This study will evaluate members in families with a history of small bowel carcinoid cancer
to study the natural history of those family members that have the disease, determine ways to
improve early detection by performing surveillance on those at risk but without disease and
to identify the gene(s) that may cause the tumors. Familial carcinoid tumors usually
originate in hormone-producing cells that line the small intestine or other cells of the
digestive tract. The tumors are slow-growing and usually take many years before they cause
symptoms. It is known that these tumors occur more often in some families and are then passed
from one generation to the next by inherited genes.
Members of families, including all siblings and offspring in which two or more immediate
blood relatives have had small bowel carcinoid tumors are eligible for this study. In some
cases unaffected spouses of family members diagnosed with carcinoid cancer are also requested
to participate by donating a sample of blood only.
Participants undergo a medical evaluation every 3 years during a 3- to 5-day hospital stay at
the NIH Clinical Center. All participants have a personal and family medical history obtained
and undergo a physical examination, blood and urine tests.
People who already have a small bowel carcinoid tumor or are at risk of developing a
carcinoid tumor have some or all of the following procedures to determine the presence of
carcinoid tumor and its (omit next two words- location or) spread to other areas of the body:
- Video Capsule Endoscopy: Visualization of the gastrointestinal tract by ingesting a
disposable, "vitamin-pill sized" video capsule that has its own camera and light source.
- CT of the chest abdomen and pelvis with oral and IV contrast : X-ray examination of the
chest, abdominal and pelvis organs.
- 18 FDOPA Positron emission tomography (PET) with CT for localization: Nuclear imaging
scan to look at tumor activity.
- MRI Liver with contrast - to determine if disease has spread to liver
- Gallium 68 PET/CT-limited to individuals that have residual tumor.
- Clinical and research blood work
Should mid gut carcinoid tumors be found every participant will be assisted in determine what
the best course of treatment will be for them.
Carcinoid tumors are rare and cause either no or few nonspecific symptoms. Therefore,
patients with carcinoid tumors most often present late in the course of their illness when
there is already progression to an incurable state as a result of metastatic disease. At
present there are neither practical population screening tests nor effective therapies and
hence the 5 year survival rate is low. Due to the rareness of sporadic carcinoid tumors,
large scale genetic analysis and development of sensitive and specific diagnostic tests have
not been successful. While kindreds with familial carcinoid tumors that are not ascribable to
known genetic syndromes are exceedingly rare, they provide a unique opportunity to facilitate
the identification of the responsible gene mutation. In addition, the mutated gene in the
rare familial form may also underlie the origin of the more common sporadic occurrence of
carcinoid tumors. We propose to study families in which there are at least two known affected
members with carcinoid tumors. We aim to diagnose patients with early and therefore
potentially curable occult disease. Therefore, family members who have up to a 50% lifetime
risk of harboring a carcinoid tumor will undergo an intensive diagnostic evaluation using
biochemical, endoscopic and imaging modalities at initial and subsequent two year follow up
encounters. Early phenotypic assignment of affected family members and collection of germline
and tumoral DNA from multiple kindreds should also facilitate the genetic analysis leading to
the identity of the disease gene. Evaluation of affected family members at varying stages of
disease will contribute to our understanding of the natural history of carcinoid tumors and
the relative utility of a variety of diagnostic and surveillance tests. Hopefully, such
knowledge gained will also be applicable to patients with carcinoid tumors occurring
sporadically or in the setting of other familial cancer syndromes. There is no planned
treatment for patients with existing or newly diagnosed primary or metastatic carcinoid
tumors. However, these patients may be evaluated by consultation with oncology and surgery
for potential treatment on their service under their preexisting protocols.
- INCLUSION CRITERIA:
1. Adult patients who who a) have a present diagnosis of small intestinal carcinoid
tumor and have at least one blood relation with an immediate or distant family
member with a documented diagnosis of either small intestinal, pulmonary or
gastropancreatic neuroendocrine tumor or b) do not have a diagnosis of small
intestinal carcinoid tumor and have at least two immediate or distant family
members with documented diagnoses of either small intestinal, pulmonary or
gastropancreatic neuroendocrine tumor. This includes family members of patients
with carcinoid tumors even if the patients with tumors are unwilling to
participate so long as we have appropriate documentation confirming the diagnosis
of the carcinoid tumors in the affected family members. Adult patients who are
unable to provide informed consent but whose wishes suggest they are willing to
donate samples for research purposes will be considered for study enrollment.
2. Unaffected spouses of patients with a carcinoid tumor and who have children.
1. Families with multiple endocrine neoplasia (MEN) I, MEN II or other familial tumor
syndromes such as Von Hippel Lindau Syndrome and Neurofibomatosis for which there is a
known genetic predisposition to non-carcinoid tumors as well as carcinoid tumors will
be excluded from the study.
2. Pregnancy, breastfeeding.
3. Anticoagulation, seizures, severe systemic disease of any sort, advanced metastatic
carcinoid may be relative exclusion criteria prohibiting a full evaluation as
described above under protocol design. However, these medical conditions should not
absolutely exclude participation in the protocol. Participation in each protocol
delineated evaluation procedure will be judged on a case by case basis with patient
safety as the paramount consideration.