people run for a treatment which then may disappoint them badly. I have to see a lot of research first, before I write it as good for you my dearest friends. But now we have seen enough research and more proof that it is worth quoting - at least in excerpts - this

oncologist medical doctor Mark Sircus. Especially after reading enough about Dr. Simoncini M.D. in Italy who proved his theory with enough research and healings

that these facts stood for themselves. Quote: “Tonight we are going back to medical basics with the application of the least expensive, safest and perhaps most effective cancer medicine there is. Sodium bicarbonate has been on many cancer patients’ minds

this past year. It has not been easy though to get to Rome or even contact Dr. Tullio Simoncini for treatment. And doctors willing to give bicarbonate IV’s are not on

every corner so it’s been somewhat frustrating to have something so simple and effective remain elusive. If doctors doing such treatments want to be listed by the IMVA for referral please contact us.” (International Medical Veritas Association at www.winningcancer.

com/about-the-book/author/

) Though we have known that oral intake of sodium

bicarbonate will have the ‘Simonicini’ effect on oral, esophagus and stomach cancer we have not focused at all on the systemic effect of bicarbonate taken orally. Every cancer patient and every health care practitioner should know that oral intake of sodium bicarbonate offers an instant and strong shift of blood pH into the alkaline. So strong is the effect that athletes can notice he difference in their breathing as more oxygen

is carried throughout the system and as more acids are neutralized. The difference can

be stunning for those whose respiration is labored under intensive

exercise loading. This tells us to take very seriously the oral use of bicarbonate for cancer

treatment no matter what other treatment is used. …If the amount of H+ and CO2 exceed the capacity of hemoglobin, they affect the carbonic acid equilibrium….As a result, the pH of the blood is lowered, causing acidosis. The

lungs and kidneys respond to pH changes by removing CO@,HCO3-, and H+ from the blood. When one reads about these, on different medicine substances, one has to always remember that I am a protocol man who does not support single shot cures for anything. With the publication of today’s

chapter on sodium bicarbonate and maple syrup sodium bicarbonate, slips securely into the number three spot right behind magnesium chloride and iodine. Each of

these three substances effects directly onto basic human physiology in a way most pharmaceutical drugs do not. When used together we have a super threesome that will

inexpensively go far to resolving many of the physical and even some of the emotional problems we, and our children face. And if you have not made the connection please note that all three of these substances are used in emergency rooms and intensive care wards and they do commonly save lives every day with their inherent healing powers. See my chapter on emergency room medicine and cancer treatment. All cancer sufferers and in fact every chronic disease

patient should hold clearly in mind that pH is the regulatory authority that controls most cellular processes. The pH balance of the human bloodstream is recognized by medical physiology texts as one of the most important biochemical balances in all of human body chemistry pH is the acronym for “Potential Hydrogen”. …The following excerpts are of the text in the Yeast and Fungi Invaders section of the Winning the War on Cancer book. Please note that sodium bicarbonate taken in water alone will have a powerful effect on entire body physiology because of the instant shift into alkaline ph

levels. Bicarbonate can be taken frequently throughout the day with half teaspoons amounts though for long term use lower doses are safer. For cancer patient initial

use should be heavy and frequent to force a greater shift because smaller pH shifts can actually stimulate cancer growth. …..Though this cancer treatment is very inexpensive,

do NOT ASSUME it is not effective. The bicarbonate maple syrup cancer treatment is a very significant cancer treatment every cancer patient should be familiar with and it can easily be combined with other safe and effective natural treatments. This cancer treatment is similar in principle to Insulin Potentiation Therapy (IPT). IPT treatment consists of

giving doses of insulin to a fasting patient sufficient to lower blood sugar into the 50mt/dl. In a normal person when you take in sugar the insulin levels go up to meet the need of getting that sugar into the cells. In IPT they are artificially injecting insulin to deplete the blood of all sugar then injecting the lower doses of toxic chemo drugs when the blood sugar is driven down the lowest possible value. During the low peak, it is said that the receptors are more sensitive and take on medications more rapidly and in higher amounts.

