This section provides links to published papers that relate to the
diagnosis and surveillance of carcinoid and neuroendocrine tumors.
These topics are divided into:
Flushing:
Is It Carcinoid or Something Else?
Flushing can be an exaggeration of a physiological process or a
manifestation of a serious condition that needs to be identified
and treated. Christian Nasr, M.D., presents guidelines that will
help determine when a biochemical work-up is warranted
from The
Cleveland Clinic Disease Management Project,
published December 2004.
Imaging
of advanced neuroendocrine tumors with (18)F-FDOPA PET (Abstract)
This link is to a PubMed abstract. The full text requires a subscription to The Journal of Nuclear Medicine Online.
Alexander Becherer, M.D. ; Monica Szabo, M.D. ; Georgios Karanikas, M.D. ; Patrick Wunderbaldinger, M.D. ; Peter Angelberger, PhD; Markus Raderer, M.D. ; Amir Kurtaran, M.D. Robert Dudczak, M.D. and Kurt Kletter, M.D. , PhD
J . Nucl Med 2004; 45:1161-1167
Whole-body
11C-5-hydroxytryptophan positron emission tomography as a universal
imaging technique for neuroendocrine tumors - comparison with
somatostatin receptor scintigraphy and computed tomography This link is to a PubMed abstract.The full text is
available online from the PUB MED abstract.
Orlefors H, Sundin A, Garske U, Juhlin C, Öberg K, Langstrom
B, Bergstrom M, Eriksson B.
J Clin Endocrinol Metab. 2005 Mar 8; Conclusion:
This study indicates that 11C-5-HTP-PET is a sensitive method
for detection of NET´s and it exceeds both SRS and CT in
tumor visualization. The contribution of patient tumor status
with this technique is considerable. With the exception for poorly
differentiated NET´s and possibly non functioning tumors,
we believe that 11C-5-HTP can be used as a universal technique
for imaging of NET´s, with the greatest benefit in imaging
of small tumor lesions e.g. primary tumors. This study also reflects
that many different NET´s process biogenic amines to some
degree regardless of functionality and endocrine syndrome. NOTE: This scan is currently only available
in Sweden but presently in clinical trials in the US
PET
(11C-5-HTP-PET) in the Diagnosis of Neuroendocrine Tumors
This link is to a PubMed abstract. The full text requires a subscription
to subscription
to Annals of the New York Academy of Sciences Online.
Sundin A, Eriksson B, Bergstrom M, Langstrom B, Oberg K, Orlefors
H.
Ann N Y Acad Sci. 2004 Apr;1014:246-57
".......... In comparative studies of patients with carcinoids and endocrine
pancreatic tumors, 5-HTP-PET proved better than CT and somatostatin receptor
scintigraphy for tumor visualization, and many small, previously overlooked
lesions were diagnosed by 11C-5-HTP-PET........."
"...With new, more sensitive PET cameras, larger field of view and procedures
for whole-body coverage, the PET examination with 5-HTP is now routinely performed
as reduced whole-body PET examinations with coverage of the thorax and abdomen.
With this method we have been able to visualize small neuroendocrine lesions
in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not
detectable by any other method, including octreotide scintigraphy, MRI, and
CT. ..." NOTE: This scan is currently only available
in Sweden
The author briefly reviews radiopeptides currently approved for
use in the United States. They present a short review of the peptide
somatostatin's actions and also note the five somatostatin receptors
(SSTRs) to which the peptide and its synthetic analogs octreotide,
lanreotide, and vapreotide bind. The many conditions besides neuroendocrine
tumors having SSTRs are listed.
Abstract:
The measurement of general and specific biochemical markers in
patients with neuroendocrine tumours assists with diagnosis, gives
an indication of the effectiveness of treatment and may be used
as prognostic indicators. There is much agreement that Chromogranin
A is the most universally helpful marker which is found to be elevated
in the circulation of about 90% of patients with metastatic neuroendocrine
tumours and there are several excellent commercially available
kits, which give reliable estimations of chromogranin A. Specific
markers are useful for diagnosis also, and are helpful indicators
of the effectiveness of treatment particularly where tumour bulk
may not change so much as tumour activity. Sporadic pancreatic
neuroendocrine tumours may secrete more that one peptide and this
indicates worsening prognosis. Because of the wide variation in
the progression of neuroendocrine tumours, a prognostic indicator
gives a significant advantage to the clinician in order to facilitate
optimum treatment at the optimum stage of disease. Both chromogranin
A and neurokinin A have been used as powerful prognostic indicators
for midgut carcinoid tumours.
