Recurrence After Surgery for Primary Hyperparathyroidism in 517 Patients With Multiple Endocrine Neoplasia Type 1: An Association Francophone de Chirurgie Endocrinienne and Groupe d'étude des Tumeurs Endocrines study.

OBJECTIVE: To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. BACKGROUND: In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. METHODS: MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. RESULTS: Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). CONCLUSIONS: Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.

Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

Accidental parathyroidectomy during total thyroidectomy and hypoparathyroidism in a large series of 766 patients: incidence and consequences in a referral center.

PURPOSE: Transient hypoparathyroidism is the most common complication after total thyroidectomy, and accidental parathyroidectomy (AP) may be a cause. The aim of this study was to investigate the incidence of AP and its impact on postoperative calcemia. MATERIALS AND METHODS: From February 2016 to May 2018, 766 patients undergoing total thyroidectomy were prospectively included. Surgical indications, hormonal status, definitive histology, and postoperative calcium and PTH levels were analyzed. RESULTS: 578/(75.45%) were women and 188/(24.55%) men with mean age of 53.4 years. Parathyroid tissue on the thyroid specimen was observed in 40 (5.2%) patients: 30 APs and 10 parathyroid fragments. Among the 30 APs, 12 glands were intrathyroid and 18 (2.3%) in eutopic location. 97 (12.6%) patients were treated for postoperative hypocalcemia: 90 (11.7%) had transient and 5 (0.6%) definitive hypoparathyroidism; 2 were lost in follow-up. 13/30 (43.3%) with AP had transient hypoparathyroidism. A strong correlation was found (p < 0.0001) between AP and postoperative hypocalcemia. 1/30 (3.3%) patient with APs had definitive hypoparathyroidism. Transient and persistent nerve palsies were found in 10 (1.3%) and 3 (0.4%) patients, respectively. DISCUSSION: A careful examination of the thyroid gland after resection help to identify an AP that could be autotransplanted. Surgeon and hospital activity volume per years seem to reduce the risk of hypoparathyroidism. CONCLUSION: Total thyroidectomy and intrathyroid localization of parathyroid glands are risk factors for the AP. The incidence of AP was 2.3%, and this remains low due to our longstanding experience in thyroid and parathyroid surgery.

Watchman FLX vs. Watchman 2.5 in a Dual-Center Left Atrial Appendage Closure Cohort: the WATCH-DUAL study.

AIMS: No studies have compared Watchman 2.5 (W2.5) with Watchman FLX (FLX) devices to date. We aimed at comparing the FLX with W2.5 devices with respect to clinical outcomes, left atrial appendage (LAA) sealing properties and device-related thrombus (DRT). METHODS AND RESULTS: All consecutive left atrial appendage closure (LAAC) procedures performed at two European centres between November 2017 and February 2021 were included. Procedure-related complications and net adverse cardiovascular events (NACE) at 6 months after LAAC were recorded. At 45-day computed tomography (CT) follow-up, intra- (IDL) and peri- (PDL) device leak, residual patent neck area (RPNA), and DRT were assessed by a Corelab. Out of 144 LAAC consecutive procedures, 71 and 73 interventions were performed using W2.5 and FLX devices, respectively. There were no differences in terms of procedure-related complications (4.2% vs. 2.7%, P = 0.626). At 45-day CT, the FLX was associated with lower frequency of IDL [21.3% vs. 40.0%; P = 0.032; odds ratio (OR): 0.375; 95% confidence interval (CI): 0.160-0.876; P = 0.024], similar rate of PDL (29.5% vs. 42.0%; P = 0.170), and smaller RPNA [6 (0-36) vs. 40 (6-115) mm2; P = 0.001; OR: 0.240; 95% CI: 0.100-0.577; P = 0.001] compared with the W2.5 group. At 45 days, rate of DRT as detected by CT and/or transoesophageal echocardiography (TOE), was higher with W2.5 (6.0% vs. 0%, P = 0.045). At 6-month follow-up, NACE did not differ between groups. CONCLUSIONS: In this cohort of consecutive LAACs, FLX as compared to W2.5, was associated with similar procedure-related complications and 6-month NACE, but with improved LAA neck coverage, and lower IDL and DRT.