The bicarbonate maple syrup treatment works in reverse to IPT. Dr. Tullio Simoncini acknowledges that cancer cells gobble up sugar so when you encourage the intake of sugar it’s like sending in a Trojan horse. The sugar is not going to end up encouraging the further

growth of the cancer colonies because the baking soda is going to kill the cells before they have a chance to grow. Instead of artificially manipulating insulin and thus forcefully driving down blood sugar levels to then inject toxic chemo agents we combine the sugar with the bicarbonate and present it to the cancer cells, which at first are going to love the present. BUT NOT FOR LONG! When mixed and heated together the maple syrup

and baking soda bind together. The maple syrup targets cancer cells (which consume 15 times more glucose than normal cells) and the baking soda, which is dragged into the cancer cells by the maple syrup, being very alkaline forces a rapid shift in pH killing the cell. The actual formula is to mix on part baking soda with three parts (pure 100%) maple syrup in a small saucepan. Stir briskly and heat the mixture for 5 minutes. Take 1 tspn

daily is what is suggested by Cancer Tutor but one could probably do this several times a day. “There is not a tumor on God’s green earth that cannot be licked with a little baking soda and maple syrup.” That is the astonishing claim of controversial folk healer

Jim Kelmun who says that this simple home remedy can stop and reverse the deadly growth of cancers. His loyal patients swear by the man they fondly call Dr. Jim and say he is a miracle worker. “Dr. Jim cured me of lung cancer,” said farmer Ian Roadhouse. “Those other doctors gold me that I was goner and had less than sick months to live. But the doc put me on his mixture and in a couple of months the cancer was gone. It did not even

show up on the x-rays.” Dr. Jim discovered this treatment accidentally somewhere in the middle of the last century when he was treating a family plagued by breast cancer. There

were five sisters in the family and four of them had died of breast cancer. He asked the remaining sister if there was anything different in her diet an she told him that she was partial to sipping maple syrup and baking soda. Since then, reported by a newspaper in Ashville, North Carolina, Dr. Jim dispensed this remedy to over 200 people diagnose with terminal cancer and amazingly he claims of that number 185 lived at least 15 more years

and nearly half enjoyed a complete remission of their disease. When combined with other safe and effective treatments like transdermal magnesium therapy, iodine, vitamin C, probiotics and other items like plenty of good sun exposure, pure water and clay treatments we should expect even higher remission rates. It’s very important not to use baking soda which has had aluminum added to it. The Cancer Tutor site reports that Arm & Hammer does have aluminum but the company insists that is not true. One can buy a product which specifically states it does not include aluminum or other chemicals. (ex; Bob’s Red Mill, Aluminum Free, Baking Soda). Sodium bicarbonate is safe, extremely

inexpensive and unstoppably effective when it comes to cancer tissues. It’s an irresistible chemical, cyanide to cancer cells for it hits the cancer cells with a shock

wave of alkalinity, which allows much more oxygen into the cancer cells than they can tolerate. Cancer cells cannot survive in the presence of high levels of oxygen.

Studies have already shown how manipulation of tumor pH with sodium bicarbonate enhances some form of chemotherapy. The therapeutic treatment of bicarbonate salts can be administered orally, through aerosol, intravenously and through catheter for direct targeting of tumors,” says oncologist Dr. Tullio Simonicini. “Sodium bicarbonate

administered orally, via aerosol or intravenously can achieve positive results only in some tumors, while others – such as the serious ones of the brain or the bones – remain unaffected by the treatment.” The maple syrup apparently enables and increases penetration of bicarbonate into all compartments of body, even those which are difficult or impossible to penetrate by other means. These compartment include the central nervous

system (CNS), through the blood-brain-barrier, joints, solid tumors, and perhaps even the eyes. IPT make cell membranes more permeable, and increases uptake of drugs into cells. The maple syrup will make tissues morepermeable, too. It will transport the bicarbonate across the bloodbrain-barrier, and every other barrier in the body for

sugar is universally needed by all cells in the body.… Both IPT and bicarbonate maple syrup treatments use the rapid growth mechanism of the cancer cells against them…. With the discovery of Dr. Jim’s work bicarbonate comes back into the number three spot

behind magnesium chloride and iodine….Dr. Simoncini says that, …“Fungus, which is the most powerful and the most organized micro-organism known, seems to be an extremely logical candidate as a cause of neoplastic proliferation.” …“Sodium bicarbonate therapy is

harmless, fast and effective because it is extremely diffusible. A therapy with bicarbonate for cancer should proceed from the beginning to the end without interruption for at least 7-8 days. In general a mass of 2-3-4 centimeters will begin to consistently regress from the third to the fourth day, and collapses from the fourth to the fifth,” Says Dr. Simoncini. These are the most important excerpts of the article by Mark Sircus Ac.OMD Director

