5-HIAA Urine Tests
No. Bananas and other serotonin containing food need only be avoided when collecting urine for 5HIAA testing. Tumors make their own serotonin independent of dietary sources. See page for how to prepare for the urine 5-HIAA test.
The urine 5-HIAA test for carcinoid is crude and can be strongly influenced by special diet and drugs. The patient must be on a special diet before and during the urine collection. Even then the test can miss up to 50% of the cases. It should not be relied on alone. Other markers for carcinoid tumor are blood serotonin, tryptophan, chromogranin A, pancreatic polypeptide and, of course, the OctreoScan.
5HIAA Test
It is not 100% certain. In fact, the urine 5HIAA test will miss 50% of cases. Therefore other tests are usually done in conjunction with these tests. Among the most common tests done for diagnostic purposes are blood serotonin and blood chromogranin A. Other tests such as substance P and VIP may also be done.
Adenocarcinoid
Over 50 cases treated, over 10 years longest survival rate. For more information about adenocarcinoma we suggest that you visit the Pancreatic Cancer Action Network website. The familial occurrence of carcinoid is a recognized but exceedingly rare event. This occurrence in two first cousins is suggestive. A blood test of DNA for the chromosomal abnormality thought to be present in the genetic aberration in such cases is under study and development at present. Hopefully it will be perfected and available for general clinical use in a few years. Until then surveillance of individuals thought to be at risk should, in my opinion, consist of yearly testing of urine 5-HIAA and blood serotonin, tryptophan, chromogranin A and substance P starting after the second decade of life.
Alternative Treatments
The use of nutmeg is an old folk remedy originating in the middle ages in Europe. Centuries of anecdotal observation and more recent experience in carcinoid patients under medical care on nutmeg for at least several years indicates no apparent side effects from the dose she is taking.
Anesthesia
Morphine is okay for carcinoid patients but epinephrine is not since it can provoke carcinoid crisis. Epinephrine is sometimes used with local anesthesia to prolong the anesthesia by causing vasoconstriction. Novocain and other local anesthesia do come without epinephrine. Demerol and Fentazine can be used for post operative pain in people who are intolerant of morphine and Percocet.
Anticancer Drugs
DTIC is an anticancer drug also known as dacarbazine. Like many other anticancer drugs, its mode of action is not known, but it may act via one of the following three hypotheses:
1. Inhibiting DNA synthesis by acting as a purine analog.
2. Acting as an alkylating agent.
3. Interacting with SH group.
It is effective in 50% of carcinoid cases.
Antidepressants
A Selective Seratonin Reuptake Inhibitor (SSRI) is an antidepressant medication that typically decreases anxiety as well as depression (Prozac, Zoloft, Paxil). It acts by blocking the reuptake of serotonin. It is contraindicated in patients with carcinoid syndrome. It may preciptate a carcinoid crisis or worsen symptoms of carcinoid syndrome.
Zoloft is okay for patients without carcinoid syndrome but not those who have it. They are better are better treated with Elavil or Nortryptyline.
Appendix
Are you assuming that the hot spot in your RLQ on the OctreoScan is a primary carcinoid in the appendix, which is the origin of the small, presumably metastatic lesion, in the liver ? Very unlikely. More likely a carcinoid originates in the terminal ileum (which is so close to the appendix that the scan cannot differentiate between the two). Furthermore, appendiceal carcinoid only rarely spreads so far as the liver while carcinoids of the terminal ileum much more frequently do so. But if neither was seen as a mass on the CT scan or on colonoscopy or small intestine barium X-ray series (was this done?), they would be too small for, and it would be too dangerous, to do a needle biopsy. In short, needle biopsy of the liver is easier and safer.
Bone Metastases
Radiotherapy is helpful for painful bone lesions.
Bronchial Carcinoid
The term benign bronchial carcinoid is a misnomer. These tumors all have malignant potential but are usually very slow growing, hence the misuse of the adjective benign. Whether a lobectomy is required or bronchoscopic destruction of the tumor or some lesser type of surgery depends on the size, precise location and other features of any given tumor. These are rare tumors and unless you are at a large major medical center, your doctor probably has limited experience with this condition. A second opinion is advised but will only be as good as the experience of your consultant. Be CERTAIN to see one who is a known expert in this condition. Although it depends upon the specific case, in general most people who have lung surgery for this condition do well thereafter.
Carcinoid and Conception
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week. There is no effect on conception thereafter.
Carcinoid and Heredity
Over 50 cases treated, over 10 years longest survival rate. For more information about adenocarcinoma we suggest that you visit the Pancreatic Cancer Action Network website. The familial occurrence of carcinoid is a recognized but exceedingly rare event. This occurrence in two first cousins is suggestive. A blood test of DNA for the chromosomal abnormality thought to be present in the genetic aberration in such cases is under study and development at present. Hopefully it will be perfected and available for general clinical use in a few years. Until then surveillance of individuals thought to be at risk should, in my opinion, consist of yearly testing of urine 5-HIAA and blood serotonin, tryptophan, chromogranin A and substance P starting after the second decade of life.
Carcinoid Cancer, What Is It?
It is not 100% certain. In fact, the urine 5HIAA test will miss 50% of cases. Therefore other tests are usually done in conjunction with these tests. Among the most common tests done for diagnostic purposes are blood serotonin and blood chromogranin A. Other tests such as substance P and VIP may also be done.
No.
Yes.
In general, it can take 3-5 years and even up to 10 or longer for carcinoid tumors to grow. These are generally very slow-growing tumors.
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week. There is no effect on conception thereafter.
No.
No to both questions.
The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.
Carcinoid is a slow growing cancer. If it is all removed a person can be cured. However, there is always the risk of undetected microscopic cells remaining. These cells may show up after a number of years and would require chemotherapy or they could gradually kill a patient. The patient should be on periodic surveillance for at least 10 years. I recommend that you read the more comprehensive “Review of Carcinoid Disease” for a more in-depth answer to these questions.
Carcinoid is a slow growing cancer. If it is all removed a person can be cured. However, there is always the risk of undetected microscopic cells remaining. These cells may show up after a number of years and would require chemotherapy or they could gradually kill a patient. The patient should be on periodic surveillance for at least 10 years. I recommend that you read the more comprehensive “Review of Carcinoid Disease” for a more in depth answer to this questions.
The term Goblet Cell Carcinoid or adenocarcinoid, mucinous carcinoid is applied to two types of carcinoid. Both types of carcinoid are quite different from the ordinary carcinoid. Unfortunately, adenocarcinoid is a more aggressive tumor and carries a poor prognosis. One type arises in the ovary (reference: Primary Ovarian Carcinoid Tumors, K.P. Davis et. a:l., Gyn.Oncol 61; 259-265, 1996) and the second type is also referred to as collision tumor in the intestine and is more often called adenocarcinoid. You can find references to it (do a PubMed search from our website) if you search for collision tumor. Because of the poor prognosis of these types of tumors, the pathologic interpretation of the tumor biopsy should be confirmed by an EXPERT second opinion.
Neurokinin B is a nonspecific peptide hormonal substance sometimes co-secreted into the blood along with one of the other carcinoid products such as serotonin, chromogranin A, substance P and pancreatic polypeptide.
The answers below stem from the review of over 13,000 carcinoid cases covering five decades published in 2003, authored by Irvin Modlin and collegues.
What is the most common site of carcinoid in the human body? primary site is small intestine
What is the most common site of malignant carcinoid in body? primary site is small intestine
What is the most common site of carcinoid in gut? primary site is terminal ileum
What is the most common site of malignant carcinoid in gut? primary site is terminal ileum
Also, the most common sites of regional spread for all carcinoids are lymph nodes and the most common site for distant spread for all carcinoids is the liver.
Reference: See Dr. Modlin’s article A 5-Decade Analysis of 13,715 Carcinoid Tumors (Full text PDF)
By Irvin M. Modlin, M.D., Kevin D. Lys, M.D., Mark Kidd, Ph.D.
Cancer 2003 Feb 15;97(4):934-59
Serotonin is a chemical product produced by some carcinoids in various amounts. It does not regulate the tumors. When in large amounts, it causes symptoms but in any amount, it is a useful marker for the presence of each tumor. 5HTP is the chemical precursor (for the substance) from which serotonin is made and is also a useful marker sometimes.
