Frederic Sebag

Shear Wave Elastography: A New Ultrasound Imaging Mode for the Differential Diagnosis of Benign and Malignant Thyroid Nodules

CONTEXT Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new technique that estimates tissue stiffness in real time and is quantitative and user independent. OBJECTIVES The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. DESIGN Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1=US Score), and with the same parameters plus EI (Score 2=US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. RESULTS A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±sd) EI was 150±95 kPa (range, 30-356) in malignant nodules vs. 36±30 (range, 0-200) kPa in benign nodules (P<0.001, Students t test). For a positive predictive value of at least 80%, characteristics of tissue elasticity (cutoff, 65 kPa) were: sensitivity=85.2%, and specificity=93.9%. Characteristics of the US Score were: sensitivity=51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity=97% (95% CI, 93.6; 1). Characteristics of the US+SWE Score were: sensitivity=81.5% (95% CI, 66.9; 96.1), and specificity=97.0% (95% CI, 93.6; 1). CONCLUSION Promising results have been obtained with SWE. This technique may be applied to multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective places of SWE, US, and FNA.

Results of Laparoscopic Adrenalectomy for Large and Potentially Malignant Tumors

ndoscopic adrenalectomy is the procedure of choice for patients with small functioning adrenal tumors. For most surgeons invasive adrenal carcinoma is an absolute contraindication for laparoscopic adrenalectomy (LA). Whether LA should be proposed for large (> 6 cm), potentially malignant tumors is questionable. The aim of this study was to evaluate the risks and outcome of LA performed in our department in patients with tumors > 6 cm and potentially malignant. We performed a retrospective study of 216 patients who underwent 233 LAs in our department from 1994 to 2000. We selected 19 patients with a tumor > 6 cm and potentially malignant: 8 nonfunctional tumors, 4 cortisol-secreting tumors, 1 virilizing tumor, and 6 pheochromocytomas. In none of these patients did preoperative investigations demonstrated invasive carcinoma. The median tumor size was 70 mm. LA was performed by a transperitoneal flank approach. Conversion to open adrenalectomy was performed in two patients owing to intraoperative evidence of invasive carcinoma. The median operating time was 150 minutes (range 95–240 minutes). Capsular disruption occurred during the dissection of two pheochromocytomas. There was no postoperative morbidity. Six patients had an adrenocortical carcinoma on pathologic diagnosis: three of the eight nonfunctional tumors, one of the four cortisol-secreting tumors, and one virilizing tumor. One patient presented with liver metastases 6 months after surgery and died. The five other patients are disease-free with a follow-up ranging from 8 to 83 months. The 13 patients with benign lesions (6 cortical adenomas, 1 ganglioneuroma, 6 pheochromocytomas) are disease-free with a median follow-up of 47 months (range 10–81 months). In experienced hands LA can be proposed for large, potentially malignant tumors. Conversion to open adrenalectomy should be performed if local invasion is observed during surgery. At present the risk of intraabdominal recurrence is unknown.

18F-FDG Avidity of Pheochromocytomas and Paragangliomas: A New Molecular Imaging Signature?

Our objective was to evaluate 18F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Methods: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). 18F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. Results: All but 2 patients showed significantly increased 18F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean ± SD, 8.2 ± 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean ± SD, 9.7 ± 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase–related tumors were notable in being the most 18F-FDG–avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau–related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome–related tumors (P = 0.02). 18F-FDG PET was superior to 131I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, 18F-FDG PET underestimated the extent of the disease, compared with 6-18F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain 18F-FDG uptake since most tumors were highly avid for 18F-FDG. Conclusion: 18F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels.

Measuring serum calcitonin (CT) in patients with thyroid diseases allows preoperative diagnoses of sporadic medullary thyroid carcinoma (MTC) and C-cell hyperplasia (CCH). The aim of this prospective study was to distinguish biochemically between CCH and MTC. Basal CT (bCT) was determined in 7276 consecutive patients referred for thyroid disease. Patients with recurrent, persistent, or familial MTC were excluded. When bCT was > 10 pg/ml a pentagastrin-stimulated CT (sCT) assay was performed. Patients were routinely operated on when bCT > 30 pg/ml or sCT > 100 pg/ml or when other indications for surgery were present. An extensive search for CCH or microscopic MTC was conducted by immunochemistry. Pathologic findings were correlated with the bCT and sCT values. In this study 66 patients were included. No morphologic alterations of C-cells were observed in 5 patients; 16 patients presented with CCH and 45 with MTC. Statistical analysis revealed a correlation of sCT and overall bCT with tumor size and staging (p <0.001). Considering cutoff values for bCT of ≤ 30 pg/ml and for sCT of ≤ 200 pg/ml, the positive predictive value of the test to detect MTC was 100% and the negative predictive value 63%. No patients with MTC at stage 2 to 4 had bCT <30 pg/ml or sCT <200 pg/ml. A bCT value of ≤ 30 pg/ml or sCT ≤ 200 pg/ml (or both) is highly predictive of MTC, requiring total thyroidectomy with lymph node dissection. Values of bCT <30 pg/ml and sCT <200 pg/ml do not distinguish between CCH and MTC at stage 1. In this case total thyroidectomy at least is recommended, and the role of nodal dissection might be discussed.

