5-HIAA Urine Tests

Are there any dietary restrictions for patients other than during the 5-HIAA test?

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.

Why do 5-HIAA urine tests sometimes come back high and other times low after carcinoid tumors have been removed?

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

Are the 5-HIAA test and the serotonin test conclusive for detecting a carcinoid tumor?

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

How many cases of adenocarcinoid have you treated and what is the longest survival rate?

Over 50 cases treated, over 10 years longest survival rate. For more information about pancreatic neuroendocrine tumors and adenocarcinoma we suggest that you visit the Pancreatica.orgwebsite.
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

My mom takes 1 tsp. of nutmeg 3 times a day to help control diarrhea. Are there any possible side effects?

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

Which anesthetics and painkillers are okay to use if you have carcinoid?

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

What is 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.

Antidepressants

Is it okay to use Prozac if you have a lung carcinoid?

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.

Is Zoloft an acceptable antidepressant for carcinoid patients ?

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

Why would my doctor mention my appendix if an OctreoScan showed a hot spot in my lower right quadrant?

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

What is recommended for bone metastases?

Radiotherapy is helpful for painful bone lesions.

Bronchial Carcinoid

With benign bronchial carcinoid tumors, what is the percentage of people who usually undergo lobectomy surgery?

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

Is there a problem with attempting to conceive soon after the OctreoScan?

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

How many cases of adenocarcinoid have you treated and what is the longest survival rate?

Over 50 cases treated, over 10 years longest survival rate. For more information about pancreatic neuroendocrine tumors and adenocarcinoma we suggest that you visit the Pancreatica.orgwebsite.
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?

Are the 5-HIAA test and the serotonin test conclusive for detecting a carcinoid tumor?

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.

Can menopause bring on carcinoid or endocrine tumors?

No.

Do all carcinoids start out as microcarcionids?

Yes.

How is a microcarcinoid different than a carcinoid tumor?

It is microscopic in size and then grows.

How long does it take for a carcinoid tumor to grow to the size of 2 cm?

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.

How long does the octreotide/radioisotope remain in the body?

Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.

If a microcarcinoid is found, are there likely to be others?

Yes, particularly when found in the stomach and lung.

Is there a problem with attempting to conceive soon after the OctreoScan?

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.

Is there any indication that mercury contamination might have something to do with carcinoid?

No.

Is there some relationship between the hormones of menopause and the hormones coming from carcinoid/neuroendocrine tumors?

No to both questions.

What does the OctreoScan test show?

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.

What is carcinoid cancer and what will happen to someone found to have carcinoid during surgery for something else?

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.

What is carcinoid cancer and what will happen to someone found to have carcinoid during surgery for something else?

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.

What is Goblet Cell Carcinoid (adenocarcinoid, mucinous carcinoid)?

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.

What is Neurokinin B and its relationship to carcinoid syndrome?

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.

What is the most common site of carcinoid in the body? What is the most common site of malignant carcinoid in body?

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

 

What relationship does the serotonin level have in the regulation of carcinoid tumors?

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

How do carcinoids in the liver affect heart valves and what are some of the current treatments of the heart valves?

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

What are the side effects of 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.

Carcinoid Syndrome

Does the body build up a tolerance to Sandostatin LAR or IR over time so that it becomes less effective?

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

If I have a patient with severe asthma, facial flushing, and elevated serum 5-HIAA, could this be carcinoid syndrome?

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 have been diagnosed with carcinoid syndrome due to a high 5-HIAA & symptoms, but nothing shows on a CT scan, what’s next?

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.

What about other vitamin or dietary supplements?

I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.

Which symptoms need to be present to diagnose carcinoid syndrome?

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

How long does the octreotide/radioisotope remain in the body?

Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.

Is there a problem with attempting to conceive soon after the OctreoScan?

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

Are the 5-HIAA test and the serotonin test conclusive for detecting a carcinoid tumor?

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

How does Sandostatin work in conjunction with 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

Are there any chemotherapy agents more than 30% effective in carcinoid of the large and small bowel?

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.

What is the effect of chemotherapy on carcinoid?

