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Abramson Cancer CenterNCI CANCERLIT® Search: Thyroid Cancer - October 2001
National Cancer Institute®
Last Modified: November 21, 2001
Table of Contents
1
UI - 20389342
AU - Kraimps JL; Bouin-Pineau MH; Mathonnet M; De Calan L; Ronceray J; Visset
TI -
J; Marechaud R; Barbier J
Multicentre study of thyroid nodules in patients with Graves' disease.
SO - Br J Surg 2000 Aug;87(8):1111-3
AD - Departments of Endocrine Surgery, Jean Bernard Hospital, Poitiers,
France.
BACKGROUND: The association of Graves' disease with thyroid nodules and
thyroid carcinoma is rarely reported. The incidence seems to be
increasing according to recent literature. The aim of this multicentre
study was to review patients who had surgery for Graves' disease
associated with thyroid nodules, and to evaluate the risk of thyroid
carcinoma. METHODS: A retrospective study was made of 557 consecutive
patients who underwent operation for Graves' disease between 1991 and
1997 in five endocrine surgery departments. Each patient underwent
clinical, biochemical, ultrasonographic and scintigraphic evaluation.
None of the patients had had previous radioactive iodine therapy or
external irradiation. Surgery consisted of either a subtotal or total
thyroidectomy. RESULTS: Nodules were observed before operation in 140
patients (25.1 per cent). Thyroid carcinoma was diagnosed in 21 patients
(15.0 per cent), always inside a nodule. The incidence of thyroid
carcinoma associated with Graves' disease was 3.8 per cent (21 of 557
patients): 20 papillary and one follicular carcinoma. The carcinoma was
multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A
nodule was palpable in four patients. CONCLUSION: This multicentre study
of patients having thyroidectomy for Graves' disease showed that 3.8 per
cent had a carcinoma; the rate of carcinoma in cold nodules was 15.0 per
cent. Surgery should be advised in any patient with Graves' disease and
a thyroid nodule; the operation should be total thyroidectomy.
2
UI - 21095496
AU - Mishra A; Mishra SK
TI -
Multicentre study of thyroid nodules in patients with Graves' disease
(Br J Surg 2000; 87: 1111-13).
SO - Br J Surg 2001 Feb;88(2):313
3
UI - 21256508
AU - Goto A; Sakamoto A; Machinami R
TI -
An immunohistochemical analysis of cyclin D1, p53, and p21waf1/cip1
proteins in tumors originating from the follicular epithelium of the
thyroid gland.
SO - Pathol Res Pract 2001;197(4):217-22
AD - Department of Pathology, Kyorin University School of Medicine, Mitaka,
Tokyo, Japan.
This study aimed at clarifying the factors closely related to the tumor
progression of thyroid neoplasms. We examined the immunoreactivity of
cyclin D1, p53, and p21waf1/cip1 proteins in 179 thyroid tumors
originating from the follicular epithelium using an immunohistochemical
technique. Cyclin D1 positivity was frequent in well-differentiated
thyroid carcinomas (39/122 cases), but it was rarely seen in follicular
adenomas (1/33 cases), (p < 0.05). Positivity for p53 was more frequent
in poorly differentiated carcinomas (7/19 cases) and undifferentiated
carcinomas (4/5 cases) than in well-differentiated carcinomas (14/122
cases) (p < 0,05, respectively). P21waf1/cip1 positivity was more
frequent in well-differentiated thyroid carcinomas (43/122 cases) than
in follicular adenomas (4/33 cases) (p < 0.05). Regarding the
relationships of these proteins, co-positivity for cyclin D1 and p53 was
observed more often in poorly differentiated carcinomas (5/7 cases) than
in well-differentiated carcinomas (7/39 cases) (p < 0.05). Most cases
with cyclin D1 positivity did not show p21waf1/cip1 expression in poorly
differentiated carcinomas (6/7 cases). Three cases examined showed
co-positivity of p53 and p21waf1/cip1. Our results suggest that cyclin
D1 is invoved in thyroid oncogenesis. Moreover, p53 might be closely
related to the development of poorly differentiated carcinomas and
undifferentiated carcinomas originating from well-differentiated
carcinomas.
4
UI - 21340681
AU - Pollinger B; Duhmke E
TI -
External radiotherapy of thyroid cancer.
SO - Onkologie 2001 Apr;24(2):134-8
AD - Klinik und Poliklinik fur Strahlentherapie und Radioonkologie der
Ludwigs-Maximilians-Universitat Munchen.
Differentiated thyroid cancer comprises papillary, mixed
papillary-follicular and follicular adenocarcinomas. They are mostly
hormone-sensitive and respond to thyroid-stimulating hormone (TSH)
suppression. The standard treatment is total thyroidectomy, (131)I
therapy and thyroid hormone suppression therapy. Adjuvant external
radiotherapy is discussed controversially. Most authors recommend
adjuvant external radiotherapy for extra-capsular tumor extension.
Decision on an individual basis should be made for patients with lymph
node involvement. In the case of incomplete surgical resection, external
radiotherapy should be applied if second surgery is not possible. For
medullary thyroid cancer, external beam radiotherapy seems to be
beneficial for patients with surgically inaccessible disease, with
microscopic residual or gross tumor after surgery, with recurrent
locoregional disease, or with surgically unmanageable metastases.
Patients suffering from anaplastic thyroid cancer should receive
combined treatment consisting of extensive surgery, external irradiation
with total doses up to 60 Gy, and chemotherapy. The combined treatment
modality leads to higher local control rates and prolongs survival.
