Long-Term Outcome of Lobectomy for Thyroid Cancer.

INTRODUCTION: Recent guidelines of the American Thyroid Association (ATA) suggest that a lobectomy may be sufficient to treat low- to intermediate-risk patients with thyroid tumors ≤40 mm, without extrathyroidal extension or lymph node metastases. The present study aimed to evaluate long-term recurrence after lobectomy for differentiated thyroid cancer and to analyze factors associated with recurrence. METHODS: In this retrospective cohort study, patients who underwent a lobectomy for thyroid cancer in a tertiary center between 1970 and 2010 were included. The outcome was the proportion of pathology-confirmed thyroid cancer recurrence, assessed in the whole cohort or in subgroups according to tumor size (≤ or >40 mm). RESULTS: A total of 295 patients were included, and these were followed-up for a mean (standard deviation, SD) 19.1 (7.8) years (5,649 patient-years); 61 (20.7%) were male and the mean (SD) age at diagnosis was 39.7 (12) years. Histological subtype was papillary in 263 (89.2%) patients and mean cancer size was 22.9 (16.9) mm. According to the 2015 ATA guidelines, 271 (91.9%) cancers had a low risk of recurrence and 24 (8.1%) an intermediate risk. A reoperation was performed in 54 patients (18.3%) and recurrence was confirmed in 40 (13.6%), diagnosed for 55% of cases more than 10 years after their initial surgery. Among recurrent patients, 14 (4.8% of the cohort) were operated for a contralateral papillary thyroid microcarcinoma and 26 (8.8% of the cohort) for a locoregional or metastatic recurrence. Non-suspicious nodular recurrences were monitored without reoperation in 53 (18.0%) patients. At the end of follow-up, 282 (95.6%) patients were in remission. Tumors with locoregional or metastatic recurrence were more frequent among tumors with aggressive histology (19.2 vs. 4.1%, p = 0.015) and of intermediate risk category (28.6 vs. 7.1%, p = 0.018). Tumors >40 mm, which would have been treated by thyroidectomy according to the 2015 ATA guidelines criteria, were found in 34 (11.5%) patients and were associated with a higher frequency of recurrence (20.6 vs. 7.3%, p = 0.024) and less remission (85.3 vs. 96.9%, p = 0.001). CONCLUSION: The outcome of thyroid cancer treated by lobectomy is very good, particularly for cancer ≤40 mm. A prolonged follow-up is required due to the risk of late recurrence.

Impact of thyroid surgery volume and pathologic detection on risk of thyroid cancer: A geographical analysis in the Rhône-Alpes region of France.

OBJECTIVE: To investigate the impact of the volume of thyroid surgery and pathologic detection on the risk of thyroid cancer. METHODS: We investigated the influence of the volume of thyroid surgery in a first study that included 23 384 thyroid surgeries and 5302 thyroid cancers collected between 2008 and 2013. Standardized incidence ratios (SIRs) and thyroid intervention rates (STIRs) were used as indicators of cancer risk and surgery volume, respectively. The influence of pathologic detection, using the number of cuts per gram of tissue as the indicator, was studied in a second study that included 1257 thyroid specimens, collected in 2014. RESULTS: We found departmental variations in SIRs and a significant effect of the STIR on the SIR (men, P = 0.0008; women, P < 0.0001). A 1/100 000 increase in the STIR resulted in a 3% and 1.3% increase in the SIR in men and women, respectively. This effect was greatest for microcancers and absent for tumours >4 cm. The risk of cancer diagnosis was significantly associated with the number of cuts per gram of tissue (OR 6.1, P < 0.001), and was greater for total thyroidectomy than for lobectomy (P = 0.014) and when FNA cytology had been preoperatively performed (P < 0.001). The prevalence of incidental microcancers was highest in the centres performing the highest number of cuts per gram. CONCLUSIONS: The risk of thyroid cancer, particularly microcancer, is related to the volume of surgery and to the level of pathologist scrutiny. Both factors contribute to the increase in overdiagnosis. This further advocates for appropriate selection of patients for thyroid surgery.

Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

BACKGROUND: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk. METHODS: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas. RESULTS: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk. CONCLUSION: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

PURPOSE: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk. METHODS: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status. RESULTS: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years). CONCLUSION: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.

Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer.

Expression of CD133 in differentiated thyroid cancer of young patients.

AIMS: CD133 expression in cancer is frequently associated with poor outcome. Thyroid carcinomas are rare in childhood and adolescence and are associated with a higher risk of recurrence and more metastases than the adult tumours. The aim of the study was to assess whether the expression of CD133 in thyroid carcinomas of children, adolescents and young adults was correlated with clinical prognostic factors. METHODS: Tissue microarrays were constructed with 235 tumours coming from 208 young adults with a median age of 28 years and 27 children with a median age of 13 years. An immunohistochemical study was performed with anti-CD133 antibody. CD133 expression was evaluated, using a semiquantitative score based on the percentage of positive cells. The mutation status of tumours was evaluated by reverse transcriptase PCR. Three cell lines were used to confirm CD133 expression by western blot. RESULTS: CD133 expression was found in 43% of adult and 37% of child tumours and was confirmed by western blot in cell lines. In young adults, the expression of CD133 was significantly more frequent in patients with tumours >3 cm (p=0.04) and in patients with lymph node metastases (p=0.02). The expression of CD133 was more frequent in patients in whom the tumour presented a BRAF mutation (p=0.03). CONCLUSIONS: CD133 expression is correlated with tumour size, lymph nodes metastases and BRAF mutations in young adults. The presence of these cancer stem cells could offer new therapeutic alternatives for aggressive thyroid cancers.

Thyroid tumors of uncertain malignant potential: morphologic and imunohistochemical analysis of 29 cases.

INTRODUCTION: Thyroid tumors of uncertain malignant potential (TT-UMP) include follicular and well-differentiated tumors of UMP (FT-UMP/WDT-UMP), as it refers to the presence of questionable capsular/vascular invasion or incompletely developed papillary thyroid carcinoma (PTC)-type nuclear changes. However, these tumors are difficult to diagnose in most cases. We aimed to investigate whether immunohistochemistry (HBME-1, cytokeratin-19, galectin-3, CD56 and p63) provides additional information concerning such lesions. MATERIALS AND METHODS: We performed an immunohistochemical analysis on 29 TT-UMP cases (22 WDTs-UMP and 7 FTs-UMP) selected from the Rhone Alpes thyroid cancer registry and Departement of Pathology, Tîrgu-Mures Emergency County Hospital database. The clinicopathological and follow-up data were obtained. RESULTS: In the WDT-UMP group, HBME-1 was positive in 9/22 (40.9%) cases. CD56, a marker whose expression is reduced or absent in thyroid carcinoma, showed a "malignant" profile (no expression) in 13/22 (59.1%) cases. 7/22 (31.9%) cases were both HBME-1+ and CD56-. One case showed the co-expression of HBME-1, CD56, galectin-3 and cytokeratin-19. In the FT-UMP group, two cases were positive for HBME-1, other two for both galectin-3 and CK19 and only one case revealed a "malignant" CD56 profile. The follow-up data showed no distant metastases or persistent disease. CONCLUSION: Our study demonstrated very heterogeneous immunohistochemical profiles for TTs-UMP, further supporting the borderline nature of these lesions. WDTs-UMP revealed a certain tendency toward a PTC profile, suggesting a possible pathogeneticlink between these two entities. However, immunohistochemistry is still to be regarded more as a supporting diagnostic tool, while morphological criteria should always prime in the diagnostic decision.

Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study.

The incidence of thyroid cancer has increased in eastern Europe since the Chernobyl nuclear power plant accident. Although the radioactive fallout was much less severe and the thyroid radiation dose was much lower in France, a case-control study was initiated in eastern France. The present study included 633 young women who were diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006 and matched with 677 controls. Face-to-face interviews were conducted from 2005 to 2010. Odds ratios were calculated using conditional logistic regressions and were reported in the total group and by histopathological type of cancer ("only papillary" and "excluding microcarcinomas"). The risk of thyroid cancer was higher in women who had a higher number of pregnancies, used a lactation suppressant, or had early menarche. Conversely, breastfeeding, oral contraceptive use, and late age at first pregnancy were associated with a lower risk of thyroid cancer. No association was observed between thyroid cancer and having irregular menstrual cycle, undergoing treatment for menstrual cycle regularity shortly after menarche, having a cessation of menstruation, use of another contraceptive, history of miscarriage or abortion for the first pregnancy, or having had gestational diabetes. This study confirms the role of hormonal and reproductive factors in thyroid cancer, and our results support the fact that exposure to estrogens increases thyroid cancer risk.

