Biomedical subjects

R Elisei

Publications and source records attributed to R Elisei.

At least 19 recordsLinked to original sources

PubMed2007

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients.

OBJECTIVE: The cytological patterns of follicular and Hupsilonrthle cell nodules are included among the indeterminate results of fine-needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hupsilonrthle cell thyroid nodules at cytology. DESIGN AND PATIENTS: The study included 505 consecutive patients who had undergone thyroidectomy from the period 2002-2005. RESULTS: Histological diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the follicular variant of papillary carcinoma being the most frequent histotype. Only atypia at cytology (P < 0.0001) and spot microcalcifications at ultrasound (P = 0.009) were predictive of malignancy. Male gender, normal thyroid volume, single nodularity, nodule hypoechogenicity, size and blurred margins were associated with malignancy, although not significantly. An arbitrary clinical score allowed the identification of patients with high (41%, 110 patients) and low (16%, 242 patients) risk of malignancy. Combining the clinical score with the presence of atypia at cytology we could identify 30 patients (6%) in whom the risk of malignancy was as high as 63%. CONCLUSIONS: Twenty-five per cent of patients with a cytological result of follicular and Hupsilonrthle cell thyroid lesion had a final diagnosis of malignancy. Only atypia at cytology and spot microcalcifications at thyroid ultrasound were significantly associated with malignancy. Other clinical parameters and thyroid ultrasound patterns can be used to set up a clinical score useful for predicting the individual risk of malignancy before surgery.

Adenocarcinoma, Follicular↗

PubMed2006

Video-assisted central compartment lymphadenectomy in a patient with a positive RET oncogene: initial experience.

BACKGROUND: Prophylactic surgery for patients carrying a positive RET proto-oncogene proved to be highly effective in curing those likely to experience the development of a medullary carcinoma. Video-assisted procedures have been proved feasible for central compartment dissection. METHODS: A total of 15 patients (7 men and 8 women) with a positive RET proto-oncogene underwent total thyroidectomy and central compartment lymphadenectomy via a video-assisted approach. The mean age of the patients was 32.5 years. The echographically estimated mean volume was 10.3 ml, and the mean diameter of the main nodule was 8.8 mm. Preoperative ultrasound showed an absence of lateral neck lymph node involvement in all cases. No drain was used. Direct laryngoscopy was performed in all cases 1 month after surgery. RESULTS: The mean operative time was 67.3 min. A transient hypoparathyroidism occurred in one patient, and a permanent hypoparathyroidism occurred in another patient. No laryngeal nerve palsy was present. All the patients were discharged on postoperative day 1. Histology showed a medullary carcinoma in 10 patients and diffuse C-cell hyperplasia in 5 patients. The mean number of lymph nodes removed was 5.1. None of these nodes proved to be metastatic. Calcitonin levels were undetectable in all six patients who had a follow-up period longer than 1 year. CONCLUSION: Video-assisted central compartment lymphadenectomy was proved to be effective and safe. The procedure demonstrated a complication rate comparable with that for the conventional procedure, a better cosmetic outcome, and less postoperative pain. Although the video-assisted access proved to be a valid option for the treatment of patients carrying a positive RET proto-oncogene, a greater number of cases with a longer follow-up period is necessary to estimate the impact of the video-assisted approach on central neck lymphadenectomy.

Adolescent↗

PubMed2006

Interventional bronchoscopy in the treatment of tracheal obstruction secondary to advanced thyroid cancer.