International Medical Veritas Association (Nov. ‘08) Update Concerning the use of Sodium Bicarbonate in the Treatment of Cancer Oral Bicarbonate options. You can go to

www.winningcancer.com site to download and purchase this very important 274 page book... The information in this book is absolutely essential for all of us. The great question when considering the oral intake of bicarbonate is whether or not to take it with maple

syrup, molasses, honey or even with lemon. (My personal choice would be with Molasses, as you can see from the book

Crude Black Molasses by Cyril Scott, Molasses is used as a sole therapeutic agent been successful with some individuals in resolving their tumors. We also know that molasses has such a concentration of all the

minerals and trace elements, that it will provide a broadspectrum of mineral/alkalizing support to work well with the sodium rich bicarbonate ed.)

Bill Henderson, author of Cancer Free, Your Guide to Gentle, Non Toxic Healing, mixes 3 parts, grade 3maple syrup with one part baking soda and heats the

mixture for a couple of minutes on the stove. As soon as the baking soda foams up, he takes it off. He keeps it in the fridge and twice a day stirs it up (it settles) and eats one teaspoon. There follows an extract from the same chapter giving

an example of how sodium bicarbonate can be combined with molasses in the treatment of

BONE cancer. (Note: some of this text has been edited for space and clarity) My first PSA test registered 22.3 and my doctors made appointments for a biopsy. The biopsy report indicated that I did indeed have prostate cancer. This called for the next step; a bone scan. The report from this scan as well as a pelvic Cat scan is where the doctors decided I was afflicted with aggressive prostate cancer dated March 17, 2008 reviewed CT and Bone scan. Bone scan showed metastatic disease at R sacrum and L illiac wing. So they patted me on the back and told me I had aggressive prostate cancer that had spread to the bone. ….The radio nuclide bone scan and plain films confirm the presence of skeletal metastasis, in the sacrum and left illium. In addition, on review of the CT scan of

the pelvis, a number of other small sclerotic lesions are noted within the pelvis. …I was becoming used to the fact that I was a walking dead man. I was anxious to try Caesium Chloride treatment but my order got lost in the mail. That is when I decided to do baking soda therapy except that I decided to add blackstrap molasses as the carrier. I started June 2, 2008 and quit June 12, 2008. I

was nervous and didn’t want to open it. As a matter of fact I am crying right now just thinking about it. I finally opened it to the words: “No convincing evidence of an osseous metastatic process” I bawled like a baby. Two days later I got another report in the mail about my blood test: PSA is now

Insulin is the most important hormone for controlling the concentration of glucose in the blood. As food is eaten, blood glucose rises and the pancreas secretes insulin to keep the blood glucose in the normal range. Insulin acts by driving glucose into the cells of the body. This action of insulin has two effects 1) maintaining blood glucose between 3.3mmol/L to 5mmol/L (60 to 90 mg/dl) and 2) storing glucose particularly as glycogen in the liver. Once feeding is completed and the glucose levels fall, insulin secretion is turned off, allowing the stores of glucose in glycogen to be released into the bloodstream to keep blood glucose normal. In addition, with the switching off of insulin secretion, protein and fat stores become accessible and can be used instead of glucose as sources of fuel. In this manner, whether one eats or is starved (fasted), blood glucose levels remain in the normal range and the body has access to energy at all times.
With hyperinsulinism, however, this close regulation of blood glucose and insulin secretion is lost. The pancreas, which is responsible for insulin secretion, is blind to the blood glucose level and makes insulin regardless of the blood glucose concentration. As a result, the child with hyperinsulinism can develop hypoglycaemia at any time but particularly when fasting. In the most severe form of hyperinsulinism this glucose blindness causes frequent, random episodes of hypoglycaemia. With one of the rarer forms of hyperinsulinism, hypoglycaemia is related to protein ingestion.

