Publications by authors named "Jean-Paul Travagli"

30 Publications

  • Page 1 of 1

Surgery for Neck Recurrence of Differentiated Thyroid Cancer: Outcomes and Risk Factors.

J Clin Endocrinol Metab 2017 Mar;102(3):1020-1031

Department of Nuclear Medicine and Endocrine Oncology and.

Background: Persistent/recurrent disease in the neck is frequent in patients with differentiated thyroid cancer (DTC).

Objective: Assess efficacy, safety, and prognostic factors of first neck reoperation in DTC.

Methods: Retrospective study of consecutive patients undergoing neck reoperation for recurrent/persistent DTC in a referral cancer center. Response after reoperation was defined according to the 2015 American Thyroid Association guidelines.

Findings: One hundred sixty-one DTC patients were enrolled (64% females, median age 35 years, 96% papillary DTC). Initial stage was pT3 in 43% and pT4 in 10%, pN1 in 74%. Aggressive histology was present in 25% of the patients, in both primary and persistent/recurrent tumor. Four patients had no malignancy in the reoperative specimen, and 1 patient died due to postoperative hematoma and was excluded from further analysis. Following reoperation, 15 patients (10%) had persistent structural disease, 16 (10%) had biochemical incomplete response, 26 (17%) had indeterminate response, and 99 (63%) had complete response (CR), among whom 24 relapsed later. After a median follow-up of 5 years, only 83 patients (53%) had CR without the need for further treatments. The rate of permanent complications was: hypoparathyroidism 2%, laryngeal nerve palsy 0.6%, other 6%. Age ≥45 years, aggressive histology, and lymph node ratio ≥0.6 at initial surgery were independent risk factors for incomplete response after reoperation. Male sex, aggressive histology, and ≥10 metastases at reoperation were independent risk factors of secondary relapse following CR achieved with reoperation.

Conclusion: A careful risk-benefit analysis should guide surgical decision, particularly in patients with risk factors for incomplete response.
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http://dx.doi.org/10.1210/jc.2016-3284DOI Listing
March 2017

Preoperative localization of neck recurrences from thyroid cancer: charcoal tattooing under ultrasound guidance.

Thyroid 2015 Mar 26;25(3):341-6. Epub 2015 Feb 26.

1 Radiology Department, Hôpital Pitié Salpétrière, APHP, UPMC , Paris, France .

Background: Reoperation for thyroid cancer recurrence is a surgical challenge in previously dissected necks, and there is a need for a reliable procedure for surgeon guidance. In this study, the usefulness of preoperative charcoal tattooing for surgical guidance was evaluated.

Methods: From July 2007 to May 2010, 53 patients (40 females; Mage=44 years, range 19-76 years) were prospectively included for preoperative localization of neck recurrences from differentiated (n=46) or medullary thyroid cancer (n=7). Preoperative cytological assessment was performed for at least one lesion in each patient. Ultrasound (US) imaging was performed with high-frequency probes (8-14 Mhz). Micronized peat charcoal (0.5-3 mL) was injected under US guidance using a 25 gauge needle, 0-15 days preoperatively.

Results: A total of 106 lesions were selected for charcoal tattooing. Of these, 101 had been tattooed, and 102 were removed (85 metastases, 17 benign on pathology). The tolerance of charcoal injection was good in all but three patients. A mean volume of 1 mL of charcoal was injected with a mean of two targets per patient. Charcoal labeling facilitated intraoperative detection in 56 "difficult" lesions (i.e., small size, dense fibrosis, anatomical pitfalls), and charcoal trace facilitated intraoperative guidance in 17 lesions. Feasibility and usefulness rates were 83% and 70.7% respectively.

Conclusion: These findings suggest that charcoal tattooing under US guidance is an easy to implement, safe, and useful procedure for surgeon guidance in neck reoperation for thyroid cancer.
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http://dx.doi.org/10.1089/thy.2014.0329DOI Listing
March 2015

Optimization of staging of the neck with prophylactic central and lateral neck dissection for papillary thyroid carcinoma.