Immunohistochemical markers in the diagnosis of papillary thyroid carcinomas: The promising role of combined immunostaining using HBME-1 and CD56.

We aimed to evaluate the expression and diagnostic value of five immunohistochemical markers (HBME-1, Galectin-3, CK19, CD56 and p63) in a very large series of unequivocal papillary thyroid carcinoma (PTC) cases, including both the classic (CPTC) and the follicular variant (FVPTC). We performed an immunohistochemical analysis on a tissue micro-array of 204 PTCs (98 CPTCs, 90 FVPTCs, and 16 other variants). HBME-1 was the most sensitive marker, staining 95.9% of CPTCs and 81.1% of FVPTCs. CD56, a marker whose expression is reduced or absent in thyroid carcinoma, revealed a negative, "malignant" profile in 93.9% of CPTCs and 73.3% of FVPTCs. Galectin-3, CK19 and p63 were positive in 64.7%, 45.6% and 6.9% of PTCs, respectively. The immunopanel consisting of HBME-1, CD56 and/or CK19 reached the highest sensitivity (95.6%). The co-expression of 2 or more proteins was observed in 88.2% of PTCs, with HBME-1 and CD56 being the most frequent positive association (79.4%). We report a new panel of antibodies consisting of HBME-1, CK19 and CD56 that was found to be highly sensitive for both CPTC and FVPTC. This panel could be recommended as a supplement to the morphological criteria in the diagnosis of difficult FVPTC cases.

Thyroid cancers in children, adolescents, and young adults with and without a history of childhood exposure to therapeutic radiation for other cancers.

BACKGROUND: The thyroid is highly sensitive to the carcinogenic effect of radiation in children. We compared, in patients with and without earlier childhood radiation, the features of papillary thyroid cancer (PTC) diagnosed in later childhood through young adulthood. METHODS: Patients were from the Rhône-Alpes Thyroid Cancer Registry. Twenty-four patients (RAD group) had been treated by radiation therapy for nonthyroid neoplasms at the age of 8.0±6.0 years (mean±SD) and by surgery for PTC at the age of 17±6.4 years. They were compared with 413 patients with PTC but no radiation exposure (sPTC group, age 23±4.8 years). The two groups were subdivided into three subgroups, ages 8-14 (children), 15-20 (adolescents), and 21-29 years (adults) at time of PTC diagnosis, and compared to matched subgroups from 80 patients in the sPTC group (M-sPTC). Age in years at PTC diagnosis (RAD vs. M-sPTC) was 12±2 compared with 12±2 for children, 17±1 compared with 19±1 for adolescents, and 25±3.2 compared with 25±2.5 for adults. The matched subgroups had comparable pTNM, treatments, and follow-up. We compared the histopathological characteristics of the initial specimens and the outcome events. RESULTS: The RAD group and the sPTC group were similar in terms of age when PTC was diagnosed. RAD tumors had significantly more lymph node metastases (p=0.007) and a higher proportion of invasive pTN3 stage tumors (p=0.01). The adult RAD subgroup (n=8) was more likely to have lymph node metastases (p=0.004) and a higher proportion of invasive pT3N+ stage tumors (p=0.01) than the adult sPTC subgroup (n=316). During the 6.5 years of follow-up, there was no difference in the risk of cervical recurrence between the RAD group and the M-sPTC groups. Risk of cervical recurrence was also similar for tumors that were high risk (pT3N+). CONCLUSION: Young adults with PTC associated with radiation therapy for nonthyroid neoplasms in childhood have a more aggressive initial presentation than young adults with sporadic PTC. The risk of recurrent disease in patients who received radiation in early childhood through adolescence and who developed PTC in late childhood through early adulthood is similar to those who did not receive radiation.

Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery.