Carcinoid Heart Disease
Serotonin and other tumor products in the blood cause overgrowth of fibrous tissue on the heart valve in an unknown way. Treatment consists of neutralizing vasoactive tumor products by injection of octreotide (Sandostatin) and, when very advanced and severe, replacing the valves via heart surgery.
Carcinoid Medications
The main toxic side effect of streptozotocin is on the kidney and the 8th cranial nerve, the nerve that transmits hearing and the equilibrium function of the inner ear. Kidney damage is the more common side effect and is related to the dose and total amount of the drug given. Careful monitoring of the urine analysis and blood test and blood tests for kidney function before each treatment, with aborting treatment if the starts of abnormalities are seen can prevent any significant renal damage. This should be done in all cases. Therefore, no patient need suffer side effects from this drug. Similarly, periodic audiograms and checks of the patients vestibular function will prevent irreversible 8th nerve damage. Monitoring blood counts and adjusting dosage or withholding the drug will avoid serious suppression of the white blood cells. Cardiac damage is not a regular complication of this drug and would be extraordinary.
Carcinoid Syndrome
Usually NOT. It may infrequently produce antibodies that make it less effective, but this is in only a very small minority of cases. In some other cases it becomes less effective AT THE SAME DOSAGE because the tumors are growing. In most cases it is better to take it early in the disease, especially if carcinoid syndrome is present and blood serotonin levels are elevated because it will prevent carcinoid heart disease and inhibit tumor growth as well as prevent carcinoid syndrome symptoms
It can be carcinoid syndrome. How high is the 5-HIAA and was the urine collected on a serotonin-free diet? If it was more than just slightly elevated, then confirm its significance by testing blood serotonin, which should be increased; blood tryptophan, which should be decreased; and chromogranin, A which should be increased. If one or two of these are clearly abnormal, you should check the liver for metastatic tumor – by CT scan with contrast or MRI. If negative, do an OctreoScan to search for tumor foci not seen by the other imaging techniques.
If I understand your question correctly, you state that a diagnosis of carcinoid syndrome is suspected because of symptoms and high urine 5-HIAA, but the CT scan is normal and you want to know what other tests should now be done to prove the diagnosis. Failure to find carcinoid tumors when proven carcinoid syndrome is present is not so rare. This occurs initially in 10% of cases.
First, other findings must prove the syndrome. The various blood markers should be tested to confirm the 5-HIAA significance. This would at least include blood serotonin, chromogranin A, calcitonin, neuron specific enolase, substance P and pancreatic polypeptide; if any of these is positive it would support the diagnosis and then an OctreoScan should be done.
I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.
Carcinoid syndrome requires one or more of the following for laboratory confirmation of the diagnosis: increased blood serotonin with decreased blood tryptophan, increased chromogranin A and increased urine 5HIAA or indole-3-acetic acid. In spite of the symptoms, if these criteria are not present, carcinoid syndrome is not the diagnosis.
Carcinoid Tests
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week. There is no effect on conception thereafter.
Carcinoid Urine Test
It is not 100% certain. In fact, the urine 5HIAA test will miss 50% of cases. Therefore other tests are usually done in conjunction with these tests. Among the most common tests done for diagnostic purposes are blood serotonin and blood chromogranin A. Other tests such as substance P and VIP may also be done.
Chemotherapy
Sandostatin when given in large doses (if OctreoScan is positive) along with alpha interferon (with which it works synergistically) causes tumor regression in 2/3 of the cases.
Chemotherapy and Carcinoid
In atypical carcinoid VP16 and Cisplatin is 67% effective. In typical carcinoid DTIC as a single agent has been reported effective in greater than 50%. Dr. Kjell Oberg (as well as myself through observation) reports greater than 60% effectiveness from CHRONIC treatment with large dosage octreotide along with small to moderate dosage alpha interferon. This combo (octreotide and alfa interferon) must be taken for at least 6 months before results are seen. Finally, leucovorin and LOW dose 5FU with streptozotocin given at frequent (weekly intervals) CHRONICALLY is effective in greater than 40% of cases. Note that if one chemotherapy program fails, the next one or two may be effective; i.e., failure to respond to one drug combo has no bearing on responsiveness to another. Aggressive treatment, rather than a wait-and-see approach, is better in the long run.
Chemotherapy is effective in 1/3 of midgut carcinoids and in a larger percentage of foregut (including pancreatic) carcinoids. It is also more effective in atypical carcinoids. Sandostatin in large doses (300 mcg every 6-8 hours) often controls symptoms not responding to smaller doses. In addition, when combined with low dose alpha-Interferon, stabilizes or regresses tumor in up to three-quarters of cases.
Chemotherapy Types
In atypical carcinoid VP16 and Cisplatin is 67% effective. In typical carcinoid DTIC as a single agent has been reported effective in greater than 50%. Dr. Kjell Oberg (as well as myself through observation) reports greater than 60% effectiveness from CHRONIC treatment with large dosage octreotide along with small to moderate dosage alpha interferon. This combo (octreotide and alfa interferon) must be taken for at least 6 months before results are seen. Finally, leucovorin and LOW dose 5FU with streptozotocin given at frequent (weekly intervals) CHRONICALLY is effective in greater than 40% of cases. Note that if one chemotherapy program fails, the next one or two may be effective; i.e., failure to respond to one drug combo has no bearing on responsiveness to another. Aggressive treatment, rather than a wait-and-see approach, is better in the long run.
CT Scan
An OctreoScan can very occasionally show a carcinoid before CT scan or chemistries indicate its presence, but this situation is very infrequent. Visually it is used to help locate a tumor when chemistries show it is present and CT scan doesn’t image it. Also when CT scan is positive the OctreoScan may show additional sites of the tumor not seen on CT.
Finally even when tumor is seen on a CT scan and chemistries are positive, the OctreoScan is useful because a positive result indicates the presence of SST2 receptors in the tumor and that means the patient will most likely respond well to treatment with Sandostatin and also has a better prognosis than does the patient with carcinoid tumor but a negative OctreoScan.
Dental Anesthesia
Morphine is okay for carcinoid patients but epinephrine is not since it can provoke carcinoid crisis. Epinephrine is sometimes used with local anesthesia to prolong the anesthesia by causing vasoconstriction. Novocain and other local anesthesia do come without epinephrine. Demerol and Fentazine can be used for post operative pain in people who are intolerant of morphine and Percocet.
Dental Anesthetics
All adrenaline (epinephrine) containing drugs must be avoided.
Dental Work and Carcinoid
All adrenaline (epinephrine) containing drugs must be avoided.
In general all carcinoid syndrome patients should be given a booster dose of regular octreotide just prior to any anesthesia, surgery or dentistry.
Depression
A Selective Seratonin Reuptake Inhibitor (SSRI) is an antidepressant medication that typically decreases anxiety as well as depression (Prozac, Zoloft, Paxil). It acts by blocking the reuptake of serotonin. It is contraindicated in patients with carcinoid syndrome. It may preciptate a carcinoid crisis or worsen symptoms of carcinoid syndrome.
Diagnosis and Surveillance
An OctreoScan can very occasionally show a carcinoid before CT scan or chemistries indicate its presence, but this situation is very infrequent. Visually it is used to help locate a tumor when chemistries show it is present and CT scan doesn’t image it. Also when CT scan is positive the OctreoScan may show additional sites of the tumor not seen on CT.
Finally even when tumor is seen on a CT scan and chemistries are positive, the OctreoScan is useful because a positive result indicates the presence of SST2 receptors in the tumor and that means the patient will most likely respond well to treatment with Sandostatin and also has a better prognosis than does the patient with carcinoid tumor but a negative OctreoScan.
5-FU is a form of chemotherapy. It might shrink a carcinoid and hence lower 5-HIAA in the urine, but it also can cause a transient increase in 5-HIAA since more is released temporarily by decaying tumors. However, the drug itself does not interfere with the 5-HIAA test.
Eugene Woltering, MD, FACS, answers: ” Well, the procedure that I use is to:
1. Look at the path report and look for key words like mitotic indices necrosis and the key word differentiation.
2. Get a Ki -67 and clearly, the lower this number the better. Numbers over 20% ( some say 10%) are atypical indicators.
3. Get stain on the tumor for CGA and synaptophysin and ask the path guy/gal to actually count the percentage of cells that are positive/negative.”