Ann Surg 2012 Apr;255(4):777-83

Departments of Otolaryngology Head and Neck Surgery, Institut Gustave Roussy and University Paris-Sud, Villejuif Cedex, France.

Objective: To analyze the yield and rate of node metastases (pN1) for prophylactic central (CND) and lateral neck dissection (LND) for papillary thyroid carcinoma, the risk factors for pN1, and outcomes.

Background: Prophylactic CND and LND are not routinely employed. Adjuvant radioiodine treatment may be modulated, however, by surgical staging of the neck.

Methods: Retrospective study, consecutive patients ultrasonographically classified cN0 treated with prophylactic CND, and lateral LND (levels III and IV). The number of nodes was resected and the incidence of pN1 was recorded.

Results: For 317 patients (254 women, mean age 44 years, mean tumor size 17 mm), the number of lymph nodes was 5 for unilateral CND, 9 for bilateral CND, and 12 for LND. pN1 stage was 42% overall: 23% for unilateral CND, 39% for bilateral CND, and 23% for LND (median number of metastatic nodes = 2 for each). Fifty-five percent of the patients staged pN1 had metastatic nodes in the lateral neck. Ten percent had more than 10 metastatic nodes and/or more than 3 nodes with extra capsular spread. pN1 was correlated with tumor size (P = 0.0025), extrathyroidal tumor extension (P < 0.0001), male sex (P = 0.0006), and age younger than 45 years (P = 0.0003). Permanent hypoparathyroidism and unintentional recurrent nerve paralysis occurred in 2 cases each. Patients staged pN0 received less radioiodine than patients staged pN1 (median 30 vs 100 mCi, P < 0.0001).

Conclusions: For staging, bilateral prophylactic CND is preferable to unilateral CND. Prophylactic CND with LND optimizes staging providing a basis for a personalized approach for adjuvant radioiodine.
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http://dx.doi.org/10.1097/SLA.0b013e31824b7b68DOI Listing
April 2012

Is (18)F-fluorodeoxyglucose-PET/CT useful for the presurgical characterization of thyroid nodules with indeterminate fine needle aspiration cytology?

Thyroid 2012 Feb 18;22(2):165-72. Epub 2012 Jan 18.

Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Villejuif, France.

Background: Thyroid nodules found incidentally on (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) have been shown to be malignant in 30%-50% of cases. The American Thyroid Association recommends performing fine needle aspiration cytology (FNAC) for thyroid nodules showing FDG uptake. On the other hand, the role of FDG-PET in characterizing thyroid nodules with indeterminate cytology before surgery is not clear. The goal of this study was to evaluate the role of FDG-PET/computed tomography (CT) in predicting malignancy of thyroid nodules with indeterminate FNAC and to correlate FDG uptake with pathological and ultrasonographic (US) features.

Methods: Between November 2006 and October 2009, 55 patients (42 women, mean age: 50 years) planned for surgery for 56 thyroid nodules with indeterminate FNAC were prospectively included and considered for analysis. All patients underwent presurgical FDG-PET/CT (Siemens Biograph, mean FDG injected activity: 165 MBq) and neck US. Pathology of the corresponding surgical specimen was the gold standard for statistical analysis.

Results: At pathology 34 nodules were benign, 10 were malignant (7 papillary and 3 follicular carcinomas), and 12 were tumors of uncertain malignant potential (TUMP). The median size of the thyroid nodules was 21 mm (range: 10-57). Sensitivity, specificity, positive (PPV), and negative predictive (NPV) values of FDG-PET in detecting cancer/TUMP were 77%, 62%, 57%, and 81%, respectively. In multivariate analysis, cellular atypia was the only factor predictive of FDG uptake (p<0.001). Hurthle cells and poorly differentiated components were independent predictive factors of high (≥5) SUV Max (p=0.02 and p=0.02). Sensitivity, specificity, PPV, and NPV of US in detecting cancer/TUMP were 82%, 47%, 50%, and 80%, respectively. In multivariate analysis, hypervascularization was correlated with malignancy/TUMP (p=0.007) and cystic features were correlated with benignity (p=0.03).

