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J P Travagli

Publications and source records attributed to J P Travagli.

At least 19 recordsLinked to original sources

Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy.

AIM: The goal of this study was to estimate the cumulative activity of (131)I to be administered to patients with distant metastases from thyroid carcinoma. METHODS: A total of 444 patients were treated from 1953-1994 for distant metastases from papillary and follicular thyroid carcinoma: 223 had lung metastases only, 115 had bone metastases only, 82 had both lung and bone metastases, and 24 had metastases at other sites. Treatment consisted of the administration of 3.7 GBq (100 mCi) (131)I after withdrawal of thyroid hormone treatment, every 3-9 months during the first 2 yr and then once a year until the disappearance of any metastatic uptake. Thyroxine treatment was given at suppressive doses between (131)I treatment courses. RESULTS: Negative imaging studies (negative total body (131)I scans and conventional radiographs) were attained in 43% of the 295 patients with (131)I uptake; more frequently in those who were younger, had well-differentiated tumors, and had a limited extent of disease. Most negative studies (96%) were obtained after the administration of 3.7-22 GBq (100-600 mCi). Almost half of negative studies were obtained more than 5 yr after the initiation of the treatment of metastases. Among patients who achieved a negative study, only 7% experienced a subsequent tumor recurrence. Overall survival at 10 yr after initiation of (131)I treatment was 92% in patients who achieved a negative study and 19% in those who did not. CONCLUSION: (131)I treatment is highly effective in younger patients with (131)I uptake and with small metastases. They should be treated until the disappearance of any uptake or until a cumulative activity of 22 GBq has been administered. In the other patients, other treatment modalities should be used when tumor progression has been documented.

Adenocarcinoma, Follicular↗

Sodium iodide symporter expression and radioiodine distribution in extrathyroidal tissues.

The functional role of the sodium iodide symporter (NIS) in extrathyroidal tissues was investigated by examining its mRNA and protein expression, together with the evidence of radioiodine (131)I uptake in 302 patients who underwent (131)I total body scanning, following the administration of high doses of (131)I for a papillary or follicular thyroid carcinoma. By using a real-time kinetic quantitative RT-PCR and immunohistochemistry, the expression of NIS protein was detected mainly in secretory tissues. In parallel, 1311 uptake was evidenced in the majority of patients in the salivary glands (in 39%) and stomach (in 78%), but was found in breast in only 4 young female patients. These data demonstrate a strong correlation between the organ radioactivity distribution, as observed in vivo, and NIS protein expression. Interestingly, (131)I is rarely concentrated by mammary glands, even when large doses are administered. Moreover, a (131)I transfer in secretion fluids may represent a potential source of contamination responsible for false positive images and diagnostic pitfalls.

Adenocarcinoma, Follicular↗

The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile.

The aim of this study was to determine the chemosensitivity of infiltrating lobular breast carcinoma (ILC) in comparison with infiltrating ductal carcinoma (IDC). Between 1987 and 1995, 457 patients with invasive T2>3 cm-T4 breast carcinomas were treated with primary chemotherapy (CT), surgery, radiation therapy. Clinical response, the possibility of breast preservation, pathological response and survival were evaluated according to the histological type. In order to evaluate the biological differences between ILC and IDC patients and their implication with regard to tumour chemosensitivity, additional immunohistochemical stainings (oestrogen receptor (ER), Bcl2, p53, c-erbB-2 and Ki67) were performed on 129 pretherapeutical specimens. 38 (8.3%) ILC were diagnosed by core needle biopsy before CT. ILC was an independent predictor of a poor clinical response (P=0.02) and ineligibility for breast-conserving surgery after neoadjuvant chemotherapy (P=0.03). Histological and biological factors predicting a poor response to CT (histological grade, ER, Ki67 and p53 status) were more frequent in ILC than in IDC patients. After a median follow-up of 98 months (range: 3-166), the low chemosensitivity of ILC did not result in a survival disadvantage. Our results demonstrate that ILC achieved a lower response to CT than IDC because of their immunohistochemical profile. Preoperative CT did not allow a high rate of conservative treatment for ILC and therefore the use of neoadjuvant CT for ILC patients should be questioned.