Dr. Woltering is The James D. Rives Professor of Surgery and Neurosciences, Chief of Sections of Surgical Oncology and Endocrinology, and Director of Surgical Research, LSUHSC Neuroendocrine – Carcinoid Tumors at Ochsner Medical Center — Kenner in Louisiana. The Neuroendocrine Tumor Program at Ochsner Medical
Center – Kenner specializes in the diagnosis and management of all forms of neuroendocrine tumors
of the gastroenteropancreatic axis. In partnership with Louisiana State University Health
Sciences Center, the Neuroendocrine Tumor Program offers multidisciplinary clinical care for the neuroendocrine patient: medical, surgical and nutritional.
Our Medical Director, Richard R.P. Warner MD, states that ALL PPI’s (example, Nexium) will alter CgA results and
should therefore be withheld for about 1 month prior to the chromogranin A (CgA) test. Zantac or Tagamet can be substituted during this period.
It can be carcinoid syndrome. How high is the 5-HIAA and was the urine collected on a serotonin-free diet? If it was more than just slightly elevated, then confirm its significance by testing blood serotonin, which should be increased; blood tryptophan, which should be decreased; and chromogranin, A which should be increased. If one or two of these are clearly abnormal, you should check the liver for metastatic tumor – by CT scan with contrast or MRI. If negative, do an OctreoScan to search for tumor foci not seen by the other imaging techniques.
I can provide some general suggestions that should be useful, as regulations restrict me from answering specific questions. Carcinoid crisis is characterized by abrupt flushing of face and sometimes upper body, usually severe fall in blood pressure and even bronchospasm with wheezing can (infrequently) occur. The attack may look like an anaphylactic attack. Diarrhea is an important part of carcinoid syndrome but is not usually simultaneous with the carcinoid crisis. It more commonly occurs as part of the anaphylactic reaction or an allergic or pseudoallergic reaction.
Standard allergy tests are not usually positive in such cases. 24 hour urine histamine, blood histamine and blood tryptase tests, particularly if obtained at the time of attack or just afterwards will establish diagnosis of allergic or pseudo allergic so called idiopathic anaphylactic attacks and mast cell disease. Epinephrine will provoke – not help – carcinoid attacks. Urine 5HIAA is helpful when positive but if depended on as the sole chemical test for carcinoid syndrome will miss 50% of cases! Better also to measure blood serotonin, tryptophan and chromogranin A.
Other blood markers associated with rare cases of severe attacks of flushing, diarrhea and fall in blood pressure are VIP, calcitonin and gastrin. They too should be measured. If any of all of the above are positive – as I expect may occur – further elaborate tests and treatment will be needed with details depending on which test(s) are positive. You should consult an expert for this if and when you arrive at this stage.
Urine 5-HIAA will correctly diagnose almost all midgut carcinoid tumors causing carcinoid syndrome but only 1/2 of foregut carcinoids causing an endocrine syndrome and almost none of the hindgut carcinoid (which rarely cause any endocrine syndrome even when metastatic). Therefore, the combined use of other neuroendocrine markers (blood serotonin and chromogranin A) should also be used in diagnosis and surveillace/follow-up of carcinoid.
Chemical markers are important to measure and follow since they change before imaging tests do and before physical conditions (symptoms) change. They are useful early indicators of the tumor status.
The tempo of the disease varies from one patient to the next and hence the frequency with which the tests should be done may vary from yearly to every 3 months. The average is twice a year. Chromogranin A (CgA) is the most stable and dependable marker in 90% of cases. In many cases it can be supplemented by other markers which should have been tested originally and those found abnormal can also be followed subsequently.
In carcinoid, we initially include: Urine 5HIAA, Blood Serotonin, Neuron Specific Enolase, Pancreastatin, Substance P, Pancreatic Polypeptide and Atrial Naturetic Hormone (ANH) (fasting). The later (ANH) helps indicate development of carcinoid heart disease in patients with functioning tumors.In other neuroendocrine tumors, depending on type, we measure Gastrin, VIP, Calcitonin, CEA, Insulin, Glucagon, Alpha/Beta subunits of HCG and ACTH. In all cases we check CgA which is most often positive in most tumors regardless of presence or absence of any specific endocrine function.
Appropriate imaging tests such as CT scan with contrast, MRI with contrast and OctreoScan are also included in monitoring with frequency customized for each case. Included in the initial workup is also tumor-stain for Chromogranin A, Ki-67 and mitosis count.
For more information on Diagnostic and Surveillance protocolsCLICK HERE.
In general it can be stated that practically all carcinoid syndrome cases exhibit some increase in at least one of the many endocrine chemical products elaborated by the tumor and producing the syndrome. These include not only blood serotonin and urine 5HIAA but also chromogranin A, Neuron Specific Enolase, Pancreatic Polypeptide, Calcitonin, Substance P, Neurokinin A, Prostaglandin A,E and D, Histamine and Pancreastatin.
Furthermore there are a number of look alike syndromes such as Zollinger Ellison, VIPoma and Mast Cell Disease which can mimic carcinoid and be suspected by respectively measuring Gastrin, VIP, Histamine and Tryptase. Medullary Thyroid Carcinoma can cause a carcinoid-like syndrome and usually produce Calcitonin, CEA and at least one of the prostaglandins. Certain pituitary tumors make prolactin and can be associated with carcinoid like features. Prolactin is useful in this diagnosis.
An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.
This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.
Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.
Pheochromocytoma, mast cell disease, gastrointestinal allergies, VIPoma, medullary carcinoma of the thyroid, certain rare brain tumors and also certain rare neuropsychiatric disorders, to mention a few.
Octreoscan is the imaging technique of choice in addition to CT scan and MRI. In appropriate cases, Neotect Scan, FDG PET scan or F18 Dopa PET Scan and MIBG Scan in expert hands are useful. Measurement of urine and blood catecholamine could unmark a pheochromocytoma which causes flushing , fluctuating blood pressure and even diarrhea.
Carcinoid syndrome requires one or more of the following for laboratory confirmation of the diagnosis: increased blood serotonin with decreased blood tryptophan, increased chromogranin A and increased urine 5HIAA or indole-3-acetic acid. In spite of the symptoms, if these criteria are not present, carcinoid syndrome is not the diagnosis.
The urine 5-HIAA test for carcinoid is crude and can be strongly influenced by special diet and drugs. The patient must be on a special diet before and during the urine collection. Even then the test can miss up to 50% of the cases. It should not be relied on alone. Other markers for carcinoid tumor are blood serotonin, tryptophan, chromogranin A, pancreatic polypeptide and, of course, the OctreoScan.
Diarrhea
The use of nutmeg is an old folk remedy originating in the middle ages in Europe. Centuries of anecdotal observation and more recent experience in carcinoid patients under medical care on nutmeg for at least several years indicates no apparent side effects from the dose she is taking.
Diet for Carcinoid Patients
No. Bananas and other serotonin containing food need only be avoided when collecting urine for 5HIAA testing. Tumors make their own serotonin independent of dietary sources. See page for how to prepare for the urine 5-HIAA test.
I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.
DTIC
DTIC is an anticancer drug also known as dacarbazine. Like many other anticancer drugs, its mode of action is not known, but it may act via one of the following three hypotheses:
1. Inhibiting DNA synthesis by acting as a purine analog.
2. Acting as an alkylating agent.
3. Interacting with SH group.
It is effective in 50% of carcinoid cases.
Exercise
An extra shot of Sandostatin before nonstressful exercise is unnecessary but should be taken before known stress of either physical (surgery, dental work) or emotional type (IRS audit, unpleasant court appearance, funeral, etc.).
Massage is okay for carcinoid patients as long as the massage is not done over the tumor ( i.e. the liver area or the abdomen if that is where the tumor/s are). Also physical activity of the nonviolent type such as walking, swimming and exercising (not heavy weight lifting or contact sports) are good for noids.
Mild exercise short of being stressful is desirable and not harmful.