Copyright 2001 S. Karger GmbH, Freiburg
5
UI - 21415194
AU - Kacker A; Komisar A
TI -
Unilateral versus bilateral neck exploration in parathyroid surgery: an
assessment of 55 cases.
SO - Ear Nose Throat J 2001 Aug;80(8):530-2, 534
AD - Department of Otolaryngology-Head and Neck Surgery, Lenox Hill Hospital,
100 E. 77th St., New York, NY 10021, USA.
We retrospectively evaluated the cases of 55 patients who had undergone
surgery for primary hyperparathyroidism at our institution to determine
whether their parathyroid glands were abnormal on both sides. Thirty-six
of these patients had undergone a bilateral neck exploration, and 19 had
had a unilateral investigation. Of the 36 bilaterally explored patients,
30 had a solitary adenoma and no parathyroid pathology on the opposite
side, five patients had hyperplastic glands with more than one gland
involved, and one patient had two adenomas. In the unilaterally explored
group, all 19 patients had a solitary adenoma. There were no failures in
the way of persistent hypercalcemia in either group. Based on our
findings, we conclude that a unilateral neck exploration should be
performed during surgery for primary hyperparathyroidism whenever a
large parathyroid adenoma and a normal parathyroid gland are found on
the same side. Bilateral exploration should be reserved for patients in
whom pathology cannot be found on the initially explored side during
surgery and for patients who have obvious parathyroid hyperplasia.
6
UI - 21415702
AU - Klein I; Esik O; Homolya V; Szeri F; Varadi A
TI -
Molecular genetic diagnostic program of multiple endocrine neoplasia
type 2A and familial medullary thyroid carcinoma syndromes in Hungary.
SO - J Endocrinol 2001 Sep;170(3):661-6
AD - Institute of Enzymology of the Hungarian Academy of Sciences, Budapest,
Hungary. klein@enzim.hu
Medullary thyroid carcinoma (MTC) occurs usually in sporadic form, but
about a quarter of the cases are hereditary and appear as part of one of
the multiple endocrine neoplasia type 2 (MEN2) syndromes. Mutations in
the RET protooncogene are known to be the cause of the MEN2A and
familial medullary thyroid carcinoma (FMTC) syndromes in the majority of
the families. Direct DNA testing allows prophylactic thyroidectomy to be
offered to individuals carrying a mutation in the above codons, and in
mutation-negative cases it reduces the yearly screening-related burden
on family members at risk of the disease. By DNA sequencing and
PCR-restriction fragment length polymorphisms, 65 MTC probands were
examined for mutations in residues 609, 611, 618, 620 of exon 10, and in
residues 634, 768, 804 of exons 11, 13, and 14 respectively of the RET
protooncogene. In our study, mutations in the above codons were detected
in all of the 14 clinically MEN2A and FMTC families. One of these
mutations, TGC609 TCC has not been reported previously. Of the 14
probands with the mutation, 25 relatives also had the identified
mutation and 18 relatives proved to be non-carriers. Among the 51
probands with clinically sporadic MTC, none was found to carry a
mutation in the above positions even if indirect signs of MTC,
pheochromocytoma or hyperparathyroidism could be detected in some
families. The frequency of the TGC634AGC mutation is unexpectedly high
in our samples, which can probably be attributed to a founder effect. We
conclude that screening for mutations in these codons is effective in
families fulfilling the strict clinical criteria of MEN2A or FMTC.
7
UI - 21449447
AU - Zdon MJ; Fredland AJ; Zaret PH
TI -
Follicular neoplasms of the thyroid: predictors of malignancy?
SO - Am Surg 2001 Sep;67(9):880-4
AD - Department of Surgery, Finch University of Health Sciences/The Chicago
Medical School at Mount Sinai Hospital Medical Center, Illinois 60064,
USA.
Follicular neoplasms of the thyroid present a therapeutic challenge.
Initial limited thyroidectomy may result in some patients requiring
completion thyroidectomy for malignancy. In the current study we
examined age, gender, race, time from nodule discovery to operation in
months, history of radiation exposure, tumor size (cm), and cell type in
patients with follicular neoplasms identified at the time of
thyroidectomy in two socioeconomically diverse settings from 1993
through 2000 to identify possible factors associated with a greater
chance of malignancy. Of 36 follicular lesions identified in 35 patients
seven (19%) were malignant on permanent section. Hurthle cell histology
was present in six of 36 lesions. Mean age of patients with benign
lesions was 47 +/- 13 versus 50 +/- 15 in malignant cases (P > 0.05).
Benign lesions measured 2.6 +/- 1.2 cm versus 3.1 +/- 1.7 cm in
malignant (P > 0.05). Other factors found not to be significant included
gender and time nodule was present (12.8 +/- 19 months benign vs 11.8
+/- 20 months malignant) (P > 0.05). Hurthle cell histology was
associated with a 50 per cent malignancy rate (three of six) versus 13
per cent (four of 30) with non-Hurthle cell histology (P < 0.05). Two
patients with exposure to radiation fallout had malignancies in lesions
of one and 2 cm (P < 0.05). Patients from a socioeconomically
disadvantaged setting had a malignancy rate of 50 per cent (six of 12)
compared with a malignancy rate of 3 per cent (one of 24) from a
socioeconomically affluent population (P < 0.05). In conclusion Hurthle
cell histology and exposure to radiation fallout were associated with
significantly higher rates of malignancy in follicular neoplasms and
should be taken into account when deciding on the initial extent of
thyroidectomy. The difference in malignancy rates observed between
socioeconomic settings while significant requires further investigation.
