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Introduction: Post-surgical hypoparathyroidism often occurs after total thyroidectomy (TT). The aim of this study is to investigate whether the use of near-infrared autofluorescence (NIRAF) of parathyroid glands (PGs) can aid experienced surgeons in identifying more PGs during surgery, potentially reducing unintended resection, and assessing its impact on post-surgical hypoparathyroidism., Materials and Methods: All patients undergoing at least a TT by two experienced surgeons, between 2020 and 2021, were enrolled and randomized into two cohorts: NIRAF group (NG) and CONTROL group (CG). Transient hypoparathyroidism was defined by serum concentration of PTH<12 ng/mL at the 1st post-operative day and permanent by the need of calcium-active vitamin D treatment >6 months from the surgery with still undetectable PTH or <12 ng/m., Results: Among 236 patients (111 in NG, 125 in CG), the number of PGs identified was higher in NG (93.9%, 417/444) compared to CG (81.4%, 407/500) (p < 0.001), with a mean of 3.76 ± 0.44 PGs per patient in NG and 3.25 ± 0.79 in CG. The number of unintendedly resected PGs was 14 in NG and 42 in CG (p < 0.0001). Transient hypoparathyroidism was observed in 18 patients (16.2%) in NG and 40 patients (32.0%) in CG (p = 0.004). Permanent hypoparathyroidism affected 1 patient in NG and 7 patients in CG (p = 0.06). The mean operative time was longer in NG (104.3 ± 32.08 min) compared to CG (85.5 ± 40.62 min) (p < 0.001)., Conclusions: NIRAF enhances the identification of PGs, preventing their inadvertent resection and reducing the overall incidence of post-surgical hypoparathyroidism., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Patients with thyroid carcinoma often undergo cervical lymph node dissection, which is associated with high rates of both transient and permanent postoperative hypoparathyroidism. The impact of near-infrared fluorescence imaging + indocyanine green (ICG) fluorescence on postoperative hypoparathyroidism rates after total thyroidectomy and central neck lymph node dissection was evaluated., Methods: All patients undergoing surgery between January 2019 and March 2023 were included and divided into three groups: a control group (parathyroid glands identified visually), a near-infrared fluorescence imaging alone group, and a near-infrared fluorescence imaging + ICG fluorescence group. The primary outcome was the transient and permanent postoperative hypoparathyroidism rates. Secondary outcomes were: length of surgery and number of parathyroid glands identified, inadvertently resected, and autotransplanted., Results: A total of 131 patients were included in the study (47 in the control group, 45 in the near-infrared fluorescence imaging alone group, and 39 in the near-infrared fluorescence imaging + ICG fluorescence group). The transient hypoparathyroidism rate was 48.9% in the control group, 37.8% in the near-infrared fluorescence imaging alone, and 5.1% in the near-infrared fluorescence imaging + ICG fluorescence group (P < 0.0001), while the permanent hypoparathyroidism rate was 8.5% in the control group, 2.2% in the near-infrared fluorescence imaging alone group, and 0% in the near-infrared fluorescence imaging + ICG fluorescence group (P = 0.096). The number of parathyroid glands identified was 159 of 188 in the control group, 165 of 180 in the near-infrared fluorescence imaging alone group, and 149 of 156 in the near-infrared fluorescence imaging + ICG fluorescence group (P = 0.002). Inadvertent resection of parathyroid glands occurred for 29 of 188 in the control group, 15 of 180 in the near-infrared fluorescence imaging alone group, and 7 of 156 in the near-infrared fluorescence imaging + ICG fluorescence group (P = 0.002), with subsequent parathyroid gland autotransplantation for 2 of 29 in the control group, 2 of 15 in the near-infrared fluorescence imaging alone group, and 3 of 7 in the near-infrared fluorescence imaging + ICG fluorescence group (P = 0.040). There was no difference in the median operating time between groups., Conclusion: The use of near-infrared fluorescence imaging + ICG fluorescence decreased both transient and permanent hypoparathyroidism rates in patients undergoing total thyroidectomy and central neck lymph node dissection., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Steroids are often used for the management of vocal cord palsy after thyroid surgery. There are no reports in the current literature of their intraoperative use, immediately after a loss of signal during neuromonitoring (LOS). We evaluate the impact of a single dose of 4 mg of dexamethasone on laryngeal nerve function, administrated at the time of a LOS during a nerve-monitored thyroidectomy., Methods: A prospective not randomized study was performed, dividing patients in two groups, when a LOS was detected. LOS was defined as an electromyographic signal (EMG) inferior to 100 μV when stimulating the inferior laryngeal nerve, according to international guidelines. In group 1 (G1), surgeon waits for signal's recovery up to 20 min. Absence of a detectable signal after 20 min was predictive of vocal cord palsy; if it affected the first side of surgery the procedure was interrupted to avoid the risk of bilateral nerve palsy. In group 2 (G2), 4 mg of dexamethasone were injected within 10 min from a detected LOS, waiting 10 min for its effects. An EMG value > to 200 μV within 20' after steroid administration was predictive of full recovery and normal post-operatory vocal cord function. Vocal cords motility was checked at postoperative day 1 in all patients by an experienced ENT., Results: Between January 2017 and December 2018, 702 patients underwent thyroid surgery under intermittent intraoperative nerve monitoring by two expert surgeons. A LOS was found in 22 patients in G1 and 16 in G2. Four patients in G1 spontaneously recovered electric signal (18.2%), while in G2 a signal was recovered in 14/16 patients (87.5%) (p < 0.001). This immediate effect was monitored by EMG, showing the increase in potentials at 10, 15 and 20 min after injection. ENT evaluation found vocal cord palsy, respectively, in 18/22 and 1/16 patients (G1 vs G2, p < 0.001). One of the patients in G2 who recovered electric signal presented transient palsy, fully recovered at 2 months, while the two patients who had a signal < 200 μV did not present postoperative cord palsy. In G1, 10/18 palsy were definitive. No permanent palsies were presents in G2., Conclusion: A single 4 mg iv dexamethasone injection within 10 min form a LOS during thyroid surgery exerts a therapeutic action, measurable by EMG modifications. It avoids vocal nerve palsy and the need of a staged thyroidectomy. It may also protect from permanent cord palsy, but the mechanism is unknown.

