Parathyroid near-infrared autofluorescence use for parathyroidectomy in mild primary hyperparathyroidism: Results from a randomized monocentric trial.

BACKGROUND: Multiglandular parathyroid disease, which is particularly frequent in patients with mild primary hyperparathyroidism, is a surgical challenge requiring bilateral cervicotomy with 4-gland exploration. Near-infrared autofluorescence of the parathyroid is increasingly used to prevent hypocalcemia after total thyroidectomy. However, its utility in decreasing operating time and aiding parathyroid identification during bilateral 4-gland exploration remains debated. METHODS: In our prospective trial, we enrolled consecutive patients with sporadic mild primary hyperparathyroidism (serum calcium <2.85 mmol/L with elevated or nonadapted serum parathyroid hormone levels). With randomization, we assigned patients to classic parathyroidectomy or parathyroidectomy with near-infrared autofluorescence using the Fluobeam 800 device (near-infrared autofluorescence group). All procedures involved planned bilateral neck exploration conducted by 2 experienced surgeons. The primary outcome was mean operating time. Secondary outcomes included the number of visualized and excised glands, complication rates, and cure rates. RESULTS: In total, 132 patients were included (66 per group). Mean age was 64.0 ± 12.0 years, with 85.6% female. Mean preoperative serum calcium level was 2.63 ± 0.11 mmol/L, and median serum PTH level 86.1 [65.6-109.8] pg/mL. The mean operating time did not significantly differ between the classic parathyroidectomy and near-infrared autofluorescence groups (46.9 ± 15.3 minutes and 51.2 ± 22.9 minutes, respectively, P = .21). The use of near-infrared autofluorescence did not significantly modify the number of identified or resected glands nor the rate of complications. Cure rates were similar between groups (92.2% and 94.8%; P = .72). CONCLUSION: In this study, near-infrared autofluorescence, in the hands of experienced surgeons, did not reduce operating time for parathyroidectomy during bilateral neck exploration in mild primary hyperparathyroidism. Although not increasing operating time, further evaluation is needed, particularly regarding its role in the surgeon's training.

A Cohort Study of CNS Tumors in Multiple Endocrine Neoplasia Type 1.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Thus, we aimed to describe the frequency, incidence, and specific clinical and histological features of central nervous system (CNS) tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed up in the French MEN1 national cohort. The standardized incidence ratio (SIR) was calculated based on the French Gironde CNS Tumor Registry. Genomic analyses were performed on somatic DNA from seven CNS tumors, including meningiomas and ependymomas from patients with MEN1, and then on 50 sporadic meningiomas and ependymomas. RESULTS: A total of 29 CNS tumors were found among the 1,498 symptomatic patients (2%; incidence = 47.4/100,000 person-years; SIR = 4.5), including 12 meningiomas (0.8%; incidence = 16.2/100,000; SIR = 2.5), 8 ependymomas (0.5%; incidence = 10.8/100,000; SIR = 17.6), 5 astrocytomas (0.3%; incidence = 6.7/100,000; SIR = 5.8), and 4 schwannomas (0.3%; incidence = 5.4/100,000; SIR = 12.7). Meningiomas in patients with MEN1 were benign, mostly meningothelial, with 11 years earlier onset compared with the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified as World Health Organization grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from patients with MEN1, whereas MEN1 deletion in one allele was present in 3/41 and 0/9 sporadic meningiomas and ependymomas, respectively. CONCLUSIONS: The incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Beyond MEN1, When to Think About MEN4? Retrospective Study on 5600 Patients in the French Population and Literature Review.

CONTEXT: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. DESIGN: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. PATIENTS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French Oncogenetic Network on Neuroendocrine Tumors network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants (ie, with genetically confirmed MEN4 diagnosis) in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. RESULTS: From 5600 MEN1-suspected patients analyzed, 4 with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, primary hyperparathyroidism (PHPT) and adrenal nodule, isolated PHPT, PHPT, and pancreatic neuroendocrine tumor. We listed 29 patients with CDKN1B class 4/5 variants from the literature. Compared with matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. CONCLUSION: The prevalence of MEN4 is low. PHPT and pituitary adenoma represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

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.

Parathyroidectomy for primary hyperparathyroidism: effect on quality of life after 3 years - a prospective cohort study.