8
UI - 21452375
AU - Arda IS; Yildirim S; Demirhan B; Firat S
TI -
Fine needle aspiration biopsy of thyroid nodules.
SO - Arch Dis Child 2001 Oct;85(4):313-7
AD - Baskent University Faculty of Medicine, Department of Pediatric Surgery,
Fevzi Cakmak caddesi 10. sokak No: 45, 06490 Bahcelievler Ankara,
Turkey.
BACKGROUND: Fine needle aspiration biopsy (FNA) is a routine diagnostic
technique for evaluating thyroid nodules. Many reports in adults
consider that FNA is superior to thyroid ultrasonography (USG) and
radionuclide scanning (RS). Only five studies have been published on FNA
of childhood thyroid nodules. AIMS: To investigate the reliability of
FNA in the evaluation and management of thyroid nodules, and compare the
results of FNA, USG, and RS with regard to final histopathological
diagnosis. METHODS: FNA was performed in 46 children with thyroid
nodules after USG and RS examination. We investigated the sensitivity,
specificity, accuracy, and positive and negative predictive values of
USG, RS, and FNA in their management. RESULTS: Six patients who had
malignant or suspicious cells on FNA examination underwent immediate
surgery. The other 40 patients received medical treatment according to
their hormonal status. Fifteen of these nodules either disappeared or
decreased in number and/or size. Surgery was performed in 25 patients
who did not respond to therapy. Statistical analysis revealed
sensitivity, specificity, accuracy, and positive and negative predictive
values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG;
30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for
FNAB. CONCLUSION: FNAB is as reliable in children as in adults for
definitive diagnosis of thyroid nodules. Using this technique avoids
unnecessary thyroid surgery in children.
9
UI - 21268064
AU - Zabel M; Gebarowska E; Drag-Zalesinska M; Wysocka T; Flig K
TI -
Effect of octreotide on proliferation of in vitro cultured thyroid
medullary carcinoma cells.
SO - Folia Histochem Cytobiol 2001;39(2):185-6
AD - Department of Histology and Embryology, University of Medical Sciences,
Wroclaw, Poland. mazab@am.wroc.pl
In TT cells, originating from medullary carcinoma of the human thyroid,
the presence of receptors for somatostatin was demonstrated at the
ultrastructural level. Inhibitory effect of octreotide (a somatostatin
analogue) was observed on proliferation of in vitro cultured TT cells
and confirmed by evaluating levels of PCNA and Ki-67
proliferation-associated antigens and examining the extent of DNA damage
using the comet assay. Our studies indicate a potential for application
of somatostatin analogues to diagnosis and adjunct treatment in thyroid
medullary carcinomas.
10
UI - 21268065
AU - Dadan J; Wolczynski S; Sawicki B; Chyczewski L; Azzadin A; Dzieciol J;
TI -
Puchalski Z
Preliminary evaluation of influence of gemcitabine (Gemzar) on
proliferation and neuroendocrine activity of human TT cell line:
immunocytochemical investigations.
SO - Folia Histochem Cytobiol 2001;39(2):187-8
AD - 1st Department of General Surgery, Medical Academy, Bialystok, Poland.
klchirog@amb.ac.bialystok.pl
The choice treatment of medullary thyroid carcinoma (MTC) is total
thyroidectomy. It is difficult to evaluate effectiveness of chemotherapy
due to the rare incidence of MTC. Gemcitabine is a new drug of
antimetabolite nucleoside group used in treatment of cancers since 1996.
The aim of this study was to evaluate the influence of gemcitabine on
proliferation and neuroendocrine activity of human TT cell line derived
from MTC. The cells were exposed to gemcitabine in the concentration of
10, 25 and 50 microg/ml for 24 hours. Immunocytochemical examinations
were carried out by the method of avidin-biotin peroxidase complex (ABC)
according to Hsu et al. to detect calcitonin, chromogranin A,
synaptophysin and neuron-specific enolase in TT cells. A
concentration-dependent inhibitory influence of gemcitabine on
proliferative activity of TT cells was observed. It was also shown that
the immunostaining was reduced, especially in case of neuron-specific
enolase. Only the reaction detecting calcitonin was enhanced in
persistin
11
UI - 21300311
AU - Tancredi M; Foppiani L; Giordano GD; Ansaldo GL; Torre GC; Ceppa P;
TI -
Giusti M
Magnetic resonance imaging: a complementary tool in the evaluation of
thyroid nodules?
SO - J Endocrinol Invest 2001 May;24(5):384-5
12
UI - 21366972
AU - Komisarenko IV; Rybakov SI; Bahirov MM; Bondarenko IuH; Sheptukha AI
TI -
[Urgent interventions for invasive thyroidal carcinoma]
SO - Klin Khir 2000 Sep;(9):40-2
There was summarized the experience of treatment of the thyroid gland
cancer, invading trachea (larynx) and other neighboring structures of
the neck in 42 patients, whose state was estimated as severe one and
neoplastic process--as nonoperable. Optimal surgical methods were
applied depending on clinical signs of thyroidal carcinoma. In 36
patients the palliative resection of thyroid gland (in 6--with
tracheostomy addition) was done, in 6--intervention was restricted by
tracheostomy formation. The method of tracheostomy formation in cases of
massive spreading of tumor along trachea is adduced.
