pancreas... Our body is always trying to communicate with us. The messages generally start in the areas easiest to feel and work with - muscle tension, tendonitis, runny nose - and then progress to more systemic manifestations - high blood pressure, diabetes, anxiety - before they settle in to the most extreme cry for help - heart attack, irritable bowel, autoimmune disease, cancer.

It may seem overwhelming, when faced with a diagnosis of cancer, to think that the body is actually trying to help us figure out something important, some significant imbalance, or some life-shattering event that we have been unable to deal with. But this may indeed be the time to examine whether there are any issues that we should consider.

The pancreas lies deep in the abdomen, between the intestines and the spine, in the most protected place of the body. It is the physical location of the third chakra, the power chakra. When this chakra is out of balance, we experience a feeling of helplessness and hopelessness, and utter lack of power. Is it a real lack of power? Or just a perception of lack? The brain really does not know the difference, and puts out the same “victim” messages, whether the situation is real or simply perceived. So... this might be a good time to consider whether there are things in your life over which you feel you have no control, and how to deal with them in a way where you do not accept the role of the victim. We have professionals on staff who can help you explore those issues, should you care to travel that road.

Why the pancreas? Why not the bone marrow (in the form of leukemia) or the stomach or any other organ of the body? This is where genetics plays a part. If you have a KRAS mutation, you may not be able to deal as well with pollution caused by organic solvents or insecticides. So in the context of the above “hopeless and helpless” scenario, you manifest these “we need to deal with this issue” messages in the pancreas.

Does healing come through chemotherapy? Nutritional modification? Spiritual experience? Does it really matter? All the levels are connected. The physical level takes longer to manifest, being more dense material than the other levels. But healing will occur on all levels, as long as the root cause is examined and dealt with.

Looking to the Future

The Hedgehog gene was identified in genetic screens used to understand body segmentation of fruit flies of the genus Drosophila (Nusslein-Volhard et al; 1980). Loss of the secreted Hedgehog sign aling protein was found to cause Drosophila embryos to develop as spiny balls reminiscent of hedgehogs.

Ever heard of the “sonic hedgehog pathways?” Your cells have. Hedgehog molecules are signaling proteins that can switch genes on or off. These molecules can also affect genes by increasing their concentration. The body uses them any place where it is measuring out, partitioning, and organizing a pattern of cells.

The hedgehog signaling pathway gives cells information to the embryo to develop differentiated body parts - like digits on fingers and toes. Developmental pathways in the immune system are also regulated by the Sonic hedgehog pathway.[12] In the embryo, when this gene is abnormal, we see midline defects - cleft lip or palate, Cyclops, etc.

hedgehogIn adults, this signaling pathway controls cell division of adult stem cells. When the pathway malfunctions, it can result in erectile dysfunction and cancer. The sonic hedgehog messenger system is abnormally active in pancreatic cancer.

However, in the lab, when this signaling is blocked, the growth of pancreatic cancer cells is slowed.

This work is still in the very early stages, and not yet developed to the point where it can be used. We have no idea what other pathways are affected when we block this one. But therein lies the promise that someday, we may be able to block the signaling pathway and slow pancreatic cancer long enough to get on top of it and work with the body to eradicate it.


[1] NCI website, http://www.cancer.gov/cancertopics/types/pancreatic downloaded July 11, 2010.[2] NEJM 362:17 1605-1617(April 29,2010).[3] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4.[4] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4. [5] Bergmann U, Funatomi H et al. Insulin-like Growth Factor I Overexpression in Human Pancreatic Cancer: Evidence for Autocrine and Paracrine Roles. Cancer Res May 15, 1995 55; 2007. [6] Li DH, Xie KP et al. Pancreatic cancer. The Lancet 363:1049-1057 (March 27, 2004). [7] Hidalgo M. Pancreatic Cancer. N Engl J Med 2010;362:1605-17. doi 10.1056/NEJMra0901557 [8] Li CW, Heidt DG et al. Identification of Pancreatic Cancer Stem Cells. Cancer Res February 1, 2007 67; 1030. [9] Mouria M, Gukovskava AS et al. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. IJC 98;5:761-69. [10] Chan JM, Wang F et al. Vegetable and Fruit Intake and Pancreatic Cancer in a Population-Based Case-Control Study in the San Francisco Bay Area. Cancer Epidemiology, Biomarkers & Prevention September 2005 14; 2093; doi: 10.1158/1055-9965.EPI-05-0226 [11] Härtel C, Strunk T et al. Immunomodulatory Effect of Vitamin C on Intracytoplasmic Cytokine Production in Neonatal Cord Blood Cells. Neonatology 2007;91:54-60. DOI: 10.1159/000096972. [12] Downloaded from http://scienceblogs.com/pharyngula/2008/08/basics_sonic_hedgehog.php July 17, 2010.
Pancreatic Cancer

Genetic disposition may play a role; 5%-10% of those diagnosed with cancer of the pancreas have relatives who also suffered from the disease.