Diagnostic Rechallenge with 18F-FCH PET/CT Often Allows Minimally Invasive Parathyroidectomy While Maintaining Exceptional Cure Rates.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has gained acceptance as the preferred surgical procedure for management of primary hyperparathyroidism (pHPT). Appropriate selection of patients for a MIP is a crucial step in its utilization. The aim of the study was to evaluate the role of 18F-FCH PET/CT as second-line imaging for accurately directing MIP. METHODS: This is a retrospective single-center study. Seventy-two patients with biochemical evidence of pHPT and a non-conclusive or negative first-line imaging (ultrasound and dual isotope subtraction scintigraphy) received 18F-FCH PET/CT between January 2018 and February 2020. All imaging studies were performed at our institution. Assessment of therapeutic changes and outcomes was performed. RESULTS: of the 72 patients imaged with 18F-FCH PET/CT, 54 subsequently underwent parathyroidectomy. When considering the ability of 18F-FCH PET/CT alone to predict a uniglandular disease, the sensitivity, specificity, PPV and NPV were 92.7% (95%CI: 80.1-98.5), 46.2% (19.2-74.9), PPV 87.3% (80.5-92) and NPV 61.2% (31.4-84.5), respectively. When we combined the data provided by 18F-FCH PET/CT with the data already collected from 1st line imaging we were able to complete a minimally invasive surgery in 38 of the 41 (92%) patients with a uniglandular disease. Thirteen patients (24%) had a multiglandular disease, all of them except one underwent bilateral neck exploration based on the data collected by all imaging modalities combined. Overall, cure was achieved in 53 (98%) patients. CONCLUSION: 18F-FCH PET/CT, interpreted along with first-line imaging results in selected patients, can better facilitate utilization of MIS while maintaining exceptional cure rates.

Impact of Permanent Post-thyroidectomy Hypoparathyroidism on Self-evaluation of Quality of Life and Voice: Results From the National QoL-Hypopara Study.

OBJECTIVE: The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy. SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice. METHODS: The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms. RESULTS: A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%). CONCLUSIONS: Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication.

Partial Versus Total Thyroidectomy: What Influences Most Surgeons' Decision? Analysis of a Nationwide Cohort of 375,810 Patients Over 10 Years.

National and international guidelines about thyroid surgery seem to be moving more and more towards less radical surgical procedures but everyday practice does not seem to always align with them. We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery. OBJECTIVE: The ain of this study was to describe thyroid surgery and to identify the factors leading to either a total or a partial thyroidectomy regardless of the severity of the thyroid disease. SUMMARY BACKGROUND DATA: National and international guidelines about thyroid surgery seem to be moving more and more toward less radical surgical procedures but everyday practice does not seem to always align with them. METHODS: We based this nationwide retrospective cohort study on a national database that compiles discharge abstracts for every admission for thyroidectomy to French acute healthcare facilities (PMSI database 2010 to 2019). RESULTS: In this study, 375,810 patients (male: 23%; age = 53 ±â€Š15 years) had a thyroidectomy (partial: 28%) for cancer (17%), hyperthyroidism (16%), nonfunctioning goiter (64%), or other (3%). We noticed a global trend toward more partial thyroidectomy (P < 0.001) with a significant increase in the proportion of lobectomy in the post-ATA recommendations' period (P < 0.001) as well as in the "French Levothyrox crisis" period, in which we saw an unexpected rise of adverse events notifications associated with the marketing of a new formula of Levothyrox (P < 0.001) amid widespread media coverage. In a multivariate analysis, we also identified that complete resection was more frequently performed in centers with a caseload >40/year [P < 0.001, odds ratio (OR) = 1.48], for obese patients (body mass index >30 kg/m2; P < 0.001, OR = 1.42), and according to the indication of surgery (OR benign = 1, OR cancer = 2.25, OR hyperthyroidism = 4.13). CONCLUSION: We describe for the first time the role of non-surgical parameters in the surgeon's choice for thyroid surgery.

