Biomedical subjects

Sophie Leboulleux

Publications and source records attributed to Sophie Leboulleux.

14 recordsLinked to original sources

PubMed2006

Prognostic parameters of metastatic adrenocortical carcinoma.

CONTEXT: Prognostic parameters of metastatic adrenocortical carcinoma (ACC) are poorly characterized. OBJECTIVE: The objective of the study was to describe the clinical presentation of metastatic ACC and determine prognostic factors for survival. DESIGN: This was a retrospective cohort study (1988-2004). SETTING: The study was conducted in an institutional practice. PATIENTS: Participants included 124 consecutive patients with metastatic ACC, 70 from Gustave-Roussy Institute (main cohort) and 54 patients from the Cochin Hospital (validation cohort). Clinical data concerning all patients, histopathologic slides of primary tumors (44 in the main cohort and 40 in the validation cohort), and molecular biology data on 15 primary tumors (main cohort) were analyzed. INTERVENTION: There was no intervention. MAIN OUTCOME: The main outcome was the specific survival after discovery of the first metastasis (Kaplan-Meier method). This included univariate analysis on the main cohort, confirmed on the validation cohort and then analyzed in a multivariate analysis. RESULTS: In the main cohort, overall median survival was 20 months. In univariate analysis, the presence of hepatic and bone metastases, the number of metastatic lesions and the number of tumoral organs at the time of the first metastasis, a high mitotic rate (>20 per 50 high-power field), and atypical mitoses in the primary tumor predicted survival (P = 0.05, 0.003, 0.046, 0.001, 0.01, and < 0.001, respectively). The number of tumoral organs and a high mitotic rate were confirmed on the validation cohort (P = 0.009 and 0.03, respectively). These two parameters were confirmed in multivariate analysis (P = 0.0058 and 0.049). CONCLUSION: Metastatic ACC is a heterogeneous disease with poor outcome. The combination of the number of tumoral organs at the time of the first metastasis and the mitotic rate can predict different outcomes.

Adolescent↗

PubMed2006

Thyroid metastases from colorectal cancer: the Institut Gustave Roussy experience.

The prevalence of thyroid metastases in colorectal cancer (CRC) patients is unknown. We retrieved the records of all patients with CRC and pathologically proved thyroid metastasis for the period 1993-2004. Among 5,862 consecutive patients with CRC, 6 (0.1%) were diagnosed with thyroid metastases, a median of 61 months after the diagnosis of primary tumour, and a median of 19 months after the last surgical resection or radiofrequency ablation of other metastases (which were present in all cases). Signs and symptoms, when present (n=3), consisted of cervical pain, cervical adenopathy, goitre, dysphagia, and/or dysphonia. In other cases, the diagnosis was made by positron emission tomography scanning. Thyroidectomy was performed in the 5 patients with isolated thyroid metastases, with cervical lymph node dissection being required in all cases. The only patient treated conservatively because of concomitant liver and lung metastases developed life-threatening dyspnoea, which required emergent tracheal stenting. Median overall survival was 77 months, 58 months, and 12 months after the diagnosis of primary CRC, initial metastases, and thyroid metastasis, respectively. It is concluded that thyroid metastases are rare and occur late in the course of CRC. Thyroidectomy (with cervical lymph node dissection) may result in prevention or improvement of life-threatening symptoms and prolonged survival.

Biopsy, Needle↗

PubMed2006

Rapidly progressing high o,p'DDD doses shorten the time required to reach the therapeutic threshold with an acceptable tolerance: preliminary results.

INTRODUCTION: It has been reported that the therapeutic threshold of mitotane, plasma level above 14 microg/ml, is achieved within 3-5 months after o,p'DDD treatment initiation in patients with adrenocortical carcinoma (ACC). OBJECTIVE AND DESIGN: We evaluated pharmacokinetic and tolerance of a high-dose schedule of pure o,p'DDD treatment given in 500-mg tablets of mitotane (Lysodren, Bristol-Myers Squibb, HRA Pharma, Paris, France) in four patients with ACC and two patients with Cushing's syndrome-related endocrine tumours. It was administered at a starting dosage of 3 g/day, which was rapidly increased to 6-9 g/day within 2 weeks according to digestive tolerance and then adjusted according to tolerance and plasma o,p'DDD monitoring. Patients were followed up until they reached the therapeutic threshold of mitotane, and toxicity was recorded. A relationship between o,p'DDD dose and plasma level was sought. RESULTS: The highest starting dosage given ranged between 6 and 9 g a day, during the first two weeks. The daily maintenance dose ranged 4.5-9 g during the next 2 weeks and 3-9 g by the second month of treatment. The therapeutic threshold was reached in all four patients who received o,p'DDD treatment for at least 1 month. Among these four patients, the toxic threshold (plasma mitotane level > 20 microg/ml) was even reached at 6 weeks of therapy in three patients. Grade 1, 2 or 3 toxicity was observed in 3, 2 and 1 patients, respectively. Toxicity resolved after reduction or discontinuation of o,p'DDD therapy. A significant linear correlation was found between plasma mitotane dose and plasma level. CONCLUSIONS: These results suggest that a high-dose o,p'DDD therapeutic schedule is feasible with an acceptable toxicity and may shorten the time required to reach the therapeutic schedule from 3-5 months to 4 weeks. These patients require a close follow-up, combining clinical and plasma o,p'DDD level monitoring every second week. A confirmatory study is ongoing.