13
UI - 21332880
AU - Nutting CM; Convery DJ; Cosgrove VP; Rowbottom C; Vini L; Harmer C;
TI -
Dearnaley DP; Webb S
Improvements in target coverage and reduced spinal cord irradiation
using intensity-modulated radiotherapy (IMRT) in patients with carcinoma
of the thyroid gland.
SO - Radiother Oncol 2001 Aug;60(2):173-80
AD - Academic Department of Radiotherapy, Institute of Cancer Research,
Surrey, SM2 5PT, Sutton, UK.
BACKGROUND AND PURPOSE: External beam radiotherapy for thyroid carcinoma
poses a significant technical challenge as the target volume lies close
to or surrounds the spinal cord. The potential of intensity-modulated
radiotherapy (IMRT) to improve the dose distributions was investigated.
MATERIALS AND METHODS: A planning study was performed on patients with
thyroid carcinoma. Plans were generated to irradiate the thyroid bed
alone or to treat the thyroid bed and the loco-regional lymph nodes in
two phases. Conventional plans with minimal beam shaping were compared
to three-dimensional conformal radiotherapy (3DCRT) and inverse-planned
IMRT plans to assess target coverage and normal tissue sparing. IMRT
techniques were optimized to find the minimum number of equispaced beams
required to achieve the clinical benefit and a concomitant boost
technique was explored. RESULTS: For the thyroid bed alone and the
thyroid bed plus loco-regional lymph nodes, conventional and conformal
techniques produced low minimum doses to the planning target volume
(PTV) if spinal cord tolerance was respected. 3DCRT reduced the
irradiated volume of normal tissue (P=0.01). IMRT plans achieved the
goal dose to the PTV (P<0.01) and also reduced the spinal cord maximum
dose (P<0.01). IMRT, using a concomitant boost technique, produced
better target coverage than a two-phase technique. For both the
two-phase and concomitant boost techniques, IMRT plans with seven and
five equispaced fields produced similar dose distributions to nine
fields, but three fields were significantly worse. CONCLUSIONS: 3DCRT
reduced normal tissue irradiation compared to conventional techniques,
but did not improve PTV or spinal cord doses. IMRT improved the PTV
coverage and reduced the spinal cord dose. A simultaneous integrated
boost technique with five equispaced fields produced the best dose
distribution. IMRT should reduce the risk of myelopathy or may allow
dose escalation in patients with thyroid cancer.
14
UI - 21344931
AU - Arslan N; Ilgan S; Yuksel D; Serdengecti M; Bulakbasi N; Ugur O; Ozguven
TI -
MA
Comparison of In-111 octreotide and Tc-99m (V) DMSA scintigraphy in the
detection of medullary thyroid tumor foci in patients with elevated
levels of tumor markers after surgery.
SO - Clin Nucl Med 2001 Aug;26(8):683-8
AD - Department of Nuclear Medicine, Gulhane Military Medical Academy and
Medical Faculty, Ankara, Turkey. nuria@gata.edu.tr
PURPOSE: In this retrospective study, the authors evaluated the utility
of In-111 octreotide (OctreoScan) and Tc-99m (V) DMSA scintigraphy for
the localization of recurrent metastatic tumor foci in patients with
medullary thyroid cancer (MTC) and compared the findings with those of
conventional radiologic imaging methods. METHODS: The scintigraphic
images were compared with computed tomography (CT) and magnetic
resonance imaging (MRI) and ultrasonography (US) in 14 patients (8 men,
6 women; age range, 22 to 74 years) with elevated calcitonin and
carcinoembryonic antigen levels after total thyroidectomy. All
scintigraphic image findings were evaluated qualitatively as mild uptake
(+) and moderate to marked uptake (++). RESULTS: In-111 octreotide may
be superior to Tc-99m (V) DMSA for the detection of tumor foci of
patients with MTC on a patient basis (78.5% versus 57.1%) and on a
lesion basis (44.1% versus 30.2%). The sensitivity rate for In-111
octreotide (78.5%) was also similar to that of CT and MRI on a patient
basis. Conversely, the combined use of Tc-99m (V) DMSA and In-111
octreotide revealed the best sensitivity rate (85.7%) on a patient
basis, whereas the combined use of CT and MRI showed the best
sensitivity rate (81.3%) on a lesion basis. CONCLUSIONS: These findings
suggest that In-111 octreotide is superior to Tc-99m (V) DMSA and has a
similar sensitivity rate to CT and MRI for the diagnosis of recurrent or
metastatic MTC. Although the combined use of In-111 octreotide and
Tc-99m (V) DMSA was most sensitive, the combined use of CT and MRI with
radionuclide imaging methods may better detect more metastatic tumor
foci.
15
UI - 21366175
AU - Bal CS; Padhy AK; Kumar A
TI -
Clinical features of differentiated thyroid carcinoma in children and
adolescents from a sub-Himalayan iodine-deficient endemic zone.
SO - Nucl Med Commun 2001 Aug;22(8):881-7
AD - Department of Nuclear Medicine, All India Institute of Medical Sciences,
New Delhi, 110029, India. csbal@hotmail.com
Northern India is an identified sub-Himalayan iodine-deficient endemic
zone. We retrospectively analysed the case files of children with
differentiated thyroid carcinoma from this endemic zone and attempted to
define the disease in terms of its presentation, clinical course and
patients with thyroid cancer were treated in our centre and 80 (7%) were
less than 20 years of age. There were 45 females and 35 males.