Risk stratification of adrenal masses by [18 F]FDG PET/CT: Changing tactics.

CONTEXT: [18 F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy. OBJECTIVES: To assess the performance of Tumour standardized uptake value (SUV)max :Liver SUVmax for malignancy-risk and to build and evaluate a prediction model. DESIGN/METHODS: The cohort consisted of consecutive patients with adrenal masses evaluated by [18 F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in nonoperated cases. The performance of the previously reported cut-off for Tumour SUVmax :Liver SUVmax (>1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study). RESULTS: Sixty-four patients were evaluated; 28% of them had a Cushing's syndrome. Fifty-four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [18 F]FDG uptake. CT-derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUVmax :Liver SUVmax  > 1.5 showed a good diagnostic performance: Se = 90.0%/Sp = 92.6%/PPV = 69.2%/NPV = 98.0% and accuracy = 92.2%. A predictive model based on tumour size and tumour-to-liver uptake SUVmax ratio for malignancy-risk was validated and provides a complementary approach to the ratio. CONCLUSIONS: Tumour SUVmax :Liver SUVmax uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision-making process.

Pheochromocytoma surgery without systematic preoperative pharmacological preparation: insights from a referral tertiary center experience.

BACKGROUND: Despite significant advances in imaging and genetics, as well as surgical and anesthetic innovations, morbidity in pheochromocytoma surgery remains significant. The aim of this study was to identify the predictive factors of global and cardiovascular morbidity following unilateral laparoscopic adrenalectomy for pheochromocytoma. METHODS: We conducted a retrospective study from a unicentric cohort. All patients who underwent non-converted laparoscopic unilateral adrenalectomy for pheochromocytoma between 2000 and 2017 were included. Our patients did not systematically benefit from preoperative pharmacological preparation. It is to be noted that they never received alpha-blockers. Preoperative, intraoperative, and postoperative data during follow-ups were collected. Univariate and multivariate analyses by logistic regression were performed. RESULTS: A total of 134 patients were included. Fifty-three percent of patients did not receive preoperative pharmacological preparation (PPP) and 33% neither preoperative antihypertensives nor PPP before surgery. There was no postoperative mortality. The global morbidity was 13.4%, while cardiovascular morbidity was 4.5%. The main factors associated with global morbidity were preoperative diuretics, a medical history of stroke, and the need for pressor amines postoperatively. The main factor associated with cardiovascular morbidity was the need for pressor amines postoperatively. Predictive factors of postoperative need for pressor amines for hypotension were the tumor size, preoperative beta-blockers, and/or diuretics. CONCLUSION: In this large cohort of patients, our data revealed no mortality and low global and cardiovascular morbidity rates, showing that pheochromocytoma surgery without systematic PPP and even without preoperative antihypertensives is feasible and safe for selected patients. Our data also highlight the need for a good preoperative evaluation of the patient and the tumor, in order to optimize treatments and to help the detection of high-risk patients. This also allows us to better prevent and anticipate their possible complications.

Predicting risk factors of postoperative hypocalcemia after total thyroidectomy: is safe discharge without supplementation possible? A large cohort study.

