Thank God for His healing power and for Dr. Mani for a successful operation. After my operation, I changed my diet and begin looking up for information for neuroendrocine tumour in the internet. I hope to create an awareness and to educate the public about this disease which is so unknown to many. And where do I start? Thank God for the internet, I manage to find few websites on this disease and learn about this disease and the treatment available for it. This is a rare slow growing tumour which is gaining notice by medical doctors which are specialised in this field. Then, I came across Susan’s website for carcinoid and neuroendrocrine tumours awareness and learned so much about this tumour. www.carcinoidinfo.info
WHAT IS CARCINOID SYNDROME? Carcinoid is part of a group of tumors called neuroendocrine tumors that grow in the hormone producing cells, is listed with the National Organization of Rare Disorders. Because neuroendocrine (NET) cancer is considered rare and due to a lack of public awareness the disease has had a low priority for medical research.
The following extract is by Dr. Richard R.P. Warner, M.D. Medical Director of the Carcinoid Cancer Foundation TM
Carcinoid cells can make hormones. Those carcinoid tumors which produce large amounts of hormones and other potent chemical substances and which are usually found to have spread to the liver, can cause hot red flushing of the face, diarrhea, and asthma like wheezing attacks. These episodes of “carcinoid crisis” may be very infrequent at first but gradually occur more often and are usually associated with abrupt low blood pressure and even fainting. However, in a few cases the attacks are accompanied by high blood pressure. Alcohol or stress (physical or emotional) sometimes provoke attacks but they often occur spontaneously. After a while the flush may become persistent in some individuals and may not be felt or noticed by them. The diarrhea may also be chronic and weight loss can occur. A specific type of heart valve damage can occur in some cases as well as other cardiac disturbances. All of these features constitute the Carcinoid Syndrome.
The potent chemicals and hormones made by the “functioning” carcinoid tumors (as versus the more frequent “non-functioning” carcinoid tumors), through their effects on the cardiovascular, gastrointestinal, pulmonary and other systems of the body, cause the Carcinoid Syndrome. In many cases the symptoms of the Carcinoid Syndrome resulting from the hormones and chemicals produced are worse than the symptoms from the growth of the tumor itself.
Carcinoids belong to a group of growths called neuroendocrine tumors. Each type of neuroendocrine tumor produces a different main hormone and hence a different syndrome – that is, it causes different symptoms. Why is this important for us to include in a discussion of carcinoid? First, and most important, each of these syndromes, though having different features, can prominently include flushing and/or diarrhea and be confused with Carcinoid Syndrome. Secondly, a carcinoid can occasionally have “mixed” function causing one of these other syndromes along with Carcinoid Syndrome. This is the result of the carcinoid producing one or more of these other hormones along with production of its own specific hormones. Thirdly, an inherited familial (genetic) condition can cause the development in an individual of several different types of neuroendocrine tumors (and their respective syndromes). This can include carcinoid along with other types of neuroendocrine tumors. This is called MEN ( multiple endocrine neoplasm )syndrome.
Diagnosis
Non-functioning carcinoid tumors are so slow growing that many years may pass between the onset of any symptoms and the diagnosis. They can cause intermittent abdominal pain and then a change in bowel habits that may lead to intestinal obstruction. In some cases they cause obscure intestinal bleeding or sometimes don’t declare themselves until they cause painful enlargement of the liver due to large deposits of carcinoid metastases that have spread to that organ. The diagnosis is not usually suspected prior to surgery but is then established by biopsy.