The
Chromogranin-Secretogranin Family This link is to a review of the article. The full text
requires a subscription
to The New England Journal of Medicine. A 24 hours of full
access account is available. By Laurent Taupenot, Ph.D., Kimberly L. Harper,
M.D., and Daniel T. O'Connor, M.D
N Engl J Med. 2003 Mar 20;348(12):1134-49.
"
The highest levels of serum chromogranin A (up to 1000 times the
upper limit of the normal range) have been found in patients with
metastatic carcinoid tumors. The stability of serum chromogranin
A speaks favorably for its use in detecting carcinoid tumors and
monitoring their progression; alternative diagnostic tests for
carcinoid tumors include tests of urinary 5-hydroxyindoleacetic
acid, serum serotonin (5-hydroxytryptamine), and serum neuron-specific
enolase. In multiple endocrine neoplasia type I, there is a clear
correlation between the tumor mass and the circulating level of
chromogranin A. In patients with midgut carcinoid tumors, an elevated
chromogranin A level is an independent predictor of death."
Clinical Significance
of Blood Chromogranin A Measurement in Neuroendocrine Tumours (Full
text PDF)
By E. Seregni, L. Ferrari, E. Bajetta, A Martinetti, E. Bombarderi
Annals of Oncology 12 ( Suppl. 2: S69-S72, 2001)
Conclusions: CgA was confirmed to be the best tumour marker currently
available for identifying patients suffering from NETs of the GEP
system, lung carcinoids and neuroblastomas. CgA is recommended
in the follow-up of patients with such tumours
Neuroendocrine
Tumour Markers This link is to the PubMed abstract. From the abstract,
there are direct lines to the full text article on the Science
Direct website (requires subscription payment.) By Lamberts SW, Hofland LJ, Nobels FR.
Frontiers in Neuroendocrinology. 2001 Oct;22 (4):309-39. Review.
"Markers, such as chromogranin A, neuron-specific enolase,
and alpha-subunit, as well as peptide receptor visualization, are
of increasing importance in the diagnosis and follow-up of neuroendocrine
and non-neuroendocrine tumors"
Additional references on
Chromogranin A
"At the moment, chromogranin A is considered the best general
neuroendocrine marker available for both diagnostic, therapeutic
and prognostic evaluation."
Gastroenteropancreatic (GEP) endocrine tumors (ETs) are neoplasms
showing different hormonal profiles and different clinical and
prognostic features, which depend consistently on the site of origin.
Histological features and general endocrine markers do not differentiate
tumors in relation to their location, making it difficult to establish
the site of origin of a GEP ET that has metastasized to the liver
or lymph nodes. A site-specific marker would be particularly useful
in the examination of small specimens where there is not sufficient
material for an extensive study of the hormonal expression. CDX2
is a transcription factor that has been recently proposed as a
marker of intestinal adenocarcinomas. Our aim was to evaluate the
immunohistochemical expression of CDX2 in normal tissues and in
184 formalin-fixed and paraffin-embedded ETs to verify whether
it could be used to identify intestinal ETs with a high degree
of sensitivity and specificity. Of these cases, 154 were primary
tumors (99 GEP and 55 non-GEP tumors), 101 were well-differentiated
endocrine tumors, and 53 were poorly differentiated endocrine carcinomas
(PDECs). Of the cases, 30 were metastases from differently located
ETs. Nuclear CDX2 immunoreactivity was found in all EC-cells (serotonin-producing
cells), in about 10% of G-cells (gastrin-producing cells), in about
30% of GIP-cells (gastric inhibitory peptide cells) and in a few
motilin-positive cells of the normal intestinal mucosa, while other
gastrointestinal endocrine cell types were CDX2 negative. All midgut
EC-cell tumors, their metastases, and two of three pancreatic EC-cell
ETs were diffusely and intensely CDX2 positive. The other GEP ETs,
their metastases, as well as the non-GEP ETs, were all CDX2 negative,
with the exception of four PDECs, five gastrinomas and one pheochromocytoma,
which were only focally positive. We conclude that CDX2 may be
considered a sensitive and specific marker of midgut EC-cells and
EC-cell tumors, and its expression may be useful in the diagnosis
of metastases from occult ETs.