Background: The outcome of adrenalectomy carried out by laparoscopy or open surgery for solid tumor metastases was assessed., Methods: A total of 317 patients with histologically confirmed adrenal metastatic disease collected from 30 centres in Europe underwent adrenalectomy by laparoscopy (n=146) or open laparotomy (n=171). Differences between laparoscopic and open adrenalectomy were assessed by a single Cox analysis for both procedures., Results: The median overall survival was 24.0 [95% confidence interval (CI): 21.4-26.6] months for open adrenalectomy and 45.0 (95% CI: 22.6-67.4) for laparoscopic adrenalectomy (P=0.008). Survival rates were 68%, 49%, 35% and 29% at 1, 2, 3 and 5 years for open surgery vs. 88%, 62%, 52% and 46% for laparoscopy, respectively. In the subgroup of R0 resections, the difference in survival in favor of laparoscopy (median 46 vs. 27 months) was marginally significant (P=0.073). Renal cancer [hazard ratio (HR) 0.42; 95% CI: 0.23-0.76, P=0.005], surgery of the primary tumor (HR 0.33; 95% CI: 0.19-0.54), and use of chemotherapy (HR 0.62; 95% CI: 0.43-0.88) were associated with a better survival, whereas type of resection (R1/R2 vs. R0) was associated with a worse prognosis (HR 2.29; 95% CI: 1.52-3.44, P<0.001)., Conclusions: Laparoscopic adrenalectomy patients showed a longer survival than open adrenalectomy individuals, as minimally invasive approach was attempted more common in less advanced disease which led to higher number of R0 resections., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

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.

Importance: In MEN1 patients with gastric and duodenopancreatic neuroendocrine tumors (GPD-NET), surgery aims to control secretions or to prevent metastatic spread, but after GPD-NET resection, postoperative mortality may be related to the surgery itself or to other associated MEN1 lesions with their own uncontrolled secretions or metastatic behavior., Objective: To analyze the causes of death within 1 year following a GPD-NET resection in MEN1 patients., Design: An observational study collecting data from the Groupe d'étude des Tumeurs Endocrines (GTE) database. The analysis considered the time between surgery and death (early deaths [<1 month after surgery] versus delayed deaths [beyond 1 month after surgery]) and the period (before 1990 vs after 1990). Causes of death were classified as related to GDP surgery, related to surgery for other MEN1 lesions or not related to MEN1 causes., Setting: GTE database which includes 1220 MEN1 patients and 441 GPD-NET resections., Participants: Four hundred and forty-one GPD-NET resections., Main Outcome Measures: The primary end point was postoperative mortality within 1 year after surgery., Results: Twenty-four patients met the inclusion criteria (2%). Median age at death was 50.5 years. Sixteen deaths occurred in the 30-day postoperative period (76%). Among the 8 delayed deaths, 3 occurred as a result of medical complications between 30 and 90 postoperative days. After 1990, mean age at death increased from 48 to 58 years (p = 0.09), deaths related to uncontrolled acid secretion disappeared (p < 0.001) and deaths related to associated MEN1 lesions increased from 8 to 54% (p = 0.16)., Conclusion: Surgery and uncontrolled secretions remain the two main causes of death in MEN1 patients operated for a GPD-NET tumor. Improving the prognosis of these patients requires a strict evaluation of the secretory syndrome and MEN1 aggressiveness before GDP surgery.

Background: Hypocalcemia is the most common complication following total thyroidectomy. Few factors may relate with increased risk of postoperative hypocalcemia. Preoperative vitamin D values have been evaluated in few studies, but reports present conflicting data. Aim of our study is to evaluate the association of preoperative vitamin D values and hypocalcemia following total thyroidectomy., Methods: A retrospective analysis of patients undergoing total thyroidectomy in our department of endocrine surgery between November 2012 and November 2015 was performed., Results: Mean age of patients was 56.2 years (±14.0) and sex ratio (F:M) was 4.3:1. Sixty-four patients (17.4%) had preoperative vitamin D insufficiency (x<25 nmol/L), 138 patients (37.5%) vitamin D deficiency (2550 nmol/L). Following total thyroidectomy for both benign and malignant pathology, 66 patients (17.9%) had symptomatic hypocalcemia (x<2.0 mmol/L) requiring medical treatment (group 1), 64 patients (17.4%) biochemical hypocalcemia (22.1 mmol/L, group 3). Mean postoperative PTH value was 25.4 pg/ml (range 2-61). No statistical correlation between postoperative serum calcium and preoperative vitamin D values (R=-0.001, P=0.9849) was found nor associations were found regarding age, sex, type of thyroid disease or BMI., Conclusions: In our cohort of patients, preoperative vitamin D levels were not associated with a higher risk of hypocalcemia following total thyroidectomy. Postoperative PTH appears to be the most sensible item to predict the risk of postoperative symptomatic hypocalcemia.