Ectopic acromegaly is very rare and since the discovery of growth hormone-releasing hormone (GHRH), 30 years ago, only 74 cases have been reported in the literature. Except for a recent French series of 21 cases, most of them were case reports. The present review summarizes the current knowledge on clinical presentation, diagnosis and prognosis. Tumors secreting GHRH are neuroendocrine tumors, usually well differentiated and mainly from pancreatic or bronchial origin. They are usually large and easy to localize using TDM and somatostatin receptor scintigraphy. Clinical presentation is an acromegaly of variable intensity, whose features are similar to that of a somatotropic adenoma. Pituitary may be normal or enlarged at MRI which may be difficult to interpret especially in MEN1 patients where the association of a microprolactinoma to a pancreatic tumor secreting GHRH may be misleading. GHRH plasmatic measurement has an excellent specificity for the diagnosis, using a threshold of 250 to 300ng/L and is a good tool for follow-up of patients after treatment. These tumors have a good overall prognosis, even in metastatic forms which represent 50% of cases. Surgical approach is recommended and, when a complete tumoral resection is feasible, results, in most patients, in long-lasting remission. In such cases, GHRH concentration is normalized and its increase is an accurate indicator of recurrence. In uncured patients, somatostatin analogs control GH secretion but inhibit, only partially, GHRH secretion. MEN1 mutation should be systematically investigated in patients with a pancreatic tumor.

Pregnant French women living in the Lyon area are iodine deficient and have elevated serum thyroglobulin concentrations.

BACKGROUND: Iodine deficiency (ID) remains common in Europe, and may be especially detrimental during pregnancy. The aim of our study was to assess iodine status and thyroid function in healthy pregnant women in the Lyon metropolitan area. METHODS: In a cross-sectional study, healthy pregnant women (n=228) with no history of thyroid disease were consecutively recruited from an obstetric clinic during all trimesters. Thyrotropin (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO) antibodies, thyroglobulin (Tg), and urinary iodine concentration (UIC) (n=100) were measured. Thyroid functions were compared with those in a control group of nonpregnant adults. RESULTS: The median (range) UIC was 81 (8-832) µg/L, and 77% of pregnant women had a UIC <150 µg/L, indicating inadequate iodine intake. Overall, 11% of women had abnormal TSH or anti-TPO. The median FT4 (pmol/L) was 14.9, 12.6, and 11.5 in the first, second, and third trimesters, respectively. The median Tg in pregnant women was 16.2 µg/L, did not differ across trimesters, and was significantly higher than in the control group of nonpregnant adults (11.7 µg/L) (p=0.02). Controlling for maternal age and week of gestation, UIC was not a significant predictor of any of the thyroid function tests. CONCLUSIONS: Pregnant women in the Lyon area are iodine deficient and have increased serum Tg concentrations compared with nonpregnant controls, likely due to physiological thyroid hyperstimulation during gestation exacerbated by ID.

Clinical characteristics and outcome of acromegaly induced by ectopic secretion of growth hormone-releasing hormone (GHRH): a French nationwide series of 21 cases.

CONTEXT: Ectopic GHRH secretion is a rare cause of acromegaly, and case reports are mainly isolated. SETTING: From the registry of the sole laboratory performing plasma GHRH assays in France, we identified cases of ectopic GHRH secretion presenting with acromegaly between 1983 and 2008. PATIENTS: Twenty-one patients aged 14-77 yr were identified from 12 French hospitals. Median GHRH was 548 (270-9779) ng/liter. MAIN OUTCOME MEASURES: Outcome measures included description of tumor features and outcome and the relation between plasma GHRH values and tumor site, size, and spread. RESULTS: The primary neuroendocrine tumor was identified for 20 of 21 patients (12 pancreatic, seven bronchial, one appendicular). Tumors were large (10-80 mm), identified on computed tomography scan in 18 cases and by endoscopic ultrasound and somatostatin receptor scintigraphy in two. Somatostatin receptor scintigraphy had a similar sensitivity to computed tomography scan (81 vs. 86%). Tumors were all well differentiated; 47.6% had metastasized at the time of diagnosis of acromegaly. After a median follow-up of 5 yr, 85% of patients were alive. Ninety-one percent of patients whose tumor was completely removed were considered in remission, and most had normalized plasma GHRH. The remaining patients were treated with somatostatin analogs: IGF-I normalized except for one patient who required pegvisomant, but GHRH levels remained elevated. No correlations were found between GHRH levels and tumor site or size or the existence of metastases. Identification of increased plasma GHRH during follow-up was an accurate indicator of recurrence. CONCLUSIONS: The prognosis of endocrine tumors responsible for GHRH secretion appears relatively good. Plasma GHRH assay is an accurate tool for diagnosis and follow-up.