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

Are there any chemotherapy agents more than 30% effective in carcinoid of the large and small bowel?

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

Can you provide some suggestions about the preferred use of OctreoScans?

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

Which anesthetics and painkillers are okay to use if you have carcinoid?

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

Are there medications to avoid with dentistry?

All adrenaline (epinephrine) containing drugs must be avoided.

Dental Work and Carcinoid

Are there medications to avoid with dentistry?

All adrenaline (epinephrine) containing drugs must be avoided.

Is subcutaneous rescue sandostatin indicated for dentistry?

In general all carcinoid syndrome patients should be given a booster dose of regular Sandostatin just prior to any anesthesia, surgery or dentistry.

Depression

Is it okay to use Prozac if you have a lung carcinoid?

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

Can you provide some suggestions about the preferred use of OctreoScans?

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.

Does 5-FU effect the 5-HIAA test?

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.

Does Levovist, an ultrasound contrast agent made up of milk sugar (galactose), work for carcinoid in imaging tests?

This is a  contrast agent to help sonographic imaging of the portal vein and certain types of liver tumors (hepatocellular carcinoma – HCC). It does not have current immediate application in carcinoid disease since there is very limited or no experience with it in this tumor.

How do you determine if a carcinoid tumor is typical or atypical?

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.

I would like to know if taking a PPI (Nexium) will alter the chromogranin A count?

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.

If I have a patient with severe asthma, facial flushing, and elevated serum 5-HIAA, could this be carcinoid syndrome?

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 have anaphylactic episodes, with flushing, diarrhea & low blood pressure, could I have carcinoid syndrome?

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.

If I have been diagnosed with carcinoid syndrome due to a high 5-HIAA & symptoms, but nothing shows on a CT scan, what’s next?

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.

If the 5-HIAA test misses up to 50% of carcinoid tumors, does this refer to both symptomatic & asymptomatic carcinoid tumors?

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.

Is a colonoscopy to rule out GI lesions or an OctreoScan required after removal of an appendix with a small carcinoid?

If the carcinoid was greater than 1.5 cm diameter, or if it extended through the appendiceal wall to the serosa or the fat regardless of size, or if mesoappendix or nodes involvement were present – a right hemicolectomy should be done preceded by an OctreoScan.  If it was small and did not meet the above criteria, no colonoscopy or further workup is needed.  Carcinoid syndrome almost always requires a fairly large bulk of metastatic carcinoid and even then almost never results from appendiceal carcinoid.  There are only 2 such cases in the world literature.

Once we have been diagnosed with carcinoid, what should the follow-up surveillance program include? Which tests and how often?

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.

What hormones do carcinoid tumors secrete to produce the symptoms of carcinoid syndrome?

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.

What is an 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.

What other conditions are similar to carcinoid?

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.

What tests are needed in the diagnosis of carcinoid or whatever it can be?

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.

Which symptoms need to be present to diagnose carcinoid syndrome?

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.

Why do 5-HIAA urine tests sometimes come back high and other times low after carcinoid tumors have been removed?

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

My mom takes 1 tsp. of nutmeg 3 times a day to help control diarrhea. Are there any possible side effects?

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

Are there any dietary restrictions for patients other than during the 5-HIAA test?

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.

What about other vitamin or dietary supplements?

I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.

DTIC

What is 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

If a person wants to exercise, should he/she take an extra shot of Sandostatin beforehand? Doesn’t stress bring on symptoms?

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.).

Is there any contraindication for Carcinoid patients regarding massage by a physical therapist?

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.

What about exercise? Doesn’t it bring out more hormones released from the tumors, thereby exacerbating symptoms?

Mild exercise short of being stressful is desirable and not harmful.

Familial C

Could two first cousins suffer from the same form of cancer and, if so, does that indicate that it is hereditary?

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

Could two first cousins suffer from the same form of cancer and, if so, does that indicate that it is hereditary?

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.

How many cases of adenocarcinoid have you treated and what is the longest survival rate?

