SPECT/CT sentinel lymph node identification in papillary thyroid cancer: lymphatic staging and surgical management improvement.

PURPOSE: Lymphadenectomy in papillary thyroid carcinoma (PTC) continues to be controversial. A better staging method is needed to provide adequate individual surgical treatment. SPECT/CT lymphoscintigraphy and sentinel lymph node (SLN) biopsy may improve lymphatic staging and surgical treatment. Our main objectives were to describe the lymphatic drainage of PTC using lymphoscintigraphy, to evaluate the lymphatic spread (comparing SLN and lymphadenectomy results) and to analyse the impact of SLN identification in surgery. METHODS: We prospectively studied 24 consecutive patients with PTC (19 women; mean age 52.7 years, range 22-81 years). The day before surgery, lymphoscintigraphy with ultrasound-guided intratumoral injection ((99m)Tc-nanocolloid, 148 MBq) was performed, obtaining planar and SPECT/CT images. All patients underwent total thyroidectomy, SLN biopsy (hand-held gamma probe) with perioperative analysis, central compartment node dissection, or laterocervical lymphadenectomy if perioperative stage N1b or positive SLNs in this lymphatic basin. RESULTS: Lymphoscintigraphy revealed at least one SLN in 19 of 24 patients (79 %) on planar and SPECT/CT images, and in 23 of 24 patients (96 %) during surgery using a hand-held gamma probe. Lymph node metastases were detected with classical perioperative techniques (ultrasound guidance and surgical inspection) in 3 of 24 patients, by perioperative SLN analysis in 10 of 23, and by definitive histology in 13 of 24. The false-negative (FN) ratio for SLN was 7.7 % (one patient with bulky lymph nodes). The FN ratio for perioperative frozen sections was 15.4 % (two patients, one with micrometastases, the other with bilateral SLN). Lymphatic drainage was only to the central compartment in 6 of 24 patients (3 of the 6 with positive SLNs for metastases), only to the laterocervical basin in 5 of 24 patients (all unilateral, 2 of 5 positive SLNs) and to the central and laterocervical compartments in 12 of 24 patients (6 of 12 and 3 of 12 positive SLNs, respectively). CONCLUSION: Lymphoscintigraphy reveals the lymph node drainage in a high proportion of patients. It detects laterocervical drainage in a significant percentage of patients, allowing the detection of occult lymph node metastases and improving the surgical management in PTC.

Genetic Testing to Predict Weight Loss and Diabetes Remission and Long-Term Sustainability after Bariatric Surgery: A Pilot Study.

INTRODUCTION: The aim of this pilot study was to assess genetic predisposition risk scores (GPS) in type 2 diabetic and non-diabetic patients in order to predict the better response to bariatric surgery (BS) in terms of either weight loss or diabetes remission. RESEARCH DESIGN AND METHODS: A case-control study in which 96 females (47 with type 2 diabetes) underwent Roux-en-Y gastric by-pass were included. The DNA was extracted from saliva samples and SNPs were examined and grouped into 3 GPS. ROC curves were used to calculate sensitivity and specificity. RESULTS: A highly sensitive and specific predictive model of response to BS was obtained by combining the GPS in non-diabetic subjects. This combination was different in diabetic subjects and highly predictive of diabetes remission. Additionally, the model was able to predict the weight regain and type 2 diabetes relapse after 5 years' follow-up. CONCLUSIONS: Genetic testing is a simple, reliable and useful tool for implementing personalized medicine in type 2 diabetic patients requiring BS.

MEN1-associated primary hyperparathyroidism in the Spanish Registry: clinical characterictics and surgical outcomes.

Primary hyperparathyroidism is the most frequent manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). Eighty-nine patients (49 men and 40 women, 34.2 ± 13 years old) were included. Sixty-four out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs 7/12, P < 0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.

Metabolic Fingerprint of Acromegaly and its Potential Usefulness in Clinical Practice.

