Roger Tabah

Explaining the increasing incidence of differentiated thyroid cancer

The thyroid is the largest of the endocrine glands and by far the most common site of all primary endocrine cancers. However, thyroid cancer is relatively rare, accounting for only 1% of all cancers. The number of new cases diagnosed each year is comparable to that of leukemia, pancreatic cancer and

The role of sentinel lymph node biopsy in differentiated thyroid carcinoma.

OBJECTIVE To determine whether sentinel lymph node (SLN) biopsy can accurately predict central compartment metastasis in patients with differentiated thyroid carcinoma. DESIGN Prospective clinical study. SETTING Academic tertiary care center. PATIENTS Ninety-eight patients (82 women and 16 men; mean age, 48.3 years) underwent a total thyroidectomy and central compartment dissection. INTERVENTION Peritumoral injection of methylene blue dye, 1%, followed by SLN biopsy. MAIN OUTCOME MEASURES The final pathology report established the presence of metastasis among SLNs and lymph nodes that did not stain blue (non-SLNs [NSLNs]). RESULTS Differentiated thyroid carcinoma was found in 75 of 98 patients (77%). Seventy of 75 patients with differentiated thyroid carcinoma presented with SLNs and/or NSLNs within the central compartment. Fifteen of 70 patients had metastasis-positive SLNs, while 55 had metastasis-negative SLNs. Six of 15 patients with positive SLNs also had positive NSLNs. No patients with negative SLNs were found to have positive NSLNs. Sentinal lymph node status was a highly significant predictor of NSLN result (Fisher exact test, P < .001). The accuracy, sensitivity, specificity, and positive and negative predictive values of SLN biopsy were 87%, 100%, 86%, 40%, and 100%, respectively. CONCLUSIONS To our knowledge, this is the largest series of SLN biopsy in patients with differentiated thyroid carcinoma. Our experience suggests that this is an accurate and noninvasive means to identify subclinical lymph node metastasis. Because negative SLNs correlate strongly with a negative central compartment (100% in this study, P < .001), this technique can be used as an intraoperative guide when determining the extent of surgery necessary in cervical level VI.

Cost-Effectiveness of Molecular Testing for Thyroid Nodules With Atypia of Undetermined Significance Cytology

CONTEXT Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. OBJECTIVE The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. DESIGN AND SETTING We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. PATIENTS Low-risk patients with AUS thyroid nodules were simulated. INTERVENTIONS We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. MAIN OUTCOME MEASURES Lifetime costs and quality-adjusted life-years were measured. RESULTS From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN

Determinants of Urolithiasis Before and After Parathyroidectomy in Patients With Primary Hyperparathyroidism

24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. CONCLUSIONS In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Primitive neuroectodermal tumor (PNET) as somatic-type malignancy arising from an extragonadal germ-cell tumor: clinical, pathological and molecular features of a case.

OBJECTIVE To assess the determinants of urolithiasis in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTX). METHODS Institutional Research Ethics approval was obtained. A retrospective review was performed for patients presenting with PHPT to the stone, surgical oncology, and otolaryngology clinics at 2 tertiary-care centers from January 2006 to November 2011. Demographic, clinical, and surgical data were collected together with 24-hour urine collections before and after PTX. RESULTS Of 332 patients undergoing PTX, 255 (68.2% female patients) had PHPT. Mean age was 60.3 years (range, 18-91). Before PTX, renal calcification was detected in 51 (20%) patients, nephrolithiasis in 48 (18.8%), and nephrocalcinosis in 3 (1.2%) patients. Compared with PHPT patients without stones, PHPT patients with stones were significantly younger (56.4 vs 61.3 years, P=.02), less likely to be female (54.9% vs 71.9%, P=.03), and had significantly lower levels of vitamin D (19.7 vs 23.5 ng/mL, P=.03). Nine patients (3.5%) developed stones after PTX and were found to have significantly higher post-PTX total serum calcium levels when compared with those without stones. Although hypercalciuria was detected in 62% of pre-PTX stone formers, none of those who tested had post-PTX hypercalciuria (P<.001). On multivariate regression analysis, post-PTX stone formation was associated with male gender (adjusted odds ratio [95% confidence interval]: 6.8 [5.3-7.2], P=.01) and post-PTX hypercalcemia (adjusted odds ratio [95% confidence interval]: 1.48 [1.33-2.12], P=.02). CONCLUSION Pre-PTX urolithiasis was associated with younger age, male gender, and lower levels of vitamin D, whereas post-PTX urolithiasis was independently predicted by male gender and hypercalcemia.

Invasion and migration of coordinated cell clusters in rhabdomyosarcoma and other head and neck tumors in a 3-D collagen matrix

We report a rare case of a 34-year-old man with a right axillary mass. Ten years previously, he had been diagnosed with a right scapular nonseminomatous germ-cell tumor consisting of teratoma, completely resected without any further treatment. Presently he was found to have a metastatic malignant small round cell tumor consistent with a secondary somatic malignancy arising in the background of nonseminomatous germ-cell tumor, teratoma, yolk sac tumor, and primitive neuroectodermal tumor with distinct chromosome 22 translocation. Although the patient initially responded well to chemotherapy with etoposide, cisplatin, ifosfamide and mesna, he relapsed shortly after.

Migration of Coordinated Cell Clusters in Mesenchymal and Epithelial Cancer Explants in Vitro

EXPRESSION OF NM23-H1 AND NM23-H2 IN HUMAN EPITHELIOID SARCOMA CELL LINES OF DIFFERENT INVASIVE POTENTIAL IN VITRO T. Heymer, R. Engers, C.D. Gerharz, R. Krause-Paulus, N. EIBadawy, H.E. Gabbert Objective: Although epithelioid sarcoma is a very aggressive tumor with high metastatic potential in vivo, no investigations of metastasis associated molecules have been reported yet. Therefore, three clonal subpopulations (GRU-1A, GRU-1B, GRU-1C), derived from the same human epithelioid sarcoma cell line (GRU-1), were characterized with regard to their invasive potential in vitro and the expression of the two candidate metastasis suppressor genes nm23-H1 and nm23-H2. Methods: In vitro invasivaness was determined by the Matrigel invasion assay and by adhesion assays to laminin, fibronectin, collagen IV, hyaluronic acid and plastic. Nm23-H1 and nm23-H2 expression were investigated by RT-PCR and subsequent isoform specific oligonucleotide-hybridisation. Results: In the Matrigel invasion assay GRU-1A exhibited the highest invasive potential while GRU-1B and GRU-1C were significantly less invasive (GRU1A: 112_+12; GRU-1B: 12+_2; GRU1C: 23+_3 transmigrated tumor cells/counting area). Adhesion assays revealed major differences in the adhesive capacity for laminin (GRU-1A: 60_+7; GRU-1B: 18_+9; GRU-1C: 29_+ 7 adherent cells) and plastic (GRU-1A: 115-+1; GRU-1B: 106+_2; GRU-1C: 50 9 +5 adherent cells), while no significant differences could be detected for fibronectin, collagen IV and hyaluronic acid. These results were paralleled by differences in the expression of nm23-H1 and nm23-H2. While in the highly invasive cell line GRU-IA only nm23-H1 was detected, the cell lines of low invasive potential GRU-1B and GRU-1C both expressed nm23-H2. Furthermore, in GRU-1B also nm23-Hl was detected. Conclusions: In our tumor model the expression of nm23-H2 is inversely correlated with the invasive phenotype in vitro and the adhesive capacity to laminin. These results suggest a possibly inhibitory function of nm23-H2 in tumor invasion. Transfection experiments are under progress in order to examine a causative role of nm23-H2.