Adult↗

Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging.

Imaging-detected relapses are observed in a significant proportion of patients with medullary thyroid carcinoma (MTC) with normal postoperative imaging studies. The aim of this study was to search for prognostic factors of imaging-detected relapse. This retrospective study was performed in 63 consecutive MTC patients with normal postoperative medical imaging. After surgery, the basal calcitonin (CT) level was undetectable in 35 patients and elevated in 28. During follow-up, 18 patients developed a clinical or imaging-detected relapse (29%) in the neck and/or at distant sites: 15 had an elevated postoperative basal CT level and three had an undetectable postoperative basal CT level. At multivariate analysis, the significant parameters predictive of imaging-detected relapse were the postoperative plasma CT level and the tumour extension (pT). The 3- and 5-year relapse-free survival rates were 94 and 90% in patients with an undetectable postoperative basal CT level, and 78 and 61% in patients with a detectable basal CT level (P<0.05). The 3- and 5-year relapse-free survival rates were 92 and 85% in the pT1-3 patients, and 57 and 46% in the pT4 patients (P<0.01). These results show that postoperative CT level and tumour extension are critical prognostic factors for the identification of patients at a high risk of relapse.

Adolescent↗

Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients.

The follow-up of patients with papillary and follicular thyroid carcinoma after thyroidectomy and radioiodine ablation is mainly based on serum thyroglobulin (Tg) level deter-mination. The positive predictive value (PPV) of serum Tg level after thyroid hormone withdrawal, measured during the first 6-12 months of follow-up (initial off L-T(4) Tg), was studied in 256 consecutive differentiated thyroid cancer patients. All underwent a total thyroidectomy and 3.7 GBq (131)I ablation; 37 patients had an elevated initial off L-T(4) Tg level. This study focuses on these 37 patients, 9 of whom had a clinical recurrence. The present data confirm that in this selected cohort of patients, 74-185 MBq (131)I-total body scan (TBS) has no clinical interest in the initial work-up and during the subsequent follow-up because it was negative in all patients, except in one with recurrent disease. The PPV of initial serum off L-T(4) Tg level above 5 ng/ml and 10 ng/ml was 42% and 53%, respectively; this PPV was only 50% at the time of recurrence or subsequent control. This relatively low PPV is related to the low recurrence rate in this series of patients, despite a prolonged follow-up, and to the subsequent decrease of serum Tg level in 14 of 37 (38%) patients in the absence of any further treatment. In contrast, the PPV of the increasing slope of serum Tg levels obtained after thyroid hormone withdrawal (83%) was excellent. In conclusion, we confirm that (131)I-TBS has a limited interest for the follow-up of thyroid cancer patients. Follow-up should rely on serum Tg level and prognostic parameters; however, initial serum Tg may be produced by thyroid tissues of various significance, an increase at two consecutive determinations indicating disease progression and a decrease being related to late effects of therapy. The best PPV is brought by the slope of serum Tg levels.

Adenocarcinoma, Follicular↗

Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course.

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill-defined. PATIENTS: All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single-center retrospective study. RESULTS: There were 9 men and 9 women with a mean age of 13 years (range, 2-27 years) at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN 2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 was found in the 16 patients in whom it was investigated. At diagnosis, 2 patients had Stage I MTC, 15 patients had Stage III, and 1 patient had Stage IV disease. T1 MTC was found in 4 patients aged 2.1-3.7 years. However, two of these patients already had N1 disease. One patient with Stage I MTC, aged 3.4 years and 2 patients with Stage III disease, aged 14 and 25 years, had undetectable basal calcitonin (CT) after initial surgery. During follow-up, basal CT became detectable in one of three patients. Among the 15 other patients with an elevated postoperative CT level, metastases were demonstrated in 5 patients after a mean follow-up of 2 years. Five patients died, three of MTC, one of the MEN 2B syndrome, and one of intercurrent disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. CONCLUSIONS: This study confirms the need for early treatment of MTC in patients with the MEN 2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN 2B syndrome was not more aggressive than sporadic MTC or MTC occurring in other familial syndromes.

