Safety Attitude of Operating Room Personnel Associated With Accurate Completion of a Surgical Checklist: A Cross-sectional Observational Study.

OBJECTIVE: How the checklist is executed in routine practice may reflect the teamwork and safety climate in the operating room (OR). This cross-sectional study aimed to identify whether the presence of a fully completed checklist in medical records was associated with teams' safety attitudes. METHODS: Data from 29 French hospitals, including 5677 operated patients and 834 OR professionals, were prospectively collected. The degree of checklist compliance was categorized for each patient in 1 of 4 ways: full, incomplete, inaccurate, and no checklist completed. The members of OR teams were invited to complete a questionnaire including teamwork climate measurement (Safety Attitudes Questionnaire) and their opinion regarding checklist use, checklist audibly reading, and communication change with checklist. Multilevel modeling was performed to investigate the effect of variables related to hospitals and professionals on checklist compliance, after adjustment for patient characteristics. RESULTS: A checklist was present for 83% of patients, but only 35% demonstrated full completion. Compared with no checklist, full completion was associated with higher safety attitude (high teamwork climate [adjusted odds ratio for full completion, 4.14; 95% confidence interval, 1.75-9.76]; communication change [1.31, 1.04-1.66]; checklist aloud reading [1.16, 1.02-1.32]) and was reinforced by the designation of a checklist coordinator (2.43, 1.06-5.55). Incomplete completion was also associated with enhanced safety attitude contrary to inaccurate completion. CONCLUSIONS: Compliance with checklists is associated with safer OR team practice and can be considered as an indicator of the extent of safety in OR practice.

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.

Influence of Daily Variations in Individual Surgeon's Operative Time on Patient Outcomes.

BACKGROUND: Evidence is lacking regarding the potential association between daily variation in individual surgeon's operative time, procedure after procedure, and risk of patient complication. We assumed that surgeon deviation from the expected procedure duration may be harmful for patient. METHOD: All patients who underwent a thyroidectomy undertaken in five hospitals during a 1-year period were included prospectively. For each thyroidectomy, we estimated the expected operative time from a multilevel linear regression considering the attending surgeon who performed the operation, the patient preoperative risk, and the procedure complexity. Three groups of thyroidectomies were identified according to whether the observed duration is: slower than expected, as expected, or faster than expected. Rates of permanent recurrent laryngeal nerve palsy and hypoparathyroidism at 6 months were then compared between these groups. RESULTS: A total of 3102 patients who underwent a thyroidectomy undertaken by 22 surgeons were considered. Risk of laryngeal nerve palsy was higher in the "slow" group than in the "normal" group (OR = 4.63, 95% confidence interval 2.21-9.70), as was that of hypoparathyroidism (OR = 2.43, 95% confidence interval 1.21-4.88). There was no significant difference between "fast" and "normal" groups for either complication. Deviation from expected procedure duration was more frequent at the end than at the beginning of the daily operation schedule (29.4% vs. 18.3%, respectively, P < .001). CONCLUSION: Patients had a greater risk of complication when the surgeon performed thyroidectomy slower than expected. Surgeons avoiding excessive deviations from their expected procedures durations reflect safer practice.

Predictive factors of outcome in poorly differentiated thyroid carcinomas.

BACKGROUND: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis. METHODS: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome). RESULTS: All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10-0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions -124 (C228T) and -146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations. CONCLUSION: PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness.

Correction to: Does Surgery Without Lugol's Solution Pretreatment for Graves' Disease Increase Surgical Morbidity?

In the original article, Mathieu Bonal's last name was spelled incorrectly. It is correct as reflected here. The original article has also been updated.

Does Surgery Without Lugol's Solution Pretreatment for Graves' Disease Increase Surgical Morbidity?