BACKGROUND: Surgery is the choice treatment for symptomatic tracheal obstruction due to malignant thyroid disease. Few additional therapeutic alternatives are available: radiotherapy (RT), chemotherapy (CT) or radioiodine therapy (1311). Only few studies on interventional bronchoscopy (IB) as well as alternative or palliative procedures have been reported so far. This study is a retrospective report of results of IB performed in patients with severe tracheal obstruction due to advanced thyroid cancer. SETTING: Pulmonary and Endocrinology Units of a University Hospital. PATIENTS AND INTERVENTIONS: From January 2, 2000 to March 1, 2004 14 consecutive patients [5 males, mean age: 62.2+/-10.7 (SD) yr] underwent IB due to tracheal obstruction for anaplastic (ATC: 7 patients), differentiated (DTC: 5), medullary (MTC: 1) and non-epithelial malignant (NEMN: 1) thyroid cancer. Eight out of 14 patients had local advanced inoperable disease, 6 had local relapse after surgery, 1311 or RT. Ten out of 14 patients suffered from severe dyspnea. In 4 patients airway patency was maintained by insertion of a stent; in 3 the tracheal lesion was removed by Nd-YAG laser; in 7 both procedures were performed. RESULTS: All 10 patients with dyspnea showed an improvement in symptoms. Early and late complications were observed in 4 and in 3 patients, respectively. All but 4 DTC patients died 11.9+/-14.2 months after the diagnosis (4.20+/-5.1 after IB). In 4 DTC patients still alive 90.7+/-59.2 since diagnosis and 16.7+/-9.2 months since IB, the airway dilatations allowed further treatments like 131-I and/or RT. CONCLUSIONS: Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable thyroid-induced tracheal obstruction. Moreover, airway dilatation improves dyspnea and may allow further treatment.

Aged↗

PubMed2006

Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature.

Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype-phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of chi2/Fisher's exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF (V600E) mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF (V600E) was significantly associated with the classic variant of PTC (P = 0.0001) and with an older age at diagnosis (P = 0.01). No statistically significant correlation was found among the presence of B-RAF (V600E) and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF (V600E) (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38-40%. Furthermore, B-RAF (V600E) was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

Adolescent↗

PubMed2005

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.

CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.

Adolescent↗

PubMed2004

Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan.

In a young patient with differentiated thyroid carcinoma (DTC), previously submitted to total thyroidectomy and I-131 therapy for ablation of thyroid remnant, a follow-up 1-131 diagnostic whole body scan (WBS) demonstrated four small abnormal I-131 uptake areas. Two of these were projected over the thoracic region and corresponded to lung nodules, as later demonstrated by lung computerized tomography (CT)-scan. The remaining two areas were found in the lumbar-pelvic region, but their precise location could not be determined. Standard bone Rx examination and bone scan were negative. After I-131 therapy, we simultaneously acquired a I-131 WBS and a Tc-99m oxidronate bone scan by setting a dual window on the gamma camera. Comparing the I-131 and bone images we were able to identify the 4th lumbar vertebra and right ilium as the bone segments to be studied by a radiological approach. Eventually, the thin slice CT-scan demonstrated the presence of two small osteolytic lesions in these areas. In conclusion, the simultaneous acquisition of images both from I-131 and a bone-seeking agent may be useful to locate functioning bone metastases from DTC.

Adult↗

PubMed2004

Video assisted prophylactic thyroidectomy and central compartment nodes clearance in two RET gene mutation adult carriers.

Activating point mutations of RET gene have been demonstrated to be causative of the familial form of medullary thyroid cancer (MTC), both isolated (FMTC) and associated to other endocrine neoplasia [multiple endocrine neoplasia (MEN) 2A and 2B]. In RET gene mutation carriers, who are prone to developing MTC, prophylactic thyroidectomy is recommended to obtain their definitive cure. The simultaneous excision of the central node compartment is mandatory when the stimulation pentagastrin test for serum calcitonin is positive. Although the minimally invasive video assisted thyroidectomy (MIVAT) is nowadays currently adopted in many centers, it has never been employed for the prophylactic thyroidectomy of RET gene mutation carriers. The fear of obtaining an incomplete lymphadenectomy of the central compartment was the main reason for this reluctance. Since RET gene mutation carriers have often normal thyroid volume and, if involved, small lymph nodes, they indeed represent the best candidates to this approach especially when considering that they are usually young and concerned about the cosmetic results and the period of hospitalization. The excellent results obtained by MIVAT in the last few years induced us to propose this procedure together with a central compartment lymphadenectomy to 2 RET gene mutation carriers recently found by genetic screening. As assessed by a negative pentagastrin stimulation test performed after 6 months from the MIVAT, they were definitively cured without any surgical complication with the exception of a transient hypoparathyroidism. They showed a great satisfaction for both the cosmetic results and the very short period of hospitalization, thus supporting the idea that MIVAT can be used in association with the central node dissection for the prophylactic treatment of RET mutation gene carriers whose thyroid volume is still normal.