Oncogenic alterations in papillary thyroid cancers of young patients.

BACKGROUND: Papillary thyroid carcinoma (PTC) in young people usually has an aggressive initial presentation, though a good general prognosis despite recurrences in 10%-20% of patients. A number of genetic alterations that activate the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some of these alterations have been identified as prognostic factors of PTC in adults. The objective of the current study was to comprehensively characterize all known oncogenic alterations of the MAPK pathway in young people. METHODS: One hundred three PTCs removed from 9 children, 19 adolescents, and 75 young adults were submitted to molecular analyses. RESULTS: Altogether, 57 alterations were found in 56 PTCs (55%) corresponding to V600E BRAF in 20.3%, RAS mutations in 12.6%, RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The prevalence of all alterations increased with age (22.2% in children; 52.6% in adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years). Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to BRAF mutations. Classic-type PTC was associated with a larger prevalence of alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This association was found in the adult group. There were no associations of BRAF or RAS mutations with ET or LNM. A 3-year median follow up was available for 90 patients. RET/PTC 1 and 3 was associated with short-term disease dissemination (cervical lymph node recurrences and distant metastases) in young adults (p=0.001). Persistent illness was more prevalent in patients with (15%) than in patients without (7%) genetic alterations. CONCLUSION: PTCs in young patients display a low prevalence of the already identified oncogenic alterations. The increasing prevalence with age is mainly due to V600E BRAF mutation. There is no relation between tumor aggressiveness and BRAF mutation. There is a relation between the presence of RET/PTC (1 and 3) and the histological and clinical short-term aggressiveness of PTC in the population of young adults. Such a relation is not found in children and adolescents.

Geographical correlation between incidence of benign disease and that of cancer of the thyroid among the population of the Rhône-Alpes Région of France.

OBJECTIVE: To analyze, at a population level, the relation between the incidences of benign thyroid diseases in patients submitted to surgery and that of thyroid cancers based on their respective geographical distributions. METHODS: The study included 3169 cases (691 cancers and 2478 benign diseases) operated on in 2002 in the Rhône-Alpes région, which is subdivided into eight départements and 311 cantons. RESULTS: The total thyroid intervention rate was 54.6/100 000 (23.4 and 86.4), and the annual cancer incidence was 11.9/100 000 (4.7 and 13.8) for men and women respectively. The prevalence of cancer among thyroid surgery was 21.8% and that of cancer discovered in goiters increased with age (44% at 60 years). Intervention rates varied from départment to département. In women, the incidence of microcancers was correlated to the thyroid intervention for benign pathologies rate. In men, the incidence of supracentimetric cancers was related to the TIBR. At the canton level, the relative risk of benign diseases was correlated to that of cancers. TIBR and incidence of cancers were higher in urban cantons than in nonurban ones. The density of endocrinologists influenced the prevalence of cancers among all the cases submitted to surgery. CONCLUSION: In the Rhône-Alpes population with high rates of thyroid cancer incidence and of thyroid surgery, a number of correlations were found according to gender and tumor size. However, the general incidence of cancer was not directly related to surgical activity. Geographical variability may be related to the heterogeneous medical and pathological practices.

Thyroid cancer: is the incidence rise abating?