Histologically, 85% of patients had papillary carcinoma and the rest
follicular carcinoma. Cervical lymph node involvement was seen in 66% of
patients, and distant metastasis, mainly pulmonary, in 29%. In children
less than 10 years of age, 75% of patients had distant metastasis at the
time of presentation. The post-surgery 48 h radioiodine neck uptake was
12.2+/-9.6%. Ninety-six per cent of the residual thyroid, 90% of nodal
metastases and 57% of pulmonary metastases were ablated. Although nine
patients had nodal recurrence between surgery and radioiodine treatment,
no recurrence was observed thereafter, and three disease-related deaths
(all in children less than 10 years of age) were seen in the mean
follow-up of 6 years. We conclude that, except for the relatively higher
incidence of follicular thyroid cancer and the higher mortality in the
less than 10 year age group, the course and outcome of differentiated
thyroid carcinoma in children from iodine-deficient areas is no
different from that in children in iodine-sufficient areas.
16
UI - 21369699
AU - Kjellman P; Lagercrantz S; Hoog A; Wallin G; Larsson C; Zedenius J
TI -
Gain of 1q and loss of 9q21.3-q32 are associated with a less favorable
prognosis in papillary thyroid carcinoma.
SO - Genes Chromosomes Cancer 2001 Sep;32(1):43-9
AD - Department of Molecular Medicine, Endocrine Tumour Unit, Karolinska
Hospital, Stockholm, Sweden. petra.kjellman@ks.se
In order to approach the genetic mechanisms behind initiation and
progression of papillary thyroid carcinoma (PTC) tumorigenesis, we
characterized numerical chromosomal imbalances in a panel of 25 PTCs
with varying histopathological and clinical features using comparative
genomic hybridization (CGH). The most frequently detected imbalance was
gain of 9q33-qter, which was seen in close to 30% of the cases. The
commonly occurring regions of loss were assigned to 22q (12%) and
9q21.3-q32 (12%), while gains preferentially involved the entire X
chromosome (20%), 1q (16%), 17q (16%), and 22q (12%). The distribution
of CGH alterations supports the idea of a progression of genetic events
in the development of PTC, where gain of 9q33-qter would represent a
relatively early event that is followed by loss of 22q and gain of X,
1q, 17q, and 22q. When the detected CGH alterations were compared with
the clinical outcome and the histopathological features of the 25 PTC
cases, several statistically significant correlations were revealed. The
total number of genetic alterations was higher in tumors from patients
with aggressive disease as compared to those without signs of
aggressiveness. Gain of 1q and loss of 9q21.3-q32 were exclusively seen
in tumors from patients with aggressive disease, and the presence of
distant metastases was associated with gain of 1q. A sex-dependent
distribution was also evident for one of the common alterations, with
gain of X exclusively seen in male cases. Taken together, the findings
identify several candidate locations for tumor suppressor genes and
oncogenes that are potentially involved in the establishment and
progression of papillary thyroid carcinogenesis. Copyright 2001
Wiley-Liss, Inc.
17
UI - 21423319
AU - Krohn K; Reske A; Ackermann F; Muller A; Paschke R
TI -
Ras mutations are rare in solitary cold and toxic thyroid nodules.
SO - Clin Endocrinol (Oxf) 2001 Aug;55(2):241-8
AD - III Medical Department, University of Leipzig, Leipzig, Germany.
OBJECTIVE: Activation of ras proto-oncogenes as a result of point
mutations is detectable in a significant percentage of most types of
tumour. Similar to neoplasms of other organs, mutations of all three ras
genes can be found in thyroid tumours. H-, K- and N-ras mutations have
been detected in up to 20% of follicular adenomas and adenomatous
nodules which were not functionally characterized. This raises the
question as to whether ras mutations are specific for hypofunctional
nodules and TSH receptor mutations for hyperfunctioning nodules. DESIGN:
To investigate ras and TSH receptor mutations with respect to functional
differentiation we studied 41 scintigraphically cold nodules and 47
toxic thyroid nodules. To address the likelihood of a somatic mutation
we also studied the clonal origin of these tumours. MEASUREMENTS:
Genomic DNA was extracted from nodular and surrounding tissue.
Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR
amplified and sequenced using big dye terminator chemistry. Denaturing
gradient gel electrophoresis (DGGE) was used to verify sequencing
results for the H-ras gene and to analyse the N-ras gene because its
greater sensitivity in detecting somatic mutations. Clonality of nodular
thyroid tissue was evaluated using X-Chromosome inactivation based on
PCR amplification of the human androgen receptor locus. RESULTS:
Monoclonal origin was detectable in 14 of 23 informative samples from
cold thyroid nodules. In toxic thyroid nodules the frequency of clonal
tissue was 20 in 30 informative cases. Only one point mutation could be
found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous
nodule which was monoclonal. In toxic thyroid nodules no ras mutation
was detectable. CONCLUSION: Our study suggests that ras mutations are
rare in solitary cold and toxic thyroid nodules and that the frequent
monoclonal origin of these tumours implies somatic mutations in genes
other than H-, K- and N-ras.
18
UI - 21434012
AU - Braga M; Cavalcanti TC; Collaco LM; Graf H
TI -
Efficacy of ultrasound-guided fine-needle aspiration biopsy in the
diagnosis of complex thyroid nodules.