Many different genes on multiple chromosomes have been implicated in the development of pancreatic cancer.[6] These include the BRCA2 gene which has been found in about 10% of women with breast cancer, as well as at least two other tumor suppressor genes. Pancreatic cancer occurs after cells in your pancreas develop genetic mutations. These mutations cause the cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor. This is similar to what we see with cancer of the cervix, or the breast, or the colon, or most other cancers.

Insecticides may play a big role in this form of cancer. More than 90 percent of people with pancreatic cancer have mutations in the KRAS gene and abnormally high levels of organophosphates in their tissues. The organophosphate family includes some 37 insecticides, and they are the most widely used insecticides today. Do you have diazinon in your garden shed? That’s an organophosphate. Do you sweeten your iced tea with the artificial sweetener Splenda®? It is a chlorinated hydrocarbon, which makes it also a member of this insecticide family.

The KRAS gene makes a protein involved in cell signaling pathways, cell growth, and apoptosis. Mutations of the KRAS gene make the cells more active in signaling. It is now known that KRAS mutations occur long before the formation of the actual cancer, within lesions called Pancreatic Intraepithelial Neoplasia.

The Cancer Antigen19-9 test is typically ordered when trying to diagnose pancreatic cancer. It is a blood test that measures proteins shed by pancreatic cancer cells. It is helpful to differentiate between cancer of the pancreas and other conditions, such as pancreatitis (inflammation of the pancreas). It is not always able to accurately detect cancer. If the results are positive and high, then yes, that is indicative of cancer. But if not positive, that doesn’t mean that you don’t have pancreatic cancer. It just means that if you do have pancreatic cancer, it’s not producing a lot of CA 19-9.

Getting an image of the organ is the first step to a solid diagnosis. An abdominal CT scan with contrast material (barium) is the best way to diagnose a pancreatic mass.[7] Endoscopic ultrasound is a relatively new procedure that can be used to probe the pancreas for cancers by inserting a long tube down the throat. microscopeBecause the ultrasound probe is close to the pancreas, it is possible to identify small cancers within the pancreas. The cancers also can be biopsied through the endoscope.

As with any suspected cancer, the formal diagnosis requires that a piece of tissue be evaluated under a microscope.

This may have to wait until the time of surgery, if there is obstruction to the bile ducts, or if there are signs of large tumor or apparent metastatic disease, and surgery is clearly needed. There is concern about spreading the tumor if needle biopsy is attempted.

Surgical excision of the tumor is the only currently known “curative” modality - although even with so-called curative surgery, fewer than 5% of patients are alive after 5 years. Because pancreatic cancer is often advanced when it is first found, few pancreatic tumors can be removed by surgery.

Current recommendations include either pre-operative or post-operative treatment with chemotherapeutic agents - mainly gemcitabine and/or fluorouracil/leucovorin. This combination does appear to improve disease-free progression and overall survival by a relatively small amount. More recently erlotinib, an epidermal growth factor receptor inhibitor, has been shown to benefit a certain number of patients. The toxicity is high, and the benefit accrues only to those small numbers of patients who do not have the KRAS2 mutation, perhaps 10% of the total.

Pancreatic cancer is notoriously resistant to standard chemotherapy and radiation. Chemotherapy works best when it makes contact with cells at the time they are dividing because that is when they are weakest, most vulnerable to the drug. With pancreatic cancer, however, the cancer cells don’t divide often. Emerging evidence suggests that a tumor’s ability to grow and propagate is dependent on a small subset of cells within a tumor, called cancer stem cells. Pancreatic cancer stem cells[8] are very slow growing, and therefore not particularly affected by the chemotherapeutic agents currently in use.

If the body does not survive, then the rest becomes a moot point. So first, we treat the body.