PURPOSE: With increasing economic pressures to shorten the length of hospital stay, there has been much recent interest in studying risk factors for the development of postoperative hypocalcemia after total thyroidectomy. The aim of this study was to investigate whether serum calcium and/or PTH levels can predict post-thyroidectomy hypoparathyroidism. METHODS: From January to December 2014, 477 consecutive patients undergoing total thyroidectomy were included. Corrected calcemia and PTH were systematically performed on postoperative day 1/(POD1). Symptomatic patients were treated on POD1 or POD2 with calcium and vitamin D. RESULTS: Sixty-eight patients (14.25%) were treated for postoperative hypocalcemia. No patients with calcemia ≥ 2.16 mmol/l and PTH ≥ 1.9 pmol/l were supplemented and therefore were safely discharged on POD1 (specificity = 100%). All patients with calcemia ≤ 1.89 mmol/l were treated regardless the PTH values (n = 10) (specificity = 100%). For calcium value between 1.9 and 2.16 mmol/l with a PTH > 4.7 pmol/l, nobody was treated. With a calcemia between 1.9 and 2.16 mmol/l and a PTH > 1.9 pmol/l, 44 patients did not develop any symptom. ROC curve analysis showed that combination of Cac = 2.16 mmol/l and iPTH = 4.7 pmol/l provided a sensitivity of 97.06% and a specificity of 76.53% (p < 0.0001). We therefore propose an algorithm that would allow to 70% of patients could have been discharged on POD1 without risk of hypocalcemia or overtreatment. CONCLUSION: Combination of corrected calcemia and PTH on POD1 can efficiently predict hypocalcemia and be integrated into clinical practice for personalizing lengths of hospitalization and appropriate treatment. TRIAL REGISTRATION: ClinicalTrials.gov PRS. Unique Identifying number or registration ID: NCT04372225.

Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy: Conclusions From a Comprehensive Nationwide Database of 13,247 Interventions Over 6 Years.

BACKGROUND: Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers. OBJECTIVE: To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT. METHODS: We performed a nationwide retrospective cohort study on the "Programme de Medicalisation des Systemes d'Information," the French administrative database that collects information on all healthcare facilities' discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method. RESULTS: In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate. CONCLUSION: Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients' features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center.

Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1: A GTE and AFCE Cohort Study (Groupe d'étude des Tumeurs Endocrines and Association Francophone de Chirurgie Endocrinienne).

OBJECTIVE: To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size. SUMMARY BACKGROUND DATA: DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known. METHODS: The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d'étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases. RESULTS: Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared. CONCLUSIONS: DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.

Interrelationships between interventricular electrical delays in cardiac resynchronization therapy.

INTRODUCTION: In cardiac resynchronization therapy, pacing the left ventricle (LV) at sites of prolonged electrical delay is associated with better outcomes. We sought to characterize the interrelationships between intrinsic, right-ventricular (RV)-paced, and LV-paced interventricular delays. METHODS AND RESULTS: The following electrical timings were measured at implantation for all electrodes of the LV quadripolar leads: QLV, interventricular delay in intrinsic rhythm (RVs-LVs), in RV-paced rhythm (RVp-LVs), and in LV-paced rhythm (LVp-RVs). We included 32 patients (78% men, age 72 years, LV ejection fraction 29%, left bundle branch block 84%). QLV and RVs-LVs were correlated (R2 = .72, p < .0001), as were RVs-LVs and RVp-LVs (R2 = .27, p = .002) and RVp-LVs and LVp-RVs (R2 = .60, p < .001). Direction of activation along the four LV lead electrodes was concordant between RVs-LVs and RVp-LVs in only 17 (53%) patients. The latest-activated electrodes in RVs-LVs and RVp-LVs were concordant in 26 (81%) patients, adjacent in 3 (9%) patients, and remote in 3 (9%) patients. Biventricular-paced QRS duration varied by more than 10 ms between the two electrodes in half of the patients with dissimilar latest electrodes. Among the seven echocardiographic nonresponders at 6 months, the programmed electrode was remote from the latest electrode in RVs-LVs in five patients and in RVp-LVs in three patients. CONCLUSION: Intrinsic and RV-paced interventricular electrical delays are correlated, but there is substantial heterogeneity between patients. The latest-activated electrode may be different between RVs-LVs and RVp-LVs, and this might have important implications in selecting the optimal LV vector.

Reproducibility of pulmonary vein isolation guided by the ablation index: 1-year outcome of the AIR registry.