Familial C
There are several types of carcinoid and related neuroendocrine tumors which are genetically determined and are inherited conditions. They are quite rare, as a group comprising only 4% of all carcinoids. One type in particular, known as familial carcinoid, is very rare but must be considered when two family members have had carcinoid or other NETs. There is no preventive treatment, but early diagnosis could cure the condition if found in an early stage in an individual. Blood and urine markers should be tested at least once a year and OctreoScan as well as CT scan of the abdomen with IV contrast should be considered.
Familial Carcinoid/ MEN1
There are several types of carcinoid and related neuroendocrine tumors which are genetically determined and are inherited conditions. They are quite rare, as a group comprising only 4% of all carcinoids. One type in particular, known as familial carcinoid, is very rare but must be considered when two family members have had carcinoid or other NETs. There is no preventive treatment, but early diagnosis could cure the condition if found in an early stage in an individual. Blood and urine markers should be tested at least once a year and OctreoScan as well as CT scan of the abdomen with IV contrast should be considered.
Over 50 cases treated, over 10 years longest survival rate. For more information about adenocarcinoma we suggest that you visit the Pancreatic Cancer Action Network website. The familial occurrence of carcinoid is a recognized but exceedingly rare event. This occurrence in two first cousins is suggestive. A blood test of DNA for the chromosomal abnormality thought to be present in the genetic aberration in such cases is under study and development at present. Hopefully it will be perfected and available for general clinical use in a few years. Until then surveillance of individuals thought to be at risk should, in my opinion, consist of yearly testing of urine 5-HIAA and blood serotonin, tryptophan, chromogranin A and substance P starting after the second decade of life.
4% of carcinoids are hereditary. The best known of the 2 varieties of inherited carcinoids is associated with the MEN-1 syndrome in which 50% of the family develop the condition which is almost always associated with the presence of other endocrine tumors. These other tumors usually involve the parathyroid glands in the neck and/or the pancreas and core symptoms of their own. There is an obvious strong family history in these cases which can be proved by appropriate blood tests as well as blood chromosomal testing for the MEN gene. This test is expensive but worthwhile in at least the 1 member of such a suspect family who has had proven carcinoid. If that person tests positive it is almost certain that the family has the inheritable condition.
The 2nd type of inherited carcinoid is “familial carcinoid” which can occur without any other endocrine tumors and is more erratic in the percent of family members who will be afflicted. There is no test for a suspected family with carcinoid at the present time. The diagnostician must rely on the family history and careful testing for obscure carcinoid. The entire panel of carcinoid chemical markers should be tested as well as all clinical imaging techniques should be utilized such as OctreoScan, CT scan, upper and lower GI endoscopy, wireless capsule endoscopy, etc. I am participating in studies of familial carcinoid at the NIH which are presently underway.
Only 1-2% of carcinoids are familial. If you have symptoms suggestive of carcinoid syndrome, the tests to do are urine 5-HIAA, blood serotonin, tryptophan and chromogranin A. All large commercial laboratories can do these tests and your family doctor can order them if s/he understands them, otherwise they can be ordered by an endocrinologist, oncologist or general internist. They are expensive, but often covered by most health insurance plans.
Hereditary Carcinoid
There are several types of carcinoid and related neuroendocrine tumors which are genetically determined and are inherited conditions. They are quite rare, as a group comprising only 4% of all carcinoids. One type in particular, known as familial carcinoid, is very rare but must be considered when two family members have had carcinoid or other NETs. There is no preventive treatment, but early diagnosis could cure the condition if found in an early stage in an individual. Blood and urine markers should be tested at least once a year and OctreoScan as well as CT scan of the abdomen with IV contrast should be considered.
Inherited Cancers
There are several types of carcinoid and related neuroendocrine tumors which are genetically determined and are inherited conditions. They are quite rare, as a group comprising only 4% of all carcinoids. One type in particular, known as familial carcinoid, is very rare but must be considered when two family members have had carcinoid or other NETs. There is no preventive treatment, but early diagnosis could cure the condition if found in an early stage in an individual. Blood and urine markers should be tested at least once a year and OctreoScan as well as CT scan of the abdomen with IV contrast should be considered.
Inherited Carcinoid
Over 50 cases treated, over 10 years longest survival rate. For more information about adenocarcinoma we suggest that you visit the Pancreatic Cancer Action Network website. The familial occurrence of carcinoid is a recognized but exceedingly rare event. This occurrence in two first cousins is suggestive. A blood test of DNA for the chromosomal abnormality thought to be present in the genetic aberration in such cases is under study and development at present. Hopefully it will be perfected and available for general clinical use in a few years. Until then surveillance of individuals thought to be at risk should, in my opinion, consist of yearly testing of urine 5-HIAA and blood serotonin, tryptophan, chromogranin A and substance P starting after the second decade of life.
Liver
Are you assuming that the hot spot in your RLQ on the OctreoScan is a primary carcinoid in the appendix, which is the origin of the small, presumably metastatic lesion, in the liver ? Very unlikely. More likely a carcinoid originates in the terminal ileum (which is so close to the appendix that the scan cannot differentiate between the two). Furthermore, appendiceal carcinoid only rarely spreads so far as the liver while carcinoids of the terminal ileum much more frequently do so. But if neither was seen as a mass on the CT scan or on colonoscopy or small intestine barium X-ray series (was this done?), they would be too small for, and it would be too dangerous, to do a needle biopsy. In short, needle biopsy of the liver is easier and safer.
Lung Carcinoid
The term benign bronchial carcinoid is a misnomer. These tumors all have malignant potential but are usually very slow growing, hence the misuse of the adjective benign. Whether a lobectomy is required or bronchoscopic destruction of the tumor or some lesser type of surgery depends on the size, precise location and other features of any given tumor. These are rare tumors and unless you are at a large major medical center, your doctor probably has limited experience with this condition. A second opinion is advised but will only be as good as the experience of your consultant. Be CERTAIN to see one who is a known expert in this condition. Although it depends upon the specific case, in general most people who have lung surgery for this condition do well thereafter.
MEN1
There are several types of carcinoid and related neuroendocrine tumors which are genetically determined and are inherited conditions. They are quite rare, as a group comprising only 4% of all carcinoids. One type in particular, known as familial carcinoid, is very rare but must be considered when two family members have had carcinoid or other NETs. There is no preventive treatment, but early diagnosis could cure the condition if found in an early stage in an individual. Blood and urine markers should be tested at least once a year and OctreoScan as well as CT scan of the abdomen with IV contrast should be considered.
Menopause and Carcinoid
No.
No to both questions.
Needle Biopsy of the Liver
Are you assuming that the hot spot in your RLQ on the OctreoScan is a primary carcinoid in the appendix, which is the origin of the small, presumably metastatic lesion, in the liver ? Very unlikely. More likely a carcinoid originates in the terminal ileum (which is so close to the appendix that the scan cannot differentiate between the two). Furthermore, appendiceal carcinoid only rarely spreads so far as the liver while carcinoids of the terminal ileum much more frequently do so. But if neither was seen as a mass on the CT scan or on colonoscopy or small intestine barium X-ray series (was this done?), they would be too small for, and it would be too dangerous, to do a needle biopsy. In short, needle biopsy of the liver is easier and safer.
Niacin
Low doses of niacin (25 mg twice a day after meals) should not cause flushing, is sufficient, and is easily metabolized. However, if you are hypersensitive, you can take ½ (81 mg) of a pediatric aspirin just before each niacin dose to prevent flushing or else do use niacinamide. The mechanism of niacin flush is quite different from, and unrelated to, that of carcinoid syndrome.
I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.
Niacinamide
Low doses of niacin (25 mg twice a day after meals) should not cause flushing, is sufficient, and is easily metabolized. However, if you are hypersensitive, you can take ½ (81 mg) of a pediatric aspirin just before each niacin dose to prevent flushing or else do use niacinamide. The mechanism of niacin flush is quite different from, and unrelated to, that of carcinoid syndrome.
Novocain
Morphine is okay for carcinoid patients but epinephrine is not since it can provoke carcinoid crisis. Epinephrine is sometimes used with local anesthesia to prolong the anesthesia by causing vasoconstriction. Novocain and other local anesthesia do come without epinephrine. Demerol and Fentazine can be used for post operative pain in people who are intolerant of morphine and Percocet.
Nuclear Medicine Imaging
An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.
This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.
Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.
Nuclear Medicine Testing for Carcinoid
The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.