We begin with what is going in to the body. Is nutrition adequate? And healthy? Is it mostly sugars and starches? Hormone-fed meats? Pesticide-free fruits and vegetables? Is the patient still able to eat enough of the right kind of calories to sustain life? If not, then we immediately start intravenous nutrition with vitamins, minerals, and other immune stimulating substances, so that the body can begin to deal with this cancerous growth that is out of control.

We have nutritional counselors on staff who help you figure out what is most healthy for you to eat and what you are capable of eating, so that you can begin to restore the health of your digestive system - of which the pancreas is an important part.[9,10]

We move on to dealing with the cancer cells. It is important to know what they may be sensitive to, and so immediately we test for chemosensitivity - which drugs will work best for you. If we are seeing you early in the course of your disease, we may wait for the results of those tests before deciding which chemotherapeutic agents to use with our Insulin Potentiation Therapy - low dose™ (IPT-LD) method of treatment. If it is later in the course of the disease and you are very ill, then we will follow the conventional standard of care recommendations, using IPT-LD treatment with gemcitabine and fluorouracil/leucovorin - until the results of the chemosensitivity tests come back. At that time, we can switch to something which would be more effective with your particular circulating tumor cells.

What makes IPT-LD fundamentally different from conventional chemotherapy is its ability to prompt the cells to divide; slowly dividing cancer stem cells are an issue with pancreatic cancer. Insulin stimulates cells to grow, which they do by dividing. So when insulin is administered a few minutes prior to administering the drugs, we are prompting the cells to divide which makes the chemotherapy more effective for pancreatic cancer.

Insulin also makes possible a more effective delivery of chemotherapy. All cancer cells are endowed with extra insulin receptors - you could call them doors into the cells. Insulin opens the “doors” to the cancer cells and efficiently shuttles the drugs inside where they can kill the cells. Healthy cells, which don’t have nearly as many insulin receptors, are largely bypassed. This targeted approach allows us to use about one-tenth the conventional amount of drugs. The body’s immune system is not heavily damaged with IPT-LD as it is with conventional chemotherapy.

In addition to IPT-LD treatments, we also use multiple forms of complementary and alternative therapies - orthomolecular and herbal therapies to stimulate the immune system, so the body can begin to distinguish normal tissue from tumor tissue, and encourage the tumor tissue to self-destruct (apoptosis). We use high-dose vitamin C infusions[11], as well as other forms of immune system modulation, both oral and injectable, to restore your immune system to a more functional state. In this way, we enable your own immune system to fight this abnormal growth which, for its own survival, hijacked your body’s normal mechanisms.

Other Messages Which This Cancer Giving Us

When we get out of balance, our own bodies make every effort to let us know something is not right. We all develop illness in our own particularly vulnerable organs - some in the heart, some in the lungs, some in the breasts or testes, some in the pancreas... Our body is always trying to communicate with us. The messages generally start in the areas easiest to feel and work with - muscle tension, tendonitis, runny nose - and then progress to more systemic manifestations - high blood pressure, diabetes, anxiety - before they settle in to the most extreme cry for help - heart attack, irritable bowel, autoimmune disease, cancer.

It may seem overwhelming, when faced with a diagnosis of cancer, to think that the body is actually trying to help us figure out something important, some significant imbalance, or some life-shattering event that we have been unable to deal with. But this may indeed be the time to examine whether there are any issues that we should consider.

The pancreas lies deep in the abdomen, between the intestines and the spine, in the most protected place of the body. It is the physical location of the third chakra, the power chakra. When this chakra is out of balance, we experience a feeling of helplessness and hopelessness, and utter lack of power. Is it a real lack of power? Or just a perception of lack? The brain really does not know the difference, and puts out the same “victim” messages, whether the situation is real or simply perceived. So... this might be a good time to consider whether there are things in your life over which you feel you have no control, and how to deal with them in a way where you do not accept the role of the victim. We have professionals on staff who can help you explore those issues, should you care to travel that road.

Why the pancreas? Why not the bone marrow (in the form of leukemia) or the stomach or any other organ of the body? This is where genetics plays a part. If you have a KRAS mutation, you may not be able to deal as well with pollution caused by organic solvents or insecticides. So in the context of the above “hopeless and helpless” scenario, you manifest these “we need to deal with this issue” messages in the pancreas.