BACKGROUND: Total thyroidectomy can be performed for Graves' disease after a euthyroid state is achieved using inhibitors of thyroid hormone synthesis (thioamides). However, hypervascularization of the thyroid gland is associated with increased hemorrhage risk, in addition to complicating identification of the recurrent laryngeal nerve and parathyroid gland. Saturated iodine solution (Lugol's solution) has been recommended to reduce thyroid gland hypervascularization and intraoperative blood loss, although this approach is not used at our center based on our experience that it induces thyroid firmness and potentially hypoparathyroidism. METHODS: This retrospective single-center study evaluated patients who underwent total thyroidectomy for Graves' disease between November 2010 and November 2015. The rates of various complications at our center were compared to those from the literature (e.g., cervical hematoma, hypocalcemia, and recurrent laryngeal nerve palsy). RESULTS: Three hundred and eighty consecutive patients underwent total thyroidectomy without preoperative Lugol's solution (311 women [81.84%] and 69 men [18.16%], mean age 43.41 years). No postoperative deaths were reported, although 30 patients (7.89%) experienced recurrent laryngeal nerve palsy and 9 patients experienced permanent injuries (2.37%). Hypoparathyroidism was experienced by 87 patients (25.53%) and 14 patients experienced permanent hypoparathyroidism (3.68%). Four patients required reoperation for cervical hematoma (1.05%; 2 deep and 2 superficial hematomas). CONCLUSION: Despite the recommendation of iodine pretreatment, few of our non-pretreated patients experienced permanent nerve injury (2.37%) or permanent hypoparathyroidism (3.68%). These results are comparable to the outcomes from the literature. Randomized controlled trials are needed to determine whether iodine pretreatment is necessary before surgery for Graves' disease.

Predicting thyroid nodule malignancy at several prevalence values with a combined Bethesda-molecular test.

Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center. The test relied on a transcriptomic array of 20 genes selected from a previous study. An optimal set of seven genes was identified using a logistic regression model. Comparison between the combined predictor (TBSRTC + molecular) and TBSRTC alone used the area under the ROC curve (AUC). Performance of the combined predictor was calculated according to various malignancy prevalence values and benefit-to-harm ratios (B/Hr) (favoring sensitivity or specificity). In our population (36% malignancy prevalence) and with a B/Hr of 1, the combined predictor achieved 95% specificity and 76% sensitivity. The AUC was 93.5%; higher than that of TBSRTC (P = 0.004). Among indeterminate nodules (30% malignancy prevalence), sensitivity and specificity were 52.2% and 96.2%, respectively, with a B/Hr of 1, or 95.7% and 64.2% with a B/Hr of 4 (favoring sensitivity), allowing avoidance of 64% of unnecessary surgeries at the cost of only one false-positive result. In conclusion, this predictor could improve the detection of thyroid nodule malignancy, taking into account malignancy prevalence and B/Hr, and reduce the number of unnecessary thyroidectomies.

Determinants of operative time in thyroid surgery: A prospective multicenter study of 3454 thyroidectomies.

OBJECTIVE: To identify the determinants of operative time for thyroidectomy and quantify the relative influence of preoperative and intra-operative factors. BACKGROUND: Anticipation of operative time is key to avoid both waste of hospital resources and dissatisfaction of the surgical staff. Having an accurate and anticipated planning would allow a rationalized operating room use and may improve patient flow and staffing level. METHODS: We conducted a prospective, cross-sectional study between April 2008 and December 2009. The operative time of 3454 patients who underwent thyroidectomy performed by 28 surgeons in five academic hospitals was monitored. We used multilevel linear regression to model determinants of operative time while accounting for the interplay of characteristics specific to surgeons, patients, and surgical procedures. The relative impact of each variable on operative time was estimated. RESULTS: Overall, 86% (99% CI 83 to 89) of operative time variation was related to preoperative variables. Surgeon characteristics accounted for 32% (99% CI 29 to 35) of variation, center location for 29% (99% CI 25 to 33), and surgical procedure or patient variables for 24% (99% CI 20 to 27). Operative time was significantly lower among experienced surgeons having practiced from 5-19 years (-21.8 min, P<0.05), performing at least 300 thyroidectomies per year (-28.8 min, P<0.05), and with increasing number of thyroidectomies performed the same day (-11.7min, P<0.001). Conversely, operative time increased in cases of procedure supervision by a more experienced surgeon (+20.0 min, P<0.001). The remaining 13.0% of variability was attributable to unanticipated technical difficulties at the time of surgery. CONCLUSIONS: Variation in thyroidectomy duration is largely explained by preoperative factors, suggesting that it can be accurately anticipated. Prediction tools allowing better regulation of patient flow in operating rooms appears feasible for both working conditions and cost management.

Can we consider immediate complications after thyroidectomy as a quality metric of operation?

BACKGROUND: Permanent recurrent laryngeal nerve palsy and hypoparathyroidism are 2 major complications after thyroid operation. Assuming that the rate of immediate complications can predict the permanent complication rate, some authors consider these complications as a valid metric for assessing the performance of individual surgeons. This study aimed to determine the correlation between rates of immediate and permanent complications after thyroidectomy at the surgeon level. METHODS: We conducted a prospective, cross-sectional study in 5 academic hospitals between April 2008 and December 2009. The correlation between the rates of immediate and permanent complications for each of the 22 participating surgeons was calculated using the Pearson correlation test (r). RESULTS: The study period included 3,605 patients. There was a fairly good correlation between rates of immediate and permanent recurrent laryngeal nerve palsy (r = 0.70, P = .004), but no correlation was found for immediate and permanent hypoparathyroidism (r = 0.18, P = .427). CONCLUSION: The immediate hypoparathyroidism rate does not reflect the permanent hypoparathyroidism rate. Consequently, immediate hypoparathyroidism should not be used to assess the quality of thyroidectomy or to monitor the performance of surgeons.

Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis.

CONTEXT: Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 have been identified in aldosterone-producing adenomas (APAs). The question as to whether they are responsible for both nodulation and aldosterone production is not solved. CASE DESCRIPTION: We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26 years, followed by hemorrhagic stroke 4 years later. Abdominal computed tomography showed bilateral macronodular adrenal hyperplasia. Identification of lateralized aldosterone secretion led to right adrenalectomy, followed by normalization of biochemical and hormonal parameters and amelioration of blood pressure. The resected adrenal showed three nodules, one of them expressing aldosterone synthase and harboring a somatic KNCJ5 mutation. A Weiss revisited index of 3 of the APA prompted us to perform a second 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography after surgery, which revealed abnormal rectal activity despite the absence of clinical symptoms. Gastrointestinal exploration showed multiple polyps with severe dysplasia, and the diagnosis of familial adenomatous polyposis was established in the presence of a germline heterozygous APC gene mutation. Sequencing of somatic DNA from the APA and a second adrenal nodule revealed biallelic APC inactivation due to loss of heterozygosity in both nodules. CONCLUSIONS: This case report underlines the need for establishing the frequency of germline APC variants in patients with primary aldosteronism and bilateral macronodular adrenal hyperplasia because their presence may predispose to APA development and severe hypertension well before the first familial adenomatous polyposis symptoms appear. From a mechanistic point of view, it supports a two-hit model for APA development, whereby the first hit drives increased cell proliferation whereas the second hit specifies the pattern of hormonal secretion.

Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study.

INTRODUCTION: Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data. MATERIALS AND METHODS: Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors. RESULTS: Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048). CONCLUSION: Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.

[Not Available]. / Qualité en chirurgie thyroidienne: Critères d'évaluation et applications pratiques.

Evaluation and research of quality factors in surgery necessitates the consideration of 3 types of indicators: indicators of structures, indicators of processes and indicators of outcomes. We used these 3 types of indicators to assess the quality of thyroid surgery and to evaluate quality indicators. These studies allowed us to demonstrate the importance of a permanent monitoring of the outcomes of the thyroid surgery and the presence of human and organizational factors in the mechanisms of the surgical complications. This type of evaluation and research in quality of health care should be extended to all the surgical subspecialties.

Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study.

OBJECTIVE: Management of insulinomas in the context of MEN1 remains poorly studied. The aim of this study was to evaluate long-term results of various surgical approaches in a large cohort of insulinoma-MEN1 patients. DESIGN AND METHODS: Consecutive insulinoma-MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications. RESULTS: The study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5-16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54-24.8); P=0.010) for E vs DP and 9.51 ((95% CI: 1.85-48.8); P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002). CONCLUSION: In the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.

Role of preoperative basal calcitonin levels in the timing of prophylactic thyroidectomy in patients with germline RET mutations.

BACKGROUND: The American Thyroid Association (ATA) published recommendations for the timing of prophylactic surgery for medullary thyroid carcinoma based on the specific mutation, patient age, family history, and serum calcitonin levels. The aim of this study was to assess the role of preoperative basal calcitonin (prebCt) levels in predicting the presence of medullary carcinoma of the thyroid in patients with RET mutations. METHODS: We conducted a retrospective study in two endocrine surgery departments. Between 1986 and 2012, a total of 32 patients with RET mutations underwent prophylactic thyroidectomy. The patients were stratified into four ATA risk levels: A, B, C, and D. RESULTS: All of the patients were biologically cured. Microcarcinoma was observed in the final pathology report for four of the 20 patients with normal prebCt (25 %) and for nine of the 12 patients with elevated prebCt (75 %). In the level A group, four patients with normal prebCt and one patient with elevated prebCt presented with microcarcinoma. In the level C group, one patient with normal prebCt and six of the seven patients with elevated prebCt (86 %) presented with microcarcinoma. CONCLUSIONS: PrebCt can predict the presence of microcarcinoma according to surgical pathological analysis. Patients with microcarcinoma can be biochemically and clinically cured using prophylactic thyroidectomy.