Thyroid surgery: postoperative hematoma—prevention and treatment

Background and aimsPostoperative haematoma formation is a fortunately rare but potentially life-threatening complication of thyroid surgery. This paper aims to identify potential aetiological factors, describe surgical techniques and newer haemostatic agents that may be used to minimise the risk of haematoma formation and propose surgical strategies to deal with haematoma formation.Materials and methodsAn extensive literature search as well as own considerable experience in a tertiary referral centre endocrine surgical unit was drawn upon to review this topic.ConclusionsPostoperative haematoma may have a multifactorial aetiology. Numerous manoeuvres and surgical haemostatic agents may be employed to minimise the risk of haematoma formation but are no substitute for meticulous haemostasis. In the event of haematoma formation, early surgical re-intervention is strongly advocated with due care given to at risk structures.

Endoscopic Parathyroid Surgery: Results of 365 Consecutive Procedures

In recent years, several series have documented the feasibility of endoscopic approaches for parathyroid diseases. We performed a retrospective study to evaluate the results of endoscopic parathyroidectomy (EP) in the management of our patients with primary hyperparathyroidism (PHPT). During a 5.5 year period (1998–2003), we operated on 644 patients with PHPT. EP was proposed for patients with sporadic PHPT, without associated goiter, and without previous neck surgery in whom a single adenoma was localized by means of sonography and sestamibi scanning. EP was performed by the lateral approach with insufflation for patients with an adenoma located deep in the neck and by a gasless midline approach for patients whose adenoma was located anteriorly. A quick parathyroid (QPTH) assay was used during the surgical procedures. Among 644 patients with PHPT, 279 (43.3%) were not eligible for EP for the following reasons: associated nodular goiter (116 cases), previous neck surgery (52 cases), suspicion of multiglandular disease (31 cases), lack of preoperative localization (61 cases), and miscellaneous causes (19 cases). EP was performed in 365 patients with sporadic PHPT: 339 lateral access, 25 midline access, and one thoracoscopy. The median operating time was 49 minutes (16–130 minutes). Conversion to conventional parathyroidectomy was required in 49 patients (13.4%) for these reasons: missed adenomas (14 cases), difficulty with the dissection (8 cases), multiglandular disease correctly predicted by QPTH (11 cases), false-negative QPTH assay results (4 cases), false-positive sestamibi scan results (11 cases), and 1 false-positive sonography result. One patient presented with definitive recurrent nerve palsy. Three patients remained hypercalcemic, and one other patient had recurrent hypercalcemia. In conclusion, EP can be proposed for more than half of the patients with PHPT. Immediate results of EP are similar to those obtained with conventional parathyroidectomy, but no conclusions can be drawn in terms of the influence of EP on the outcome of the patients operated on for PHPT.

Long-term Outcome following Laparoscopic Adrenalectomy for Large Solid Adrenal Cortex Tumors

IntroductionLaparoscopic adrenalectomy (LA) is the procedure of choice for small benign adrenal tumors. In the absence of local invasion or metastases, the preoperative diagnosis of an adrenocortical carcinoma (ACC) is difficult, often leaving size as the principal predictor of malignancy. Large tumors are resectable laparoscopically, but the long-term outcome and therefore appropriateness of LA for cortical tumors > 6 cm is not known.MethodsWe reviewed the LA experience in our institution since its introduction in June 1994. Patients who underwent LA for solid cortical tumors ≥ 60 mm in diameter without preoperative or intraoperative evidence of malignancy were reviewed. Follow-up data, including clinical examination, biochemical analysis, and repeat scans, were reviewed for evidence of local or systemic recurrent disease.ResultsBetween 1994 and 2004 a total of 462 adrenalectomies were performed, 391 of which were done laparoscopically. Among them, 19 were solid cortical tumors ≥ 60 mm in diameter with no overt malignant preoperative or intraoperative characteristics: 9 nonsecreting tumors, 8 Cushing’s syndrome tumors (including 2 virilizing variants), 1 virilizing tumor, and 1 aldosteronoma. The mean age of the patients was 49.9 years (range 22–77 years), and the mean tumor size was 69.0 mm (range 60–80 mm). Histology confirmed a cortical adenoma in eight patients, malignant tumors in three, and indeterminate tumors in eight. The mean follow-up was 34 months (range 4–108 months). Two patients died of systemic recurrent disease (liver metastases) at 10 and 19 months, respectively, following surgery; two other patients died 12 and 21 months, respectively following surgery owing to unrelated cardiovascular and cerebrovascular pathology. One patient underwent surgery for local recurrence 54 months after primary surgery; the remaining 14 patients are well with no clinical or radiologic evidence of recurrent disease.ConclusionsLaparoscopic adrenalectomy for large solid cortical tumors without pre- or intraoperative evidence of malignancy is not contraindicated, and it is unlikely to have a deleterious effect on long-term outcome. Each case should be considered individually. We provide an algorithm for the approach to adrenocortical tumors ≥ 6 cm.