Nuclear Medicine Tests
An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.
This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.
Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.
Nutmeg
The use of nutmeg is an old folk remedy originating in the middle ages in Europe. Centuries of anecdotal observation and more recent experience in carcinoid patients under medical care on nutmeg for at least several years indicates no apparent side effects from the dose she is taking.
Nutritional Concerns
No. Bananas and other serotonin containing food need only be avoided when collecting urine for 5HIAA testing. Tumors make their own serotonin independent of dietary sources. See page for how to prepare for the urine 5-HIAA test.
They are both pancreatic extracts of animal active origin, made by different manufacturers, and are roughly equal in effectiveness. They come in several strengths and each include lipase, amylase and protease (enzymes that break down fats, carbohydrates and protein). They help the digestion (and thereby) of fats, carbohydrates and protein. They help people with conditions in which they have a deficiency of pancreatic secretions of these digestive enzymes, including: partial pancreatectomy surgery, post gastrectomy bypass surgery, chronic pancreatitis, cystic fibrosis, short bowel syndrome, various diarrheal diseases with rapid intestinal transit (carcinoid syndrome) and suppression of pancreatic function which often occurs as a side effect of Sandostatin treatment.
Xanthines and theobromines, as well as various foods and wines, contain substances that are provocative for carcinoid crisis and hence can interfere with the effectiveness of Sandostatin. I do agree with Dr. Woltering in recommending carcinoid patients avoid these agents.
Food tolerances are highly individual and not necessarily related to carcinoid.
Low doses of niacin (25 mg twice a day after meals) should not cause flushing, is sufficient, and is easily metabolized. However, if you are hypersensitive, you can take ½ (81 mg) of a pediatric aspirin just before each niacin dose to prevent flushing or else do use niacinamide. The mechanism of niacin flush is quite different from, and unrelated to, that of carcinoid syndrome.
All alcohol should be avoided because of its ability to trigger carcinoid crisis.
The only reason for carcinoid patients to eat a low fat diet would be to reduce steatorrhea (fat-containing diarrhea) if they have malabsorption due to short bowel syndrome or as a side effect of Sandostatin. If fat malabsorption is present or even suggested, then I treat with pancreatic enzymes. I encourage a high protein diet and that includes lean meat (beef, pork and lamb all have lean parts that would fall into this category). Tryptophan normally is the only raw material from which protein and niacin are formed and only a little goes to make serotonin, but in an active carcinoid making lots of serotonin, tryptophan is diverted to this use and protein and niacin synthesis suffer.
I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.
Other than a well-rounded diet supplemented by the standard one-a-day vitamin, there is no recognized specific dietary treatment for metastatic carcinoid in the liver if liver failure or carcinoid syndrome are not present. If a significant degree of liver function impairment is present, a diet used for any cause of liver failure (high carbohydrate, low protein and fat) is indicated along with standard vitamins and extra fat-soluble vitamins (A, D and E). if carcinoid syndrome is present, low dose supplements of niacin and a high protein diet are advised.
Niacin synthesis is deficient in carcinoid syndrome because of metabolic diversion of its precursor, tryptophan, to form serotonin. In some untreated individuals this can even lead to pellagra. Hence the recommendation for niacin supplementation. Niacin supplementation (in the nicotinic acid form) of up to 10 times the RDA (recommended dietary allowances which range from 15-20 mg/day to prevent pellagra), i.e., up to 200 mg per day, does usually not cause flushing or other side effects. Megadoses of nicotinic acid (100 mg – 3 g), which are sometimes given to people with hypercholesterolemia, on the other hand, have well-documented side effects of flushing, hyperuricemia, abnormalities in liver function, and occasionally hyperglycemia. Not a very good idea for carcinoids. The purpose for supplementation in carcinoids is to prevent pellagra not hypercholesterolemia, therefore lower levels of niacin intake is prudent (in either the acid or amide form). Megadoses of nicotineamide (as well as other water-soluble vitamins) may also have equally detrimental effects. Since very little documentation exists about the toxicity of large doses of this form (except in mice), it is recommended to stay within close proximity of the RDAs. The statements regarding various treatment options on our web page are very general, on purpose, since they are not meant to be used as self-treatment unsupervised by a physician or, in the case of nutrition, by a trained professional, but rather informational as to most available treatment today. Therefore, an amendment to this statement cannot be made.
Octreoscan
An OctreoScan can very occasionally show a carcinoid before CT scan or chemistries indicate its presence, but this situation is very infrequent. Visually it is used to help locate a tumor when chemistries show it is present and CT scan doesn’t image it. Also when CT scan is positive the OctreoScan may show additional sites of the tumor not seen on CT.
Finally even when tumor is seen on a CT scan and chemistries are positive, the OctreoScan is useful because a positive result indicates the presence of SST2 receptors in the tumor and that means the patient will most likely respond well to treatment with Sandostatin and also has a better prognosis than does the patient with carcinoid tumor but a negative OctreoScan.
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week. There is no effect on conception thereafter.
The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.
An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.
This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.
Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.
Octreoscan is the imaging technique of choice in addition to CT scan and MRI. In appropriate cases, Neotect Scan, FDG PET scan or F18 Dopa PET Scan and MIBG Scan in expert hands are useful. Measurement of urine and blood catecholamine could unmark a pheochromocytoma which causes flushing , fluctuating blood pressure and even diarrhea.
Are you assuming that the hot spot in your RLQ on the OctreoScan is a primary carcinoid in the appendix, which is the origin of the small, presumably metastatic lesion, in the liver ? Very unlikely. More likely a carcinoid originates in the terminal ileum (which is so close to the appendix that the scan cannot differentiate between the two). Furthermore, appendiceal carcinoid only rarely spreads so far as the liver while carcinoids of the terminal ileum much more frequently do so. But if neither was seen as a mass on the CT scan or on colonoscopy or small intestine barium X-ray series (was this done?), they would be too small for, and it would be too dangerous, to do a needle biopsy. In short, needle biopsy of the liver is easier and safer.
Octreotide
Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.
Pancreatic Enzymes
They are both pancreatic extracts of animal active origin, made by different manufacturers, and are roughly equal in effectiveness. They come in several strengths and each include lipase, amylase and protease (enzymes that break down fats, carbohydrates and protein). They help the digestion (and thereby) of fats, carbohydrates and protein. They help people with conditions in which they have a deficiency of pancreatic secretions of these digestive enzymes, including: partial pancreatectomy surgery, post gastrectomy bypass surgery, chronic pancreatitis, cystic fibrosis, short bowel syndrome, various diarrheal diseases with rapid intestinal transit (carcinoid syndrome) and suppression of pancreatic function which often occurs as a side effect of Sandostatin treatment.
Pellagra
I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.
PPI
Our Medical Director, Richard R.P. Warner MD, states that ALL PPI’s (example, Nexium) will alter CgA results and
should therefore be withheld for about 1 month prior to the chromogranin A (CgA) test. Zantac or Tagamet can be substituted during this period.
Prognosis
The 5-year survival rate of a rectal carcinoid depends on the probability of its having metastasized at the time of removal. This in turn is related to the tumor’s size. If less than 1-cm diameter, fewer than 5% will have metastasized and if more than 2 cm in diameter, 75% will have metastasized. The odds for a tumor sized 1-2 cm are in the 40-45% range. If the tumor has not spread, the 5-year survival rate is 81%. If it has spread locally, 47% will survive 5 years and if distant metastases have occurred, only 18% will survive 5 years (without treatment). However, these figures may improve a bit with some of the newer therapies available or becoming available.
There is a 50% chance of recurrence when the original tumor was 2 cm or greater, but much depends on the specific findings of the resected tumor. Such as: Was there any extra bronchial extension, lymph node involvement ? Question: How was it removed (wedge resection, lobectomy, bronchoscopically)? Question: Was it central, peripheral. etc.? When these recur, it can be either locally or at a distant site such as elsewhere in the lung, liver, bones, etc. Usually it takes many years to recur if it is going to do so. There are many ways to check on these such as – blood and urine chemical markers, CT scans, bronchoscopy, OctreoScan, etc.
Psychological Issues
Low dose Atarax might help alpha interferon-induced irritability.