Adult↗

PubMed2004

A new germline RET mutation apparently devoid of transforming activity serendipitously discovered in a patient with atrophic autoimmune thyroiditis and primary ovarian failure.

Gain-of-function RET mutations are responsible for multiple endocrine neoplasia syndromes (MEN) 2A and 2B and familial medullary thyroid carcinoma (FMTC), whereas loss-of-function mutations are found in Hirschsprung disease. We report a new RET point mutation [R694Q (CGG-->CAG)], serendipitously found in a 23-yr-old woman with hypothyroidism due to atrophic Hashimoto's thyroiditis and primary ovarian failure, without altered calcitonin secretion. Familial history and clinical and biochemical evaluation of first-degree relatives were negative for FMTC, MEN 2A and 2B, and Hirschsprung disease. Genetic analysis showed that the mutation was inherited from the mother, who was submitted 2 yr before to thyroidectomy for goitrous Hashimoto's thyroiditis. Histological revision and immunohistochemical studies documented normal C cell number and morphology. We cloned the mutation in an expression vector encoding a full-length RET protein. The construct was transiently expressed in 293T cells in parallel with a wild-type RET and a C634R MEN 2A-associated RET mutant. Proteins were harvested from transfected cells, and tyrosine phosphorylation levels were assayed. The mutation did not exert significant potentiating effects on RET kinase. A focus assay was also performed on NIH3T3 fibroblasts; the mutant did not exert significant transforming activity. In conclusion, a new RET mutation was found in two subjects without any evidence of MEN and FMTC. In keeping with clinical data, transfection studies confirmed lack of activating activity. This serendipitous discovery, apparently devoid of oncogenic potential, underscores the problems that may be encountered in genomic studies on RET.

Adult↗

PubMed2004

Thyroid papillary carcinoma: preliminary evidence for a germ-line single nucleotide polymorphism in the Fas gene.

The expression of Fas in thyroid tumours and Graves' disease was analysed by mRNA transcript expression. As compared with unaffected thyroid tissue, Fas expression was enhanced in Graves' disease, adenomas, and papillary and follicular carcinomas. This pattern was also reflected in immunohistochemical studies. The PCR single-strand conformational polymorphism (SSCP) method and DNA sequencing were used to analyse Fas exons 1-9. The study was carried out on five different histotypes of thyroid tumours (n=93) and tissue from Graves' disease patients. As compared with a group of healthy blood donors (n=64), a significant association (P=0.006) emerged between papillary thyroid carcinoma and a silent single nucleotide polymorphism (SNP, 988C-->T) in exon 7 of the Fas gene. Other forms of thyroid pathology were not associated with the above polymorphism. Patients with neoplasia showed the same SNP in tumour tissue, in the unaffected contralateral thyroid lobe, and in peripheral blood cells. Thus, the 988C-->T polymorphism appeared to be of germ-line origin.

Adenoma↗

PubMed2003

Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma.

Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.

Adolescent↗

PubMed2002

Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment.

The follow-up of differentiated thyroid cancer after total thyroidectomy and thyroid ablation is commonly based on serum Tg determination and 131-iodine ((131)I) diagnostic whole-body scan (WBS) performed in the hypothyroid state, 6-12 months after thyroid ablation. Based on the greater sensitivity of Tg measurement, with respect to WBS, the diagnostic yield of diagnostic WBS has been questioned in patients who are off L-T(4) therapy and have undetectable Tg levels. The aim of the present retrospective study was to evaluate the diagnostic relevance of (131)I WBS performed after thyroid remnant ablation, in patients with undetectable serum Tg and off thyroid hormone therapy. The study included 315 of 662 consecutive patients (47.6%) treated in our department between 1980 and 1990, who, at the first control WBS after thyroid ablation, had undetectable serum Tg levels in the hypothyroid state. There were 54 men (17%) and 261 women (83%), with a mean age of 40.9 +/- 13.1 yr (range, 12-76), followed for a mean of 12 +/- 2.8 (range, 9-19) yr. The control WBS was negative in 225 (71.4%) patients and positive for persistent areas of thyroid bed uptake, frequently of very low significance, in 90 (28.6%). No local or distant metastases were discovered. At the last follow-up visit (1999-2000), 281 (89.2%) patients showed complete remission, with undetectable serum Tg off L-T(4) and negative WBS. Persistent thyroid bed uptake, with undetectable levels of Tg, was observed in 29 patients (9.2%) studied during L-T(4) withdrawal. Only 2 patients (0.6%) experienced local recurrence (lymph-node metastases) during their follow-up. In conclusion, our data suggest that the presence of undetectable levels of serum Tg off L-T(4) at the time of the first control WBS after initial treatment, is highly predictive of complete and persistent remission. With the exception of detecting persistent thyroid bed uptake in a minority of cases, the control WBS has never given information that could influence the following therapeutic strategy. On this basis, we propose that the diagnostic (131)I WBS may be avoided in patients with undetectable levels of Tg off L-T(4). These patients may be monitored with clinical examination, neck ultrasound, and serum Tg measurements on L-T(4).