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels are the main targets for monitoring acromegaly activity, but they are not in close relationship with the clinical course of the disease and the associated comorbidities. The present study was aimed at identifying metabolites that could be used as biomarkers for a better disease phenotyping. For this purpose, metabolic fingerprint using an untargeted metabolomic approach was examined in serum from 30 patients with acromegaly and 30 age-matched controls. Patients with acromegaly presented fewer branched-chain amino acids (BCAAs) compared to the control group (valine: 4.75 ± 0.87 vs. 5.20 ± 1.06 arbitrary units (AUs), p < 0.05; isoleucine: 2.54 ± 0.41 vs. 2.80 ± 0.51 AUs; p < 0.05). BCAAs were also lower in patients with active disease compared to patients with normal levels of IGF-1 with or without medical treatment. GH, but not IGF-1, serum levels were inversely correlated with both valine and isoleucine. These findings indicate that low levels of BCAAs represent the main metabolic fingerprint of acromegaly and that GH, rather than IGF-1, might be the primary mediator. In addition, our results suggest that the assessment of BCAAs could help to identify active disease and to monitor the response to therapeutic strategies.

Expression of p21cip1, p27kip1, and p16INk4a cyclin-dependent kinase inhibitors in papillary thyroid carcinoma: correlation with clinicopathological factors.

In a variety of human malignancies, aberrant expression of proteins involved in the control of cell-cycle progression has been reported. In this study, p21cip1, p27kip1, and p16INk4a cyclin-dependent kinase inhibitors were analyzed to evaluate their usefulness in clinical management of papillary thyroid carcinoma (PTC). Archived material derived from 46 cases of PTC was analyzed immunohistochemically. Protein expression was ascertained on tissue microarrays, and results were correlated with clinicopathological features of the patients. Positive immunostaining was observed in 14 (30,4%) p21cip1, 26 (56,5%) p27kip1, and 14 (30,4%) p16INk4a cases. No significant correlation between p21cip1 or p27kip1 and clinical factors was found. In contrast, p16INk4a expression showed a significant correlation with initial extension of the disease. Therefore, 45.8% of patients with loco-regional extension were p16INk4a positive, whereas overexpression was only seen in 15.7% of cases with intrathyroid disease (p < 0.05). Moreover, all patients with simultaneous p16INk4a positivity and lack of p27kip1 staining (four patients) presented lymph node metastases. In contrast, only 12 (28.5%) of the remaining patients showed lymph node tumor involvement. In conclusion, p16INk4a expression suggests extrathyroid neck extension of PTC. This effect is enhanced when p27kip1 is negative. We think that their analysis by immunohistochemistry could be useful in the management of patients with PTC.

[Six-month effectiveness and tolerability of pioglitazone in combination with sulfonylureas or metformin for the treatment of type 2 diabetes mellitus]. / Efectividad y tolerabilidad a 6 meses de la pioglitazona en combinación con sulfonilureas o metformina en el tratamiento de la diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Pioglitazone has been reported to improve common cardiovascular risk factors in addition to glycemic control in patients with type 2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were evaluated comparatively in large cohorts either treated or not with pioglitazone-containing combinations in the current clinical setting within Spain. PATIENTS AND METHOD: A nationwide prospective, controlled, observational cohort clinical study was performed in 2294 patients with T2DM who started, at the criterion of the treating physician, oral antihyperglycemic treatment with either pioglitazone plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723) or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood pressure and certain anthropometric parameters were measured at baseline and after 6 months of treatment. RESULTS: Serum high density lipoprotein-cholesterol increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same cohorts. Inter-group differences were significant (p<0.001 in both parameters). Total cholesterol decreased significantly more with SU+Met than in the pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions were significantly greater in the pioglitazone cohorts than in the SU+Met cohort: 27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg) groups. CONCLUSIONS: Treatment with pioglitazone was associated with significant improvements of lipid and glycemic parameters that are linked to insulin resistance and cardiovascular risk in patients with T2DM in their routine clinical care. The non-randomised allocation of patients to treatments, inherent to its observational design, is an important limitation of the present study.

Occult secretion of acth and bilateral adrenalectomy: sometimes the messenger has to be shot.

Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion is infrequent, the most frequent cause being bronchial carcinoid; nevertheless, in a considerable proportion of cases (up to 16%), the origin of ACTH secretion is not found. Treatment of Cushing's syndrome due to ectopic ACTH secretion is surgical resection of the tumor. However, surgical excision is not always feasible, either because the tumor has not been located, or because it is unresectable; in these cases the question is when to carry out a bilateral adrenalectomy. We present a case of ACTH-dependent hypercortisolism, in which the ectopic origin of ACTH secretion was established from the results of complementary tests (suppression tests, petrosal sinus sampling, imaging); nevertheless, none of the imaging tests was able to identify the secreting tumor. Consequently, after a reasonable interval, a bilateral adrenalectomy was performed, with good clinical results.

Response to oral sucrosomial iron supplementation in patients undergoing bariatric surgery. The BARI-FER study.

BACKGROUND: Chronic intravenous iron administration is often required after bariatric surgery. Oral sucrosomial iron has a particular form of absorption and may represent an alternative treatment. OBJECTIVE: To assess the effect of switching to oral sucrosomial iron in patients receiving intravenous iron supplementation after bariatric surgery. PATIENTS AND METHODS: A case-control study was conducted on 40 women of childbearing age, of whom 20 were switched to oral sucrosomial iron, while 20 patients continued on intravenous iron sucrose every three months. RESULTS: No significant differences were seen in Hb, ferritin, and TSI levels before and after three months of treatment with sucrosomial iron. CONCLUSION: Oral sucrosomial iron could be an alternative in patients who require parenteral treatment with iron after bariatric surgery.

Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis. / Biopsia selectiva del ganglio centinela en el carcinoma papilar de tiroides en pacientes sin evidencia preoperatoria de metástasis ganglionar.

INTRODUCTION: Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. OBJECTIVE: To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. PATIENTS AND METHOD: A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. RESULTS: Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. CONCLUSIONS: Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors.

Detection of ketonemia and its relationship with hyperglycemia in type 1 diabetic patients.

The aims of this study were to assess the prevalence of ketosis in type 1 diabetic patients with casual hyperglycemia (>250 mg/dl), to establish the relationship between glycemia and ketonemia during daily life, and to determine the utility of ketonemia. Capillary glycemia levels from 562 type 1 diabetic patients were recorded. Prevalence of casual hyperglycemia was 27.58%, and prevalence of asymptomatic ketonemia was 8.39%. Regarding blood ketone levels, 110 out of 155 patients (70.96%) had blood ketone levels of between 0 and 0.1 mmol/l and 32 out of 155 patients (20.63%) had blood ketone levels of between 0.2 and 0.4 mmol/l. Surprisingly, the mean glycemia levels in these subgroups did not differ and was consistently high (around 300 mg/dl), leading to the observation that even ketone levels considered as non-pathologic should probably be taken into account for a proper diabetes control. Some discrepancies between quantitative determination of ketonuria and qualitative determination of ketonemia were observed. That is in 20 patients with positive ketonuria, ketonemia was not detected, probably because ketosis was already resolved. Asymptomatic ketosis was observed in the hyperglycemic type 1 diabetic population, and metabolic control of these patients with a point of care device is recommended, together with a subsequent revision of insulin treatment. Furthermore, this study supports the opinion that the presence of ketosis, detected by beta-OHB levels, even below levels considered as pathologic, together with hyperglycemia, must be taken into account for proper monitoring and therapeutic control of diabetic patients.

New Oral Hypoglycemic Agents and Cardiovascular Risk. Crossing the Metabolic Border.

Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes.