SO - J Clin Endocrinol Metab 2001 Sep;86(9):4089-91
AD - Servico de Endocrinologia e Metabologia do Parana do Hospital de
Clinicas, Universidade Federal do Parana, Curitiba 80.060-240, Brazil.
bragamd@aol.com
Cystic thyroid nodules are considered to be one of the major causes of
nondiagnostic and false-negative results on conventional fine-needle
aspiration biopsy, thus limiting the potential of this method for the
evaluation of complex (solid-cystic) thyroid nodules. Although
ultrasound-guided fine-needle aspiration biopsy has emerged as a highly
effective diagnostic method for the assessment of nonpalpable and
difficult to palpate nodules, its role in complex nodules has not yet
been carefully evaluated. In this study, we report the efficacy of
ultrasound-guided fine-needle aspiration biopsy in 124 complex nodules
in 113 patients. This method proved to be highly effective, yielding a
satisfactory specimen for cytological evaluation in 94% of the nodules,
suggesting that it is an excellent modality for the evaluation of
complex nodules and also for the reevaluation of those nodules with a
nondiagnostic result on conventional fine-needle aspiration biopsy.
19
UI - 21434013
AU - Pacini F; Agate L; Elisei R; Capezzone M; Ceccarelli C; Lippi F;
TI -
Molinaro E; Pinchera A
Outcome of differentiated thyroid cancer with detectable serum Tg and
negative diagnostic (131)I whole body scan: comparison of patients
treated with high (131)I activities versus untreated patients.
SO - J Clin Endocrinol Metab 2001 Sep;86(9):4092-7
AD - Department of Endocrinology and Metabolism, Section of Endocrinology,
University of Pisa, 56124 Pisa, Italy.
Detectable serum Tg levels associated with negative diagnostic (131)I
whole body scan are not infrequently found in patients with
differentiated thyroid cancer. Several researchers have shown that in
these patients the administration of high (131)I activity (100 mCi or
more) increases the sensitivity of a posttherapy diagnostic (131)I whole
body scan performed a few days later and allows the detection of
neoplastic foci not seen with diagnostic doses of (131)I. Empirical
radioiodine treatment has also been advocated by some researchers, but
its therapeutic effect is controversial. In our institute, positive
serum Tg/negative diagnostic (131)I whole body scan patients were not
treated with high (131)I activities before 1984; afterward, almost all
patients with positive serum Tg/negative diagnostic (131)I whole body
scan patients were treated with radioiodine, and a posttherapy
diagnostic (131)I whole body scan was performed. In the present
retrospective study we compared the outcome of these two groups of
patients, 42 treated and 28 untreated, followed for mean periods of 6.7
+/- 3.8 and 11.9 +/- 4.4 yr, respectively. In the treated group the
first posttherapy diagnostic (131)I whole body scan was negative in 12
patients and positive in 30 patients. (131)I treatment was further
administered only in the latter group. At the end of follow-up in
treated patients a complete remission (normalization of serum Tg off
L-thyroxine and negative diagnostic (131)I whole body scan) was observed
in 10 patients (33.3%). In 9 cases (30%) posttherapy diagnostic (131)I
whole body scan became negative, and serum Tg was reduced but still
detectable; in 11 patients (36.6%) serum Tg was detectable, and
posttherapy diagnostic (131)I whole body scan was positive. The
resolution of (131)I uptake in lung metastases was observed in 8 of 9
cases (88.8%) and in cervical node metastases in 11 of 18 cases (61.1%).
In patients treated only once because the posttherapy diagnostic (131)I
whole body scan was negative (n = 12), 2 patients (16.7%) were in
apparent remission, 7 (58.3%) had detectable Tg values without evidence
of disease, 2 (16.7%) showed lymph node metastases in the mediastinum,
and 1 patient (8.3%) died because of lung metastases. Of the 28
untreated patients, none with radiological evidence of disease, serum Tg
off L-thyroxine therapy became undetectable in 19 cases (67.9%),
significantly reduced in 6 cases (21.4%), and unchanged or increased in
3 patients (10.7%), 1 of whom developed lung metastases 14 yr after the
diagnosis. In summary, our results indicate that in patients with
detectable serum Tg and negative diagnostic (131)I whole body scan,
treatment with high doses of (131)I may have therapeutic utility in
patients with lung metastases and, to a lesser extent, in those with
lymph node metastases. However, in view of the frequent normalization of
Tg values in untreated patients, we believe that treatment with (131)I
should be considered according to the result of the first posttherapy
scan. If positive in the lung, (131)I treatment should be continued up
to total remission; surgical treatment should be preferred in patients
with node metastases, and no treatment should be used in those with
thyroid bed uptake or no uptake.
20
UI - 21434042
AU - Kitamura Y; Shimizu K; Ito K; Tanaka S; Emi M
TI -
Allelotyping of follicular thyroid carcinoma: frequent allelic losses in
chromosome arms 7q, 11p, and 22q.
SO - J Clin Endocrinol Metab 2001 Sep;86(9):4268-72
AD - Department of Molecular Biology, Institute of Gerontology, Nippon
Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
The genetic mechanisms involved in development of follicular thyroid
carcinoma are poorly understood, although allelic losses (LOH) in this
type of tumor have been reported in small panels of follicular thyroid
carcinomas examined in earlier studies. To clarify the real frequency of
allelic loss we carried out a genome-wide allelotyping study of 66
follicular thyroid carcinomas using 39 microsatellite markers
representing all nonacrocentric autosomal arms. The mean frequency of
LOH was 9.2%, and the mean fractional allelic loss was 0.09. The most
frequent allelic losses were detected in 7q (28%), 11p (28%), and 22q
(41%). When we compared these results with our previous allelotyping
studies using identical markers in other types of thyroid cancers, the
9.2% mean frequency of allelic loss detected in follicular thyroid
carcinomas was higher than that in papillary thyroid carcinomas (3%),
but not as high as that detected in anaplastic thyroid carcinomas (20%).