Adolescent↗

PubMed2001

Post-surgical ablation of thyroid residues with radioiodine in Ukrainian children and adolescents affected by post-Chernobyl differentiated thyroid cancer.

Post-surgical ablation of thyroid residues with 131-iodine (131-I) is usually recommended after near-total thyroidectomy in high-risk patients, including children, with differentiated thyroid cancer (DTC). We report here the results of post-surgical radioiodine thyroid ablation in 249 children and adolescents of Ukraine with post-Chernobyl DTC initially treated with near-total thyroidectomy at the Institute of Endocrinology and Metabolism in Kiev, during a 2-year period. The patients' age at the time of the Chernobyl accident (1986), ranged from <1 to 14 yr in 223 subjects (children) and from 15 to 18 yr in 26 subjects (adolescents). Six weeks after surgery a diagnostic 131-I whole body scan revealed the presence of residual thyroid tissue in all cases. All patients received one or more courses of radioiodine therapy, for a total of 468 courses. One hundred and twenty-nine out of 249 patients (51.8%) were successfully ablated. The total number of treatment courses needed in these patients was 219. Most patients required multiple doses of radioiodine, only 63 required a single dose. One hundred and twenty patients (48.2%) treated with radioiodine were not ablated and are still under treatment program. The clinical features and the amount of thyroid residue were not different in ablated or not-ablated patients. Our results indicate that in this particular population of post-Chernobyl thyroid carcinomas, thyroid ablation is a rather difficult task. Only 51.8% were successfully ablated. Possible explanation for this finding may be the young age of the patients, other particular features of post-Chernobyl thyroid carcinoma or technical aspects, such as less radical surgical procedures.

Adolescent↗

PubMed2001

Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients.

Total (or near-total) thyroidectomy (TT) is considered by many as the most adequate treatment for papillary thyroid carcinoma (PTC). In patients who have undergone lobectomy, the necessity of performing a completion thyroidectomy (CT) is still discussed. The aim of this retrospective study was to evaluate tumor bilaterality in patients initially treated with partial thyroidectomy for PTC and who then underwent CT. We studied 182 patients treated with CT after lobectomy and/or isthmectomy for PTC diagnosed from 1969-1998. Mean age at diagnosis was 40+/-14.5 years and mean interval between partial thyroidectomy and CT was 19.8+/-56.8 months. At CT, 80 of 182 patients (44%) had one or more foci of tumor in the remaining thyroid lobe, always of the same papillary histotype, associated with ipsilateral lymph node metastases in 22 cases. In addition, 10 patients with no tumoral foci in the thyroid specimen had evidence of lymph node metastases. The rate of bilateral tumor was not different when patients were analyzed according to the classification of "low-" or "high-risk." Among several clinical features, the presence of lymph node metastases at the first surgical treatment and time interval between first treatment and CT were correlated with higher frequency of bilaterality (p = 0.033 and p = 0.044, respectively). The postsurgical 131I whole-body scan revealed the presence of persistent lymph node metastases or diffuse micronodular lung metastases in 7 and 6 patients, respectively. In conclusion, PTC was frequently bilateral in our series and this bilaterality was independent from the "low-" or "high-risk" classification. On these bases, we believe that PTC should be treated with TT when diagnosed before surgery and submitted to CT, if partial surgery was the initial intervention.