Conclusion: Adding FDG-PET findings to neck US provided no diagnostic benefit. The sensitivity and specificity of FDG-PET in the presurgical evaluation of indeterminate thyroid nodules are too low to recommend FDG-PET routinely.
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http://dx.doi.org/10.1089/thy.2011.0255DOI Listing
February 2012

Role of prophylactic thyroidectomy in RET 790 familial medullary thyroid carcinoma.

Head Neck 2012 Apr 17;34(4):493-8. Epub 2011 Jun 17.

Department of Endocrinology, Diabetology and Metabolic Disease, Avicenne Hospital, Paris XIII University and Assistance Publique-Hôpitaux de Paris, Bobigny, France.

Background: We describe a family harboring RET 790 mutation and review the role of prophylactic thyroidectomy for medullary thyroid carcinoma.

Methods: We evaluated in detail both clinical and biological follow-up and reviewed literature reports.

Results: Among 86 family members, 15 of 22 members screened harbored the 790 mutation. Abnormal calcitonin levels were found in 8/15. Total thyroidectomy with lymph node dissection cured the 5 operated patients (range, 45-76 years). Tumor staging was pT1N0M0. Among 10 carriers who did not undergo surgery, 3 patients had abnormal calcitonin levels. For the others, calcitonin levels remained <30 pg/mL. Two asymptomatic carriers were older than 70 years. Four subjects were lost to follow-up.

Conclusions: In RET codon 790 mutations families, a case-by-case decision instead of systematic prophylactic thyroidectomy should be discussed. Difficulties of follow-up should be taken into account and represent the main challenge.
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http://dx.doi.org/10.1002/hed.21763DOI Listing
April 2012

Central compartment neck dissection for thyroid cancer: a surgical technique.

World J Surg 2011 Jul;35(7):1553-9

Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif, France.

Several professional societies have in the past few years joined forces to standardize and define terminology for central compartment neck dissection, with the objective of improving communication among professionals and encouraging a more uniform surgical approach to neck nodes. Precisely defining and describing a technique has the advantage of providing a basis for communication and for discussion. A basic technique should be reproducible with low morbidity and teachable to surgeons in training. We herein describe a basic technique for bilateral central compartment neck dissection for thyroid cancer.
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http://dx.doi.org/10.1007/s00268-011-1105-8DOI Listing
July 2011

18F-fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer.

Eur J Nucl Med Mol Imaging 2010 Dec 6;37(12):2277-85. Epub 2010 Aug 6.

Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy and University Paris-Sud XI, 94805, Villejuif Cedex, France.

Purpose: Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients the value of 18F-FDG PET/CT compared with total body computed tomography (CT) using intravenous contrast material for initial staging, prognostic assessment, therapeutic monitoring and follow-up.

Methods: Twenty consecutive ATC patients underwent PET/CT for initial staging. PET/CT was performed again during follow-up. The gold standard was progression on imaging follow-up (CT or PET/CT) or confirmation with another imaging modality.

Results: A total of 265 lesions in 63 organs were depicted in 18 patients. Thirty-five per cent of involved organs were demonstrated only with PET/CT and one involved organ only with CT. In three patients, the extent of disease was significantly changed with PET/CT that demonstrated unknown metastases. Initial treatment modalities were modified by PET/CT findings in 25% of cases. The volume of FDG uptake (≥300 ml) and the intensity of FDG uptake (SUVmax≥18) were significant prognostic factors for survival. PET/CT permitted an earlier assessment of tumour response to treatment than CT in 4 of the 11 patients in whom both examinations were performed. After treatment with combined radiotherapy and chemotherapy, only the two patients with a negative control PET/CT had a confirmed complete remission at 14 and 38 months; all eight patients who had persistent FDG uptake during treatment had a clinical recurrence and died.

Conclusion: FDG PET/CT appears to be the reference imaging modality for ATC at initial staging and seems promising in the early evaluation of treatment response and follow-up.
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http://dx.doi.org/10.1007/s00259-010-1570-6DOI Listing
December 2010

Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.

Endocr Relat Cancer 2010 Sep 16;17(3):797-807. Epub 2010 Aug 16.

Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave-Roussy, Université Paris XI, 39 rue Camille Desmoulins, Villejuif Cedex, France.

To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.
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http://dx.doi.org/10.1677/ERC-09-0341DOI Listing
September 2010

High rate of multifocality and occult lymph node metastases in papillary thyroid carcinoma arising in thyroglossal duct cysts.

Ann Surg Oncol 2009 Sep 30;16(9):2595-601. Epub 2009 Jun 30.

Department of Otolaryngology Head and Neck Surgery, Institut Gustave Roussy, Villejuif, France.

Background: The incidence of cancer in thyroglossal duct cysts (TDC) is low and management is controversial. The objective was to report the rate of multifocality, lymph node metastases, and long-term results for TDC carcinomas in adults.

Materials And Methods: Files from 1979 to 2008 were reviewed for tumor stage, multifocality in the lobes, lymph node metastases, treatment, and follow-up.

Results: A total of 18 patients (13 females, 5 males, average age 41.5 years) were treated for papillary carcinoma arising in a TDC. Of these, 15 underwent total thyroidectomy, 1 isthmusectomy and 2 a Sistrunk procedure only. Also, 16 patients underwent neck dissection of the central and/or lateral compartments. Tumors were staged pT1 (n = 15), pT3 (n = 3), pN0 (n = 4), pN1a (n = 3), pN1b (n = 9), Nx (n = 2), M0 (n = 17), and M1 (n = 1, lung metastases). Tumor foci were found in the thyroid lobes in 9 of 16 patients(56%). Lymph node metastases were found in 12 of 16 (75%). Nodes were positive in 6 of 15 central compartment dissections (40%) and in 9 of 15 lateral neck dissections (60%). Metastases to the lateral compartment, with no central compartment metastasis, were found in 6 of 15 patients (40%). Radioiodine was administered to 12 patients. Median follow-up was 12 years (range 1-22 years). All had negative ultrasound. Stimulated Tg levels available for 11 patients were undetectable for 10 and 2 ng/mL for the remaining patient.

Conclusions: This series shows a high rate of thyroid lobe foci and lymph node metastases but an excellent long-term outcome, characteristics shared with classic papillary carcinoma. Lateral neck metastases seem to be more frequent. These findings are in favor of following the current guidelines for differentiated thyroid cancer in general for the treatment of these rare tumors.
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http://dx.doi.org/10.1245/s10434-009-0571-9DOI Listing
September 2009

Charcoal suspension tattoo localization for differentiated thyroid cancer recurrence.

Ann Surg Oncol 2009 Sep 24;16(9):2602-8. Epub 2009 Jun 24.

Department of Otolaryngology Head and Neck Surgery, Institut Gustave Roussy, Villejuif, France.

Background: The high sensitivity of ultrasound and thyroglobulin determination for follow-up of differentiated thyroid cancer allows early detection of nonpalpable recurrences. Intraoperative localization of these small foci in previously dissected necks is a surgical challenge. We describe a new technique for ultrasound-guided tattooing to facilitate excision.

Methods: Prospective study of 15 consecutive patients with suspected recurrence of differentiated carcinoma. Whole-body scan after administration of 100 mCi (131)I, performed in 14 cases, was negative in 13. TSH stimulated thyroglobulin averaged 31 ng/ml (<1-182 ng/ml). During ultrasound 19 lesions were discovered in regions already addressed by en bloc neck dissection. Lymph node metastasis was confirmed by cytology in 11 and by washout thyroglobulin in 2. Fine-needle aspiration (FNA) was insufficient for analysis in 1 and was not performed for 5 because of the size (<5 mm). Colloidal charcoal (1-4 ml) was injected under ultrasound, 1-15 days preoperatively. Tolerance, intraoperative charcoal localization, and success of resection were recorded.

Results: The injection was well tolerated. Charcoal was found in or just next to 16 lesions (84%). In 1 case it was found several centimeters away. In 1 case, no charcoal was found. In 1 case, hematoma caused by injection impaired surgical exploration. Surgery removed 18 lesions (95%) in 14 patients (93%): carcinoma (16), benign lymphadenitis (2).