Background: Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists., Methods: All patients from 9 high-volume endocrine surgery departments who underwent surgery between 2005 and 2015 and whose final surgical pathology revealed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (>10 mm) were included in this study. The primary outcome was to determine the potential for recurrent disease in these patients., Results: Among the 363 patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 76% were female with a median age of 50 years (5-86 years); 345 patients (95%) underwent total thyroidectomy. A total of 65 patients had an associated micropapillary thyroid carcinoma. In the group of 133 patients who underwent prophylactic lymph node dissection (37%), 1 patient had a micrometastasis but with an associated micropapillary thyroid carcinoma. Over a median follow-up period of 5 years, 1 patient with an associated micropapillary thyroid carcinoma had recurrent disease at 6 years. All patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features without micropapillary thyroid carcinoma had no lymph node metastasis or recurrent disease., Conclusion: We found that noninvasive follicular thyroid neoplasm with papillary-like nuclear features presents with indolent behavior. However, the identification of an associated micropapillary thyroid carcinoma should be carefully evaluated because it could be a factor for lymph node metastasis and/or of recurrence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Few long-term studies define the appropriate extent of surgery and recurrence rates for unilateral multinodular goiter. We compared the rate and time to reoperation in patients with multinodular goiter who underwent lobectomy to that of patients with benign solitary nodule., Methods: Retrospective study of a prospective database of all patients who underwent lobectomy for multinodular goiter or solitary nodule from 1991 to 2017. We analyzed reoperation rates and time to reoperation. Reoperation was defined as the need for completion thyroidectomy determined the following citeria: nodule greater than 3 cm, multiple nodules, nodule growth or suspicion for malignancy by ultrasound or fine-needle aspiration biopsy, or compressive symptoms., Results: Included in the study were 2,675 lobectomies; 852 (31.85%) for multinodular goiter. In total, 394 patients (14.7%) underwent reoperation: 261 (30.6%) with a previous multinodular goiter and 133 (7.29%) with solitary nodule (P < .0001). A total of 80% of the patients with multinodular goiter and 67.66% with solitary nodule recurred as multinodular goiter; 3.5% of all recurrences were carcinomas. The mean time to reoperation was 14.8 years, without difference between groups (P = .5765). Patients without reoperation were younger (47 ± 15 vs 54 ± 13 years of age, P < .0001) and more likely to be male (P < .0001)., Conclusion: Lobectomy for unilateral multinodular goiter is the procedure of choice given the length of time to reoperation. Patients and surgeons should be aware of the need for long-term surveillance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the validity of hospital administrative databases compared to prospective collection of medical data assessing thyroid surgery complications., Background: Administrative data are increasingly used to track surgical outcomes., Methods: All patients undergoing thyroid surgery at three French university hospitals between April 2008 and April 2009 were prospectively included. Using diagnosis and procedural codes from hospital administrative database, we designed three indicators for measuring complications of thyroid surgery: recurrent laryngeal nerve palsy, postoperative hypoparathyroidism, and postoperative hemorrhage. Gold standard was obtained from a prospective collection of medical data after systematically screening each patient for the above-mentioned complications. Their ability to monitor surgical outcomes over time within individual hospitals was estimated using control charts. Spatial comparison between hospitals was performed by funnel plots., Results: A total of 1909 patients were included. Complication rates extracted from administrative data were significantly lower compared to medical data (nerve palsy 2.4% vs. 6.7%, hypoparathyroidism 10.6% vs. 22.3%, p<0.0001). Indicator sensitivity was 30.4% for nerve palsy, 45.4% for hypoparathyroidism and 71.4% for postoperative hemorrhage. Corresponding positive predictive values were 84.4%, 95.1% and 68.2%. In two of the three hospitals, administrative data were not able to track temporal variations in complications rates. Regarding inter-hospital comparisons, 2 out of 3 hospitals were considered outliers according to administrative data despite having an average performance based on medical data., Conclusions: The ability of indicators extracted from administrative databases to measure thyroid surgery outcomes depends on the quality of underlying data coding. Validation in every center should be a prerequisite before implementing such metrics for tracking performance., Competing Interests: The authors have declared that no competing interests exist.

Background: Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery., Methods: A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up., Results: PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/β blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications., Conclusions: PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