Immunohistochemical Expression of Estrogen Receptor-α and Progesterone Receptor in Patients with Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) prevalence is nearly 3 times higher in females than in males. This gender difference suggests that growth and progression of PTC might be influenced by female sex hormones. OBJECTIVES: To analyze the expression of both estrogen receptor (ER)-α and progesterone receptor (PR) by immunohistochemistry in 203 PTC patients. METHODS: ER-α and PR expression was evaluated in paraffin-embedded tumor tissue samples of 45 males and 158 females followed up for 7.2 ± 3.7 years. RESULTS: ER-α was expressed in 52 (25.6%) patients (41 females and 11 males) and PR in 94 (46.3%) patients (75 females and 19 males). ER-α and PR were coexpressed in 31 (15.3%) patients (27 females and 4 males). ER-α expression correlated significantly with tumor size in the whole sample (ER-α positive 22.8 ± 11.8 mm vs. ER-α negative 15.1 ± 12.4 mm; p = 0.02) and in the subgroup of women (ER-α positive 18.8 ± 12.8 mm vs. ER-α negative 14.9 ± 12.3 mm; p = 0.048). In addition, ER-α expression significantly correlated with remission of the disease. In fact, of the 192 patients followed up, 50/153 (32.7%) disease-free patients were ER-α positive, in contrast to only 3/39 (7.7%) with evidence of disease persistence/recurrence (χ2 = 8.5, p = 0.0036). PR expression was not associated with any of the parameters analyzed. CONCLUSIONS: The present study confirmed recent data indicating that ER-α and PR expression is a common finding in thyroid tumor tissue. However, in contrast to previous reports, we observed an association between ER-α expression and a more favorable outcome in PTC patients.

Brown tumor of the jaw after pregnancy and lactation in a MEN1 patient.

Skeletal manifestations of primary hyperparathyroidism (pHPT) include brown tumors (BT), which are osteoclastic focal lesions often localized in the jaws. Brown tumors are a rare manifestation of pHTP in Europe and USA; however, they are frequent in developing countries, probably related to vitamin D deficiency and longer duration and severity of disease. In the majority of cases, the removal of the parathyroid adenoma is enough for the bone to remineralize, but other cases require surgery. Hyperparathyroidism in MEN1 develops early, and is multiglandular and the timing of surgery remains questionable. To our knowledge, there are no reports of BT in MEN 1 patients. We present a 29-year-old woman with MEN 1 who developed a brown tumor of the jaw 24 months after getting pregnant, while breastfeeding. Serum corrected calcium remained under 2.7 during gestation, and at that point reached a maximum of 2.82 mmol/L. Concomitant PTH was 196 pg/mL, vitamin D 13.7 ng/mL and alkaline phosphatase 150 IU/L. Bone mineral density showed osteopenia on spine and femoral neck (both T-scores = -1.6). Total parathyroidectomy was performed within two weeks, with a failed glandular graft autotransplantation, leading to permanent hypoparathyroidism. Two months after removal of parathyroid glands, the jaw tumor did not shrink; thus, finally it was successfully excised. We hypothesize that higher vitamin D and mineral requirements during maternity may have triggered an accelerated bone resorption followed by appearance of the jaw BT. We suggest to treat pHPT before planning a pregnancy in MEN1 women or otherwise supplement with vitamin D, although this approach may precipitate severe hypercalcemia. LEARNING POINTS: Brown tumors of the jaw can develop in MEN 1 patients with primary hyperparathyroidism at a young age (less than 30 years).Pregnancy and lactation might trigger brown tumors by increasing mineral and vitamin D requirements.Early parathyroidectomy is advisable in MEN 1 patients with primary hyperparathyroidism, at least before planning a pregnancy.Standard bone mineral density does not correlate with the risk of appearance of a brown tumor.Removal of parathyroid glands does not always lead to the shrinkage of the brown tumor, and surgical excision may be necessary.

[Factors influencing CRP levels in the diabetic population]. / Factores que influyen en la concentración plasmática de proteína C reactiva en la población diabética.

BACKGROUND AND OBJECTIVE: The aim of the present study was to investigate the factors influencing CRP serum levels in the diabetic population. PATIENTS AND METHOD: Eighty-six patients with type 2 diabetes mellitus were prospectively included. The following variables were considered: age, gender, smoking habit, body mass index (BMI), glucose, HbA1c, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, albumin excretion rate, CRP and E-selectin. RESULTS: CRP serum levels were associated with: gender (men: 1.4 mg/L [0.03-12.8] vs. women: 3.4 [0.07-80.7]; p = 0.02), age (r = 0.34, p = 0.001), BMI (r = 0.45, p < 0.001), triglycerides (r = 0.24, p = 0.03) and E-selectin (r = 0.21, p = 0.02). Those patients with at least one component of the metabolic syndrome, besides diabetes mellitus, had higher CRP concentrations in comparison with those patients without other components of the metabolic syndrome (2.4 mg/L [0.3-23.1] vs. 4.2 mg/L [0.6-80.7]; p = 0.05). In the multivariate analysis, gender (p = 0.001) and BMI (p = 0.01) were independently associated with the CRP concentration. CONCLUSIONS: Gender and BMI are the main factors to be considered when analyzing CRP levels in the diabetic population. Metabolic syndrome components other than diabetes are related to CRP levels in type 2 diabetic patients.