BACKGROUND: Ablation index (AI) is a new lesion quality marker that has been demonstrated to allow a high single-procedure arrhythmia-free survival in single-center studies. This prospective, multi-center study was designed to evaluate the reproducibility of pulmonary vein (PV) isolation guided by the AI. METHODS: A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV isolation and were divided in four study groups according to operator's preference in choosing the ablation catheter (a contact force (ST) or contact force surround flow (STSF) catheter) and the AI setting (330-450 or 380-500 at anterior wall or posterior wall, respectively). RESULTS: At 12 months a high rate of freedom from AF recurrences was observed in patients with both paroxysmal and persistent AF (91% vs 83.3%; P = .039). There was no difference in the rate of AF recurrence among the four study groups (4.5% in group ST330-450, 12.2% in group ST 380-500, 14.9% in group STSF330-450, 9.4% in group STSF380-500; P = .083). Recurrence was also similar between patients treated with a ST (8%) or STSF catheter (12.1%; P = .2), and within patients targeting an AI settings of 330 to 450 (10.9%) or 380 to 500 (10.3%; P = .64). In patients with paroxysmal AF, there was no difference (P = .12) in the 1-year freedom from AF recurrence among 14 operators that performed ≥10 ablation procedure. CONCLUSIONS: An ablation protocol respecting strict criteria for contiguity and quality lesion resulted in high rate of 1-year freedom from AF recurrence, irrespective of the ablation catheters, AI settings, and operator.

Mutations in BOREALIN cause thyroid dysgenesis.

Congenital hypothyroidism is the most common neonatal endocrine disorder and is primarily caused by developmental abnormalities otherwise known as thyroid dysgenesis (TD). We performed whole exome sequencing (WES) in a consanguineous family with TD and subsequently sequenced a cohort of 134 probands with TD to identify genetic factors predisposing to the disease. We identified the novel missense mutations p.S148F, p.R114Q and p.L177W in the BOREALIN gene in TD-affected families. Borealin is a major component of the Chromosomal Passenger Complex (CPC) with well-known functions in mitosis. Further analysis of the missense mutations showed no apparent effects on mitosis. In contrast, expression of the mutants in human thyrocytes resulted in defects in adhesion and migration with corresponding changes in gene expression suggesting others functions for this mitotic protein. These results were well correlated with the same gene expression pattern analysed in the thyroid tissue of the patient with BOREALIN-p.R114W. These studies open new avenues in the genetics of TD in humans.

Adrenalectomy Risk Score: An Original Preoperative Surgical Scoring System to Reduce Mortality and Morbidity After Adrenalectomy.

OBJECTIVE: To explore the determinants of postoperative outcomes of adrenal surgery in order to build a proposition for healthcare improvement. SUMMARY OF BACKGROUND DATA: Adrenalectomy is the recommended treatment for many benign and malignant adrenal diseases. Postoperative outcomes vary widely in the literature and their determinants remain ill-defined. METHODS: We based this retrospective cohort study on the "Programme de médicalisation des systèmes d'information" (PMSI), a national database that compiles discharge abstracts for every admission to French acute health care facilities. Diagnoses identified during the admission were coded according to the French adaptation of the 10th edition of the International Classification of Diseases (ICD-10). PMSI abstracts for all patients discharged between January 2012 and December 2017 were extracted. We built an Adrenalectomy-risk score (ARS) from logistic regression and calculated operative volume and ARS thresholds defining high-volume centers and high-risk patients with the CHAID method. RESULTS: During the 6-year period of the study, 9820 patients (age: 55 ±â€Š14; F/M = 1.1) were operated upon for adrenal disease. The global 90-day mortality rate was 1.5% (n = 147). In multivariate analysis, postoperative mortality was independently associated with age ≥75 years [odds ratio (OR): 5.3; P < 0.001], malignancy (OR: 2.5; P < 0.001), Charlson score ≥2 (OR: 3.6; P < 0.001), open procedure (OR: 3.2; P < 0.001), reoperation (OR: 4.5; P < 0.001), and low hospital caseload (OR: 1.8; P = 0.010). We determined that a caseload of 32 patients/year was the best threshold to define high-volume centers and 20 ARS points the best threshold to define high-risk patients. CONCLUSION: High-risk patients should be referred to high-volume centers for adrenal surgery.