Hyperinsulinism causes a particularly damaging form of hypoglycaemia because it denies the brain of all the fuels on which it is critically dependent. These fuels are glucose, ketones, and lactate. The usual protective measures against hypoglycaemia, such as conversion of protein to glucose (called gluconeogenesis) and conversion of fat into ketones (called fatty acid oxidation and ketogenesis) are prevented by insulin. Once the brain cells are deprived of these important fuels, they can not make the energy they need to work and so they stop working. This loss of function may result in seizures and coma and if prolonged may result in death of the cells. It is this cell demise which causes the damage which manifests as learning disabilities, cerebral palsy, blindness or even death.

Causes of Hyperinsulinism

A number of causes exist. Some forms will resolve and are considered transient. Others arise from genetic defects and persist for life. These genetic forms of hyperinsulinism do not go away, but in some cases, may become easier to treat as the child gets much older.

Transient Hyperinsulinism

Babies who are born small for gestational age, or prematurely, may develop hypoglycaemia due to excessive insulin secretion. In addition, infants in whom fetal distress occurred due to lack of oxygen to the brain may also have hypoglycaemia from hyperinsulinism. The cause of this inappropriate insulin secretion is unclear, but it can last a few days to months. Once recognized, this form of hyperinsulinism is usually easy to treat. Many affected infants will not have hypoglycaemia once they are fed every 3-4 hours. In the more severely affected children, intravenous glucose is needed to prevent hypoglycaemia. Rarely, drug therapy is required; in which case, diazoxide is usually a very effective treatment. Children with this form of hyperinsulinism should have a fasting study done whilst off all medications , to prove that the hyperinsulinism was transient.

A small number of babies born to mothers with diabetes mellitus may have hyperinsulinism. This hyperinsulinsim tends to occur if the mother's diabetes was not under good control. The mother's high blood glucose levels are transmitted across the placenta to the fetus. The fetus compensates by secreting extra insulin. This step-up in insulin secretion does not cause hypoglycaemia while the fetus is inside the mother, but after birth, the constant supply of high glucose from the placenta is gone and the blood sugar in the newborn falls precipitously. This form of hyperinsulinism should resolve within a few days of intensive intravenous drip feeding of glucose. Once the hypoglycaemia resolves, it should never recur.

Persistent Hyperinsulinism

Although the persistent forms of hyperinsulinism are uncommon, a number of different genetic defects causing hyperinsulinism have recently been recognized. In the past, before the different genetic forms of hyperinsulinism were recognized, hyperinsulinism was referred to by many names, including nesidioblastosis, islet cell dysregulation syndrome, idiopathic hypoglycaemia of infancy, Persistent Hyperinsulinaemic Hypoglycemia of Infancy (PHHI) and Congenital Hyperinsulinism. With the identification of the genes responsible for these disorders, the naming of the different forms of hyperinsulinism has become more exact.

KATP -HI Diffuse or Focal Disease

The KATP form of HI is considered the classic form of hyperinsulinism and previously was known as "nesidioblastosis" or "PHHI". It is usually found in newborns who have larger than normal birth weights (many weigh above 9lbs) and occurs in the first days of life. It is called KATP-HI because its genetic cause is due to defects in either of two genes that make up the potassium channel (called KATP channel) in the insulin secreting beta-cells of the pancreas. These two genes are the SUR1 gene and the Kir6.2 gene. Normally, when the beta cell senses that glucose levels are elevated, the KATP channel commences insulin secretion. When the KATP channel is defective, inappropriate insulin secretion occurs and causes hypoglycemia.

Two forms of KATP-HI exist: diffuse KATP-HI and focal KATP-HI. When these mutations are inherited in an autosomal recessive manner (one mutation in the gene inherited from each parent, neither of whom is affected) they cause diffuse disease, meaning every beta-cell in the pancreas is abnormal. Recently autosomal dominant mutations (a mutation in a single copy of the gene causes disease and whichever parent has the mutation will also have the disease) have been found in the KATP channel and also cause diffuse disease. When a loss of heterozygosity (inheritance of a mutation from the father and loss of the mother's good gene from a few cells in the pancreas) occurs a focal lesion arises. Abnormal beta cells are limited to this focal lesion and are surrounded by normal beta-cells. The beta-cells of the focal lesion have lost the mother's normal KATP channel and are only able to express the father's defective KATP channel.