Adolescent↗

Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer?

A diagnostic iodine-131 (131I) total body scan (TBS) is usually recommended 6 to 12 months after thyroid ablation for differentiated thyroid carcinoma. Its usefulness was evaluated in 256 consecutive patients treated and followed up at the Institut Gustave Roussy for papillary (n = 200), well differentiated (n = 27), or poorly differentiated (n = 29) follicular thyroid carcinomas. All patients underwent a near-total or total thyroidectomy and 131I ablation with 3.7 GBq (100 mCi). No TBS was performed before 131I ablation. The TBS performed after the administration of 131I to destroy the thyroid remnants showed uptake (<2%) limited to the thyroid bed. A diagnostic 131I-TBS was obtained after withdrawal of T4 treatment, with either 74 MBq (2 mCi; n = 82) or 185 MBq (5 mCi; n = 174), 6 to 12 months after initial treatment, with serum thyroglobulin (Tg) determination. No interference in the Tg assay was found in these 256 patients. Uptake in the thyroid bed was not detected (total ablation) in 236 patients, was visible but too low to be measured in 19 patients, and attained 1% in only 1 patient. No uptake was found outside the thyroid bed. The serum Tg level, once thyroid hormone treatment had been withdrawn, was below 1 ng/mL in 210 patients, ranged from 1-10 ng/mL in 31 patients, and was above 10 ng/mL in 15 patients. A 131I-TBS performed with 3.7 GBq in nine patients with a Tg level above 10 ng/mL, showed foci of uptake outside the thyroid bed in three patients; lung metastases were demonstrated by a CT scan in another patient, and palpable lymph node metastases were found in one patient. In conclusion, a diagnostic 131I-TBS with 74-185 MBq performed 1 yr after thyroid ablation demonstrated no abnormal uptake; it did not correlate with results of Tg determination and only confirmed the completeness of thyroid ablation. The serum Tg level obtained after withdrawal of T4 treatment permits the selection of patients with a Tg level exceeding 10 ng/mL, for scanning with 3.7 GBq (100 mCi).

Adolescent↗

[Neuro-endocrine tumors and von Hippel-Lindau disease. 3 cases].

BACKGROUND: Neuroendocrine tumors can occur in patients with hereditary syndromes predisposing to multiple endocrine neoplasia (MEN) and Von Hippel-Lindau disease (VHL). CASE REPORTS: We report the cases of three men with pheochromocytomas, one with an associated neuroendocrine tumor of the pancreas. In one case, diagnosis was suggested by the familial context of VHL in the patients father. In the two other cases, the bilateral character of the pheochromocytoma, and in one case the associated pancreatic neuroendocrine tumor led to the diagnosis of VHL. Systematic biological surveillance gave the diagnosis of contralateral pheochromocytoma in two cases. Search for associated tumoral lesions led to the diagnosis of hemangioblastoma of the cerebellum in two patients and pancreatic cyst in the third. No renal or retinal lesions were observed. Molecular study of the VHL gene evidenced point nonsense mutation of the gene in all three patients, involving codon 184 in two and codon 167 in the third (identical to the proband case). Systematic investigations in the families of the two other patients remains to be completed. CONCLUSION: The diagnosis of HVL disease should be suggested in case of familial pheochromocytoma and/or bilateral localizations, but also in case of neuroendocrine tumors of the pancreas associated with another cardinal lesion of the disease. Early screening and treatment of this potentially fatal disease is essential.

Adolescent↗

Radiosensitivity of human normal and tumoral thyroid cells using fluorescence in situ hybridization and clonogenic survival assay.