Conclusions: Ultrasound-guided charcoal tattooing is safe, easy, and well-tolerated for localization of nonpalpable lesions in previously operated necks, with a high rate of success. Excision of these small recurrences remains controversial, however, and may not impact survival or quality of life.
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http://dx.doi.org/10.1245/s10434-009-0572-8DOI Listing
September 2009

Prophylactic lymph node dissection for papillary thyroid cancer less than 2 cm: implications for radioiodine treatment.

J Clin Endocrinol Metab 2009 Apr 30;94(4):1162-7. Epub 2008 Dec 30.

Department of Oncologic Surgery, Institut Gustave Roussy, Villejuif Cedex, France.

Objective: Prophylactic neck dissection for small papillary carcinoma remains controversial. Radioiodine ablation is not recommended for tumors less than 10 mm and depends on various factors for tumors between 10 and 20 mm. The aim was to determine the effect of lymph node (LN) staging on the indication for treatment with radioiodine.

Patients And Methods: We conducted a retrospective study of 115 patients presenting with papillary thyroid carcinoma less than 2 cm without ultrasonographically detectable cervical LN treated by total thyroidectomy and complete selective dissection of the central and lateral compartment. Radioiodine treatment was based on definitive pathology (tumor and LN). Follow-up was based on neck ultrasound and thyroglobulin levels.

Results: LN were found for 41.7% of cases. Radioiodine was not used for 42% of patients with tumors less than 20 mm and no metastatic LN. Fifty-eight percent of patients were treated with radioiodine due to LN metastasis, extracapsular thyroid invasion, or unfavorable histological subtype. LN status affected the indication for radioiodine in 30.5% of cases classified as T1, 12 cases with tumors less than 10 mm but with LN metastases (who received radioiodine), and 13 cases with tumors between 10 and 20 mm but without LN metastases (who did not receive radioiodine). Definitive vocal fold paralysis and hypoparathyroidism each occurred in 0.9% of cases. At 1 yr, ultrasound was normal in all patients, and recombinant human TSH-stimulated thyroglobulin was undetectable for 97% of the patients.

Conclusion: Precise LN staging by prophylactic neck dissection for tumors initially staged T1N0 modified the indication for radioiodine ablation for 30% of patients.
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http://dx.doi.org/10.1210/jc.2008-1931DOI Listing
April 2009

Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels.

J Clin Endocrinol Metab 2007 Nov 28;92(11):4185-90. Epub 2007 Aug 28.

Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, 94805 Villejuif Cédex, France.

Purpose: Because calcitonin level remains elevated after initial treatment in many medullary thyroid carcinoma (MTC) patients without evidence of disease in the usual imaging work-up, there is a need to define optimal imaging procedures.

Patients And Methods: Fifty-five consecutive elevated calcitonin level MTC patients were enrolled to undergo neck and abdomen ultrasonography (US); neck, chest, and abdomen spiral computed tomography (CT); liver and whole-body magnetic resonance imaging (MRI); bone scintigraphy; and 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/CT scan (PET).

Results: Fifty patients underwent neck US, CT, and PET, and neck recurrence was demonstrated in 56, 42, and 32%, respectively. Lung and mediastinum lymph node metastases in the 55 patients were demonstrated in 35 and 31% by CT and in 15 and 20% by PET. Liver imaging with MRI, CT, US, and PET in 41 patients showed liver in 49, 44, 41, and 27% patients, respectively. Bone metastases in 55 patients were demonstrated in 35% by PET, 40% by bone scintigraphy, and 40% by MRI; bone scintigraphy was complementary with MRI for axial lesions but superior for the detection of peripheral lesions. Ten patients had no imaged tumor site despite elevated calcitonin level (median 196 pg/ml; range 39-816). FDG uptake in neoplastic foci was higher in progressive patients but with a considerable overlap with stable ones.

Conclusion: The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value.
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http://dx.doi.org/10.1210/jc.2007-1211DOI Listing
November 2007

Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer.