Over 50 cases treated, over 10 years longest survival rate. For more information about pancreatic neuroendocrine tumors and adenocarcinoma we suggest that you visit the Pancreatica.orgwebsite.
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.

If more than one person in my family has carcinoid, what are the chances that my children will have carcinoid?

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.

If my mother has carcinoid and I have symptoms similar to those of carcinoid, what tests should I have?

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

Could two first cousins suffer from the same form of cancer and, if so, does that indicate that it is hereditary?

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

Could two first cousins suffer from the same form of cancer and, if so, does that indicate that it is hereditary?

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

How many cases of adenocarcinoid have you treated and what is the longest survival rate?

Over 50 cases treated, over 10 years longest survival rate. For more information about pancreatic neuroendocrine tumors and adenocarcinoma we suggest that you visit the Pancreatica.org   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

Why would my doctor mention my appendix if an OctreoScan showed a hot spot in my lower right quadrant?

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

With benign bronchial carcinoid tumors, what is the percentage of people who usually undergo lobectomy surgery?

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

Could two first cousins suffer from the same form of cancer and, if so, does that indicate that it is hereditary?

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

Can menopause bring on carcinoid or endocrine tumors?

No.

Is there some relationship between the hormones of menopause and the hormones coming from carcinoid/neuroendocrine tumors?

No to both questions.

Needle Biopsy of the Liver

Why would my doctor mention my appendix if an OctreoScan showed a hot spot in my lower right quadrant?

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

Should I take niacin or niacinamide if 50 mg of niacin in my multi-vitamin caused me to flush within 1 to 2 hours of taking it?

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.

What about other vitamin or dietary supplements?

I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.

Niacinamide

Should I take niacin or niacinamide if 50 mg of niacin in my multi-vitamin caused me to flush within 1 to 2 hours of taking it?

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

Which anesthetics and painkillers are okay to use if you have carcinoid?

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

What is an 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.

Nuclear Medicine Testing for Carcinoid

What does the OctreoScan test show?

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

What is an 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.

Nutmeg

My mom takes 1 tsp. of nutmeg 3 times a day to help control diarrhea. Are there any possible side effects?

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

Are there any dietary restrictions for patients other than during the 5-HIAA test?

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.

Could you give me a brief description of Creon and Pancrease, and the benefits of each?

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.

Do you believe that foods containing xanthines or theobromine, such as coffee, interfere with Sandostatin?

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.

Do you prescribe pancreatic enzyme replacements and if so, how much and how often?

Pancreatic enzyme replacement varies from 1-3 Viokase tablets with each meal and at bedtime, or 1-2 Creon or Pancrease capsules taken with each meal and at bedtime.

Have you ever had patients report getting diarrhea from drinking coffee or tea?

Occasionally patients get diarrhea from coffee, but it is uncommon.

Is food intolerance very patient-independent?

Food tolerances are highly individual and not necessarily related to carcinoid.

Should carcinoid patients take niacin? If so, how much? Does it cause any side effects?

The nutritional deficiency disease pellagra results from niacin deficiency.  Diarrhea is one symptom of pellagra.  All carcinoid syndrome patients have subnormal blood levels of tryptophan, an evidence of its depletion by being diverted to make large amounts of serotonin.  Hence niacin deficiency can occur.  Taking niacin in low doses prevents this; high doses are not necessary and can cause flushing.   Tryptophan is obtained only via ingested food, particularly meat.

Should I take niacin or niacinamide if 50 mg of niacin in my multi-vitamin caused me to flush within 1 to 2 hours of taking it?

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.

What about alcohol? What forms should be avoided and why?

All alcohol should be avoided because of its ability to trigger carcinoid crisis.

What about fat — if red meat is tolerated is it okay to eat?

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.

What about other vitamin or dietary supplements?

I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.

What are the dietary recommendations for a patient with carcinoid of the liver?

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.

Would you consider amending your recommendation of supplementing one’s diet with niacin to supplementing with niacinamide?

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

Can you provide some suggestions about the preferred use of OctreoScans?

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.

How long does the octreotide/radioisotope remain in the body?

Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.

Is there a problem with attempting to conceive soon after the OctreoScan?