PURPOSE: By using cell survival as a reference, we evaluated the radiosensitivity of human normal and tumoral thyroid cells using of radiation-induced translocations. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing thyroidectomy. Cell cultures were established, irradiated with 60Co, and metaphases painted using commercial whole-chromosome 4 hybridization probe and pancentromeric probe. The clonogenic survival was assessed by conventional colony forming assay. RESULTS: After irradiation, normal cultured thyroid cells yielded a higher number of translocations than cultures derived from adenomas or thyroid carcinoma. The colony forming assay demonstrated, by way of the mean inactivation dose, a higher survival of thyroid carcinoma and adenoma cells than of normal thyroid cells. This difference between tumoral and nontumoral cells is significant in each method (p = 0.0001), and cannot be explained by apoptosis in irradiated malignant cells. Correlation of the results obtained by both methods is shown by comparing the survival fraction at 2 Gy (SF2) and the percentage of chromosome 4 translocations at 2 Gy. CONCLUSION: These results indicate that the yield of radiation-induced translocations serves as a good and rapid prediction of the intrinsic radiosensitivity of thyroid cells, and that this test could be applied to other tumors.

Adenoma↗

[Papillary and follicular cancers of the thyroid].

MANAGEMENT STRATEGIES: Management of papillary and follicular cancer of the thyroid varies somewhat between centers because of the generally good prognosis and the absence of well-controlled therapeutic trials. The internationally recognized TNM system is widely used to modulate treatment and follow-up to the individual situation. PRIMARY TREATMENT: Surgery is indicated in well-differentiated thyroid cancer. Total thyroidectomy is required for clinically patent tumors (> or = 1 cm) and small tumors (< 1 cm) recognized prior to surgery. For small tumors found at histology examination, reoperation is discussed in terms of prognosis. Post-operative 131-iodine is indicated when surgical resection is incomplete or in case of unfavorable prognosis. External radiotherapy is currently reserved for exceptional cases with unremoved tumoral tissue unresponsive to 131-iodine. FOLLOW-UP: All operated patients are given L-thyroxine to achieve euthyroidism and low TSH levels (< 0.1 microU/ml). Early detection of relapse is based on combined thyroglobulin assay and whole body 131-iodine scintigraphy. Both are performed during the first year of follow-up after a period of thyroid hormone withdrawal. Human recombinant TSH will soon be available allowing selection of patients with a detectable thyroglobulin level after stimulation; these patients should have a 131-iodine scintigram. If thyroglobulin remains undetectable during L-thyroxine treatment, an annual dosage is indicated and other exams are unwarranted. RELAPSE: Surgery is indicated in case of small areas of active recurrent tumoral tissue in a cervical location. If a high-sensitivity scintigram does not show iodine uptake, the surgical procedure is completed by radiotherapy or possibly chemotherapy with doxorubicin. Small recurrent tumors in other areas respond to 131-iodine (3.7 GBq). Surgery, 131-iodine and radiotherapy are usually indicated for large ectopic recurrences. Chemotherapy is ineffective. CURRENT PROTOCOLS: Standard primary therapy generally provides cure and most patients are followed by annual thyroglobulin and TSH assays. Other explorations beginning with a whole-body 131-scintigram may be indicated in selected patients.

Carcinoma, Papillary, Follicular↗

Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience.