J Clin Endocrinol Metab 2007 Sep 3;92(9):3590-4. Epub 2007 Jul 3.

Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France.

Context: Neck ultrasonography (US) has become a keystone in the follow-up of patients with differentiated thyroid cancer.

Objective: The aim of this study was to determine specificity and sensitivity of ultrasound criteria of malignancy for cervical lymph nodes (LNs) in patients with differentiated thyroid cancer.

Design: We prospectively studied 19 patients referred to the Institut Gustave Roussy for neck LN dissection. All patients underwent a neck US within 4 d prior to surgery. Only LNs that were unequivocally matched between US and pathology were taken into account for the analysis.

Results: One hundred three LNs were detected on US, 578 LNs were surgically removed, and 56 LNs were analyzed (28 benign and 28 malignant). Sensitivity and specificity were 68 and 75% for the long axis (> or =1 cm), 61 and 96% for the short axis (>5 mm), 46 and 64% for the round shape (long to short axis ratio < 2), 100 and 29% for the loss of fatty hyperechoic hilum, 39 and 18% for hypoechogenicity, 11 and 100% for cystic appearance, 46 and 100% for hyperechoic punctuations, and 86 and 82% for peripheral vascularization.

Conclusion: Cystic appearance, hyperechoic punctuations, loss of hilum, and peripheral vascularization can be considered as major ultrasound criteria of LN malignancy. LNs with cystic appearance or hyperechoic punctuations are highly suspicious of malignancy. LNs with a hyperechoic hilum should be considered as benign. Peripheral vascularization has the best sensitivity-specificity compromise. Round shape, hypoechogenicity, and the loss of hilum taken as single criteria are not specific enough to suspect malignancy.
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http://dx.doi.org/10.1210/jc.2007-0444DOI Listing
September 2007

Tattooing breast cancers treated with neoadjuvant chemotherapy.

Ann Surg Oncol 2007 Aug 16;14(8):2233-8. Epub 2007 May 16.

Department of Pathology, Institut Gustave-Roussy, rue Camille Desmoulins, 94800 Villejuif, France.

Background: In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy.

Methods: In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy.

Results: Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion.

Conclusions: On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.
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http://dx.doi.org/10.1245/s10434-006-9276-5DOI Listing
August 2007

Prognostic parameters of metastatic adrenocortical carcinoma.

J Clin Endocrinol Metab 2007 Jan 24;92(1):148-54. Epub 2006 Oct 24.

Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave-Roussy, Université Paris XI, 94800 Villejuif, France.

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.
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http://dx.doi.org/10.1210/jc.2006-0706DOI Listing
January 2007

How effective is prophylactic thyroidectomy in asymptomatic multiple endocrine neoplasia type 2A?

Nat Clin Pract Endocrinol Metab 2006 May;2(5):256-7

Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave Roussy, Villejuif, France.

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http://dx.doi.org/10.1038/ncpendmet0170DOI Listing
May 2006

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

Eur J Cancer 2006 Aug 9;42(12):1756-9. Epub 2006 Jun 9.

Department of Medicine, Gastroenterology Unit, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.

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.
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http://dx.doi.org/10.1016/j.ejca.2005.11.042DOI Listing
August 2006

Dermal lymphatic emboli in inflammatory and noninflammatory breast cancer: a French-Tunisian joint study in 337 patients.

Clin Breast Cancer 2005 Dec;6(5):439-45

Institut Gustave-Roussy, Villejuif, France.

Background: We studied whether dermal lymphatic emboli (DLE) add independent prognostic information to the clinical definition of inflammatory breast cancer (IBC).

Patients And Methods: The study was performed in 2 centers, one each in France and Tunisia. For every patient with IBC, 1-3 patients with noninflammatory breast cancer (non-IBC) were included. All patients were to have a surgical tumor biopsy, including a sample of the skin surrounding the tumor. The endpoint was the risk of a relapse at 2 years, which was estimated using univariate and multivariate Cox models.