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.

What does the OctreoScan test show?

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.

What is an 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.

What tests are needed in the diagnosis of carcinoid or whatever it can be?

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.

Why would my doctor mention my appendix if an OctreoScan showed a hot spot in my lower right quadrant?

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

How long does the octreotide/radioisotope remain in the body?

Every last trace of octreotide and the isotope Indium 111 used in the OctreoScan are gone from the body within 1 week.

Pancreatic Enzymes

Could you give me a brief description of Creon and Pancrease, and the benefits of each?

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

What about other vitamin or dietary supplements?

I do endorse a multiple vitamin supplement and all patients with carcinoid syndrome should take low doses of niacin to prevent subclinical pellagra.

PPI

I would like to know if taking a PPI (Nexium) will alter the chromogranin A count?

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

Are all carcinoid tumors cancerous or can some be benign?

The word benign is a misnomer. Benign means non-cancerous. All carcinoid cancers have the potential to spread/produce metastases. A better word for benign would be indolent (=slow, inactive, sluggish) Some are indolent but this cannot always be determined by looking at the tumor cells under the microscope.

If a carcinoid tumor is not metastatic at the time of removal and is located in the rectum, what is the 5 year survival rate?

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.

If I had a bronchial carcinoid removed, what is the likelihood of it reoccurring?

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

If no depression is present what could be used for irritability caused by interferon?

Low dose Atarax might help alpha interferon-induced irritability.

Is it okay to use Prozac if you have a lung carcinoid?

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.

Is Zoloft an acceptable antidepressant for carcinoid patients ?

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

What is recommended for bone metastases?

Radiotherapy is helpful for painful bone lesions.

Research and Statistics

Does Sandostatin inhibit or reverse the growth of carcinoid tumors?

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

Regarding the review article on this website, what is the reference used for the number of new cases diagnosed each year?

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

Can you provide some suggestions about the preferred use of OctreoScans?

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.

Do you believe that foods containing xanthines or theobromine, such as coffee, interfere with Sandostatin?

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.

Does Sandostatin cause carcinoid tumors to reduce production of their chemicals?

Sandostatin works in both ways.

Does Sandostatin inhibit or reverse the growth of carcinoid tumors?

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

How does Sandostatin work in conjunction with 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.

How does the pump work with Sandostatin?

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: http://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. “

What are the side effects of Sandostatin?

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.

What does the OctreoScan test show?

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.

What is an 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.

You, Dr. Warner, and Dr. Woltering prescribe different dosages of Sandostatin – what the pros and cons of each approach?

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

Is subcutaneous rescue sandostatin indicated for dentistry?

In general all carcinoid syndrome patients should be given a booster dose of regular Sandostatin just prior to any anesthesia, surgery or dentistry.

Serotonin Test

Are the 5-HIAA test and the serotonin test conclusive for detecting a carcinoid tumor?

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

What are the side effects of Sandostatin?

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

Can you provide information about carcinoid in the appendix?

Carcinoid is found coincidentally in approximately 1 of every 200 appendixes removed.  Its importance depends on its size and also whether its growth is limited to just the lining of the appendix.  Most of them are tiny and just a harmless curiosity.  Those few which are larger or have invaded into or through the wall of the appendix require a second, more extensive, operation to thoroughly clean out the area to which the appendix was attached.  These few patients will require periodic X-ray and blood tests in the future years to watch for recurrence or spread.

Carcinoid syndrome almost never comes from appendiceal carcinoids and the 1 or 2 cases reported required extensive and obvious metastases to cause the syndrome. Usually carcinoids of the appendix are coincidental findings and have not spread until greater than 2 cm in diameter.  However, even with a small one (under 2 cm) it is important to know that the tumor has not gone through the full thickness of the appendix wall and does not show any microscopic invasion of lymph nodes and blood vessels.  If all these criteria are okay, then you are cured and no further testing is required.

Could you please explain what adrenal neoplasms are and also the recommended treatment and prognosis?

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.

How do carcinoids in the liver affect heart valves and what are some of the current treatments of the heart valves?

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.

