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.

Surgery for Primary Aldosteronism in France From 2010 to 2020 - Results from the French-Speaking Association of Endocrine Surgery (AFCE): Eurocrine Study Group.

OBJECTIVE: Describe the diagnostic workup and postoperative results for patients treated by adrenalectomy for primary aldosteronism in France from 2010 to 2020. BACKGROUND: Primary aldosteronism (PA) is the underlying cause of hypertension in 6% to 18% of patients. French and international guidelines recommend CT-scan and adrenal vein sampling as part of diagnostic workup to distinguish unilateral PA amenable to surgical treatment from bilateral PA that will require lifelong antialdosterone treatment.Adrenalectomy for unilateral primary aldosteronism has been associated with complete resolution of hypertension (no antihypertensive drugs and normal ambulatory blood pressure) in about one-third of patients and complete biological success in 94% of patients.These results are mainly based on retrospective studies with short follow-up and aggregated patients from various international high-volume centers. METHODS: Here we report results from the French-Speaking Association of Endocrine Surgery (AFCE) using the Eurocrine® Database. RESULTS: Over 11 years, 385 patients from 10 medical centers were eligible for analysis, accounting for >40% of adrenalectomies performed in France for primary aldosteronism over the period.Preoperative workup was consistent with guidelines for 40% of patients. Complete clinical success (CCS) at the last follow-up was achieved in 32% of patients, and complete biological success was not sufficiently assessed.For patients with 2 follow-up visits, clinical results were not persistent at 1 year for one-fifth of patients.Factors associated with CCS on multivariate analysis were body mass index, duration of hypertension, and number of antihypertensive drugs. CONCLUSIONS: These results call for an improvement in thorough preoperative workup and long-term follow-up of patients (clinical and biological) to early manage hypertension and/or PA relapse.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study.

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

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.

Impact of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism: A narrative review.

AIMS: Primary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English. DATA SYNTHESIS: In the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting. CONCLUSIONS: PTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study.

AIM: To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). BACKGROUND: The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. METHODS: Thirty-one MEN1 patients from the Groupe d'étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. RESULTS: Indication for surgery was: Zollinger-Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0-433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13-110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8-98.3] and ten-year overall survival was 89.1% [CI 69.6-96.4]. After a mean follow-up of 151 months (range 0-433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. CONCLUSION: In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.

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.

Utility of a Second 99mTc-MIBI Scintigraphy Before Reoperation for Patients With Persistent Sporadic Primary Hyperparathyroidism: Results of a Retrospective Multicenter Study.

BACKGROUND: Persistent primary hyperparathyroidism (PHPT) occurs in 2.5% to 15% of cases after parathyroidectomy. Few studies have evaluated the best pre-reoperative imaging approaches for persistent sporadic PHPT. This retrospective multicenter study aimed to evaluate the benefit of a second pre-reoperative 99mTc-methoxy-isobutyl-isonitrile (MIBI) scintigraphy for patients with persistent PHPT who had a 99mTc-MIBI before their initial surgery. METHODS: The study enrolled 50 patients with persistent sporadic PHPT who had reoperation between 2006 and 2016 in three French University Hospitals (Angers, Nantes, and La Pitié Salpêtrière-Paris). Preoperative 99mTc-MIBI scan was performed before each operation. RESULTS: After the reoperation, 42 patients (84%) were cured. By the second 99mTc-MIBI, 31 patients (62%) had a removed gland identified. A new pathologic gland was identified by a second 99mTc-MIBI in 25 patients (50%), and this imaging permitted correction of an initial surgical error in six patients (12%). A second 99mTc-MIBI showed a sensitivity of 63%, a specificity of 89%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 80%. A concordant second 99mTc-MIBI and ultrasonography (17 patients) showed a sensitivity of 70%, a specificity of 81%, a PPV of 70%, and an NPV of 81%. CONCLUSIONS: Performing a second 99mTc-MIBI scan permitted 62% of the persistent PHPT patients to be cured, allowing identification of new pathologic glands in 50% of the cases and correction of an initial surgical error in 12% of the cases, with high specificity and PPV. These results reinforce the fact that a second 99mTc-MIBI scan should be performed at first intention before reoperation of patients with persistent PHPT, regardless of the result from the initial 99mTc-MIBI scan.