The Carcinoid Syndrome, due to the presence of a functioning carcinoid tumor, is easily diagnosed when all the features of the syndrome are present or even when 1 or 2 of the main symptoms are present and the Carcinoid Syndrome is thought of. The biggest impediment to making the diagnosis is not thinking of the Carcinoid Syndrome, or even considering it because of its rarity. Once considered, the diagnosis usually can be confirmed quickly and painlessly by doing a urine 5-HIAA test. This stands for 5-hydroxy indole acetic acid which is the main breakdown (waste) product of Serotonin. Its quantitative measurement in the urine which an individual excretes in a 24 hour period tells how much Serotonin is being made in the body during that time. In the presence of Carcinoid Syndrome the amount of 5-HIAA is almost always distinctly increased above normal. Certain foods and medicines must be avoided for a day or two before, and on the day of the urine collection, since they can cause false test results. These are: bananas, pineapple and its juice, red plums, avocado, walnuts and other nuts, kiwi fruit, tomatoes, various cough medicines muscle relaxing medicines, acetaminophen (Tylenol), caffeine, fluorouracil, iodine solutions (Lugol’s solution), phenacetin, MOA inhibitors (certain antidepressant drugs), isoniazid, and phenothiazine drugs (Compazine, Thorazine). Sometimes urine 5-HIAA is not increased but other carcinoid “markers” in the blood can be measured and will be increased. These are chromogranin A (CgA) and serotonin. Blood tryptophan will be decreased below normal values. The measurement of CgA is considered “the gold standard” of chemical tests for confirming the diagnosis of carcinoid and neuroendocrine tumors and following their course.
Standard X-ray and imaging techniques can be helpful in finding a carcinoid tumor and identifying its spread. This could include routine chest X-ray, CT scans, MRI, barium enema and upper GI and small bowel X-ray studies. Sometimes upper and lower GI tract endoscopy (looking inside the body with a flexible fiber optic tube through which biopsies can be taken) is also helpful.A now universally approved (though costly) way of finding carcinoid tumors, as well as other neuroendocrine tumors, is the OctreoScan It is successful in 85% of carcinoids and consists of a harmless injection of a minute dose of a short duration radioactive isotope which is specifically attracted to, and concentrated in, carcinoid tumor tissue (and any other neuroendocrine tumor) where it lights up when a radiation scan is taken over the entire body. It is dissipated in a few days, and again I emphasize it is harmless. OctreoScan should be done in almost all cases even when the diagnosis is known. This is especially important in those cases where standard imaging (i.e. CT-scans, MRI) and chemical markers have failed to reveal the diagnosis and location of tumors. There are occasional cases in which all the symptoms and chemical findings of Carcinoid Syndrome are present but standard tests fail to reveal a tumor. In these cases octreoscan can be a great help in confirming the diagnosis and locating the tumor(s). A positive octreoscan usually predicts a good response to treatment with octreotide.(Sandostatin)
Outlook (Prognosis)
Typical carcinoids are slow growers. Data on survival of patients with small tumors not causing Carcinoid Syndrome and without spread, treated by surgical removal alone, indicates that a complete cure is usually possible in these cases.
In those tumors that are somewhat larger and have spread to local tissues and local lymph nodes but which, along with these locally invaded tissues, are still totally removable surgically, the average survival has been 8 years with a range up to 23 years.
Even when the tumor from the small intestine has spread in a manner that has made complete surgical removal impossible, the older statistics show that approximately one half of the patients survive an average of 5 years. Since various types of treatment have been introduced in the past decade patients appear to have an even longer survival and improved quality of life.
Atypical carcinoids, which is a group whose microscopic appearance looks different and more aggressively malignant than the typical carcinoid, follow a much more rapid course with a more uncertain outlook. An even worse forecast can be made for the very more malignant rare group called “neuroendocrine carcinoma”. Atypical carcinoids can cause the Carcinoid Syndrome, but neuroendocrine carcinoma rarely do.