Is there a relationship between angioedema and carcinoid?

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.

Why would my doctor mention my appendix if an OctreoScan showed a hot spot in my lower right quadrant?

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.

With benign bronchial carcinoid tumors, what is the percentage of people who usually undergo lobectomy surgery?

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

Is it okay to use Prozac if you have a lung carcinoid?

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

What are the side effects of 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

Can the hormones or chemicals released by a carcinoid stimulate the thyroid gland to produce more T3 & T4 the way TSH does?

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.

Has any treatment been effective in reducing severe edema associated with a carcinoid of the liver?

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.

Is fluid buildup caused by the carcinoid tumors?

It sounds like you are describing ascites, the accumulation of fluid in the abdominal cavity. This is not exclusive for carcinoid disease but can occur in many conditions such as cirrhosis of the liver, heart failure, any widespread intra-abdominal cancers or various conditions compressing and blocking the lymph channels and/or large veins in the back of the abdominal cavity, as well as certain infections of the peritoneum (the lining of the abdominal cavity). The treatment and significance in each instance is different.

What are the main features of carcinoid syndrome?

Flushing and diarrhea. A carcinoid tumor somewhere in the body, which has spread to the liver, produces serotonin, chromogranin A and other substances and usually results in excretion in the urine of increased amounts of 5-HIAA, the breakdown product of serotonin.

What do I say to get my doctor to run the 5-HIAA test as I have been diagnosed with carcinoid?

Simply tell your doctor you have read of the urine 5-HIAA as a measure of carcinoid tumor function and you want it done.

What is carcinoid flushing?

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.

What is short bowel syndrome?

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.

When someone says diarrhea in relationship to carcinoid is that soft bowels or runny, liquid bowels?

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

Are the 5-HIAA test and the serotonin test conclusive for detecting a carcinoid tumor?

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.

What does the OctreoScan test show?

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

Are there any chemotherapy agents more than 30% effective in carcinoid of the large and small bowel?

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.

Are there medications to avoid with dentistry?

All adrenaline (epinephrine) containing drugs must be avoided.

Do you know why there is a “mushrooming effect” once the primary is removed?

Sometimes, not always, when a primary NET (neuroendocrine tumor) is removed and metastastatic tumors are already present, their growth is accelerated. However, sometimes the opposite occurs and their growth is related. These effects are thought to result from growth stimulating factor shifting to the metastases after their primary target is removed. On the other hand self-stimulating factors produced by the primary tumor also stimulate growth of metastases and these areas reduced by removing the primary tumor. It is a complicated situation which might be best handled by treating the tumor with tumor inhibiting medicines before and after surgery such as Sandostatin, alpha-interferon, chemotherapy, etc.

Does Sandostatin cause carcinoid tumors to reduce production of their chemicals?

Sandostatin works in both ways.

Does the body build up a tolerance to Sandostatin LAR or IR over time so that it becomes less effective?

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.

How does Sandostatin work in conjunction with 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.

How does the pump work with Sandostatin?

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: http://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. “

In your editorial section on treatment, liver transplant “in very special selected cases” is mentioned; what are those cases?

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.

Is subcutaneous rescue sandostatin indicated for dentistry?

In general all carcinoid syndrome patients should be given a booster dose of regular Sandostatin just prior to any anesthesia, surgery or dentistry.

My doctor feels cytotoxic treatment, after embolization, is pointless — what is your viewpoint?

Cytoxic treatment is NOT pointless, especially after embolization treatment. It prolongs life. See article by Moertel et. al. The management of patients with advanced carcinoid tumors and islet cell carcinomas.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8291824&dopt=Abstract

What are the side effects of Sandostatin?

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.

What are the side effects of 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.

What is 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.

What is recommended for bone metastases?

Radiotherapy is helpful for painful bone lesions.

What is the effect of chemotherapy on carcinoid?

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.

When is local irradiation used?

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.

Which anesthetics and painkillers are okay to use if you have carcinoid?

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.

You, Dr. Warner, and Dr. Woltering prescribe different dosages of Sandostatin – what the pros and cons of each approach?

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.