[New insulin types in type 1 diabetes mellitus]. / Nuevas insulinas en la diabetes tipo 1.

Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development.

Preoperative TSH level and risk of thyroid cancer in patients with nodular thyroid disease: nodule size contribution.

BACKGROUND: Many reports have supported the relationship between high preoperative TSH levels and risk of thyroid cancer in nodular thyroid disease (NTD). OBJECTIVES: We investigated whether TSH levels are related to the risk of differentiated thyroid carcinoma (DTC) in patients who have undergone total thyroidectomy for NTD. The relationship between TSH and size of malignant nodule was investigated. Finally, we assessed whether TSH levels are related to DTC and presence of additional benign nodules. PATIENTS AND METHODS: A retrospective study of 980 patients was conducted. Variables included age at diagnosis, TSH level, nodule size, gender, final histology (benign versus DTC), and type of malignancy. RESULTS: Malignancy was present in 261 (26.6%) patients. These patients had higher median TSH levels as compared to those with no malignancy (1.61 mU/L (0.9-2.5) versus 0.9 mU/L (0.3-1.6); p-value<0.001). TSH was higher in patients with DTC in whom the largest nodule was malignant than in patients in whom the largest nodule was benign (1.80 mU/L (1.1-2.6) versus 1.38 mU/L (0.7-2.1) respectively; p-value=0.025). A significant correlation was seen between malignant nodule size and TSH level, but not between TSH levels and size of the largest benign nodule. CONCLUSIONS: Our study supported an association between preoperative TSH levels and risk of DTC in patients with NTD. There was also a direct relationship between malignant nodule size and TSH levels. By contrast, no relationship was found between the size of benign nodules and TSH levels.

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation.

OBJECTIVE: Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634. DESIGN: The study was retrospective and multicentric. METHODS: We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1-32). RESULTS: Patients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P<0.001). CONCLUSIONS: Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.

Detection of Thyroid Papillary Carcinoma Lymph Node Metastases Using One Step Nucleic Acid Amplification (OSNA): Preliminary Results.

UNLABELLED: Purpouse: One Step Nucleic Acid Amplification (OSNA) has been previously proposed for the diagnosis of lymph node metastases (LNMs) from several malignant conditions by quantifying the number of copies of cytokeratin 19 mRNA. Our aim was to evaluate the results obtained by OSNA in the lymph nodes of patients with papillary thyroid carcinoma (PTC) by comparing our results with the findings observed using standard pathological examination. MATERIALS AND METHODS: Fifty human lymph nodes (from five patients with diagnosed PTC) were studied. Each node was divided into two: one half was used for molecular study ("OSNA-node"), and the other half was used for conventional staining with hematoxylin and eosin ("HE-non-OSNA node"). Three cytological imprints using Papanicolaou and May-Grunwald-Giemsa strains were obtained from both node halves. The results from each technique were compared, and ROC analysis was performed. RESULTS: The OSNA study showed 22 positive samples for LNM (44%), which demonstrate a high concordance rate with the results observed using conventional pathological examination (cytology of "OSNA-node" and HE of "Non-OSNA node") with specificity and sensitivity values greater than 86% and 89%, respectively. However, both comparisons differed in the number of copies of mRNA as the best cut-off (260 copies in the first case and 93 in the second case). CONCLUSIONS: The OSNA results for the detection of LNM in patients with PTC are comparable with those observed using conventional techniques. However, its quantitative nature could be useful to more accurately detect lymph node involvement.