A Selective Seratonin Reuptake Inhibitor (SSRI) is an antidepressant medication that typically decreases anxiety as well as depression (Prozac, Zoloft, Paxil). It acts by blocking the reuptake of serotonin. It is contraindicated in patients with carcinoid syndrome. It may preciptate a carcinoid crisis or worsen symptoms of carcinoid syndrome.
Zoloft is okay for patients without carcinoid syndrome but not those who have it. They are better are better treated with Elavil or Nortryptyline.
Radiotherapy
Radiotherapy is helpful for painful bone lesions.
Research and Statistics
Here are a few medical references dealing with the issue of efficacy of octreotide in control of tumor growth and/or reduction. There are more, but these are the initial ones that come to mind plus the 2009 published study. Feel free to print this article and show it to any physician who doubts the efficacy of octreotide (in this case Sandostatin):
The reference published in 2009:
New Study First to Confirm Sandostatin LAR(R) Depot Controls Tumor Growth in Patients With Rare Gastrointestinal Tumors (Read full Text)
“In recent years, a growing body of evidence has suggested that Sandostatin LAR provides antitumor effects, but these are the first data to confirm this effect from a well-designed, prospective, placebo-controlled study,” said David Epstein, President & CEO of Novartis Oncology.
EAST HANOVER, N.J., Jan. 13 /PRNewswire/ — Sandostatin LAR(R) Depot (octreotide acetate suspension for injection) demonstrated antitumor benefit in patients with metastatic neuroendocrine tumors (NETs) of the midgut, according to interim data presented today at the 2009 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology.
– Data show significant 66% reduction in risk of disease progression versus placebo
– Sandostatin LAR more than doubled time without tumor growth for a median of 14 months compared to six months on placebo
– Results support Sandostatin LAR as first treatment after surgery in certain patients with newly diagnosed neuroendocrine tumors (NETs)
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group (Read Full Text)
Abstract:
Purpose: Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.
Patients and Methods: Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.
Results: Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18)
Conclusion: Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
Carcinoid tumor regression with high-dose octreotide acetate: a patient report.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract
Efficacy of octreotide in the regression of a metastatic carcinoid tumor despite negative imaging with In-111-pentetreotide (Octreoscan).http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract
Also in a very impressive and comprehensive review:
Carcinoid tumors and the carcinoid syndrome. Jensen, R.T., Norton, JA In: DeVita, VT Jr., Hellman, S, Rosenberg S eds. Cancer; Principles Practice of Oncology, 5th ed. Philadelphia, P Lippincott-Raven; 1997; 2:1704-1723.
It is stated on page 1718: octreotide may have a tumoriostatic effect, stabalizing the extent of metastatic disease and prolonging survival (with three references).
In Metastatic carcinoid tumors and the malignant carcinoid syndrome, Kvols, LK, Reubi, JC, the authors state: Even though objective tumor regression was unusual, previously progressive disease often became stable and this seems to have translated into favorable long-term survival.
Refer to: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8323761&dopt=Abstract
And to quote from Somatostatin analogue octreotide and inhibition of tumor growth in metastatic endocrine gastroenteropancreatic tumors. Arnold, R, Trautmann, ME, Creutzfeldt, W, Benning R, Benning, M, Neuhaus, C, Jurgensen, R, Stein, K. Schafer, H, Bruns, C, Dennler, H.J. The results suggest that octreotide inhibits tumor growth in patients with metastases endocrine GEP tumors. The antiproliferative effect is, at least in some patients, long lasting.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8675099&dopt=Abstract
The references cited below were used when the home page article was prepared many years ago and along with the older references used was a newer one by Modlin and Sandler indicating an increase in frequency:
* Moertel, C. G. An Odyssey in the land of small tumors, J. Clin. Onco 1983; 5: 1503-22.
* (1.5 new cases/100,000 general population per year = 2500 new cases yearly in the U.S.)
Vinik, A I., Thompson, N.V. in HolNeoplasms of the gastroenteropancreatic endocrine system in Hollland, J.F. (Ed.): Cancer Medicine. Cancer Medicine. Philadelphia, Lea and Fibiger, 1992.
* (Annual under 10/million)
Goodwin, J.D. Carcinoid tumours: An analysis of 2837 cases. Cancer; 1975: 36: 560-69.
* (Carcinoid incidence 0.5-1.5/100,000)
Norheim, I., Oberg, K. et al. Malignant carcinoid tumors: An analysis of 103 patients with regard to tumor localization, hormone production and survival. Am. Surg. 1987; 206: 115-25.
* Modlin, I.M., Sandor A. An analysis of 8305 cases of carcinoid tumor. Cancer, 1997; 79: 813-29. (A complex meta-analysis of incidence statistics indicating even higher frequency of occurrence of carcinoid)
Dr. Modlin published an update on the incidence of Ccarcinoid tumor in February 2003.
A 5-Decade Analysis of 13,715 Carcinoid Tumors (Click here for abstract)
Irving M. Modlin, MD, Kevin D. Lys, MD, Mark Kidd, PhD; Cancer 2003 Feb 15;97(4):934-59
CONCLUSIONS: Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease.
Sandostatin
An OctreoScan can very occasionally show a carcinoid before CT scan or chemistries indicate its presence, but this situation is very infrequent. Visually it is used to help locate a tumor when chemistries show it is present and CT scan doesn’t image it. Also when CT scan is positive the OctreoScan may show additional sites of the tumor not seen on CT.
Finally even when tumor is seen on a CT scan and chemistries are positive, the OctreoScan is useful because a positive result indicates the presence of SST2 receptors in the tumor and that means the patient will most likely respond well to treatment with Sandostatin and also has a better prognosis than does the patient with carcinoid tumor but a negative OctreoScan.
Xanthines and theobromines, as well as various foods and wines, contain substances that are provocative for carcinoid crisis and hence can interfere with the effectiveness of Sandostatin. I do agree with Dr. Woltering in recommending carcinoid patients avoid these agents.
Sandostatin works in both ways.
Here are a few medical references dealing with the issue of efficacy of octreotide in control of tumor growth and/or reduction. There are more, but these are the initial ones that come to mind plus the 2009 published study. Feel free to print this article and show it to any physician who doubts the efficacy of octreotide (in this case Sandostatin):
The reference published in 2009:
New Study First to Confirm Sandostatin LAR(R) Depot Controls Tumor Growth in Patients With Rare Gastrointestinal Tumors (Read full Text)
“In recent years, a growing body of evidence has suggested that Sandostatin LAR provides antitumor effects, but these are the first data to confirm this effect from a well-designed, prospective, placebo-controlled study,” said David Epstein, President & CEO of Novartis Oncology.
EAST HANOVER, N.J., Jan. 13 /PRNewswire/ — Sandostatin LAR(R) Depot (octreotide acetate suspension for injection) demonstrated antitumor benefit in patients with metastatic neuroendocrine tumors (NETs) of the midgut, according to interim data presented today at the 2009 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology.
– Data show significant 66% reduction in risk of disease progression versus placebo
– Sandostatin LAR more than doubled time without tumor growth for a median of 14 months compared to six months on placebo
– Results support Sandostatin LAR as first treatment after surgery in certain patients with newly diagnosed neuroendocrine tumors (NETs)
Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group (Read Full Text)
Abstract:
Purpose: Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.
Patients and Methods: Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.
Results: Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18)
Conclusion: Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
Carcinoid tumor regression with high-dose octreotide acetate: a patient report.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract
Efficacy of octreotide in the regression of a metastatic carcinoid tumor despite negative imaging with In-111-pentetreotide (Octreoscan).http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract
Also in a very impressive and comprehensive review:
Carcinoid tumors and the carcinoid syndrome. Jensen, R.T., Norton, JA In: DeVita, VT Jr., Hellman, S, Rosenberg S eds. Cancer; Principles Practice of Oncology, 5th ed. Philadelphia, P Lippincott-Raven; 1997; 2:1704-1723.
It is stated on page 1718: octreotide may have a tumoriostatic effect, stabalizing the extent of metastatic disease and prolonging survival (with three references).
In Metastatic carcinoid tumors and the malignant carcinoid syndrome, Kvols, LK, Reubi, JC, the authors state: Even though objective tumor regression was unusual, previously progressive disease often became stable and this seems to have translated into favorable long-term survival.