The tempo of the course of the illness in patients with Carcinoid Syndrome is different than that of carcinoid victims without the functioning syndrome. However, this has been remarkably improved and the outlook is much more hopeful with the advent of octreotide and similar somatostatin analogues and other new modes of treatment. In the early decades before effective treatment was available the average survival from the onset of flushing for a Carcinoid Syndrome patient was 3 years, and from the time of diagnosis was 2 years, though the range extended to over 10 years. Seventy five percent of the patients would die as a consequence of the harmful effects on the body from the excessive amounts of potent hormones released into their circulation by the tumors. Tumor growth and spread itself was fatal in only 25% of cases. In the last 10 years, since we have used effective combinations of treatment with octreotide(and similar somatostain analogues), various types of surgery, chemotherapy, hepatic artery injections and biological response mediators, the average survival time from the start of treatment (which unfortunately is often quite delayed after the diagnosis is made) has increased to almost 12 years – with a wide range often being observed.
Is there a cure? What treatments are available?
Carcinoid tumors vary greatly in their size, location, symptoms and growth. Therefore the treatment in each case should be individualized to what is best for each particular patient.
Surgery, with complete removal of all of the tumor tissue, is the first and best treatment when it is possible, and if detected early can result in a complete and permanent cure. However, even when all tumor tissue cannot be removed, surgery may be necessary for various purposes such as relief of intestinal obstruction or control of intestinal bleeding. When the Carcinoid Syndrome is present, removing or destroying large portions of the tumor (debulking) can effectively diminish the amount of harmful hormones being produced and flooding the circulation. Because of the slow growth of most carcinoids, this can relieve symptoms for a long time. Technique of using a freezing probe (cryoablation) or Radiofrequency ablation (RFA) are now used at major medical centers to destroy carcinoid tumor metastases in the liver when it has not been possible to excise them surgically. Another way to debulk unresectable carcinoid tumors that have spread to the liver is to inject the liver artery supplying blood to the metastases with a combination of embolic material and chemotherapy drugs. This shuts off the blood flow with its oxygen supply to the tumors and also loads them with tumor destroying and growth inhibiting chemotherapy. Thus this chemotherapy is concentrated in the tumors where it can have a much greater effect than in the rest of the body. However, opinion is divided regarding whether chemotherapy injection with embolus is of greater benefit than embolus(bland embolization) alone.
Chemotherapy for carcinoid given by intravenous injection or by mouth has been in use for over 20 years. There are many drugs available. Individual drugs used alone have been disappointing but a number of combinations of these drugs have been beneficial. Some of these combinations are: leucovorin-fluorouracil and streptozotocin, cytoxan- Doxorubicin and cisplatin, dacarbazine-fluorouracil, etoposide-cisplatin. One or another of these combination has produced good response in only 20-30% of the cases. Fortunately however, those patients in whom one chemotherapy routine is ineffectual may respond well to one of the other drug combinations. In other words, failure to respond to one combination does not necessarily mean another combination of chemotherapy will also be ineffectual. The site of the origin has considerable influence on likelihood of the tumor(s) responding to chemotherapy. For instance pancreatic and lung carcinoids respond to some forms of chemotherapy better than intestinal carcinoid.
A number of newer drug combinations are currently being investigated.(RAD001), Sorafenib (Nexavar).Sunitinib (Sutent), Atiprimod, SOM 230, Avastin (Bevacizumab),Temozolomide (Temodar), Capecitabine (Xeloda®), and others.
Somatostatin analogue (octreotide/lanreotide and vapreotide) injections not only usually squelch the symptoms of Carcinoid Syndrome but are now believed to sometimes inhibit or even reverse growth of the tumors. This has become the mainstay of treatment for most carcinoid tumors, with or without the Carcinoid Syndrome. Somatostatin analogues (octreotide/lanreotide/vapreotide) are now available in the US and other countries in three forms; octreotide- trade name – Sandostatin s.c.®, and Sandostatin LAR®(given every 3 -4 weeks) manufactured by Novartis, lanreotide – trade name – Somatuline®, manufactured by Ipsen. In a few patients needing large amounts of octreotide continuous injection of Sandostatin s.c. is given by a special tiny injection pump as is used for insulin in some diabetics.