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.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Treatment of primary aldosteronism (PA) aims at preventing or correcting hypertension, hypokalemia and target organ damage. Patients with lateralized PA and candidates for surgery may be managed by laparoscopic adrenalectomy. Partial adrenalectomy and non-surgical ablation have no proven advantage over total adrenalectomy. Intraoperative morbidity and mortality are low in reference centers, and day-surgery is warranted in selected cases. Spironolactone administered during the weeks preceding surgery controls hypertension and hypokalemia and may prevent postoperative hypoaldosteronism. In most cases, surgery corrects hypokalemia, improves control of hypertension and reduces the burden of pharmacologic treatment; in about 40% of cases, it resolves hypertension. However, success in controlling hypertension and reversing target organ damage is comparable with mineralocorticoid receptor antagonists. Informed patient preference with regard to surgery is thus an important factor in therapeutic decision-making., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objectives/hypothesis: Intraoperative neuromonitoring identifies recurrent laryngeal nerve (RLN) injury and gives prognostic information regarding postoperative glottic function. Loss of the neuromonitoring signal (LOS) signifies segmental type 1 or global type 2 RLN injury. This study aimed at identifying risk factors for RLN injury and determining vocal fold (VF) function initially and 6 months after definitive LOS., Study Design: Prospective study encompassing 21 hospitals from 13 countries., Methods: Included in this study were patients with persistent intraoperative LOS., Results: At first postoperative laryngoscopy, early VF palsy was present in 94 of all 115 patients with LOS (81.7%): in 53 of 56 patients (94.6%) with type 1 injury and 41 of 59 patients (69.5%) with type 2 injury. In LOS type 1, women outnumbered men >5-fold. Traction produced LOS type 1 in 38 of 56 patients (67.9%) and LOS type 2 in 54 of 59 patients (91.5%). Course of the RLN posterior and/or anterior to the inferior thyroid artery, extralaryngeal branching, or tuberculum of Zuckerkandl did not increase VF palsy rates. Permanent VF palsy rates were also lower (P = .661) after LOS type 2 than after LOS type 1: 6.8% (four of 59 patients) versus 10.7% (six of 56 patients). Intraoperative administration of steroids did not diminish postoperative VF palsy rates., Conclusions: LOS type 1 entails more severe nerve damage than LOS type 2, affecting women disproportionately. Both LOS types, being primarily associated with traction injury, are unaffected by variant neck anatomy in expert hands and unresponsive to steroids., Level of Evidence: 2b Laryngoscope, 126:1260-1266, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are often discovered at a small size. No clear consensus exists on the management of NF-PNETs ≤ 2 cm. The aim of our study was to determine the prognostic value of indicators of malignancy in sporadic NF-PNETs ≤ 2 cm., Methods: Eighty patients were evaluated retrospectively in 7 French University Hospital Centers. Patients were managed by operative resection (operative group [OG]) or observational follow-up (non-OG [NOG]). Pathologic characteristics and outcomes were analyzed., Results: Sixty-six patients (58% women) were in the OG (mean age, 59 years; 95% CI, 56.0-62.3; mean tumor size, 1.6 cm; 95% CI, 1.5-1.7); 14 (72% women, n = 10) were in the NOG (mean age, 63 years; 95% CI, 56-70; mean tumor size, 1.4 cm; 95% CI, 1.0-1.7). All PNETs were ranked using the European Neuroendocrine Tumor Society grading system. Fifteen patients (19%) had malignant tumors defined by node or liver metastasis (synchronous or metachronous). The median disease-free survival was different between malignant and nonmalignant PNETs, respectively: 16 (range, 4-72) versus 30 months (range, 1-156; P = .03). On a receiver operating characteristic (ROC) curve, tumor size had a significant impact on malignancy (area under the curve [AUC], 0.75; P = .03), but not Ki-67 (AUC, 0.59; P = .31). A tumor size cutoff was found on the ROC curve at 1.7 cm (odd ratio, 10.8; 95% CI; 2.2-53.2; P = .003) with a sensitivity of 92% and a specificity of 75% to predict malignancy., Conclusion: Based on our retrospective study, the cutoff of 2 cm of malignancy used for small NF-PNETs could be decreased to 1.7 cm to select patients more accurately., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Total thyroidectomy is a well-established surgical approach for the management of papillary thyroid cancer (PTC). However, the best surgical approach for papillary microcarcinoma is nowadays still debated. Both total thyroidectomy and simple lobectomy are used. We report the experience of a single University center in the treatment of thyroid microcarcinoma., Methods: A retrospective analysis on all patients who underwent thyroid surgery at our institution over a 24-year period (1991-2015) was performed. Patients were grouped according to whether they received total thyroidectomy (Group 1) or lobectomy (Group 2). Follow-up was made by routine clinical and ultrasound examination. Specific outcomes such as recurrence and need for reoperation as well as complications (transient vocal cord paralysis and hypocalcemia) were analyzed., Results: During the study period 880 patients underwent surgery for PTC. Group 1 and 2 consisted, respectively, of 756 and 124 patients. A micro PTC (<10 mm) was present in 251 and 69 specimen of Group 1 and 2. No evidence of disease recurrence in the follow-up was reported in patients with microPTC in Group 1 and in 57 patients of Group 2. In the remaining 12 patients completion thyroidectomy was carried out due to ultrasound findings of contralateral nodules (10), lymphadenopathy (1), and capsular invasion (1). Five of these patients had a contralateral papillary carcinoma on final histopathologic examination. Thus recurrence rate for patients of Group 2 was 7.3%. Morbidity rates were, respectively, for Group 1 and 2: transient nerve palsy 81 and 5 (11 vs. 7.3%, p = ns), transient hypoparathyroidism (Calcium <2.00 mmol/L) 137 (18.6%) and 0 (p < 0.0001). Three of the 12 patients of Group 2 undergoing further surgery had a transient hypoparathyroidism., Conclusions: Thyroid lobectomy is an effective surgical strategy to manage papillary microcarcinomas with low complications. Routine completion thyroidectomy is not mandatory. Appropriate selection excluding high-risk patients is of paramount importance in order to achieve the best results.

Introduction: Hurthle cell tumors (HCTs) are rare thyroid neoplasia. To date, capsular and/or vascular invasion are the only findings predicting malignancy. Recently, mutation of 19p13, encoding two proteins involved in cell proliferation and apoptosis (GRIM-19 and p19), has been described. The aim of our study is to evaluate the cellular proliferation index (Ki67), GRIM-19 and p19 expression as diagnostic markers of malignancy in HCT., Materials and Methods: Eighty patients with HCT (32 carcinomas, 48 adenomas) whom underwent surgery in our center were included. Samples of both neoplastic lesions and adjacent normal thyroid tissue were analyzed by means of tissue micro-arrays. Correlations between expressions of Ki67, GRIM-19 and p19 and final histology were analyzed., Results: Mean size of the lesion was higher in carcinomas than in adenomas (p = 0.01). GRIM-19 and p19 were significantly underexpressed in Hurthle cells tumors compared to normal tissue (p = 0.0004 and p = 0.0001, respectively). Ki67 and GRIM-19 were, respectively, higher and down-expressed in carcinomas compared to adenomas (p = 0.0004 and p = 0.005, respectively). On multivariate analysis, size correlates with carcinoma diagnosis. Neither GRIM-19 nor Ki67 index was related to size. The expression of p19 was reduced in both adenoma and carcinoma but differences were not statistically significant (p = 0.13)., Conclusions: Our study suggest that Ki67 and GRIM-19 correlate with malignancy in HCT. The expression of p19 is down-regulated in HCT, but it is not diagnostic of carcinoma. Ki67 and GRIM-19 may potentially help as cytological markers of malignancy in HCT.