Refer to: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8323761&dopt=Abstract
And to quote from Somatostatin analogue octreotide and inhibition of tumor growth in metastatic endocrine gastroenteropancreatic tumors. Arnold, R, Trautmann, ME, Creutzfeldt, W, Benning R, Benning, M, Neuhaus, C, Jurgensen, R, Stein, K. Schafer, H, Bruns, C, Dennler, H.J. The results suggest that octreotide inhibits tumor growth in patients with metastases endocrine GEP tumors. The antiproliferative effect is, at least in some patients, long lasting.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8675099&dopt=Abstract
Sandostatin when given in large doses (if OctreoScan is positive) along with alpha interferon (with which it works synergistically) causes tumor regression in 2/3 of the cases.
The pump is a device in wide use for diabetics who need insulin. It usually is an elastic plastic ball which is filled with medicine under pressure and as it contracts very slowly it squeezes out the medicine slowly at a steady rate into a small plastic catheter attached to a needle which is correctly positioned under the skin.
In this article by Dr. Eugene Woltering (this is a technical article), he discusses the various methods for administering octreotide acetate drugs: https://www.carcinoid.org/medpro/docs/WoltPump2005.htm.
Here is some of what Dr. Woltering says about the pump: “Continuous subcutaneous infusions of octreotide acetate have been used by some physicians to take advantage of the rapid absorption of octreotide by the subcutaneous tissues. In this scenario the blood levels of octreotide begin to rise when the pump is turned on and continue to do so until the “steady state” is achieved—usually about 2-4 hours. Likewise, following the cessation of the subcutaneous infusion of octreotide, blood levels begin to fall and are back to insignificant levels after 6-8 hours (depending on dose used).Thus, the pump is ideal therapy for a patient who needs to be treated with high dose radiolabeled somatostatin analog therapy (like the 177 Lu, 90Y or 111In- based therapies) or has a negative Octreoscan in the past and wants to obtain the maximum sensitivity of this test. Another main advantage of pump- based therapy is the ability of a patient to increase or decrease the rate of infusion on a daily or weekly basis to control symptoms. “
15% of carcinoid patients cannot tolerate Sandostatin and it will not help them. There are additional medicines available which sometimes can make the Sandostatin tolerable or work. However, in some cases it must be abandoned and other forms of treatment should be tried. Somatuline Depot (lanreotide), a somatostatin analogue, by Tercica has been available in the United States since 2009.
The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.
An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.
This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.
Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.
Dr. Woltering stands somewhat alone in his use of huge doses of Sandostatin. Based on his research observations he feels that very large doses inhibit carcinoid tumor cell growth whereas conventional doses inhibit hormone production, release and effect on target cells thereby relieving or preventing symptoms of the carcinoid syndrome. Except in a few cases of people who are intolerant of Sandostatin, the high doses usually cause no more side effects than do conventional doses. The expense is an important factor which can be the deciding factor in how the drug is used. Perhaps with more experience it will become clearer whether Dr. Woltering’s conjecture is correct or incorrect.
Sandostatin and Dental Work
In general all carcinoid syndrome patients should be given a booster dose of regular octreotide just prior to any anesthesia, surgery or dentistry.
Serotonin Test
It is not 100% certain. In fact, the urine 5HIAA test will miss 50% of cases. Therefore other tests are usually done in conjunction with these tests. Among the most common tests done for diagnostic purposes are blood serotonin and blood chromogranin A. Other tests such as substance P and VIP may also be done.
Somatuline Depot
15% of carcinoid patients cannot tolerate Sandostatin and it will not help them. There are additional medicines available which sometimes can make the Sandostatin tolerable or work. However, in some cases it must be abandoned and other forms of treatment should be tried. Somatuline Depot (lanreotide), a somatostatin analogue, by Tercica has been available in the United States since 2009.
Specific Tumor Locations
The word adrenal refers to the adrenal glands. There are two, one on top of each kidney. Neoplasm means new growth. This means a new tumor. There are two categories of neoplasms, benign and malignant, the latter means cancer. Therefore, adrenal neoplasms are tumorous growths arising from the adrenal glands and can be either benign or malignant (cancerous). Furthermore, the adrenal glands are endocrine glands and make various types of hormones essential for the body, such as cortisone, adrenaline, and others. Each of these comes from separate and different types of cells in the adrenal gland and each type of cell can give rise to a separate and distinct type of neoplasm. There is no one treatment for all of these except for their surgical removal, but they often also require additional treatment with either/or radiation, chemotherapy, hormones and other medications, particularly if they are of the malignant variety and have spread.
Serotonin and other tumor products in the blood cause overgrowth of fibrous tissue on the heart valve in an unknown way. Treatment consists of neutralizing vasoactive tumor products by injection of octreotide (Sandostatin) and, when very advanced and severe, replacing the valves via heart surgery.
Angioedema (the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues, most often around the lips and eyes) is extremely rare in carcinoid disease but can occur with some foregut carcinoids.
Are you assuming that the hot spot in your RLQ on the OctreoScan is a primary carcinoid in the appendix, which is the origin of the small, presumably metastatic lesion, in the liver ? Very unlikely. More likely a carcinoid originates in the terminal ileum (which is so close to the appendix that the scan cannot differentiate between the two). Furthermore, appendiceal carcinoid only rarely spreads so far as the liver while carcinoids of the terminal ileum much more frequently do so. But if neither was seen as a mass on the CT scan or on colonoscopy or small intestine barium X-ray series (was this done?), they would be too small for, and it would be too dangerous, to do a needle biopsy. In short, needle biopsy of the liver is easier and safer.
The term benign bronchial carcinoid is a misnomer. These tumors all have malignant potential but are usually very slow growing, hence the misuse of the adjective benign. Whether a lobectomy is required or bronchoscopic destruction of the tumor or some lesser type of surgery depends on the size, precise location and other features of any given tumor. These are rare tumors and unless you are at a large major medical center, your doctor probably has limited experience with this condition. A second opinion is advised but will only be as good as the experience of your consultant. Be CERTAIN to see one who is a known expert in this condition. Although it depends upon the specific case, in general most people who have lung surgery for this condition do well thereafter.
SSRI
A Selective Seratonin Reuptake Inhibitor (SSRI) is an antidepressant medication that typically decreases anxiety as well as depression (Prozac, Zoloft, Paxil). It acts by blocking the reuptake of serotonin. It is contraindicated in patients with carcinoid syndrome. It may preciptate a carcinoid crisis or worsen symptoms of carcinoid syndrome.
Streptozotocin
The main toxic side effect of streptozotocin is on the kidney and the 8th cranial nerve, the nerve that transmits hearing and the equilibrium function of the inner ear. Kidney damage is the more common side effect and is related to the dose and total amount of the drug given. Careful monitoring of the urine analysis and blood test and blood tests for kidney function before each treatment, with aborting treatment if the starts of abnormalities are seen can prevent any significant renal damage. This should be done in all cases. Therefore, no patient need suffer side effects from this drug. Similarly, periodic audiograms and checks of the patients vestibular function will prevent irreversible 8th nerve damage. Monitoring blood counts and adjusting dosage or withholding the drug will avoid serious suppression of the white blood cells. Cardiac damage is not a regular complication of this drug and would be extraordinary.
Symptoms and Manifestations
Serotonin and the other usual products of carcinoids do not stimulate the thyroid or the adrenal glands. However, on rare occasions a carcinoid can co-produce other hormonal substances in addition to serotonin and chromogranin A. These could be TSH or catecholes like epinephrine or norephinephrine. Also, in rare cases a carcinoid develops in an individual with the MEN I syndrome who also has one or more other endocrine tumors which could produce TSH, epinephrine or a number of other active hormones.
There are many possible causes of edema in association with carcinoid involving the liver. These include: low serum albumin due to carcinoid impairing the liver’s synthetic function, impaired liver function due to chemotherapy, interference with circulation to or from the liver by pressure of carcinoid tumor on the blood vessels or from clotting of blood in the vessels due to substances released by the tumors, congestive failure of the right side of the heart due to carcinoid heart valve disease, pellagra due to tryptophan deficiency resulting from the tumors abnormal utilization of tryptophan, malabsorption due to hormone-induced small intestine pathophysiology, peritoneal spread of carcinoid tumor, retroperitoneal spread of carcinoid tumor with lymphatic obstruction, and a number of other possible causes. The treatment in each instance is somewhat different and hence must be customized for each case. The edema is not a separate disease but part of the entire carcinoid disease spectrum.