Patient Assistant Program (PAP) by Novartis Pharmaceuticals
Novartis Pharmaceuticals Corporation’s Patient Assistance Program (PAP) provides assistance to patients experiencing financial hardship who have no third party insurance coverage for their medicines.
For more information, about this program and insurance reimbursement issues, call their Hotline 1-800-282-7630. For information about Sandostatin LAR® Depot reimbursement, visit their website.Throughout the world, approximately 8-12 dozen patients with carcinoid metastases to the liver and no discernible tumors outside the liver have undergone liver transplant. Their survival has been about equal to those patients with equivalent disease treated by the more conventional means outlined above. At this time I do not see a role for this extremely expensive and debilitating treatment in any but the most extraordinary carcinoid case.Interferon is a natural substance originally derived from white blood cells that inhibits growth of carcinoid and certain other tumors as well as certain viruses. There are several varieties of interferon (Intron A and Roferon A) of which the alpha form has seen the most use for treating carcinoid and is commercially available. Drugs of this class are considered “biologic response mediators” or “immunomodulators” rather than tumor cell poisons (cytotoxins) such as chemotherapy drugs. Though beneficial in suppressing tumor growth in at least half the carcinoid patients treated, interferon often causes unpleasant side effects of extreme fatigue and flu like symptoms. Side effects are often avoided or reduced by using low doses of this medicine which even then can often be effective.
Radiotherapy in carcinoid is useful only in pain relief and regressing tumors when they have spread to the skeletal system and when causing severe pain. Radiation treatment to the specific painful spot will usually provide relief. It has not been useful in treating metastases in the liver or in other non skeletal tissues. Experimental studies are underway, using internally injected radioactive isotopes in selected carcinoid patients, in a number of research centers abroad. The current favored isotopes are Yttrium 90 (Y90), Lutetium 177 and Gallium 68. Increasing evidence of the effectiveness of these very expensive treatments is emerging and efforts to start their use in the US are under way. An additional new treatment for liver metastases emerged during the past 5-6 years and consists of injecting the hepatic artery with radioactive isotope Yttrium 90 impregnated microsphere emboli.(Therasphere, SirSpheres) Initial results are very promising. This is meeting with considerable success when the sole or dominant site of metastases is located in the liver.
Narrow beam radiotherapy such as CyberKnife, is being tried in a few places but has not yet been clearly shown to be of value.
Supportive Treatment
Besides the various anti-tumor treatments reviewed above, there are many benefits resulting from a nutritious high protein diet, vitamin supplements – particularly niacin, mineral supplements (such as potassium, magnesium, calcium, iron and even salt) when these are deficient due to diarrhea. In addition to the use of Octreotide or Lanreotide to control diarrhea, conventional anti-diarrheal medications such as Lomotil and Imodium may be helpful. Cyproheptadine (Periactin) may also help the diarrhea as well as flushing. Large portions of freshly grated nutmeg (1 teaspoon eaten 3 times a day) will sometimes control the diarrhea remarkably well. Antihistamines and alpha adrenergic blocking drugs such as Dibenzyline are sometimes used to prevent Carcinoid Syndrome attacks. All carcinoid patients should avoid alcoholic beverages and physical and emotional stress since these can precipitate carcinoid crisis attacks. Similarly, adrenaline like drugs should be avoided. These include various asthma inhalers, nasal decongestants and adrenaline itself. Certain very severe and prolonged carcinoid crises associated with bronchial (lung) carcinoids or some carcinoids of the stomach are responsive to treatment with corticosteroids (prednisone, Decadron) and Thorazine or Compazine.
Conclusion
As you can see there is good reason to be hopeful. There are abundant treatments for carcinoid tumors and syndrome though choice of treatment and their applications can be quite complex. Even though this is a rare disease there are experts available who are interested and willing to help and a great deal of research is in progress which promises additional effective therapy in the foreseeable future.