Exploring the link between tumour metabolism and succinate dehydrogenase deficiency: A 18 F-FDOPA PET/CT study in head and neck paragangliomas.

OBJECTIVES: Nuclear imaging findings by virtue of phenotyping disease heavily depend on genetic background, metabolites, cell membrane specific targets and signalling pathways. PPGL related to succinate dehydrogenase subunits mutations (SDHx mutations) are less differentiated than other subgroups and therefore may lack to concentrate 18 F-FDOPA, a precursor of catecholamines biosynthesis. However, this 18 F-FDOPA negative phenotype has been reported mostly in SDHx-PPGL of sympathetic origin, suggesting that both genotype status and location (from sympathetic vs parasympathetic paraganglia; adrenal vs extra-adrenal) could influence 18 F-FDOPA uptake. The aim of this study was to test if SDHx drives 18 F-FDOPA uptake in presence of normal epinephrine/norepinephrine concentrations. DESIGN: Retrospective study PATIENTS: A cohort of 86 head and neck PPGL patients (including three metastatic) with normal metanephrines underwent 18 F-FDOPA PET/CT. The relationships between 18 F-FDOPA uptake and tumour genotype were evaluated. RESULTS: In nonmetastatic HNPGL (50 non-SDHx/33 SDHx), no significant difference was observed between these two groups for SUVmax (P = .256), SUVmean (P = .188), MTV 42% (P = .596) and total lesion uptake (P = .144). Metastatic HNPGL also had high elevated uptake values. CONCLUSIONS: Our results suggest that SDH deficiency or metastatic behaviour have no influence on 18 F-FDOPA uptake in HNPGL probably due to their very-well differentiation status, even at metastatic stage. The potential prognosticator value of 18 F-FDOPA uptake would need to be further explored in the setting of metastatic PPGL of sympathetic origin.

Early 18F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma.

PURPOSE: Data on the diagnostic value of 18F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of 18F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among 18F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated. METHODS: Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted 18F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative 18F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1-2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20-30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth. RESULTS: 18F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher 18F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour 18F-FDOPA uptake, dopaminergic tumour volume and metabolic burden. CONCLUSION: The present study showed that 18F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.

Reproducibility of acute pulmonary vein isolation guided by the ablation index.

BACKGROUND: Atrial fibrillation (AF) ablation outcome is still operator dependent. Ablation Index (AI) is a new lesion quality marker that has been demonstrated to allow acute durable pulmonary vein (PV) isolation followed by a high single-procedure arrhythmia-free survival. This prospective, multicenter study was designed to evaluate the reproducibility of acute PV isolation guided by the AI. METHODS: A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV encircling and were divided in four study groups according to operator preference in choosing the ablation catheter (a contact force [ST] or contact force surround flow [STSF] catheter) and the AI setting (330 at posterior and 450 at anterior wall or 380 at posterior and 500 at anterior wall). Radiofrequency was delivered targeting interlesion distance ≤6 mm. RESULTS: The rate of first-pass PV isolation (ST330 90 ± 16%, ST380 87 ± 19%, STSF330 90 ± 17%, STSF380 91 ± 15%, P = .585) was similar among the four study groups, whereas procedure (ST330 129 ± 44 minutes, ST380 144 ± 44 minutes, STSF330 120 ± 72 minutes, STSF380 125 ± 73 minutes, P < .001) and fluoroscopy time (ST330 542 ± 285 seconds, ST380 540 ± 416 seconds, STSF330 257 ± 356 seconds, STSF380 379 ± 454 seconds, P < 0.001) significantly differed. The difference in the rate of first-pass isolation was not statistical different (P = .06) among the 12 operators that performed at least 15 procedures. CONCLUSIONS: An ablation protocol respecting strict criteria for contiguity and quality lesion results in high and comparable rate of acute PV isolation among operator performing ablation with different catheters, AI settings, procedure, and fluoroscopy times.

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.