Objective: Inferior laryngeal nerve (ILN) palsy and hypocalcemia remain the two most frequent major complications after thyroid surgery. Their occurrences may be explained by the influence of factors related to the patient, the surgical procedure, thyroid pathology, or the surgeon's technique. This study aims To assess whether systematically following a rigorous surgical technique during thyroidectomy affects postoperative complications and long-term patient recovery., Methods: We conducted a multicenter, cross-sectional study of prospectively collected data in five high-volume referral centers enrolling all patients who underwent thyroid surgery between April 2008 and December 2009. Inferior laryngeal nerve (ILN) palsy and hypocalcemia were systematically assessed during hospitalization based on objective criteria. A six-month follow-up was conducted in cases of early complications. Multivariate regression models were computed to quantify their relationship with potential risk factors., Results: A total of 3574 thyroid procedures were completed. Non-visualization of the ILN during dissection and a large thyroid mass were major risk factors for permanent ILN palsy (OR, 4.17 and 2.61, p<0.01) and persistent complications after initial injury (OR, 4.17 and 2.42, p<0.05). The presence of thyroiditis on the surgical specimen was an independent risk factor for permanent hypoparathyroidism and poor recovery after initial dysfunction (OR, 1.76 and 1.88, p<0.05)., Conclusions: Thorough meticulous technique in thyroid surgery is a determinant of ILN function but fails to prevent persistent hypoparathyroidism., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: This paper aims to review controversies in the management of minimally invasive follicular thyroid carcinoma (MIFTC) and to reach an evidence-based consensus., Method: MEDLINE search of the literature was conducted using keywords related to MIFTC. The search term was identified in the title, abstract, or medical subject heading. Available literature meeting the inclusion criteria were assigned the appropriate levels of evidence and recommendations in accordance with accepted international standards. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to MIFTC., Results: Published papers on MIFTC present inadequate power with a III–IV level of evidence and C grade of recommendation. Several issues demanded a comparison of published studies from different medical reports regarding MIFTC definition, specimen processing, characteristics, diagnosis, prognoses, and therapy. As a consequence, it is difficult to make valuable statements on MIFTC with a sufficient recommendation rating. MIFTC diagnosis requires clearer, unequivocal, and reproducible criteria for pathologist, surgeons, and endocrinologists to use in the management of these patients. If the distinction between MIFTC and WIFTC cannot be made, an expert in thyroid pathologist should be consulted., Conclusion: According to published papers, the following conclusions can be drawn. (a) Candidates for hemithyroidectomy are MIFTC with exclusive capsular invasion, patients <45 years old at presentation, tumor size <40 mm, without vascular invasion, and without any node or distant metastases. (b) Candidates for total thyroidectomy are MIFTC in patients ≥45 years at presentation, tumor size ≥40 mm, vascular invasion present, positive nodes, and positive distant metastases. (c) In the absence of clinical evidence for lymph node metastasis, patients with MIFTC do not require prophylactic lymph node dissection. (d) Radio iodine ablation is indicated in elderly patients (>45 years), large tumor size (>40 mm), extensive vascular invasion, presence of distant synchronous or metachronous metastasis, positive nodes, and if recurrence is noted at follow-up.

Background. Subtotal thyroidectomy (STT) was previously considered the gold standard in the surgical management of multinodular goitre despite its propensity for recurrence. Our aim was to assess whether prior STT or unilateral lobectomy was associated with increased reoperative morbidity. Methods. A retrospective analysis was conducted extracting data from our endocrine surgical database for the period from January 1991 to June 2006. Two patient groups were defined: Group 1 consisted of patients with previous unilateral thyroid lobectomy; Group 2 had undergone previous STT. Specific outcomes investigated were transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism. Results. 494 reoperative cases were performed which consisted of 259 patients with previous unilateral lobectomy (Group 1) and 235 patients with previous subtotal thyroidectomy (Group 2). A statistically significant increase relating to previous STT was demonstrated in both permanent RLN injury (0.77% versus 3.4%, RR 4.38, P = 0.038) and permanent hypoparathyroidism (1.5% versus 5.1%, RR 3.14, P = 0.041). Transient nerve injury and hypocalcaemia incidence was comparable. Conclusions. Reoperative surgery following subtotal thyroidectomy is associated with a significantly increased risk of permanent recurrent laryngeal nerve injury and hypoparathyroidism when compared with previous unilateral thyroidectomy. Subtotal thyroidectomy should therefore no longer be recommended in the management of multinodular goitre.