A single-institution 25-year review of true parathyroid cysts

BackgroundParathyroid cysts (PCs) are rare, and their origin is a subject of debate. They have been described as either functional, causing hyperparathyroidism, or non-functional in eucalcaemic patients.Patients and methodsWe have performed a 25-year departmental review of PCs. Features studied included the clinical presentation and intra-operative findings, and a histological review was performed. Cases of cystic degeneration of parathyroid adenomas and pseudocystic change were excluded.ResultsOver 25 years, 22,009 thyroidectomies and 2,505 parathyroidectomies were performed in our department. Amongst these, 38 non-functional PCs were documented in 37 patients. The mode of presentation included incidental findings on routine chest x-ray, compressive symptoms or an asymptomatic palpable neck mass. Aspiration was the initial treatment in 14 patients and was curative in 10 of these. Four out of 14 patients underwent surgical procedures for recurrence of the cyst that occurred 6 to 48 months after aspiration. In 27 patients, surgery was performed and all identified PCs were localized in the inferior parathyroid glands. Histologically, the cyst wall consisted in associations of lymphoid, muscular, thymic, salivary, adipose and mesenchymal tissues.ConclusionsPCs are rare but should be included within the differential diagnosis of a neck lump. True PCs are non-functional. Pathological and immunohistochemical findings are suggestive of a branchial origin. Fine-needle aspiration may be curative and is diagnostic due to the characteristic appearance of the fluid and high PTH levels on assay.

Endoscopic Parathyroidectomy: Why and When?

BackgroundIn recent years, several new minimally invasive techniques for parathyroidectomy (MIP) have been developed. There was a rapid worldwide acceptance of mini-open procedures by most surgeons. However, the use of an endoscope remains debatable. This study was designed to determine the role of preoperative imaging studies in the decision-making for using an endoscope during MIP.MethodsAll patients with sporadic primary hyperparathyroidism (PHPT) and candidate for MIP underwent localizing studies. MIP was proposed only for patients in whom a single adenoma was localized by both ultrasonography and sestamibi scanning. Three locations were described: (1) posterior to the two superior thirds of the thyroid lobe; (2) at the level of or below the inferior pole of the thyroid lobe but in a plane posterior to it; (3) at the level of or below the tip of the inferior pole of the thyroid lobe but in a superficial plane. In locations 1 and 2, the nerve was considered to be at risk and an endoscopic lateral approach was indicated. In location 3, a mini-open approach was indicated.ResultsOf the 165 patients operated on for PHPT in 2006, 86 underwent MIP. According to the results of imaging studies, 39 patients presented an adenoma in location 1, 21 in location 2, and 26 in location 3. In locations 1 and 2, 59 patients (1 false-positive) had an adenoma that was located posteriorly, in close proximity to the nerve; all were cured. In location 3, 25 patients (1 false-positive) presented an inferior parathyroid adenoma superficially located; all were cured. There was no transient or permanent laryngeal nerve palsy.ConclusionsIn patients who are candidates for MIP, we recommend the use of the endoscope for the resection of parathyroid adenomas that are located deeply in the neck.

Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas

While somatostatin receptors (sst), through somatostatin-radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas (PCC) and paragangliomas (PGL), the clinical significance of dopamine receptor subtype 2 (D₂) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ((18)F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D₂. The aim of this study was to quantitate D₂ and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Quantitative RT-PCR of sst(1-3) and sst₅, D₂, NAT, VMAT1/2 was performed in all tumors, while immunohistochemistry analysis of sst₂ and D₂ was performed in seven tumors. D₂ mRNA was expressed in all PCC/PGL. Mean expression was significantly higher in PCC/PGL than in GEP-NETs (4.8 vs 0.5 copy/copy β-glucuronidase (Gus)). sst₂ and sst(1) were expressed in most PCC/PGL, with sst(2)-dominant expression (mean mRNA: 1.6 vs 0.4 copy/copy β-Gus). sst₂ expression level was similar to that of GEP-NETs, whereas sst₅ expression level was significantly lower (0.12 vs 0.78 copy/copy β-Gus). Our study evidenced strong D₂ mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst₂ mRNA at levels similar to those of GEP-NETs. New drugs can target ssts and D₂ more efficiently than current somatostatin analogs. Moreover, transporters like NAT and VMAT1/2, could be co-targeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors.