Diagnosing water security in the rural North with an environmental security framework.

This study explores the nature of water security challenges in rural Alaska, using a framework for environmental security that entails four interrelated concepts: availability, access, utility, and stability of water resources. Many researchers and professionals agree that water insecurity is a problem in rural Alaska, although the scale and nature of the problem is contested. Some academics have argued that the problem is systemic, and rooted in an approach to water security by the state that prioritizes economic concerns over public health concerns. Health practitioners and state agencies, on the other hand, contend that much progress has been made, and that nearly all rural households have access to safe drinking water, though many are still lacking 'modern' in-home water service. Here, we draw on a synthesis of ethnographic research alongside data from state agencies to show that the persistent water insecurity problems in rural Alaska are not a problem of access to or availability of clean water, or a lack of 'modern' infrastructure, but instead are rooted in complex human dimensions of water resources management, including the political legacies of state and federal community development schemes that did not fully account for local needs and challenges. The diagnostic approach we implement here helps to identify solutions to these challenges, which accordingly focus on place-based needs and empowering local actors. The framework likewise proves to be broadly applicable to exploring water security concerns elsewhere in the world.

Factors predictive of lymph node metastasis in the follicular variant of papillary thyroid carcinoma.

BACKGROUND: The treatment of papillary thyroid carcinomas larger than 1 cm usually consists of total thyroidectomy and central lymph node dissection (LND). In patients with the follicular variant of papillary thyroid carcinoma (FVPTC), preoperative cytology and intraoperative frozen-section analysis cannot always establish the diagnosis. The aim of this study was to evaluate predictive factors for lymph node metastasis in patients with FVPTC and to identify patients who might benefit from LND. METHODS: The study included patients with FVPTC treated by total thyroidectomy and LND between 2000 and 2010 in four departments. When fewer than six non-involved lymph nodes were removed, the patient was excluded from the analysis. RESULTS: Some 199 patients were included. The median tumour size was 17 (range 1-85) mm, and tumours were classified as T1a in 28 patients, T1b in 40, T2 in 53, and T3 in 78. Eighty-one patients (40·7 per cent) had lymph node metastasis (51 classified as N1a and 30 as N1b). Four risk factors were predictive of lymph node metastasis in the multivariable analysis: multifocality (odds ratio (OR) 2·36, 95 per cent confidence interval 1·15 to 4·86), angiolymphatic invasion (OR 3·67, 1·01 to 13·36), absence of tumour capsule (OR 3·00, 1·47 to 6·14) and tumour involvement of perithyroid tissue (OR 3·89, 1·85 to 8·18). The rate of lymph node metastasis varied between 14 and 94 per cent depending on the presence of risk factors. CONCLUSION: The rate of lymph node metastasis in patients with FVPTC varies widely according to the presence or absence of predictive risk factors.

Pheochromocytoma revealed by acute heart failure. When should we operate? Presented at the ESES Congress, Gothenburg May 25-26, 2012.

PURPOSE: The aim of this study was to assess the safety and efficacy of adrenalectomy on patients with pheochromocytoma diagnosed at the time of an acute heart failure (AHF). METHODS: We reported cases of patients who presented an AHF secondary to a pheochromocytoma during a period of 10 years. The diagnosis of AHF was defined by a left ventricular ejection fraction of less than 30 % or the use of circulatory assistance. They had adrenalectomy as emergency surgery or later. Morbidity and mortality of surgery were studied. RESULTS: Thirteen patients required an adrenalectomy for AHF secondary to pheochromocytoma. Four patients (31 %) had an adrenalectomy in emergency. Nine patients (69 %) had a delayed surgery with a median delay of 25 days (7-180). Eight patients had circulatory assistance (61 %). Five of them had a circulatory assistance and a delayed surgery (38 %), two of them had a circulatory assistance followed by emergency surgery (at 1.5 and 3 days) and one had emergency surgery immediately followed by circulatory assistance. Emergency surgery was performed by laparotomy in all cases and delayed surgery by laparoscopy for seven patients (54 %). Perioperative complications consisted in: one circulatory arrest, two bleedings requiring transfusion, one intestinal ischaemia, one haemoperitoneum with re-operation (day 8). One patient died on day 5. Post-operative course of patients with delayed surgery was uneventful. CONCLUSIONS: AHF revealing a pheochromocytoma is a rare and serious event. Patients with emergency surgery have more complications than those with delayed surgery.

Comparison of [¹¹¹In]pentetreotide-SPECT and [¹8F]FDOPA-PET in the localization of extra-adrenal paragangliomas: the case for a patient-tailored use of nuclear imaging modalities.

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).

Mild hypercalcitoninaemia and sporadic thyroid disease.

BACKGROUND: Not operating on patients with mild hypercalcitoninaemia (MHCT) and sporadic thyroid disease carries the risk of omitting curative surgery for medullary thyroid cancer, but systematic surgery would result in unnecessary treatment of benign pathology. This study reviewed the management of MCHT and non-hereditary thyroid disease in one centre. METHODS: MCHT was defined as an increase in basal and stimulated calcitonin levels not exceeding 30 and 200 pg/ml respectively. Over 15 years, 125 patients who presented with MCHT and sporadic thyroid disease were followed. Surgery was indicated only if there were local pressure symptoms or suspicious histomorphological changes in solitary nodules. RESULTS: Fifty-five patients underwent total thyroidectomy and 18 unilateral total lobectomy. Histological examination revealed medullary microcarcinoma in six patients (two women and four men). C-cell hyperplasia was found in 54 patients (74 per cent) and 13 (18 per cent) harboured no C-cell pathology. Calcitonin levels stabilized after lobectomy and became undetectable following thyroidectomy. They normalized during follow-up in a third of patients who did not have surgery. CONCLUSION: Not all patients with MHCT and sporadic thyroid disease require surgery.

Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary thyroid carcinoma: a molecular guide to the optimal extent of surgery?

BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent. METHODS: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts. CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation (RRA) with recombinant human TSH (rhTSH): a randomized controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) has become the modality of choice for radioiodine remnant ablation (RRA) in low-risk thyroid cancer patients. AIMS AND METHODS: The aims of the present prospective randomized study were to evaluate the impact of TSH stimulation procedure (hypothyroidism vs. rhTSH) on quality of life (QoL) of thyroid cancer patients undergoing RRA and to evaluate efficacy of both procedures. L-T4 was initiated in both groups after thyroidectomy. After randomization, L-T4 was discontinued in hypothyroid (hypo) group and continued in rhTSH group. A measure of 3.7 GBq of radioiodine was given to both groups. The functional assessment of chronic illness therapy-fatigue (FACIT-F) was administered from the early postoperative period to 9 months. Socio-demographic parameters, anxiety and depression scales were also evaluated (CES-D, BDI and Spielberger state-trait questionnaires). At 9 months, patients underwent an rhTSH stimulation test, diagnostic (131)I whole body scan (dxWBS) and neck ultrasonography. RESULTS: A total of 74 patients were enrolled for the study. There was a significant decrease in QoL from baseline (t0) to t1 (RRA period) in the hypothyroid group with significant differences in FACIT-F TOI (P < 10(-3)), FACT-G total score (P = 0.005) and FACIT-F total score (P = 0.003). By contrast, QoL was preserved in the rhTSH group. In the multivariate analysis, FACIT-TOI changes were only affected by the modality of TSH stimulation performed for RRA. From 3 to 9 months, changes of QoL scales and subscales were no longer statistically different in both groups of patients. Based on serum rhTSH-stimulated Tg alone (Tg < 0.8 microg/l, BRAHMS Tg Kryptor), no difference in ablation success was observed between rhTSH and hypothyroidism groups, 91.7% and 97.1%, respectively. A higher rate of persistent thyroid remnants was observed in the rhTSH arm, although in most cases uptake was < 0.1% and of no clinical significance. CONCLUSIONS: rhTSH preserves QoL of patients undergoing RRA with similar rates of ablation success compared to hypothyrodism. However, there is a wide heterogeneity in the clinical impact of hypothyroidism.

Tumoricidal response induced by cytosine arabinoside after plasma perfusion over protein A.

In dogs with spontaneous mammary adenocarcinomas, a single nontoxic infusion of cytosine arabinoside after extracorporeal perfusion of plasms over immobilized protein A resulted in a necrotizing response rapid in onset and specific for tumorous tissue. Gross tumoricidal reactions 12 hours after this combined treatment exceeded the algebraic sum of responses to cytosine arabinoside and protein A perfusion treatments alone in the same dogs, implying a synergistic effect between the two. The magnitude, rapidity, and specificity of the tumoricidal response after the combined treatment suggests that it may be an effective chemimmunotherapeutic approach to breast adenocarcinoma.

[Acute pancreatitis and primary hyperparathyroidism: a multicentric study by the Francophone Association of Endocrine Surgeons]. / Pancréatite aiguë et hyperparathyroïdie primaire: étude multicentrique de l'Association francophone de chirurgie endocrinienne.

BACKGROUND: Primary hyperparathyroidism is an unusual cause of acute pancreatitis. The aim of this study was to analyse data from multiple centers concerning patients with primary hyperparathyroidism and associated acute pancreatitis and to analyze potential predictive factors. METHODS: In this retrospective multicentric study, 19 patients were identified (Group A) with the associated diagnoses of acute pancreatitis and primary hyperparathyroidism. Their clinical data was compared to that of a control group of 65 patients (group B) with primary hyperparathyroidism without acute pancreatitis. RESULTS: Age, parathormone levels and pathology (uni/multiglandular disease) were similar between the two groups. The mean plasma calcium level was significantly higher in group A (12.64 mg/100ml) than in group B patients without pancreatitis (11.28 mg/100ml) (p<0.0001). CONCLUSION: This study confirms the causal relationship between primary hyperparathyroidism and acute pancreatitis. The degree of hypercalcemia may play an important role in this association. Calcium levels should be measured in all patients with acute pancreatitis.

The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas.

BACKGROUND: (18)F-DOPA has emerged as a promising tool in the localization of chromaffin-tissue-derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid. AIM AND METHODS: The aim of this study was to retrospectively evaluate the results of (18)F-FDOPA and/or (18)F-FDG-PET in patients with PHEO and paragangliomas (PGLs) and to compare the outcome of this approach with the traditional therapeutic work-up. Nine patients with non-MEN2 related PHEO or PGL were evaluated. At the time of the PET studies, the patients were classified into three groups based on their clinical history, conventional and SPECT imaging. The groups were malignant disease (n = 5, 1 VHL), apparently unique tumour site in patients with previous surgery (n = 1, SDHB) and multifocal tumours (n = 3, 1 VHL, 1 SDHD). (18)F-FDOPA and (18)F-FDG-PET PET/CT were then performed in all patients. RESULTS: PET successfully identified additional tumour sites in five out of five patients with metastatic disease that had not been identified with SPECT + CI. Whilst tumour tracer uptake varied between patients it exhibited a consistently favourable residence time for delayed acquisitions. (18)F-FDOPA uptake (SUVmax) was superior to (18)F-FDG uptake in cases of neck PGL (three patients, four tumours). If only metastatic forms and abdominal PGLs were considered, (18)F-FDG provided additional information in three cases (two metastatic forms, one multifocal disease with SDHD mutation) compared to (18)F-FDOPA. CONCLUSIONS: Our results suggest that tumour staging can be improved by combining (18)F-FDOPA and (18)F-FDG in the preoperative work-up of patients with abdominal and malignant PHEOs. (18)F-FDOPA is also an effective localization tool for neck PGLs. MIBG however, still has a role in these patients as MIBG and FDOPA images did not completely overlap.

Does 18F-FDG PET/CT add diagnostic accuracy in incidentally identified non-secreting adrenal tumours?

PURPOSE: The widespread use of high-resolution cross-sectional imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the investigation of the abdomen is associated with an increasing detection of incidental adrenal masses. We evaluated the ability of (18)F-fluorodeoxyglucose positron emission tomography to distinguish benign from malignant adrenal masses when CT or MRI results had been inconclusive. METHODS: We included only patients with no evidence of hormonal hypersecretion and no personal history of cancer or in whom previously diagnosed cancer was in prolonged remission. PET/CT scans were acquired after 90 min (mean, range 60-140 min) after FDG injection. The visual interpretation, maximum standardised uptake values (SUVmax) and adrenal compared to liver uptake ratio were correlated with the final histological diagnosis or clinico-radiological follow-up when surgery had not been performed. RESULTS: Thirty-seven patients with 41 adrenal masses were prospectively evaluated. The final diagnosis was 12 malignant, 17 benign tumours, and 12 tumours classified as benign on follow-up. The visual interpretation was more accurate than SUVmax alone, tumour diameter or unenhanced density, with a sensitivity of 100% (12/12), a specificity of 86% (25/29) and a negative predictive value of 100% (25/25). The use of 1.8 as the threshold for tumour/liver SUVmax ratio, retrospectively established, demonstrated 100% sensitivity and specificity. CONCLUSION: FDG PET/CT accurately characterises adrenal tumours, with an excellent sensitivity and negative predictive values. Thus, a negative PET may predict a benign tumour that would potentially prevent the need for surgery of adrenal tumours with inconclusive conventional imaging.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.

Lifestyle behaviours and components of energy balance as independent predictors of ghrelin and adiponectin in young non-obese women.

AIM: Dysregulation of the normal levels of ghrelin, leptin and adiponectin in young non-obese subjects could promote food intake, diabetes and cardiovascular disease in later stages of life. Little information is available on how plasmatic concentrations of these hormones may be influenced by eating habits and/or components of energy balance in a young population, which if known, could facilitate their voluntary regulation. METHODS: In this cross-sectional study we examined the predictors of fasting plasma ghrelin, adiponectin and leptin in a population of well-characterized young non-obese women (N = 63). Energy intake was assessed by 24-hour dietary recall, resting metabolic rate (RMR) by indirect calorimetry, physical activity energy expenditure (PAEE) by tri-axial accelerometer, physical fitness by VO(2 peak), and eating behaviors by self administrated questionnaire. RESULTS: Lower RMR and higher HDL-cholesterol were independent predictors of higher plasma ghrelin explaining 17.6% of its variation even after correcting for BMI. Higher total or central fat mass was the only predictor of higher plasma leptin, and no other variable added any power to the prediction equation. Finally, higher energy intake and waist circumference and lower PAEE predicted lower plasma adiponectin in young non-obese women, explaining 43% of the variation in its concentrations even after correcting for total or central fat mass. CONCLUSION: Components of the energy balance (ie: energy intake and/or expenditure) influence adiponectin and ghrelin circulating levels. That is, higher energy intake and lower physical activity independently predict lower adiponectin concentrations, whereas lower resting metabolic rate independently predicts higher ghrelin levels in young non-obese women. Prospective studies are needed to examine whether circulating concentrations of ghrelin and adiponectin can be voluntarily regulated by lifestyle interventions.

Endocrine surgical technique: endoscopic thyroidectomy via the lateral approach.

BACKGROUND: Minimal access approaches are increasingly used in endocrine surgery. Several minimal access approaches to the thyroid gland have been described, including a small-incision lateral approach and a video-assisted central approach, but to date no technique has been universally accepted. METHODS: Benefiting from the experience of more than 500 endoscopic parathyroidectomies via a lateral neck approach, the authors developed an endoscopic thyroidectomy based on the same approach and principles. Patients with solitary nodules smaller than 3 cm in diameter and no history of neck surgery or irradiation were offered this operation. A detailed description of the surgical technique is provided. RESULTS: Of the 742 thyroidectomies performed in 2004, 38 (5.1%) were endoscopic thyroidectomies. The mean nodule size was 22-mm (range, 7-47-mm), and the mean operating time was 99 min (range, 64-150-min). In all cases, the recurrent laryngeal nerve was preserved intact, and the superior and inferior parathyroids were identified, respectively, in 36 and 33 of the 38 patients. Two patients required conversion to an open cervicotomy. All patients were discharged the day after surgery. CONCLUSIONS: The described endoscopic lateral approach combines the coherence of the minimal access lateral approach and the benefits of fiberoptic magnification. It is a safe and effective technique in the hands of an appropriately trained surgeon.

[Lateral endoscopic approach for thyroid and parathyroid surgery]. / L'abord latéral endoscopique en chirurgie thyroparathyroïdienne.

The endoscopic lateral approach in thyroid and parathyroid surgery is achieved by developing the plane between the carotid sheath laterally and the strap muscles medially. This approach allows direct access to the posterior aspect of the thyroid lobe, without the need for the dissection of the strap muscles and without the need for medial retraction of the thyroid during the procedure. The lateral approach aided by endoscopic magnification provides the surgeon with the ideal view with which to safely dissect the vital structures found in the retro-thyroid space such as the inferior thyroid artery, the recurrent laryngeal nerve and the parathyroid glands. This approach was initially adopted in primary hyperparathyroidism caused by a single adenoma that had been localized preoperatively. It is now also offered to patients with an isolated thyroid nodule smaller than 25 mm in diameter requiring surgical excision. Experience with 408 parathyroidectomies and the preliminary results of 38 thyroid lobectomies allows the authors to recommend this technique to appropriately selected patients.

[Abrikossoff tumor of the proximal esophagus misdiagnosed as a thyroid nodule]. / Tumeur d'Abrikossoff de l'oesophage cervical: une cause rare de faux nodule thyroïdien.

The diagnosis of thyroid nodules is straightforward and rarely mistaken. We present a case of a paraesophageal granular cell tumor, discovered incidentally during surgery for what it was diagnosed as a suspicious thyroid nodule by ultrasound and FNA. Complete resection was achieved without disruption of the esophageal mucosa. A terminal branch of the recurrent laryngeal nerve had to be resected en bloc with the tumor. Morphological and immunohistochemical diagnosis was established postoperatively. A review of the literature is presented.

[Applied embryology of parathyroid glands].

The article describes the normal structure of the parathyroid glands (PTG) and their development, anomalies of migration in the process of embryogenesis and congenital ectopias of PTG as well as possible supplementary PTG and their congenital ectopias.

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits <5% significant recurrence after 10 years of follow-up and normal glucocorticoid function in more than 50% of the cases. Therefore, cortical sparing adrenal surgery should be systematically considered in the management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2.

ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients.

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret/PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret/PTC1 and ret/PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret/PTC1 was statistically similar in the three groups. The prevalence of ret/PTC3 was significantly higher in liquidators than in French patients (P = 0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P = 0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret/PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret/PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.

Specific pattern of RAS oncogene mutations in follicular thyroid tumors.

The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors according to malignancy and histology is controversial. Differences in methodology and histological classifications may explain discrepant results. To address this issue, we first performed a pooled analysis of 269 mutations garnered from 39 previous studies. Mutations proved significantly less frequent when detected with direct sequencing than without (12.3% vs. 17%). The rate of mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%. Mutations of codon 61 of N-RAS (N2) were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them were malignant. K-RAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special epidemiological circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of the three RAS genes. Common and atypical adenomas were separated using strict cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. These results confirm the predominance of N2-RAS mutations in thyroid follicular tumors and their correlation with malignancy. They support the implication of N2-RAS mutations in the malignant progression of thyroid follicular tumors and the assumption that some atypical adenomas are precursors of follicular carcinomas.