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.

Conversion During Laparoscopic Adrenalectomy for Pheochromocytoma: A Cohort Study in 244 Patients.

BACKGROUND: Recent advances in anesthetic and laparoscopic surgical management have improved perioperative outcomes in patients with pheochromocytoma. However, patients converted to laparotomy during laparoscopic adrenalectomy for pheochromocytoma have never been evaluated specifically in terms of intraoperative hemodynamic instability and postoperative complications. METHODS: Retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent laparoscopic unilateral total adrenalectomy for pheochromocytoma. RESULTS: Two hundred forty-four patients were included. Mean tumor size was 43.9 ± 20 mm with 92 patients (38%) having a tumor diameter > 50 mm. During adrenalectomy, 19 of 244 patients (7.7%) had to be converted to laparotomy. In multivariable analysis, the need for preoperative hospitalization (3.379, 1.209-9.445; P = 0.020), tumor size > 6 cm (2.97, 0.996-8.868; P = 0.050), and ratio of intraoperative systolic blood pressure >200 mmHg duration to anesthesia duration (1.060, 1.007-1.117; P = 0.027) remained significantly associated with conversion. Conversion was significantly associated with postoperative grade II-V Clavien morbidity rate (4.259, 1.471-12.326; P = 0.007) and duration of hospitalization (12.92, 2.90-58.82; P < 0.001). CONCLUSIONS: This study shows that preoperative hospitalization and larger tumor were more frequent in patients undergoing conversion to laparotomy during laparoscopic adrenalectomy for pheochromocytoma. Conversion is associated with increased intraoperative hypertensive episodes and postoperative complications rate. Clinicians should be cognizant of these risks and prepare patients appropriately for conversion when deemed necessary.

One-Year Postoperative Mortality in MEN1 Patients Operated on Gastric and Duodenopancreatic Neuroendocrine Tumors: An AFCE and GTE Cohort Study.

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.

Mild sporadic primary hyperparathyroidism: high rate of multiglandular disease is associated with lower surgical cure rate.

BACKGROUND: Mild primary hyperparathyroidism (serum calcium ≤ 2.85 mmol/L) is the most representative form of pHPT nowadays. The aim of this study was to evaluate its subtypes and the multiglandular disease (MGD) rate as it may lower the sensitivity of preoperative parathyroid scintigraphy and the surgical cure rate. METHODS: We retrospectively included patients with mild pHPT who underwent parathyroid dual-tracer scintigraphy with 99mTc-MIBI SPECT/CT and surgery between January 2013 and December 2015. Cure was defined as normalization of serum calcium (or PTH in the normocalcemic form) at 6 months. MGD was defined by either two abnormal resected glands or persistent disease after resection of at least one abnormal gland. RESULTS: We included 121 patients. Median preoperative serum calcium was 2.68 mmol/L and median PTH was 83.4 pg/mL. A total of 141 glands were resected (95 adenomas, 33 hyperplasias). The subtypes were 57% classic, 32.2% normohormonal, and 10.7% normocalcemic. MGD occurred in 23.5% of patients divided as 13%, 30%, and 64% respectively (p = 0.0011). The surgical cure rate was 85.2%. The normocalcemic form had lower cure rate than the normohormonal (45% vs 84%, p = 0.018) and classic forms (45% vs 93%, p = 0.0006). MIBI scintigraphy identified at least one abnormal lesion, later confirmed by the pathologist in 90/98 patients, making the sensitivity per patient 91.8% (95% CI 84.1-96.2%). CONCLUSIONS: MGD is strongly associated with mild pHPT, especially the normocalcemic form where it accounts for 64% of cases. Bilateral neck exploration should be performed in this population to improve the cure rate, even if the scintigraphy shows a single focus.

Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Francophone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines.

OBJECTIVE: To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET). BACKGROUND: Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET. METHODS: Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method. RESULTS: Forty-six patients with MEN1 were followed prospectively for 10.7 ±â€Š4.2 (mean ±â€Šstandard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ±â€Š1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies. CONCLUSIONS: Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.

Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation.

Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.

Assessment of the Aldosteronona resolution score as a predictive resolution score of hypertension after adrenalectomy for aldosteronoma in French patients.

PURPOSE: Aldosteronoma Resolution Score (ARS) is a predictive score for cure of hypertension after adrenalectomy for hyperaldosteronism and has been validated in American patients. The aim of the study was to validate this score in a French population. METHOD: Data concerning patients operated from 2002 to 2015 in 7 French University Hospitals were retrospectively collected. Diagnosis of Aldosterone-producing adenoma (APA) was confirmed with clinical and biochemical hyperaldosteronism and adrenal nodule on CT scan. Adrenal venous sampling was performed when CT failed to identify laterality. ARS is based on four variables: female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, number of antihypertensive medications ≤2. One point is attributed for the first three and 2 points for the last. Patients were considered as cured if they had no hypertension and no antihypertensive medications at least 6 months after surgery. Patients with bilateral adrenal hyperplasia were excluded. RESULTS: This multicenter study included 310 patients with APA. ARS and follow-up were obtained in 257 patients. 46.6% of patients were cured and potassium serum level was normalized in 97.7%. In multivariate analysis, odds ratio for female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, and number of antihypertensive medications ≤2 were 1.60 (p = 0.09), 1.77 (p = 0.04), 1.28 (p = 0.4), 3.41 (p < 0.001), respectively. Cure rate were, respectively, 22.2, 41.4 and 74% for patients with a score ARS 0-1, 2-3, 4-5. The area under the curve (AUC) of ARS was 0.715. CONCLUSION: ARS is not a predictive score efficient enough in a French population maybe due to different metabolic data and genetic conditions.

Predictive factors for postoperative morbidity after laparoscopic adrenalectomy for pheochromocytoma: a multicenter retrospective analysis in 225 patients.

BACKGROUND: Since the 1950s, preoperative medical preparation has been widely applied in patients with pheochromocytoma to improve intraoperative hemodynamic instability and postoperative complications. However, advancements in preoperative imaging, laparoscopic surgical techniques, and anesthesia have considerably improved management in patients with pheochromocytoma. In consequence, there is no validated consensus on current predictive factors for postoperative morbidity. The aim of this study was to determine perioperative factors which are predictive for postoperative morbidity in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. STUDY DESIGN: It is a retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent non-converted laparoscopic unilateral total adrenalectomy for pheochromocytoma. RESULTS: Two-hundred and twenty-five patients were included. All-cause and cardiovascular postoperative morbidity rates were 16% (n = 36) and 4.8% (n = 11), respectively. Preinduction blood pressure normalization after preoperative medical preparation had no impact on postoperative morbidity. However, past medical history of coronary artery disease (OR [CI95%] = 3.39; [1.317-8.727]) and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 160 mmHg and MAP < 60 mmHg) (OR [CI95%] = 3.092; [1.451-6.587]) remained independent predictors for postoperative all-cause morbidity. Similarly, past medical history of coronary artery disease (OR [CI95%] = 14.41; [3.119-66.57]), female sex (OR [CI95%] = 12.05; [1.807-80.31]), and incidence of intraoperative hemodynamic instability episodes (both SBP ≥ 200 mmHg and MAP < 60 mmHg) (OR [CI95%] = 4.13; [1.009-16.90]) remained independent predictors for postoperative cardiovascular morbidity. CONCLUSIONS: This study identifies risk factors for cardiovascular and all-cause postoperative morbidity after laparoscopic adrenalectomy in current clinical setting. These data can help physicians to guide intra-operative blood pressure management and have to be taken into account in further studies.