OBJECTIVE: The aim of the present study was to determine recent trends in thyroid cancer incidence rates and to analyze histopathological characteristics and geographical distribution. METHODS: Histologically proven 5367 cases were collected over the period 1998-2006 in France from the Rhône-Alpes thyroid cancer registry. Geographical variations of incidence were analyzed using a mixed Poisson model. RESULTS: The average incidence rates, age standardized to the world population, were 3.9/100,000 in men and 12.3/100,000 in women, higher than those previously reported in France. After an initial increase during the first 3 years, a steady level of incidence was observed for the period 2001-2006. The annual incidence rate of microcarcinomas was correlated with that of all cancers in men and women (r=0.78 and 0.89; P<0.01) respectively. Papillary microcarcinomas represented 38% of tumors and two-thirds of them measured less than 5 mm in diameter. They were fortuitously discovered after thyroidectomy for benign diseases in 64% of cases. Histological marks of aggressiveness differed according to the size of the tumor. Despite recent advances in diagnosis, 13% of tumors were diagnosed at advanced stage especially in men. Geographical distribution of incidence based on subregional administrative entities showed lower incidence rates in rural than in urban zones in men (relative rate: 0.72; 95% CI: 0.62-0.84) and women (relative rate: 0.85; 95% CI: 0.73-0.93). CONCLUSION: The present study suggests that the rise in thyroid cancer incidence is now abating. It could reflect standardization in diagnostic procedures. Further studies, performed on a more prolonged period, are necessary to confirm these data.

Diagnostic management of suspected metastatic thyroid carcinoma: clinical value of octreotide scintigraphy in patients with negative high-dose radioiodine scans.

OBJECTIVES: Somatostatin receptor scintigraphy (SRS) with (111)In-octreotide has been suggested as a potential tool for the detection of recurrent or metastatic differentiated thyroid cancer when no radioiodine uptake can be demonstrated in tumour sites. However, there is no consensus concerning the performance and clinical impact of this examination in such instances. DESIGN AND METHODS: A prospective study was undertaken to evaluate SRS in 43 patients (18 men, 25 women) with papillary (n=20), follicular (n=9), insular (n=6) and oncocytic (n=8) thyroid carcinomas with elevated serum thyroglobulin (Tg) levels and no detected radioiodine uptake. RESULTS: Evaluation criteria were interpreted in terms of an assumed presence of tumoural tissue. Sensitivity of SRS was 51%, clearly lower than that of conventional imaging procedures, and of positron emission tomography using [(18)F]-2-fluoro-2-deoxy-d-glucose, performed in a subset of 27 patients. In addition, we observed two false-positive foci of uptake of octreotide that corresponded to inflammatory pulmonary sites. The sensitivity was higher in patients with Tg levels greater than 50 microg/l (76%) for detecting mediastinal lesions (93%), and in patients with oncocytic cancer (88%). Finally, SRS changed treatment strategy in four patients. CONCLUSION: In differentiated thyroid cancer, SRS is a moderately sensitive method for the detection of lesions unable to concentrate iodine and appears useful only in patients with very high Tg levels or in oncocytic cancer.

Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake?

OBJECTIVE: Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-d-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci. DESIGN AND METHODS: This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hurthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (>10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination. RESULTS: Results were interpreted in terms of assumed presence of tumoral tIssue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n=16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 microg/l (P<0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients. CONCLUSIONS: nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.

Detection of neuroendocrine tumors: 99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy.

UNLABELLED: The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, 99mTc-P829, compared with that of 111In-pentetreotide. METHODS: Forty-three patients (32 men, 11 women; age range, 24-78 y; mean age, 56 y) with biologically or histologically proven neuroendocrine tumors were prospectively included: 11 patients with Zollinger-Ellison syndrome, 16 patients with carcinoid tumors, and 16 patients with other types of functioning (n = 6) or nonfunctioning (n = 10) endocrine tumors. 111In-Pentetreotide planar images (head, chest, abdomen, and pelvis) were obtained 4 and 24 h after injection of 10 microg somatostatin analog labeled with 148 +/- 17 MBq 111In, and SPECT was performed 24 h after injection. Similar (99m)Tc-P829 planar images were obtained at 1, 4-6, and 24 h after injection of 50 microg peptide labeled with 991.6 +/- 187.59 MBq 99mTc. Abdominal SPECT was performed 4-6 h after injection. RESULTS: 111In-Pentetreotide detected 203 tumoral sites in 39 (91%) of 43 patients, whereas 99mTc-P829 detected 77 sites in 28 (65%) of 43 patients (P < 0.005). In the liver, 129 sites (in 24 patients) were detected by 111In-pentetreotide scintigraphy and 34 sites (in 10 patients) were detected by 99mTc-P829 scintigraphy. CONCLUSION: In patients with endocrine tumors, the detection rate of 99mTc-P829 scintigraphy was lower than that of 111In-pentetreotide scintigraphy, which appeared to be more sensitive, especially for liver metastases.