BACKGROUND: Patients with thyroid microcarcinoma (TMC) have favorable long term prognoses. However, recurrences in the neck and distant metastases have been reported. The authors investigated independent factors associated with recurrence in an effort to define therapeutic guidelines. METHODS: Two hundred eighty-one patients (207 females, 74 males; mean age, 41.9 years) with a differentiated thyroid carcinoma < or = 1 cm in greatest dimension (mean size +/- standard deviation, 5.9+/-3.3 mm) were analyzed. The median follow-up time was 7.3 years. RESULTS: TMC diagnosis was incidental in 189 patients, and metastases were the first manifestation of the disease in the other 92 patients. Therapy included near-total thyroidectomy for 195 patients, lymph node dissection for 195, and therapeutic administration of radioiodine for 124. Eleven recurrences (3.9%) were observed 4.3+/-2.7 years (mean +/- standard deviation) after initial treatment: all had locoregional recurrence (4 in the thyroid bed and 7 in the lymph nodes), and in one of these the local recurrence was associated with lung metastases. Multivariate analysis showed that two parameters significantly influenced TMC recurrence, namely, the number of histologic foci (P < 0.002) and the extent of initial thyroid surgery (P < 0.01). Only 3.3% of patients with unifocal TMC treated with loboisthmusectomy had tumor recurrence. CONCLUSIONS: The recurrence rate for TMC appears to be low (3.9%). In the authors' view, loboisthmusectomy is the treatment of choice for patients with TMC when only one focus of cancer is found histologically, and total thyroidectomy is the optimal treatment for patients with multiple foci.

Adolescent↗

Combination of radioiodine (131I) and probe-guided surgery for persistent or recurrent thyroid carcinoma.

To improve the completeness of surgical excision of persistent or recurrent differentiated thyroid carcinoma, the following protocol was used for the treatment of 54 patients with functioning lymph node metastases: administration of 3.7 gigabecquerels (100 mCi) 131I; total body scintigraphy (TBS) on day 4; surgery on day 5, using an intraoperative probe (Gammed 2, Eurorad); and postoperative TBS with the remaining 131I activity on day 7. The 54 patients (35 women and 19 men presenting 47 papillary carcinomas, 2 well differentiated follicular carcinomas, and 5 poorly differentiated follicular carcinomas) had already undergone surgery for differentiated thyroid carcinoma: total thyroidectomy (51 patients) or lobectomy with isthmusectomy (3 patients), with lymph node dissection in 33. One to 7 131I treatments were performed before inclusion. Preoperative 131I-TBS with a high dose of 131I allowed accurate localization of previously suspected neoplastic foci and detection of yet unknown foci in 56%; it was the most sensitive tool for localizing neoplastic foci. The use of an intraoperative probe was considered decisive in 20 patients, as neoplastic foci were found inside sclerosis due to previous surgery (n = 9), at unusual sites behind vessels or in the mediastinum (n = 10), or both (n = 1). In 26 patients, it facilitated the preoperative detection of foci with 131I uptake already depicted at preoperative 131I-TBS. In all 46 patients, the completeness of excision was demonstrated by both the probe and the postoperative 131I-TBS and was confirmed during follow-up. Of note, lymph node metastases undetected by 131I-TBS or by the probe were found in 14 patients at histological examination. This clearly shows that en block dissection is the only recommended procedure. In four patients, no neoplastic foci were found and in four patients, uptake was either due to the thymus (in two) or to the salivary glands (in two).

Adenocarcinoma, Follicular↗

Late presentation of solitary contralateral adrenal metastasis of renal cell carcinoma.

We report a case of renal cell carcinoma with solitary metachronous contralateral adrenal metastasis occurring 23 years after radical nephrectomy. The patient was treated with adrenalectomy. He is alive with no evidence of disease 1 year postoperatively. Solitary metachronous contralateral adrenal metastases from renal cell carcinoma are rare clinical conditions that may occur very late. Metastasectomy is advocated and is probably beneficial for limited metastatic renal cell cancer.

Adenocarcinoma↗

[Differentiated thyroid epithelioma].

Long term prognosis of differentiated thyroid carcinoma is favourable, being modulated by several factors, age and histology being the most relevant. Initial treatment includes firstly surgery: loboisthmusectomy in case of intra-thyroid tumor, unifocal, less than 1.5 cm in diameter in patients with favourable prognostic indicators, total thyroidectomy with the administration of an ablative dose of 131l in all the other patients. A routine dissection of the paratracheal groove and of the supraclavicular area is performed in all patients. L-thyroxine treatment is given to all patients. Relapses should be discovered early; this is made possible by the combined use of serum thyroglobulin measurements and of 131l total body scans.

Carcinoma↗