Results: Three hundred thirty-seven patients were included (150 in France and 187 in Tunisia). The IBC status was divided into 2 clinical categories according to the extent of inflammation in the breast (localized IBC, which was defined as clinical inflammation in the tumor area, vs. diffuse IBC, which was defined as inflammation of at least two thirds of the breast). In total, 57 patients presented with localized IBC, 71 with diffuse IBC, and 209 with non-IBC. Dermal lymphatic emboli were found in 7% of non-IBC cases, in 25% of localized IBC cases, and in 45% of diffuse IBC cases. We found a significant interaction between the presence of DLE and diffuse IBC (P = 0.01). In patients with diffuse IBC, the presence of DLE increased the risk of relapse 3-fold. Conversely, DLE were not associated with the risk of relapse in patients with non-IBC, nor in patients with localized IBC. In patients with diffuse IBC and no DLE, the risk of relapse was similar to that of patients with localized IBC.

Conclusion: A DLE status might be a useful prognostic indicator exclusively in patients with diffuse IBC. However, because all patients with localized and diffuse IBC generally receive similar types of treatment, additional information on the presence or absence of DLE will not have an impact on treatment practice.
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http://dx.doi.org/10.3816/CBC.2005.n.049DOI Listing
December 2005

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.

J Clin Endocrinol Metab 2005 Oct 19;90(10):5723-9. Epub 2005 Jul 19.

Department of Nuclear Medicine and Endocrine Tumors, Institut National de la Santé et de la Recherche Médicale U605, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif Cédex, France.

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.
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http://dx.doi.org/10.1210/jc.2005-0285DOI Listing
October 2005

Follicular cell-derived thyroid cancer in children.

Horm Res 2005 29;63(3):145-51. Epub 2005 Mar 29.

Institut Gustave Roussy, Villejuif, France.

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.
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http://dx.doi.org/10.1159/000084717DOI Listing
August 2005

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

Clin Endocrinol (Oxf) 2005 Mar;62(3):376-9

Department of Nuclear Medicine and Endocrine Tumours, Institut Gustave Roussy, Villejuif Cédex, France.

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.
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http://dx.doi.org/10.1111/j.1365-2265.2005.02228.xDOI Listing
March 2005

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

J Clin Endocrinol Metab 2005 May 22;90(5):3084-8. Epub 2005 Feb 22.

Department of Otolaryngology and Head and Neck Surgery, Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cédex, France.

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.
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http://dx.doi.org/10.1210/jc.2004-2533DOI Listing
May 2005

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

Int J Radiat Oncol Biol Phys 2004 Nov;60(4):1137-43

Department of Radiation Oncology, Institut Gustave-Roussy, Villejuif, France.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2004.05.032DOI Listing
November 2004

Medullary thyroid carcinoma.

Clin Endocrinol (Oxf) 2004 Sep;61(3):299-310

Institut Gustave Roussy, Villejuif, France.

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.
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http://dx.doi.org/10.1111/j.1365-2265.2004.02037.xDOI Listing
September 2004

Follicular-cell derived thyroid cancer in children.

Eur J Cancer 2004 Jul;40(11):1655-9

Service de Medecine Nucleaire, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif cedex, France.

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.
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http://dx.doi.org/10.1016/j.ejca.2004.02.009DOI Listing
July 2004

[The sentinel lymph node in cancer of the breast: clinical aspects].

Bull Cancer 2003 Mar;90(3):246-54

Département de sénologie, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805 Villejuif.

Sentinel lymph node (SLN) biopsy is effective to assess axillary nodal status and avoiding axillary lymph node dissection (ALND) in patients with clinically node-negative early stage breast cancer. No standardization of the technique has yet been established. This review discusses the feasibility, the accuracy and the different techniques for this procedure. Although the SLN can be successfully identified by either the dye or gamma probe-guided method, its identification is facilitated when the two techniques are combined. To increase the sensitivity of the pathological examination of the SLN, it is necessary to make multiple step sections with hematoxylin and eosin staining immunohistochemistry on permanent sections. The intraoperative frozen sections and imprint cytology examinations of the SLN may be useful in determining its status, but further studies are needed to establish their performance. In clinical practice, routine ALND can be avoided for small tumours when the multidisciplinary team has an extensive experience of this technique. However, long-term regional control and survival have to be studied in prospective randomised trials, before SLN biopsy can replace routine ALND as the preferred staging method for women with localized breast cancer.
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March 2003

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

J Clin Endocrinol Metab 2003 May;88(5):2070-5

Nuclear Medicine, Institut Gustave-Roussy, 94805 Villejuif cedex, France.