Does healing come through chemotherapy? Nutritional modification? Spiritual experience? Does it really matter? All the levels are connected. The physical level takes longer to manifest, being more dense material than the other levels. But healing will occur on all levels, as long as the root cause is examined and dealt with.

Looking to the Future

The Hedgehog gene was identified in genetic screens used to understand body segmentation of fruit flies of the genus Drosophila (Nusslein-Volhard et al; 1980). Loss of the secreted Hedgehog sign aling protein was found to cause Drosophila embryos to develop as spiny balls reminiscent of hedgehogs.

Ever heard of the “sonic hedgehog pathways?” Your cells have. Hedgehog molecules are signaling proteins that can switch genes on or off. These molecules can also affect genes by increasing their concentration. The body uses them any place where it is measuring out, partitioning, and organizing a pattern of cells.

The hedgehog signaling pathway gives cells information to the embryo to develop differentiated body parts - like digits on fingers and toes. Developmental pathways in the immune system are also regulated by the Sonic hedgehog pathway.[12] In the embryo, when this gene is abnormal, we see midline defects - cleft lip or palate, Cyclops, etc.

hedgehogIn adults, this signaling pathway controls cell division of adult stem cells. When the pathway malfunctions, it can result in erectile dysfunction and cancer. The sonic hedgehog messenger system is abnormally active in pancreatic cancer.

However, in the lab, when this signaling is blocked, the growth of pancreatic cancer cells is slowed.

This work is still in the very early stages, and not yet developed to the point where it can be used. We have no idea what other pathways are affected when we block this one. But therein lies the promise that someday, we may be able to block the signaling pathway and slow pancreatic cancer long enough to get on top of it and work with the body to eradicate it.


[1] NCI website, http://www.cancer.gov/cancertopics/types/pancreatic downloaded July 11, 2010.[2] NEJM 362:17 1605-1617(April 29,2010).[3] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4.[4] Wang F, Herrington M et al. The relationship between diabetes and pancreatic cancer. Molecular Cancer 2003, 2:4doi:10.1186/1476-4598-2-4. [5] Bergmann U, Funatomi H et al. Insulin-like Growth Factor I Overexpression in Human Pancreatic Cancer: Evidence for Autocrine and Paracrine Roles. Cancer Res May 15, 1995 55; 2007. [6] Li DH, Xie KP et al. Pancreatic cancer. The Lancet 363:1049-1057 (March 27, 2004). [7] Hidalgo M. Pancreatic Cancer. N Engl J Med 2010;362:1605-17. doi 10.1056/NEJMra0901557 [8] Li CW, Heidt DG et al. Identification of Pancreatic Cancer Stem Cells. Cancer Res February 1, 2007 67; 1030. [9] Mouria M, Gukovskava AS et al. Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. IJC 98;5:761-69. [10] Chan JM, Wang F et al. Vegetable and Fruit Intake and Pancreatic Cancer in a Population-Based Case-Control Study in the San Francisco Bay Area. Cancer Epidemiology, Biomarkers & Prevention September 2005 14; 2093; doi: 10.1158/1055-9965.EPI-05-0226 [11] Härtel C, Strunk T et al. Immunomodulatory Effect of Vitamin C on Intracytoplasmic Cytokine Production in Neonatal Cord Blood Cells. Neonatology 2007;91:54-60. DOI: 10.1159/000096972. [12] Downloaded from http://scienceblogs.com/pharyngula/2008/08/basics_sonic_hedgehog.php July 17, 2010.
Pancreatic Cancer

We move on to dealing with the cancer cells. It is important to know what they may be sensitive to, and so immediately we test for chemosensitivity - which drugs will work best for you. If we are seeing you early in the course of your disease, we may wait for the results of those tests before deciding which chemotherapeutic agents to use with our Insulin Potentiation Therapy - low dose™ (IPT-LD) method of treatment. If it is later in the course of the disease and you are very ill, then we will follow the conventional standard of care recommendations, using IPT-LD treatment with gemcitabine and fluorouracil/leucovorin - until the results of the chemosensitivity tests come back. At that time, we can switch to something which would be more effective with your particular circulating tumor cells.

What makes IPT-LD fundamentally different from conventional chemotherapy is its ability to prompt the cells to divide; slowly dividing cancer stem cells are an issue with pancreatic cancer. Insulin stimulates cells to grow, which they do by dividing. So when insulin is administered a few minutes prior to administering the drugs, we are prompting the cells to divide which makes the chemotherapy more effective for pancreatic cancer.