Children with either form of KATP-HI are identical in their appearance and behavior. They tend to have significant hypoglycaemia within the first few days of life and require large amounts of glucose to keep their blood glucose normal. They may have seizures due to hypoglycaemia. Diazoxide is usually an ineffective treatment for these children because diazoxide works on the broken KATP channel and it cannot fix the broken channels. Other drugs have been used to treat KATP-HI but are also usually poorly effective. Octreotide given by injection every 6 to 8 hours or by continuous infusion and nifedipine may be successful in the short term. Glucagon may be given by intravenous infusion to stabilize the blood sugar as a temporizing measure. Some centres advocate a very intensive regimen of feeding every two hours and four to six injections a day of octreotide or continuous octreotide by subcutaneous pump. We prefer the surgical approach. With the recent discovery of diffuse and focal KATP-HI, attempts to differentiate these two forms are very important: surgical therapy will cure focal HI but not diffuse HI (see below).

GDH-HI

GDH-HI has also been known as the Hyperinsulinism/Hyperammonaemia Syndrome (HI/HA), leucine-sensitive hypoglycaemia, and diazoxide-sensitive hypoglycaemia. GDH-HI is caused by a mutation in the enzyme glutamate dehydrogenase (GDH). It is inherited in either an autosomal dominant manner or may arise as a sporadically new mutation in a child with no family history. GDH plays an important role in regulating insulin secretion stimulated by amino acids (especially leucine). Individuals with GDH-HI develop hypoglycaemia after eating a high protein meal. GDH-HI affected individuals can have significant hypoglycaemia if they eat protein (for instance eggs or meat) without eating sugar containing foods such as bread, juice or pasta. GDH-HI is also associated with elevated blood concentrations of ammonia, which is derived from protein. These high ammonia levels, however, do not appear to be harmful in GDH-HI.

Patients with GDH-HI often present later that KATP channel HI. Typically, not until three to four months of age when they wean from low protein containing breast milk to infant formula. Others do not have recognizable hypoglycaemia until they sleep overnight without a middle of the night feed or after they start higher protein-containing solid foods such as yoghurt. The frequency of hypoglycaemia is usually less than that associated with KATP-HI. In addition, GDH-HI can be successfully treated with diazoxide and the avoidance of pure protein loads. Most children with GDH-HI will do very well once recognized, but if the diagnosis is delayed, they may also suffer brain damage from untreated hypoglycemia.

GK-HI

Three families are now known with mutations of the enzyme glucokinase. This defect was inherited in an autosomal dominant fashion but likely can arise sporadically. Glucokinase is the "glucose sensor" for the beta-cell. It tells the beta-cell how high the blood glucose is and when to secrete insulin. Glucokinase mutations that cause hyperinsulinism instruct the beta-cell to secrete insulin at a lower blood glucose than is normal. Like GDH-HI, GK-HI can be treated with diazoxide. Genetic tests for the GK gene are available in only a few centers.

Others

Other forms of hyperinsulinism are known to exist, but the genetic mutations responsible have yet to be identified. Their clinical features and response to therapy vary.

Diagnosis

The diagnosis of hyperinsulinism may be quite difficult if one relies on demonstrating an elevated blood insulin concentration at the time of hypoglycaemia because insulin levels fluctuate widely over time in patients with hyperinsulinism. Other signs and chemical markers must be used to provide clues to excess insulin action and are often easier to demonstrate. Hypoglycaemia which occurs while an infant is on a glucose infusion is strongly suggestive of HI. Other clues to excess insulin action are low free fatty acids and ketones at the time of hypoglycaemia. Another indicator of excess insulin can be demonstrated by the glucagon stimulation test. Glucagon is a hormone that opposes insulin action and stimulates release of glucose from liver glycogen stores. A rise in blood glucose after glucagon administration at the time of hypoglycaemia is a sensitive marker for hyperinsulinism. Ketones, free fatty acids, and the glucagon stimulation test may all be performed if a random episode of hypoglycaemia occurs. A fasting study is sometimes required to provoke hypoglycaemia and confirm the diagnosis of HI.