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.
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http://dx.doi.org/10.1210/jc.2002-021713DOI Listing
May 2003

Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma.

Thyroid 2002 Aug;12(8):707-11

Institut Gustave Roussy, Villejuif, France.

Serum thyroglobulin (Tg) is a reliable marker for detecting recurrent and persistent disease during the follow-up of patients with papillary and follicular thyroid carcinoma. The goal of this study was to assess the relationship between the serum Tg level measured after thyroid hormone withdrawal and the tumor mass in thyroid cancer patients who underwent surgery with the use of an intraoperative probe for lymph node metastases with (131)I uptake. Patients were classified into one of three groups according to the Tg level: undetectable (n = 18); 1-10 ng/mL (n = 21); and greater than 10 ng/mL (n = 33). The main clinical characteristics and the extent of the disease at the time of initial treatment were similar in these three groups. Lymph node metastases were found in 13 of the 18 patients with undetectable Tg level. Eight patients had persistent foci of uptake after surgery that were located behind the sterno-clavicular joint in six patients. The number of metastatic lymph nodes and their total surface (in mm(2)) or their total volume (in mm(3)) were significantly linked with serum Tg/thyrotropin [TSH] level (p = 0.002 and p < 0.0001, respectively). For a given metastatic surface or volume, the serum Tg/TSH value was no longer linked with the number of metastatic lymph nodes (p = 0.32), suggesting that the total surface or total volume is the characteristic that best summarizes the influence of the disease on the serum Tg/TSH level. In conclusion, patients with higher serum Tg levels tend to have more extensive disease and should undergo more aggressive treatment modalities. Nevertheless, undetectable serum Tg should not be considered as a reliable criteria to exclude a minimal tumor burden in patients who have already been treated with (131)I.
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http://dx.doi.org/10.1089/105072502760258686DOI Listing
August 2002

Propofol-sufentanil anesthesia for thyroid surgery: optimal concentrations for hemodynamic and electroencephalogram stability, and recovery features.

Anesth Analg 2002 Sep;95(3):597-605, table of contents

Department of Anesthesia, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.

Unlabelled: Hypnotics and opioids interact synergistically to block responses to surgery and different dose combinations may be used to provide adequate anesthesia. In this study, we sought to determine the optimal concentrations of propofol and sufentanil, given by target-controlled infusions, to ensure hemodynamic stability, adequate hypnosis (assessed by electroencephalogram bispectral index), and fast recovery for a moderately painful operation. Forty-five patients, ASA physical status I or II, undergoing thyroidectomy, were randomly assigned to a sufentanil target concentration (STC) that was maintained throughout surgery (0.1, 0.2, or 0.3 ng/mL). The propofol target concentration was adjusted to keep mean arterial blood pressure within 30% of a reference value, and bispectral index between 40 and 60. Adequate anesthesia was obtained in all groups. Hypertension and clinically dangerous movements were more frequent with the small STC, and hypotension requiring treatment was more frequent with the large STC. Propofol target concentration during surgery decreased significantly with increasing STC (median at thyroid removal 5.0, 4.0, and 2.5 microg/mL, respectively) as well as the propofol consumption (740, 668, 474 mg/h). The 0.3 ng/mL STC significantly delayed the return of spontaneous breathing.

Implications: Given as a target-controlled infusion for thyroid surgery, sufentanil 0.3 ng/mL for intubation and 0.2 ng/mL during surgery, combined with propofol 4 microg/mL (corresponding to a maintenance infusion rate of approximately 7-10 mg. kg(-1). h(-1)), is recommended to ensure both optimal intraoperative stability and fast recovery.
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http://dx.doi.org/10.1097/00000539-200209000-00019DOI Listing
September 2002