Insulin also makes possible a more effective delivery of chemotherapy. All cancer cells are endowed with extra insulin receptors - you could call them doors into the cells. Insulin opens the “doors” to the cancer cells and efficiently shuttles the drugs inside where they can kill the cells. Healthy cells, which don’t have nearly as many insulin receptors, are largely bypassed. This targeted approach allows us to use about one-tenth the conventional amount of drugs. The body’s immune system is not heavily damaged with IPT-LD as it is with conventional chemotherapy.

In addition to IPT-LD treatments, we also use multiple forms of complementary and alternative therapies - orthomolecular and herbal therapies to stimulate the immune system, so the body can begin to distinguish normal tissue from tumor tissue, and encourage the tumor tissue to self-destruct (apoptosis). We use high-dose vitamin C infusions[11], as well as other forms of immune system modulation, both oral and injectable, to restore your immune system to a more functional state. In this way, we enable your own immune system to fight this abnormal growth which, for its own survival, hijacked your body’s normal mechanisms.

When we get out of balance, our own bodies make every effort to let us know something is not right. We all develop illness in our own particularly vulnerable organs - some in the heart, some in the lungs, some in the breasts or testes, some in the pancreas... Our body is always trying to communicate with us. The messages generally start in the areas easiest to feel and work with - muscle tension, tendonitis, runny nose - and then progress to more systemic manifestations - high blood pressure, diabetes, anxiety - before they settle in to the most extreme cry for help - heart attack, irritable bowel, autoimmune disease, cancer.

It may seem overwhelming, when faced with a diagnosis of cancer, to think that the body is actually trying to help us figure out something important, some significant imbalance, or some life-shattering event that we have been unable to deal with. But this may indeed be the time to examine whether there are any issues that we should consider.

The pancreas lies deep in the abdomen, between the intestines and the spine, in the most protected place of the body. It is the physical location of the third chakra, the power chakra. When this chakra is out of balance, we experience a feeling of helplessness and hopelessness, and utter lack of power. Is it a real lack of power? Or just a perception of lack? The brain really does not know the difference, and puts out the same “victim” messages, whether the situation is real or simply perceived. So... this might be a good time to consider whether there are things in your life over which you feel you have no control, and how to deal with them in a way where you do not accept the role of the victim. We have professionals on staff who can help you explore those issues, should you care to travel that road.

Why the pancreas? Why not the bone marrow (in the form of leukemia) or the stomach or any other organ of the body? This is where genetics plays a part. If you have a KRAS mutation, you may not be able to deal as well with pollution caused by organic solvents or insecticides. So in the context of the above “hopeless and helpless” scenario, you manifest these “we need to deal with this issue” messages in the pancreas.

Does healing come through chemotherapy? Nutritional modification? Spiritual experience? Does it really matter? All the levels are connected. The physical level takes longer to manifest, being more dense material than the other levels. But healing will occur on all levels, as long as the root cause is examined and dealt with.

The Hedgehog gene was identified in genetic screens used to understand body segmentation of fruit flies of the genus Drosophila (Nusslein-Volhard et al; 1980). Loss of the secreted Hedgehog sign aling protein was found to cause Drosophila embryos to develop as spiny balls reminiscent of hedgehogs.

Ever heard of the “sonic hedgehog pathways?” Your cells have. Hedgehog molecules are signaling proteins that can switch genes on or off. These molecules can also affect genes by increasing their concentration. The body uses them any place where it is measuring out, partitioning, and organizing a pattern of cells.

The hedgehog signaling pathway gives cells information to the embryo to develop differentiated body parts - like digits on fingers and toes. Developmental pathways in the immune system are also regulated by the Sonic hedgehog pathway.[12] In the embryo, when this gene is abnormal, we see midline defects - cleft lip or palate, Cyclops, etc.

hedgehogIn adults, this signaling pathway controls cell division of adult stem cells. When the pathway malfunctions, it can result in erectile dysfunction and cancer. The sonic hedgehog messenger system is abnormally active in pancreatic cancer.

However, in the lab, when this signaling is blocked, the growth of pancreatic cancer cells is slowed.

This work is still in the very early stages, and not yet developed to the point where it can be used. We have no idea what other pathways are affected when we block this one. But therein lies the promise that someday, we may be able to block the signaling pathway and slow pancreatic cancer long enough to get on top of it and work with the body to eradicate it.