Adrenocortical Carcinoma↗

PubMed2006

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

UNLABELLED: The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.

Animals↗

PubMed2005

Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis.

CONTEXT: Reliable prognostic factors are needed in papillary thyroid cancer patients to adapt initial therapy and follow-up schemes to the risks of persistent and recurrent disease. OBJECTIVE AND SETTINGS: To evaluate the respective prognostic impact of the extent of lymph node (LN) involvement and tumor extension beyond the thyroid capsule, we studied a group of 148 consecutive papillary thyroid cancer patients with LN metastases and/or extrathyroidal tumor extension. Initial treatment, performed at the Institut Gustave Roussy between 1987 and 1997, included in all patients a total thyroidectomy with central and ipsilateral en bloc neck dissection followed by radioactive iodine ablation. RESULTS: Uptake outside the thyroid bed, demonstrating persistent disease, was found on the postablation total body scan (TBS) in 22% of the patients. With a mean follow-up of 8 yr, eight patients (7%) with a normal postablation TBS experienced a recurrence. Ten-year disease-specific survival rate was 99% (confidence interval, 97-100%). Significant risk factors for persistent disease included the numbers of LN metastases (>10) and LN metastases with extracapsular extension (ECE-LN >3), tumor size (>4 cm), and LN metastases location (central). Significant risk factors for recurrent disease included the numbers of LN metastases (>10), ECE-LN (>3), and thyroglobulin level measured 6-12 months after initial treatment after T4 withdrawal. CONCLUSION: We highlight an excellent survival rate and suggest risk classifications of persistent and recurrent disease based on the numbers of LN metastases and ECE-LN, LN metastases location, tumor size, and thyroglobulin level.

Adolescent↗

PubMed2005

Follicular cell-derived thyroid cancer in children.

Thyroid carcinoma is a rare disease in childhood. The only known causative factor is radiation exposure during childhood. Most cases can be cured by surgery and eventually radioiodine. The aim of initial treatment should be the total removal of neoplastic foci with a minimal morbidity. Some cancer-related deaths have been reported decades after initial treatment.

Adenocarcinoma, Follicular↗

PubMed2005

Clinical review: Current concepts in the management of unilateral recurrent laryngeal nerve paralysis after thyroid surgery.

OBJECTIVE: This study was designed to provide an update on the pathophysiological concepts and patient management in a common complication of thyroid surgery, unilateral recurrent laryngeal nerve paralysis (URLNP). METHOD: Recent publications in physiology and head and neck surgery were reviewed. RESULTS: Even for experienced surgeons, URLNP may occur after thyroid surgery, especially for thyroid cancer and in case of reoperation. URLNP is frequently well tolerated but may be life threatening by inducing aspiration pneumonia. Permanent URLNP may decrease quality of life by decreasing voice quality and increasing vocal effort. Spontaneous recovery of vocal function, with or without full recovery of vocal fold motion, may occur due to spontaneous axonal regrowth or other neurological phenomena. In the last decade, several surgical techniques have been developed to treat aspiration and poor voice quality due to URLNP by medialization of the paralyzed vocal fold. These techniques are simple, have a low complication rate, and are highly efficient in eliminating aspiration and improving voice quality and quality of life. CONCLUSIONS: The voice and swallowing handicap caused by URLNP may be efficiently treated by safe and simple techniques. The possibility to improve the quality of life should be proposed to all patients with symptomatic URLNP.

Humans↗

PubMed2005

Ectopic adrenocorticotropic hormone-syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature.