Frequent allelic losses of markers on chromosomes 7q, 11p, and 22q
suggest locations to examine for the presence of suppressor genes
associated with the development of follicular thyroid carcinoma.
21
UI - 21439902
AU - Li WB; Friedland W; Pomplun E; Jacob P; Paretzke HG; Lassmann M; Reiners
TI -
C
Track structures and dose distributions from decays of (131)I and (125)I
in and around water spheres simulating micrometastases of differentiated
thyroid cancer.
SO - Radiat Res 2001 Oct;156(4):419-29
AD - GSF-National Research Center for Environment and Health, Institute of
Radiation Protection, 85764 Neuherberg, Germany. wli@gsf.de
The disintegration of the radionuclides (131)I and (125)I and the
subsequent charged-particle tracks left behind in water (as a model
substance for a biological cell) are simulated by the Monte Carlo track
structure simulation code PARTRAC, using new inelastic electron
scattering cross sections for condensed water. Every photon and electron
emitted was followed in detail, event by event, down to 10 eV. From the
spatial information on the track structures, absorbed dose distributions
per (131)I and (125)I decay were calculated in and around water spheres
simulating micrometastases as well as in the tissue surrounding such
metastases. These radionuclides were assumed to be distributed uniformly
inside spheres of different diameters (0.01, 0.03, 0.1, 0.3, 1.0 and 3.0
mm). The respective electron degradation spectra, the nearest-neighbor
distance distributions between inelastic events, and the distance
distributions for all activations for both iodine radionuclides were
calculated. The absorbed fractions of the initial electron energies,
absorbed doses and energy depositions, and single-event distributions,
F(1)(epsilon), inside the six water spheres described above and in the
surrounding tissue were also calculated. The absorbed doses per decay
inside the six water spheres, i.e., the calculated S values (listed from
0.01 to 3.0 mm), were 6.8 x 10(-4), 7.2 x 10(-5), 5.5 x 10(-6), 4.9 x
10(-7), 3.1 x 10(-8) and 1.8 x 10(-9) Gy Bq(-1) s(-1) for (131)I, and
3.4 x 10(-3), 1.7 x 10(-4), 5.1 x 10(-6), 2.0 x 10(-7), 5.6 x 10(-9) and
2.2 x 10(-10) Gy Bq(-1) s(-1) for (125)I. It is concluded that, in the
treatment of thyroid cancer, the geometrical track structure properties
of (125)I might be superior to those of (131)I in micrometastases with
diameters less than 0.1 mm; however, in this medical context, many other
factors also have to be considered.
22
UI - 21455496
AU - Lohrer HD; Braselmann H; Richter HE; Jackl G; Herbeck J; Hieber L;
TI -
Kellerer AM; Bauchinger M
Instability of microsatellites in radiation-associated thyroid tumours
with short latency periods.
SO - Int J Radiat Biol 2001 Aug;77(8):891-9
AD - Radiobiological Institute, University of Munich (LMU), Schillerstrasse
42, D-80336 Munich, Germany. lohrer@gsf.de
PURPOSE: To determine the instability of microsatellite sequences in
post-Chernobyl thyroid tumours from children and young adults, and to
ascertain whether they correlated with the age of the patient at the
time of the accident and the tumour latency period. MATERIALS AND
METHODS: The stability of 26 microsatellite markers was investigated in
122 radiation-associated thyroid tumours (96 children, 26 adults) from
Belarus and 39 spontaneous thyroid tumours (adults) from Munich without
radiation history. RESULTS: A significant correlation between patient
age at the time of the accident and the instability of microsatellite
sequences was established. Also, a high instability of microsatellite
sequences was found in 28 early thyroid tumours from Belarus with
latency periods of 6-8 years, in contrast to a low instability of
microsatellites in 94 tumours emerging 9-11 years after the accident.
Microsatellite instability in the reference group from Munich proved
similar to the early thyroid tumours from Belarus. CONCLUSION: Early,
fast-growing and aggressive post-Chernobyl thyroid tumours are
characterized by an increase in microsatellite instability.
23
UI - 20370593
AU - Cholewinski SP; Yoo KS; Klieger PS; O'Mara RE
TI -
Absence of thyroid stunning after diagnostic whole-body scanning with
185 MBq 131I.
SO - J Nucl Med 2000 Jul;41(7):1198-202
AD - Department of Radiology, University of Rochester Medical Center, New
York, USA.
There has been recent controversy regarding the optimal protocol for
imaging and ablation of post-thyroidectomy patients. Several authors
have suggested that a scanning dose of 185-370 MBq (5-10 mCi) (131)I may
be capable of producing a stunning effect on thyroid tissue that may
interfere with the uptake and efficacy of the subsequent ablation dose
of radioiodine. The purpose of this study was to determine whether a
185-MBq (5 mCi) diagnostic dose of (131)I produces a visually apparent
stunning effect 72 h before (131)I ablation therapy. METHODS: One
hundred twenty-two consecutive post-thyroidectomy patients for
differentiated thyroid carcinoma received a 185-MBq (5 mCi) diagnostic
dose of (131)I followed by a whole-body diagnostic scan at 72 h. On the
same day the diagnostic scan was completed, the patient was admitted to
the hospital and received an (131)I ablation therapy dose of 5550 MBq
(150 mCi) in most cases. A postablation, whole-body scan was obtained at
72 h and compared with the previous diagnostic scan for any visual
evidence of stunning. RESULTS: No cases of visually apparent thyroid
stunning were observed on any of the postablation scans with regard to
the number of (131)I foci identified or the relative intensity of (131)I
uptake seen. CONCLUSION: Diagnostic whole-body scanning can be performed
effectively with a 185-MBq (5 mCi) dose of (131)I 72 h before
radioiodine ablation without concern for thyroid stunning.