Adult↗

PubMed2001

Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma.

Stimulation with recombinant human TSH (rhTSH) has been introduced in clinical practice as an effective alternative to thyroid hormone withdrawal for the diagnostic follow-up (Tg measurement and 131-iodine whole-body scan) of patients with differentiated thyroid cancer. The present study was specifically aimed to evaluate the utility of rhTSH-stimulated serum Tg measurements in patients with undetectable serum Tg values, on L-T(4) therapy, as the only test to differentiate patients with persistent disease from patients who are disease-free. We studied 72 consecutive patients with differentiated thyroid cancer, previously treated with near-total thyroidectomy and 131-I thyroid ablation. Admission criteria were: an undetectable (<1 ng/ml) serum Tg, on L-T(4) therapy, and negative anti-Tg antibodies. The study design consisted of a Tg-stimulation test after rhTSH, during L-T(4), followed by diagnostic WBS and serum Tg measurement off L-T(4). After rhTSH, serum Tg remained undetectable in 41 of 72 patients (56.9%). A negative rhTSH Tg test agreed with an undetectable hypo-Tg in 36 of 41 cases (87.8%), all without evidence of metastatic disease at hypo-WBS. In 5 of 41 cases (12.2%), hypo-Tg was detectable (1.1-7.8 ng/ml), in association with negative hypo-WBS or faint uptake in the thyroid bed. Serum Tg converted from undetectable to detectable after rhTSH in 31 of 72 patients (43.1%), with a peak Tg ranging between 1.2 and 23.0 ng/ml. Hypo-Tg was always detectable in these patients (100% concordance), and it was significantly higher than rhTSH-stimulated Tg (P < 0.0002). Hypo-WBS was positive in 23 of 31 patients (74.2%), showing thyroid residues in 12, cervical lymph nodes in 7, and lung metastases in 4 cases. In 8 of 31 cases, hypo-WBS was negative, despite detectable serum Tg. Thus, rhTSH-stimulated Tg was able to detect all cases of documented local or distant metastases. In conclusion, our data indicate that, in patients with undetectable basal levels of serum Tg, rhTSH-stimulated Tg represents an informative test to distinguish disease-free patients (not requiring WBS) from diseased patients (requiring further diagnostic and/or therapeutic procedures).

Adolescent↗

PubMed2001

RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults.

Rearrangements of the RET proto-oncogene may occur in both naturally occurring and radiation-induced papillary thyroid carcinomas. Conflicting results on the frequency and type of RET/PTC rearrangements have been reported in relation to age, radiation exposure, and histological tumor variant. We designed the present study to evaluate in a single laboratory, using the same methodologies, the pattern of RET/PTC activation in thyroid tumors from different groups of patients (exposed or not exposed to radiation, children or adults, with benign or malignant tumors) in relationship to the above mentioned variables. We studied 154 patients with benign nodules (n = 65) or papillary thyroid cancer (n = 89). In the last group, 25 were Belarus children exposed to the post-Chernobyl radioactive fallout, 17 were Italian adults exposed to external radiotherapy for benign diseases, and 47 were Italian subjects (25 children and 22 adults) with no history of radiation exposure. Among patients with benign thyroid nodules, 21 were Belarus subjects (18 children and 3 adults) exposed to the post-Chernobyl radioactive fallout, 8 were Italian adults exposed to external radiation on the head and neck, and 36 were Italian adults with naturally occurring benign nodules. The overall frequency of RET/PTC rearrangements in papillary thyroid cancer was 55%. The highest frequency was found in post-Chernobyl children and was significantly higher (P = 0.02) than that found in Italian children not exposed to radiation, but not significantly higher than that found in adults exposed to external radiation. No difference of RET/PTC rearrangements was found between samples from irradiated (external x-ray) or not irradiated adult patients, as well as between children and adults with naturally occurring, not irradiated, thyroid cancer. When analyzing the type of RET/PTC rearrangement (RET/PTC1 or RET/PTC3), no major difference was apparent. In addition, eight cases with an unknown RET/PTC rearrangement and three cases with the concomitant expression of RET/PTC1 and RET/PTC3 were found. No significant correlation was observed between the frequency and/or the type of RET/PTC rearrangement and clinical-epidemiological features of the patients such as age at diagnosis, age at exposure, histological variant, gender and tumor-node-metastasis (TNM) categories. RET/PTC rearrangements were also found in 52.4% of post-Chernobyl benign nodules, in 37.5% of benign nodules exposed to external radiation and in 13.9% of naturally occurring nodules (P = 0.005, between benign post-Chernobyl nodules and naturally occurring nodules). The relative frequency of RET/PTC1 and RET/PTC3 in rearranged benign tumors showed no major difference. In conclusion, our results indicate that the presence of RET/PTC rearrangements in thyroid tumors is not restricted to the malignant phenotype, is not higher in radiation-induced tumors compared with those naturally occurring, is not different after exposure to radioiodine or external radiation, and is not dependent from young age. Other factors, probably influenced by ethnic or genetic background, may act independently from or in cooperation with radiation, to trigger the DNA damage leading to RET proto-oncogene activation.