Background: We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers., Methods: Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible., Results: Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (≤6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86% of cases. The median overall survival was 29 months (95% confidence interval, 24.69-33.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%, 42%, and 35%, respectively. Patients with renal cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P = .017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs. 23 months; P = .038)., Conclusion: Surgical removal of adrenal metastasis is associated with long-term survival in selected patients., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Unlabelled: Intraoperative neural monitoring (IONM) during thyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual identification of the recurrent laryngeal nerve (RLN). Contrary to routine dissection of the RLN, most surgeons tend to avoid rather than routinely expose and identify the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy or parathyroidectomy. IONM has the potential to be utilized for identification of the EBSLN and functional assessment of its integrity; therefore, IONM might contribute to voice preservation following thyroidectomy or parathyroidectomy. We reviewed the literature and the cumulative experience of the multidisciplinary International Neural Monitoring Study Group (INMSG) with IONM of the EBSLN. A systematic search of the MEDLINE database (from 1950 to the present) with predefined search terms (EBSLN, superior laryngeal nerve, stimulation, neuromonitoring, identification) was undertaken and supplemented by personal communication between members of the INMSG to identify relevant publications in the field. The hypothesis explored in this review is that the use of a standardized approach to the functional preservation of the EBSLN can be facilitated by application of IONM resulting in improved preservation of voice following thyroidectomy or parathyroidectomy. These guidelines are intended to improve the practice of neural monitoring of the EBSLN during thyroidectomy or parathyroidectomy and to optimize clinical utility of this technique based on available evidence and consensus of experts., Level of Evidence: 5, (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas., Methods: This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor., Results: Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31-89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP., Conclusions: Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.

Background: Most patients with adrenocortical cancer (ACC) continue to present with advanced disease. Invasion into the inferior vena cava (IVC) defines stage III disease and the management of such patients raises additional difficulties., Method: A multicentre survey was organized by emailing a standardized proforma to members of the European Society of Endocrine Surgery (ESES). Anonymised retrospective clinical data were collected., Results: Replies were received from 18 centres in nine countries. ACC with IVC invasion was encountered in 38 patients (18F:20M, age 15-84 years, median 54 years). There were 16 nonfunctioning tumours and 22 functioning tumours predominantly right-sided (26R:12L) and measuring 18-255 mm (median 115 mm). Fourteen patients had metastatic disease at presentation. Tumour thrombus extended in the prehepatic IVC (n = 21), subdiaphragmatic IVC (n = 6) or into the SVC/right atrium (n = 3). Open adrenalectomy was associated with resection of surrounding viscera in 24 patients (nephrectomy n = 16, liver resection n = 14, splenectomy n = 3, Whipple procedure n = 2). IVC was controlled locally (n = 27), at suprahepatic levels (n = 6) or necessitated cardiac bypass (n = 5). Complete resection (R0, n = 20) was achieved in the majority of patients, with a minority having microscopic persistent disease (R1, n = 7) or macroscopic residual disease (R2, n = 4). Perioperative 30-day mortality was 13% (n = 5). Postoperative Mitotane was used in 23 patients and chemotherapy in eight patients. Twenty-five patients died 2-61 months after their operation (median 5 months). Currently, 13 patients are alive at 2-58 months (median 16 months) with known metastatic disease (n = 7) or with no signs of distant disease (n = 6)., Conclusion: This dataset is limited by the lack of a denominator as it remains unknown how many other patients with ACC presenting with IVC invasion did not undergo surgery. The relatively low perioperative mortality and the long disease-free survival achieved by some patients should encourage surgeons with adequate experience to offer surgical treatment to patients presenting with advanced adrenocortical cancers.

Purpose: The pathological diagnosis of malignancy in pheochromocytomas remains a controversial issue. According to the WHO, malignancy is defined in the presence of metastasis. Multiparameter scoring systems such as PASS (Pheochromocytoma of Adrenal gland Scaled Score) have been used but remain controversial. The aim of this study was to search for new immunohistologic elements allowing determination of pheochromocytoma malignancy., Methods: Among 53 patients operated for pheochromocytoma between 1993 and 2009, we selected pheochromocytomas with proven metastasis, seven cases in group 1 (G1) and paired two others groups: group 2 (G2), patients who had "benign" pheochromocytoma with PASS ≥4 and group 3 (G3), patients who had "benign" pheochromocytoma with PASS <4. We retrospectively analysed PASS criteria, size, weight, tumour necrosis, Ki-67 and pS100 staining., Results: The size and weight of the lesion were directly and significantly correlated to malignancy in all three groups: respectively 9.7 cm and 292.0 g (G1), 6.2 cm and 83.8 g (G2) and 3.8 cm and 37.1 g (G3) (p < 0.005 for both). Tumour necrosis (TN) was present in all G1 (p < 0.005) and respectively at 0% and 37.5% in G2 and G3. Ki-67 is directly correlated to presence of TN (p < 0.005) and malignancy (G1 14.1%, G2 1.8%, G3 2.6%; p < 0.001). All G1 had a Ki-67 index >4%, although one G3 presented an 11% Ki-67 index. There was an inverse statistically significant correlation between the three groups in staining using pS100 (p < 0.01)., Conclusions: Size and weight of the pheochromocytoma are directly related to PASS and malignancy. The presence of tumour necrosis, Ki-67 index >4% and pS100 absence impose a close histopathological evaluation and follow-up with regard to cases presenting a high risk of malignancy/recurrence.

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.

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.

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.