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

OBJECTIVE: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. DESIGN: Multicentric prospective study. PATIENTS: A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. MEASUREMENT: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. RESULTS: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. CONCLUSION: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test.

Development of a charting method to monitor the individual performance of surgeons at the beginning of their career.

BACKGROUND: Efforts to provide a valid picture of surgeons' individual performance evolution should frame their outcomes in relation to what is expected depending on their experience. We derived the learning curve of young thyroidectomy surgeons as a baseline to enable the accurate assessment of their individual outcomes and avoid erroneous conclusions that may derive from more traditional approaches. METHODS: Operative time and postoperative recurrent laryngeal nerve palsy of 2006 patients who underwent a thyroidectomy performed by 19 young surgeons in five academic hospitals were monitored from April 2008 to December 2009. The database was randomly divided into training and testing datasets. The training data served to determine the expected performance curve of surgeons during their career and factors influencing outcome variation using generalized estimating equations (GEEs). To simulate prospective monitoring of individual surgeon outcomes, the testing data were plotted on funnel plots and cumulative sum charts (CUSUM). Performance charting methods were utilized to present outcomes adjusted both for patient case-mix and surgeon experience. RESULTS: Generation of performance curves demonstrated a gradual reduction in operative time from 139 (95% CI, 137 to 141) to 75 (71 to 80) minutes, and from 15.7% (15.1% to 16.3%) to 3.3% (3.0% to 3.6%) regarding the nerve palsy rate. Charts interpretation revealed that a very young surgeon had better outcomes than expected, whereas a more experienced surgeon appeared to be a poor performer given the number of years that he had already spent in practice. CONCLUSIONS: Not considering the initial learning curve of surgeons exposes them to biased measurement and to misinterpretation in assessing their individual performance for thyroidectomy. The performance chart represents a valuable tool to monitor the outcome of surgeons with the expectation to provide safe and efficient care to patients.

Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.

BACKGROUND: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na(+) conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined. MATERIALS AND METHODS: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers. RESULTS: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005). DISCUSSION: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

Influence of experience on performance of individual surgeons in thyroid surgery: prospective cross sectional multicentre study.

OBJECTIVE: To determine the association between surgeons' experience and postoperative complications in thyroid surgery. DESIGN: Prospective cross sectional multicentre study. SETTING: High volume referral centres in five academic hospitals in France. PARTICIPANTS: All patients who underwent a thyroidectomy undertaken by every surgeon in these hospitals from 1 April 2008 to 31 December 2009. MAIN OUTCOME MEASURES: Presence of two permanent major complications (recurrent laryngeal nerve palsy or hypoparathyroidism), six months after thyroid surgery. We used mixed effects logistic regression to determine the association between length of experience and postoperative complications. RESULTS: 28 surgeons completed 3574 thyroid procedures during a one year period. Overall rates of recurrent laryngeal nerve palsy and hypoparathyroidism were 2.08% (95% confidence interval 1.53% to 2.67%) and 2.69% (2.10% to 3.31%), respectively. In a multivariate analysis, 20 years or more of practice was associated with increased probability of both recurrent laryngeal nerve palsy (odds ratio 3.06 (1.07 to 8.80), P=0.04) and hypoparathyroidism (7.56 (1.79 to 31.99), P=0.01). Surgeons' performance had a concave association with their length of experience (P=0.036) and age (P=0.035); surgeons aged 35 to 50 years had better outcomes than their younger and older colleagues. CONCLUSIONS: Optimum individual performance in thyroid surgery cannot be passively achieved or maintained by accumulating experience. Factors contributing to poor performance in very experienced surgeons should be explored further.

[Prophylactic thyroidectomy in medullary thyroid cancer]. / La chirurgie prophylactique du cancer médullaire de la thyroïde.

Medullary thyroid cancer (MTC) is genetically determined in 30% to 35% of cases, notably through multiple mutations in the RET protooncogene located on chromosome 10, for which a genotype-phenotype relationship determines age of onset. There are three phenotypes: MEN 2 A and B, and isolated familial MTC. The type of mutation determines 3 levels of aggressiveness. Current guidelines recommend thyroidectomy during the first months of life for patients with very-high-risk (level 3) mutations and before 5 years of age for high-risk (level 2) mutations. There are no precise recommendations for lower-risk mutations, for which the surgical decision also depends on the calcitonin level and family history. We describe 18 patients who underwent prophylactic surgery. Regardless of the mutation, all patients with a normal preoperative calcitonin level were cured. However, surgery was performed later than recommended, for various reasons, including late genetic diagnosis and parents' opposition.