Adolescent↗

PubMed2001

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.

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.

Adolescent↗

PubMed2001

RET protein expression has no prognostic impact on the long-term outcome of papillary thyroid carcinoma.

BACKGROUND: RET proto-oncogene rearrangements (RET/PTC) are causative events in the pathogenesis of a subset of papillary thyroid cancer (PTC). The prevalence of RET/PTC varies in different countries and according to specific clinical features: it is higher after radiation exposure and it is claimed to be higher in young patients. Conflicting results are reported regarding the prognostic role of RET/PTC activation. OBJECTIVE: To investigate the prognostic meaning of RET/PTC rearrangement on the long term outcome of PTC. METHODS: We have studied the expression of the RET encoded protein in 127 papillary thyroid carcinomas by immunohistochemistry using a polyclonal antibody against the tyrosine-kinase domain of the RET protein. These cases have been collected during 1970-1985, and have a mean (+/-S.D.) period of follow-up of 18.6+/-3.7 years (range 12-27 years). The results have been compared with the patients' outcome. RESULTS: The tyrosine-kinase domain of RET was expressed in 82 (64.6%) papillary carcinomas. Among them, RET was highly expressed in 65 (51.2%) cases and moderately expressed in 17 (13.4%). RET expression was absent in 45 (35.4%) cases. No correlation was found between RET expression and other parameters such as sex, age at diagnosis, tumor class and histological variant. Follow-up analysis showed no influence of RET expression on patients' outcome. By multivariate analysis, age (>45 years) and tumor class IV, but not sex and RET expression were adverse prognostic indicators of death. CONCLUSION: In conclusion, our analysis indicates that RET expression is frequently found in PTC, and has no influence on tumor outcome.

Adolescent↗

PubMed2000

The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway.

Activating mutations of RAS are thought to be early events in the evolution of thyroid follicular neoplasms. We used a doxycycline-inducible expression system to explore the acute effects of H-RAS12 on genomic stability in thyroid PCCL3 cells. At 2-3 days (first or second cell cycle) there was a significant increase in the frequency of micronucleation. Treatment of cells with YVAD-CHO inhibited RAS-induced apoptosis, but had no effect on micronucleation. The effects of H-RAS(V12) were mediated by activation of MAPK, as treatment with PD98059 at concentrations verified to selectively inhibit MEK1 reduced the frequency of prevalence of cells with micronuclei. In addition, doxycycline-inducible expression of a constitutively active MEK1, but not of a mutant RAC1, mimicked the effects of H-RAS(V12). The effects of H-RAS(V12) on genome destabilization were apparent even though the sequence of p53 in PCCL3 cells was confirmed to be wild-type. Acute activation of H-RAS(V12) evoked a proportional increase in both CREST negative and CREST positive micronuclei, indicating that both clastogenic and aneugenic effects were involved. H-RAS(V12) and activated MEK1 also induced centrosome amplification, and chromosome misalignment. Evidence that acute expression of constitutively activated RAS destabilizes the genome of PCCL3 cells is consistent with a mode of tumor initiation in which this oncogene promotes phenotypic progression by predisposing to large scale genomic abnormalities.

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