Background: Gap junctions are membrane structures composed of connexins (Cx) that allow diffusion of small molecules between cells. They are involved in tissue homeostasis, and various organ dysfunctions have been associated with gap junction defects. To verify their possible involvement in thyroid pathologies, the expression of connexin43 (Cx43), the major Cx in the human thyroid, was evaluated in a variety of diseases including cancer., Methods: There were 122 samples from various thyroid pathologies that were collected to analyze the presence of Cx43 by immunofluorescence. Through confocal microscopy, different patterns of Cx43 localization were identified as normal (membrane) or abnormal (cytoplasmic or lack of detection). The analysis of Cx43 expression was further performed by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in a subset of 25 papillary carcinomas and compared with nontumoral thyroid tissues., Results: The presence of Cx43 was commonly altered in thyroid cancer, as abnormal Cx43 staining was detected in 94.1% of cancer, 47.4% of adenomas, 45.7% of multinodular goiter, 16.7% of Graves' disease, and 25% of thyroiditis. In papillary carcinoma samples, the deregulation of Cx43 expression was mostly the consequence of a decrease of Cx43 mRNA (68% of cases) when compared with normal tissue. When Cx43 mRNA was not downregulated (32% of cases), both loss of membrane staining and aberrant cytoplasmic distribution of the protein were observed., Conclusions: These results show that aberrations of Cx43 expression are associated with thyroid papillary carcinoma.

Background: Ectopic abnormal parathyroid glands are relatively common in the superior mediastinum but are rarely situated in the aortopulmonary window (APW). The embryological origin of these abnormal parathyroid glands is controversial. The purpose of this investigation was to investigate the embryological origin and the surgical management of abnormal parathyroid glands situated in the APW., Methods: The databases of patients operated on for primary, secondary, and tertiary hyperparathyroidism at eight European medical centers with a special interest in endocrine surgery were reviewed to identify those with APW adenomas. Demographic features, localization procedures, and perioperative and pathology findings were documented. The embryological origin was determined based on the number and position of identified parathyroid glands., Results: Nineteen (0.24%) APW parathyroid tumors were identified in 7,869 patients who underwent an operation for hyperparathyroidism (HPT) and 181 patients (2.3%) with mediastinal abnormal parathyroid glands. Ten patients had primary, eight had secondary, and one had tertiary HPT. Sixteen patients had undergone previous unsuccessful cervical exploration. In three patients, an APW adenoma was suspected by preoperative localization studies and was cured at the initial operation. Sixteen patients had persistent HPT of whom 15 were reoperated, resulting in 6 failures. Evaluation of 17 patients who had bilateral neck exploration allowed us to determine the most probable origin of the APW parathyroid tumors: 12 were supernumerary, 4 appeared to originate from a superior, and 1 from an inferior gland., Conclusions: Abnormal parathyroid glands situated in the APW are rare and usually identified after an unsuccessful cervical exploration. Preoperative imaging of the mediastinum and neck are essential. The origin of these ectopically situated tumors is probably, as suggested by our data, from a supernumerary fifth parathyroid gland or from abnormal migration of a superior parathyroid gland during the embryologic development.

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.

Background: Thymic neuroendocrine tumors (Th-NET) present a poor prognosis for patients with multiple endocrine neoplasia type 1 (MEN1). The purpose of this article was to study the clinical, biological, and pathological features of Th-NET in a large cohort of patients with MEN1., Methods: The 761-patient MEN1 cohort from the GTE registry was used (Groupe des Tumeurs Endocrines)., Results: The actuarial probability of occurrence was 2.6% (range, 1.3-5.5%) at aged 40 years. All, except one, Th-NET patients were men. Four patients had no other associated lesions. The youngest patient was aged 16 years. Mean age at the time of diagnosis was 42.7 (range, 16.1-67.5) years. The 10-year probability of survival was 36.1% (range, 11.5-62%). Seven patients (33%) belonged to clustered MEN1 families. The spectrum of associated lesions in patients with Th-NET was not statistically different from the spectrum of the remainder of the cohort. Various endocrine markers were high, but none were sensitive or specific enough to be useful for Th-NET detection. CT-scan and MRI were always positive at the time of diagnosis. No particular mutation was found to be associated with Th-NET. Five cases underwent prophylactic thymectomy without success., Conclusions: Several end points may be helpful for future guidelines: (1) earlier detection of Th-NET in MEN1 patients is required; (2) screening of both sexes is necessary; (3) a prospective study comparing MRI vs. CT scan in yearly screening for Th-NET is needed; (4) a reinforced screening program must be established for patients who belong to clustered families; and (5) thymectomies must be performed in specialized centers.

Virilizing ovarian tumors are rare and can occur at any age. In postmenopausal women, they commonly present with signs of masculinization. These tumors should be suspected in any patient with virilization and high testosterone levels (>1ng/mL). Tumor localization is sometimes difficult. These tumors are usually benign; surgical resection is the accepted treatment. Masculinizing consequences of hormonal secretions may be managed by cosmetologic treatments which should not be overlooked.

Background: Compressive hematoma after thyroidectomy is a rare complication (1%) but can potentially be severe. The aim of this study was to search for risk factors, in particular the use of anticoagulants or antiplatelet medication, and to see if the delay of hematoma formation would require 1-day surgery performed in a careful manner., Materials and Methods: Retrospective review of 6,830 patients undergoing thyroidectomy in a single institution (1991 to 2006) identified 70 patients with hematomas requiring reoperation. Case controls (210 patients) were matched for age, gender, year of operation, type of thyroid disease, and type of operation. The notion of anticoagulant or antiplatelet medication was particularly studied. The delay of hematoma formation and the cause of bleeding were studied in univariate analysis by a chi-squared test and a Fischer's test., Results: In univariate analysis, the formation of hematoma is not related to age, gender, type of thyroid disease, or type of bleeding. The pre or intraoperatory administration of anticoagulant or antiplatelet medication did not influence hematoma formation. Thirty-seven hematomas (53%) presented within 6 h postoperatively, 26 (37%) between 7 and 24 h and seven (10%) beyond 24 h., Conclusion: Patients undergoing anticoagulant or antiplatelet treatment are not a high-risk population for hematoma formation. Forty-seven percent of the patients presented postoperative hematomas beyond 6 h postoperatively, leading to the conclusion that 1-day surgery is not safe.