24
UI - 21235398
AU - Sarmiento AJ; Sarmiento FM; Sarmiento AH
TI -
What is the best strategy to treat and study patients after near-total
thyroidectomy?
SO - J Nucl Med 2001 Mar;42(3):531-3
25
UI - 21330628
AU - Kobayashi S
TI -
[Appropriate extent of lymph node dissection in thyroid cancer]
SO - Nippon Geka Gakkai Zasshi 2001 Jun;102(6):459-64
AD - National Higashi-Nagano Hospital, Nagano, Japan.
Surgery is not always necessary for micro cancer (less than 1.0 cm in
diameter). In surgery of micro cancer, we recommended to dissect only
the central compartment (pretracheal [II]/paratracheal [III] area). In
patient with cancer (more than 1.0 cm in diameter), lymph nodes in the
central compartment, ispirateral supraclavicular area, and jugulocarotid
chain (V and VI) should be dissected. Even in incomplete surgery, lymph
node dissection of the central compartment is warranted in patients with
papillary cancer, because recurrence in the central compartment results
in dyspnea and/or hemosptum, lowering the quality of life.
26
UI - 21369212
AU - Desiaterik VI; Mikhno SP
TI -
[Results of operative treatment of the thyroid gland cancer in the
Krivorog region]
SO - Klin Khir 2001 Jan;(1):40-2
Results of treatment of the thyroid gland cancer in 251 patients were
analyzed.
27
UI - 21389189
AU - Jiang S; Altmann A; Grimm D; Kleinschmidt JA; Schilling T; Germann C;
TI -
Haberkorn U
Tissue-specific gene expression in medullary thyroid carcinoma cells
employing calcitonin regulatory elements and AAV vectors.
SO - Cancer Gene Ther 2001 Jul;8(7):469-72
AD - Clinical Cooperation Unit Nuclear Medicine, German Cancer Research
Center, Heidelberg, Germany. s.jiang@dkfz-heidelberg.de
Calcitonin (CT), the major secretory product of the C cell, is also
expressed in C-cell-derived neoplasia. To investigate the role of the CT
gene regulatory sequence in tissue-specific gene expression, the genes
coding for the herpes simplex virus thymidine kinase (HSVtk) and for the
enhanced green fluorescent protein (EGFP) regulated by the CT promoter
(rAAV/CT266tkneo), the CT promoter/enhancer element (rAAV/CTenhtkneo),
or the cytomegalovirus (CMV) promoter (rAAV/CMVtkneo) were transduced by
recombinant adenoassociated viral (AAV) vectors into the medullary
thyroid carcinoma (MTC) cell lines TT and hMTC and into HeLa cells as
controls. In TT cell lines and hMTC cell lines transiently infected by
the rAAV/CT266tkneo viruses, a significant increase in (3)H ganciclovir
uptake was observed. Upon ganciclovir treatment, TT cells infected by
rAAV/CT266tkneo revealed a significant growth inhibition, which was less
tissue-specific because HeLa cells were also affected by these particles
(74.5%). In contrast, a minor but more tissue-specific growth inhibition
(33.6%) was observed for TT cells after transient infection with the
rAAV/CTenhtkneo particles. Employing EGFP controlled by CMV promoter and
the individual CT regulatory sequences for transduction by rAAV
particles, similar results were obtained indicating that both the CT
promoter and enhancer element are required for tissue-specific gene
expression in MTC.
28
UI - 21436736
AU - Wohllk N; Becker P; Youlton R; Cote GJ; Gagel RF
TI -
[Germline mutations of the ret proto-oncogene in Chilean patients with
hereditary and sporadic medullary thyroid carcinoma]
SO - Rev Med Chil 2001 Jul;129(7):713-8
AD - Seccion de Endocrinologia, Departamento de Medicina, Hospital del
Salvador, Laboratorio IEMA, Santiago de Chile. iema@terra.cl
BACKGROUND: Medullary thyroid carcinoma (MTC) may occur either as a
sporadic or familial disease. Multiple endocrine neoplasia (MEN) type 2,
inherited as an autosomal dominant disease, is characterized by MTC only
(FMTC) or coexistence of MTC with other endocrine neoplasia (NEM 2A,
2B). Germline mutations of the RET proto-oncogene (cRet) are found in
the inherited forms and in some apparently sporadic MTC cases. AIM: To
study RET mutations in 8 families with MEN 2. MATERIAL AND METHODS: RET
mutations were screened in peripheral blood DNA from 18 patients and 87
high risk carriers belonging to 8 MEN 2 families and 52 sporadic MTC.
Exons 10, 11, 13, 14, 15 and 16 of the c-Ret were amplified by
polymerase chain reaction (PCR) and examined by direct sequencing of PCR
products and/or restriction enzyme analysis. RESULTS: Five MEN 2A and
one FMTC families with a germline mutation at
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