The identification of genetic defects responsible for hyperinsulinism and the improved understanding of the mechanism of abnormal insulin secretion have permitted the development of insulin secretion studies aimed at identifying the specific type of hyperinsulinism a child may have. The acute insulin response studies (AIRs) are performed by serially administering intravenous injections of glucose and drugs (calcium, tolbutamide which stimulates insulin secretion through SUR1 and leucine, an amino acid) over a short period of time. Insulin measurements are taken just prior to and for 5 minutes after the infusions. The specific pattern of insulin responses to these agents can help delineate the genetic defect affecting the beta-cell.

If a focal lesion is suspected based upon the acute insulin response studies, an attempt to identify the location of the lesion in the pancreas can be undertaken. Localization of the lesion helps the surgeon identify the lesion in the pancreas and may avoid subjecting needlessly an infant with a focal lesion to a 95% pancreatectomy. One of the localization studies available is called pancreatic arterial stimulation venous sampling (ASVS). ASVS involves placement of a catheter (a long intravenous line) into the artery of the leg. Through this catheter the radiologist injects calcium into each of the three arteries that supplies blood to the various regions of the pancreas (head, body, and tail). Through an intravenous line inserted into the child's neck, blood samples are obtained to measure the insulin coming out of the pancreas. An increase in insulin secretion, after injection of calcium into one of the three arteries, suggests the location of the focal lesion (head, body, or tail).

Transhepatic Portal Venous Sampling (THPVS) is another procedure designed to localize the site of a focal lesion. A catheter is inserted through the skin, into the liver, and into the veins of the pancreas. Blood samples for insulin are obtained throughout the various regions of the pancreas. The location of the focal lesion is suggested by the region of the pancreatic venous system with the highest insulin concentrations.

Treatment

Prompt treatment of hypoglycaemia due to hyperinsulinism is essential to prevent brain damage. Unlike other hypoglycaemia-causing conditions in which alternative fuels, such as ketones or lactate, may be available for the brain during periods of hypoglycaemia, hyperinsulinism prevents the production of these fuels and leaves the brain without a source of energy. Hypoglycaemia can be treated by giving a carbohydrate-containing drink by mouth or if severe, by giving glucose through the vein or by injecting glucagon. A child with a feeding tube can have glucose given through the tube. The goal of treatment is to prevent hypoglycaemia while the child has a normal feeding pattern for age with a little extra safety built in, e.g., a one year old who normally would not eat overnight for 10-12 hours should be able to fast for at least 14 -15 hours on a successful medical regimen.

Medications used to treat hyperinsulinism include diazoxide, octretide, and glucagon:

Diazoxide. Diazoxide is given by mouth 2-3 times per day. The dose varies from 5 to 20mg/kg/day. Usually, if 15 mg/kg/day does not work, higher doses will not work. Diazoxide acts on the KATP channel to prevent insulin secretion. It is generally effective for infants with stress-induced hyperinsulinism, infants with GDH-HI or GK-HI, and in a subgroup of infants whose basic defect is not known. Diazoxide rarely works in children KATP-HI.
Side effects of diazoxide include fluid retention, a particular problem for the newborn which has received large amounts of intravenous glucose to maintain the blood glucose in the normal range. A diuretic medication (hydrochlorthiazide or chlorthiazide) is sometimes used with diazoxide in anticipation of such a problem. Diazoxide also causes a cosmetic problem of excessive hair growth of the eyebrows, forehead, and back. This hair growth resolves several months after diazoxide therapy is stopped. Shaving the hair occasionally may be necessary and does not intensify hair growth.

Nifedipine. This is an oral medication, used to treat high blood pressure, that blocks calcium entry into the cells. In theory, it should work well to prevent hypoglycaemia, however in practice it rarely does. There are several publications indicating its success but overall most people who treat larger groups of children with HI say that it works in less than 10 % of patients.