TSH, via its G-protein-coupled receptor, activates cell growth of both benign and malignant thyroid tumors. G-protein-coupled receptors (GR) kinase 2 (GRK2) has been reported to regulate the TSH receptor but its role in cancer is unknown. To determine a possible function for GRK2 in the growth process of thyroid cancers, we analysed its expression in normal and tumoral thyroid tissues and studied thyroid cancer cell line proliferation after GRK2 overexpression. Thirty one thyroid tissues, including 16 non-medullary thyroid cancers and 15 adjacent normal tissues, were analysed by immunohistochemistry. Five paired tissues were also studied by western blotting for the GRK2 enzymatic activity. Immunohistochemical staining showed an increase in GRK2 in thyroid cancers including papillary, follicular, and anaplastic types, compared with their adjacent normal tissues. Immunoblot analysis and GRK2 enzymatic activity measurement confirmed immunohistochemical study. TSH and TSH in association with insulin or IGF-I stimulated GRK2 protein accumulation in normal human thyroid cells in primary culture. The TSH effect on the GRK2 expression was mimicked by forskolin. After GRK2 overexpression in two poorly differentiated thyroid cell lines, all the clones showed a significant reduction in cell proliferation, ranging from 28 to 65% inhibition compared with vector alone after 96-h culture. In conclusion, thyroid mitogenic factor-stimulated GRK2 accumulation may explain, in part, high GRK2 levels in differentiated carcinoma, because TSH, insulin, or IGF-I is known to be involved in the thyroid cancer progression. Surprisingly, instead of stimulating, GRK2 reduced cell proliferation revealing a new role for this kinase in the growth of thyroid cancers.

Purpose of the Study: To evaluate clinical characteristics and survival of patients treated for parathyroid carcinoma., Study Design: A retrospective multicenter chart review of patients treated for parathyroid carcinoma between January 1979 and January 2005., Results: 17 patients (10 women, 7 men) presenting with parathyroid carcinoma underwent surgical resection. Symptoms were largely related to hypercalcemia. Mean postoperative follow-up was seven years. Local recurrence was noted in four patients (24%) and three patients had late distant metastasis (18%). At the end of the study, nine patients were alive without evidence of recurrence (53%) and one patient was alive with recurrence at 5 years. Seven patients had died, four of whom died as a result of their parathyroid disease., Conclusion: Even when symptoms and findings are suggestive, the diagnosis of parathyroid carcinoma is oftentimes difficult. An adequate resection at the first intervention (complete tumor resection including a homolateral thyroid lobectomy and parathyroidectomy with resection of central lymph nodes) is recommended.

Background: Only a minority of patients with primary hyperparathyroidism (pHPT) present with the "classic" symptoms. Most patients have numerous nonspecific symptoms. The aim of this study was to evaluate patients' quality of life and nonspecific symptoms before and after cure for pHPT., Methods: This prospective, multicentric study, which took place from May 2003 to September 2004, included 100 patients. Six academic departments of Endocrine Surgery in France participated in the study: the University of Angers, Limoges, Nancy, Nantes, Marseille, and Poitiers. Only cured patients were included. All patients were given preoperative and postoperative questionnaires (the SF-36v2 Health Survey) at 3, 6, and 12 months to evaluate quality of life and nonspecific symptoms., Results: Preoperatively, the main nonspecific symptoms included the following: anxiety (89%); muscular, bone, or join pain (87%); abdominal distention (82%); forgetfulness (81%); headaches (81%); and mood swings (79%). Quality of life was significantly improved at 3 and 6 months (P < .05). At 1 year postoperatively, statistically significant improvement (P < .05) persisted in all 8 domains of the SF-36v2. At 1 year after parathyroidectomy, 5 symptoms remained significantly improved: appetite loss, weight loss, thirst, headache, and nausea., Conclusions: Operative cure of primary hyperparathyroidism significantly improves quality of life and nonspecific symptoms for at least 1 year.

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, which is involved in the ARF-Mdm2-p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT-PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14ARF and pl6INK4A was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14ARF and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.

Phosphorylation of the agonist-activated form of G-protein-coupled receptors (GPCRs) by a protein kinase from the G-protein-coupled receptor kinase (GRK) family initiates, with arrestin proteins, a negative feedback process known as desensitization. Because these receptors are involved in so many vital functions, it seems likely that disorders affecting GRK- or arrestin-mediated regulation of GPCRs would contribute to, if not engender, disease. Traditionally, it is believed that the desensitization process protects the cell against an overstimulation; however, in certain situations, this process is maladjusted and participes in disease progression. For example, in Oguchi disease, excessive rhodopsin stimulation due to a functional loss of GRK1 or arrestin 1 leads to light sensitization and stationary night blindness. Also, transgenic mice with vascular smooth muscle-targeted overexpression of GRK2 showed an elevated resting blood pressure, suggesting that increase in GRK2 level in humans is involved in hypertension associated with a decreased effect of beta-adrenergic receptor-mediated vasorelaxation. The restoration of normal GPCR function in modulating the desensitization process has been successfully demonstrated in animal models of heart failure, which indicates that targeting GRKs or arrestins may open a novel therapeutic strategy in human diseases with GPCR dysregulation. However, the few effective pharmacological compounds in this domain currently preclude human clinical tests.