Cushing's syndrome (CS) in medullary thyroid carcinoma (MTC) is rare. Only 50 cases have been reported. We report 10 cases of MTC with ectopic adrenocorticotropic hormone (ACTH)-dependent syndrome (EAS), analyzed retrospectively. Among 1640 patients with MTC, 13 developed EAS (0.7%). In 10 patients CS could unequivoqually be related to MTC (0.6%). CS was always clinically obvious. It revealed MTC in 3 cases and followed diagnosis by an average of 34.5 months in the others. Metastases were often present at diagnosis. Immunohistochemistry with ACTH antibodies was positive in one case. Diagnosis of ectopic CS was established according to clinical and biologic features, and absence of corticotropic adenoma as well as parallel evolution between tumor and CS. Therapy was medical and surgical: anticortisolic drugs alone or in association with somatostatin analogue, somatostatin analogue alone, and bilateral adrenalectomy. Eight patients died within 2 to 30 months, 4 of hypercortisolism complications (3 peritonitis and 1 hypokalaemia), 4 of MTC progression. EAS is a rare complication of MTC. The prognosis is poor because of frequency of metastasis at diagnosis. Persistent hypercortisolism can, by itself, lead to death, and has to be treated specifically.

Adrenocorticotropic Hormone↗

PubMed2005

Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total body scan are not reliable criteria for cure after radioiodine treatment.

BACKGROUND: Local and regional recurrences occur in up to 20% of patients with papillary and follicular thyroid carcinoma. Diagnostic work-up and treatment modalities are still controversial, because nodal control is difficult to ascertain. We assessed the value of serum thyroglobulin (Tg) determination and of high-dose 131I total body scan (TBS) for ascertaining the absence of disease in patients who had already been treated with radioiodine and who subsequently underwent surgery. METHODS: Between 1990 and 2000, 105 patients who had been treated with radioiodine for lymph node recurrence with initial 131I uptake were included in a standardized protocol performed after withdrawal of thyroid hormone treatment: on day 1, serum Tg determination and administration of 3.7 GBq 131I; on day 4, 131I TBS; on day 5, surgery; on day 8, 131I TBS. RESULTS: In 25 patients the serum Tg obtained following thyroid hormone withdrawal was undetectable: for these patients, the 131I TBS showed uptake foci in 21 and pathology disclosed neoplastic foci in 19. In 32 patients the serum Tg ranged from 1 to 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 26 and pathology disclosed neoplastic foci in 28. In 48 patients the serum Tg level was above 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 38 and pathology disclosed neoplastic foci in 46. Thus, no uptake was found preoperatively in 20 patients, among whom pathology disclosed lymph node metastases in 16. However, both tests were negative in only two of the 93 patients in whom pathology disclosed neoplastic foci. CONCLUSION: Serum Tg levels and 131I TBS cannot be considered as reliable indicators for the absence of disease in patients already treated with 131I. However, when both tests are negative, the risk of persistent disease is minimal.

Adenocarcinoma, Follicular↗

PubMed2004

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy.

PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.

Adult↗

PubMed2004

Follicular-cell derived thyroid cancer in children.

Thyroid carcinoma is a rare disease in children, and is mostly of the papillary histological type. It is often extended at presentation with frequent lymph node metastases. Treatment includes surgery (total thyroidectomy and lymph node dissection) and radioiodine therapy in case of extensive disease. Life long thyroxine treatment is given to all patients and when carefully controlled is devoided of adverse effects. Long term prognosis is favorable, but a few deaths have been reported some decades after initial treatment. Adverse prognostic indicators are younger age at discovery and presence of distant metastases.

Adenocarcinoma, Follicular↗

PubMed2004

Medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells that produce calcitonin (CT), and accounts for 5-10% of all thyroid cancers. MTC is hereditary in about 25% of cases. The discovery of a MTC in a patient has several implications: disease extent should be evaluated, phaeochromocytoma and hyperparathyroidism should be screened for and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. In this review, pathological characteristics, tumour markers and genetic abnormalities in MTC are discussed. The diagnostic and therapeutic modalities applied to patients with clinical MTC and those identified with preclinical disease through familial screening are also described. Progresses concerning genetics, initial treatment, follow-up, screening and treatment of pheochromocytoma have permitted an improvement in the long-term outcome. However, there is no effective treatment for distant metastases, and new therapeutic modalities are urgently needed.

Biomarkers, Tumor↗

PubMed2003

Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.

UNLABELLED: A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01). IN CONCLUSION: 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.

Adult↗

PubMed2002

Radioiodine therapy for papillary and follicular thyroid carcinoma.

Radioiodine ((131)I) therapy is used in patients with papillary and follicular thyroid carcinoma for ablation of thyroid remnants and for treatment of persistent or recurrent disease. It should be used selectively, i.e. only in those patients for whom a clinical benefit may be expected.

Adenocarcinoma, Follicular↗