Octreotide. Octreotide is a drug that also inhibits insulin secretion. It is administered by injection. It can be given periodically throughout the day by subcutaneous injection or may be administered continuously under the skin by a pump that is commonly used for insulin therapy in individuals with diabetes. Octreotide is often very effective initially, but its initial effectiveness may wane with time and it becomes less effective. In addition more is not always better as the higher the dose (higher than 20 -40 microgramms/kg/day) the less effective it may become. Side effects include alteration of gut motility, which may cause poor feeding. It may also cause gallstones and very rarely may produce hypothyroidism, and short stature. As with any injection, risks of pain, infection, and bruising exist.

Glucagon. Glucagon stimulates release of glucose from the liver. It is given through a vein or by injection under the skin or into the muscle. Glucagon can be used in cases of emergency when a child with hyperinsulinism has low blood glucose and cannot be fed. It can also be given in the hospital as a continuous infusion through a vein. It is most effective as a holding therapy while the child is prepared for surgery.

Surgery

Children with diffuse KATP-HI commonly require 95-99% pancreatectomies. These surgeries are not always curative, and KATP-HI children who have undergone such surgeries may continue to require frequent feeds and medications to prevent hypoglycemia. They also may need repeat surgeries. The hope with such surgery is to lessen the intense medical regimen that otherwise would be needed to protect the child from recurrent, severe hypoglycaemia.
In children with focal KATP channel HI, surgery to remove only a small part of the pancreas is the procedure of choice. This requires a team of endocrinologists, pathologists and surgeons, specialized in this procedure. Therefore it is generally only available in the major centres treating patients with hyperinsulinism. The majority of patients with Focal HI will be cured or will not require any medical therapy after the surgery. This is in stark contrast to those with diffuse disease in whom medical therapy after surgery is the rule.

Focal lesions can be cured with surgery. The difficulty, however, is that many focal lesions are found in the head of the pancreas. The immediate surroundings of the pancreatic head include important structures such as the bile ducts and duodenum. Successfully resecting a lesion in the head of the pancreas without harming these other important structures may sometimes be impossible.

Outcome

Prognosis is greatly influenced by the form (severity) of hyperinsulinism an affected child has. The most severe long term complication is brain damage. Even in the centres most experienced in treating children with hyperinsulinism, rates of up to 20% of the children suffer permanent damage. For all children, the development of permanent learning disabilities is difficult to predict and depends not only on the frequency of low blood glucose but also the duration of a hypoglycemic episode. In addition to learning disabilities, stroke like symptoms or cerebral palsy can occur. Strabismus (turned in eye) or blindness may also be caused by hypoglycaemia.

Children with diffuse disease who have a 95-99% pancreatectomy will continue to be at risk for hypoglycaemia. Occasionally a second or third surgery may be required. The hypoglycemia post surgery is usually easier to control than prior to surgery. Diabetes in both the immediate post-operative period and in the long term is a greater risk in patients with diffuse disease. Failure to absorb the food from the gut may be a problem due to loss of the enzymes produced by the pancreas for digestion of food. This may require enzyme replacement.

Children with focal lesions that are successfully resected with partial pancreatectomies are cured of their disease and are not anticipated to have an increased risk of diabetes mellitus or of food mal-absorption

Technically less disabling, but a very serious problem, are feeding difficulties. There is a lot of debate about the cause of these difficulties. The two main theories currently discussed are a primary problem in abnormal gut motility due to the genetic defect responsible for hyperinsulinism. This in theory should only therefore be found in patients with diffuse disease. Because it is found in both diffuse and focal disease, the second possibility is that feeding difficulties commonly occur as a result of the therapy of the hyperinsulinism. Long term tube feeds and the use of intravenous fluids without oral feeding, designed to prevent hypoglycaemia, may hinder the child from learning how to feed by mouth during the critical first two to three months of life. Later, excessive weight associated with forced tube feeding to prevent hypoglycemia may suppress the appetite and thus prevent the child from developing the desire to eat. Attempts should be made to encourage the child to feed by mouth from birth in addition to whatever other therapies are required, and early intervention by a feeding specialist should be implemented, to decrease the risk of development of feeding problems. In this manner, feeding difficulties will be reduced dramatically.

Children with HI/HA and other forms of hyperinsulinism which are diazoxide responsive tend to do well long-term but will need occasional in-hospital monitoring of home regimens to insure safety and for dose adjustments. The elevated blood ammonia concentrations do not seem to cause problems in GDH-HI.