Simply tell your doctor you have read of the urine 5-HIAA as a measure of carcinoid tumor function and you want it done.
Carcinoid flush means experiencing a usually abrupt feeling of heat in the face which turns red in appearance. Sometimes, in women, the episodes are confused with hot flashes of menopause which unlike carcinoid flush often are accompanied by hot or cold sweat.
Short bowel syndrome is a group of problems affecting people who have had half or more of their small intestine removed. It is characterized by malabsorption due to loss of small intestinal surface area. The degree and type of resulting nutritional deficiencies depend on the length and location of the bowel that is lost. In general, patients will develop symptoms of short bowel syndrome when less than 200 cm of functional small bowel remains. As the majority of nutrient digestion and absorption is complete within the first 100 cm of jejunum, most patients will be able to maintain nutritional balance using oral feeding if at least 100 cm of intact jejunum is still present. Patients with less than 100 cm will likely require parenteral nutrition.
Diarrhea is defined as an increase in volume and /or frequency of stools. The consistency need not be loose, though it often is.
Tests for Carcinoid
It is not 100% certain. In fact, the urine 5HIAA test will miss 50% of cases. Therefore other tests are usually done in conjunction with these tests. Among the most common tests done for diagnostic purposes are blood serotonin and blood chromogranin A. Other tests such as substance P and VIP may also be done.
The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.
Treatments
In atypical carcinoid VP16 and Cisplatin is 67% effective. In typical carcinoid DTIC as a single agent has been reported effective in greater than 50%. Dr. Kjell Oberg (as well as myself through observation) reports greater than 60% effectiveness from CHRONIC treatment with large dosage octreotide along with small to moderate dosage alpha interferon. This combo (octreotide and alfa interferon) must be taken for at least 6 months before results are seen. Finally, leucovorin and LOW dose 5FU with streptozotocin given at frequent (weekly intervals) CHRONICALLY is effective in greater than 40% of cases. Note that if one chemotherapy program fails, the next one or two may be effective; i.e., failure to respond to one drug combo has no bearing on responsiveness to another. Aggressive treatment, rather than a wait-and-see approach, is better in the long run.
All adrenaline (epinephrine) containing drugs must be avoided.
Sandostatin works in both ways.
Usually NOT. It may infrequently produce antibodies that make it less effective, but this is in only a very small minority of cases. In some other cases it becomes less effective AT THE SAME DOSAGE because the tumors are growing. In most cases it is better to take it early in the disease, especially if carcinoid syndrome is present and blood serotonin levels are elevated because it will prevent carcinoid heart disease and inhibit tumor growth as well as prevent carcinoid syndrome symptoms.
Sandostatin when given in large doses (if OctreoScan is positive) along with alpha interferon (with which it works synergistically) causes tumor regression in 2/3 of the cases.
The pump is a device in wide use for diabetics who need insulin. It usually is an elastic plastic ball which is filled with medicine under pressure and as it contracts very slowly it squeezes out the medicine slowly at a steady rate into a small plastic catheter attached to a needle which is correctly positioned under the skin.
In this article by Dr. Eugene Woltering (this is a technical article), he discusses the various methods for administering octreotide acetate drugs: https://www.carcinoid.org/medpro/docs/WoltPump2005.htm.
Here is some of what Dr. Woltering says about the pump: “Continuous subcutaneous infusions of octreotide acetate have been used by some physicians to take advantage of the rapid absorption of octreotide by the subcutaneous tissues. In this scenario the blood levels of octreotide begin to rise when the pump is turned on and continue to do so until the “steady state” is achieved—usually about 2-4 hours. Likewise, following the cessation of the subcutaneous infusion of octreotide, blood levels begin to fall and are back to insignificant levels after 6-8 hours (depending on dose used).Thus, the pump is ideal therapy for a patient who needs to be treated with high dose radiolabeled somatostatin analog therapy (like the 177 Lu, 90Y or 111In- based therapies) or has a negative Octreoscan in the past and wants to obtain the maximum sensitivity of this test. Another main advantage of pump- based therapy is the ability of a patient to increase or decrease the rate of infusion on a daily or weekly basis to control symptoms. “
The reported world experience with liver transplant for carcinoid indicates that the outcome in general is as good but no better than that resulting from the best combination of multimodality treatment ( i.e. Octreotide/Sandostatin, Hepatic Artery Chemoembolization, Alpha interferon, tumor debulking by surgical excision, RFA, cryoablation, systemic chemotherapy and supportive measures). The rare exceptions when liver transplant is better are in those few cases with severe carcinoid syndrome unresponsive to Sandostatin with tumors restricted to the liver or in young patients with extensive tumors in the liver only and no tumors elsewhere.
In general all carcinoid syndrome patients should be given a booster dose of regular octreotide just prior to any anesthesia, surgery or dentistry.
15% of carcinoid patients cannot tolerate Sandostatin and it will not help them. There are additional medicines available which sometimes can make the Sandostatin tolerable or work. However, in some cases it must be abandoned and other forms of treatment should be tried. Somatuline Depot (lanreotide), a somatostatin analogue, by Tercica has been available in the United States since 2009.
The main toxic side effect of streptozotocin is on the kidney and the 8th cranial nerve, the nerve that transmits hearing and the equilibrium function of the inner ear. Kidney damage is the more common side effect and is related to the dose and total amount of the drug given. Careful monitoring of the urine analysis and blood test and blood tests for kidney function before each treatment, with aborting treatment if the starts of abnormalities are seen can prevent any significant renal damage. This should be done in all cases. Therefore, no patient need suffer side effects from this drug. Similarly, periodic audiograms and checks of the patients vestibular function will prevent irreversible 8th nerve damage. Monitoring blood counts and adjusting dosage or withholding the drug will avoid serious suppression of the white blood cells. Cardiac damage is not a regular complication of this drug and would be extraordinary.
DTIC is an anticancer drug also known as dacarbazine. Like many other anticancer drugs, its mode of action is not known, but it may act via one of the following three hypotheses:
1. Inhibiting DNA synthesis by acting as a purine analog.
2. Acting as an alkylating agent.
3. Interacting with SH group.
It is effective in 50% of carcinoid cases.
Radiotherapy is helpful for painful bone lesions.
Chemotherapy is effective in 1/3 of midgut carcinoids and in a larger percentage of foregut (including pancreatic) carcinoids. It is also more effective in atypical carcinoids. Sandostatin in large doses (300 mcg every 6-8 hours) often controls symptoms not responding to smaller doses. In addition, when combined with low dose alpha-Interferon, stabilizes or regresses tumor in up to three-quarters of cases.
In general, radiotherapy for carcinoid tumor arising from the foregut is utilized only to treat painful metastatic bone metastases (in which instances it is usually effective), brain metastases, unresectable carcinoid of the larynx, unresectable carcinoid of the thymus and sometimes unresectable carcinoids of the lung. It is questionable whether radiotherapy is effective for lung carcinoid and it has the potential for injuring healthy parts of the adjacent lung by causing radiation pneumonitis and thereby impairing breathing further. It might be considered as a last option when all other treatments, including chemotherapy, have failed. I feel that there is no role for radiotherapy for gastric or pancreatic carcinoids.
Morphine is okay for carcinoid patients but epinephrine is not since it can provoke carcinoid crisis. Epinephrine is sometimes used with local anesthesia to prolong the anesthesia by causing vasoconstriction. Novocain and other local anesthesia do come without epinephrine. Demerol and Fentazine can be used for post operative pain in people who are intolerant of morphine and Percocet.
Dr. Woltering stands somewhat alone in his use of huge doses of Sandostatin. Based on his research observations he feels that very large doses inhibit carcinoid tumor cell growth whereas conventional doses inhibit hormone production, release and effect on target cells thereby relieving or preventing symptoms of the carcinoid syndrome. Except in a few cases of people who are intolerant of Sandostatin, the high doses usually cause no more side effects than do conventional doses. The expense is an important factor which can be the deciding factor in how the drug is used. Perhaps with more experience it will become clearer whether Dr. Woltering’s conjecture is correct or incorrect.