BACKGROUND: The impact of parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) on long-term quality of life (QoL) remains controversial. The study evaluated QoL changes 1 and 3 years after PTX. MATERIALS AND METHODS: Patients undergoing PTX for PHPT between 2016 and 2022 ( n =329) were enrolled in this monocentric, prospective cohort study. QoL was evaluated using the SF-36 questionnaire before, 1 year, and 3 years after PTX and compared with an age-matched and sex-matched French reference population. Only patients with 1-year and 3-year follow-up and complete evaluation (serum calcium, phosphorus, parathyroid hormone) were included. RESULTS: A total of 159 patients were included (mean age: 62.6±12.7 years, 79.2% females). Mean serum calcium (2.66±0.20 mmol/l) and median parathyroid hormone (96.4 [76.9-126.4] pg/ml) levels improved significantly after PTX. Before surgery, PHPT patients had impaired physical (44.6±8.9 vs. 47.6±6.8 in the reference population, P <0.001) and mental (42.3±10.9 vs. 48.9±6.8, P <0.001) component scores. The mean physical component score increased significantly at 1 and 3 years and was no longer different from the reference population (ratio: 0.94±0.15 preoperatively vs. 0.99±0.15 at 3 years, P <0.01). The mean mental component score increased significantly at 1 and 3 years, but remained significantly lower than the reference population. Before surgery, a lower physical component score and younger age were significantly associated with a 3-year physical component score increase on multiple linear regression analysis. CONCLUSION: A significant improvement in QoL is associated with PTX for PHPT at 1 year and is sustained for at least 3 years after surgery.

Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study.

OBJECTIVE: Pneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not. METHODS: This was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP. RESULTS: Twenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP. CONCLUSION: High mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.

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.

Inpatient Rehabilitation during Intensive Refeeding in Severe Anorexia Nervosa.

Severe forms of anorexia nervosa are responsible for weight loss and life-threatening consequences. Refeeding represents a real psychiatric and somatic challenge. Physical activities are usually not recommended during intensive refeeding in order to avoid energy expenditure. This study assessed the interest in an early return to controlled physical activities, during a hospitalization in a Physical Medicine and Rehabilitation (PMR) department, including continuous nasogastric refeeding and psychiatric care. A total of 37 subjects aged 32 ± 11 years old performed inpatient physical activities during nasogastric refeeding initiated after intensive care. The physical activity program was adapted according to the hyperactivity of the patients. Evaluation parameters were weight, body mass index (BMI), body composition (fat, lean, and bone masses), and function (strength, balance, walking, ventilation). Patient satisfaction, re-hospitalizations, and physical activities continuation were assessed at 12 months of follow-up. Weight, BMI, and body fat increased significantly (+2.7 ± 1.7 kg; +1.0 ± 0.6 kg/m2; +1.7 ± 2.5 kg, respectively). Muscle strength increased even if the lean mass did not. Walking distance, balance, and respiratory function were significantly improved. Weight and fat mass gains did not differ according to the presence or absence of hyperactivity. At 12 months, 46% of the patients continued to be physically active, but 21% of the patients had been re-hospitalized. The early return to controlled physical activities in PMR hospitalization does not compromise the efficiency of intensive refeeding in severe anorexia nervosa patients.

Value of Somatostatin Receptor PET/CT in Patients With MEN1 at Various Stages of Their Disease.

CONTEXT: Despite the growing evidence of the clinical value of somatostatin receptor (SSTR) positron emission tomography (PET) in the evaluation of neuroendocrine tumors (NETs), its role remains to be clarified at different time points in the journey of patients with multiple endocrine neoplasia type 1 (MEN1). The rarity of the disease is however a significant impediment to prospective clinical trials. OBJECTIVE: The goals of the study were to assess the indications and value of SSTR PET/computed tomography (CT) in patients with MEN1. METHODS: We retrospectively included patients from 7 French expert centers for whom data on SSTR PET/CT and morphological imaging performed at the same period were available. Detection rates of PET study were analyzed. RESULTS: One hundred and 8 patients were included. SSTR PET/CT was performed at screening (n = 33), staging (n = 34), restaging (n = 37), and for peptide receptor targeted radiotherapy selection (n = 4). PET detected positive pancreatic lesions in 91% of cases at screening, with results comparable with magnetic resonance imaging but superior to CT (P = .049). Metastases (mostly lymph node [LN]) were present at the screening phase in 28% of cases, possibly due to the suboptimal value of screening morphological imaging in the assessment of nodal metastases and/or a long delay between imaging studies. SSTR PET/CT was considered superior or complementary to the reference standard in the assessment of LN or distant metastases in the vast majority of cases and regardless of the clinical scenario. CONCLUSION: This study shows the potential added value of SSTR PET in the assessment of MEN1-associated NETs and provides great impetus toward its implementation in the evaluation of patients with MEN1.

What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review.

Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.

Pituitary adenoma in patients with multiple endocrine neoplasia type 1: a cohort study.

OBJECTIVE: Pituitary adenoma (PA) is one of the three major components of multiple endocrine neoplasia type 1 (MEN1). Recent studies have suggested that MEN1-associated PAs are less aggressive than initially estimated. We propose an analysis of the outcome of PAs with a standard of care treatment in a nationwide cohort of MEN1 patients. DESIGN: Retrospective observational nationwide cohort study using the MEN1 patient registry from the French Group of Endocrine Tumours (GTE). METHODS: The GTE database population consists of 1435 patients with MEN1. This analysis focused on 551 patients recruited after 2000 with at least 3 years of follow-up. The study outcome was tumour progression of PA defined by an increase in Hardy classification (HC) during follow-up according to referring physician regular reports. RESULTS: Among 551 MEN1 patients (index and related), 202 (36.7%) had PA, with 114 (56.4%) diagnosed by MEN1-related screening. PAs were defined according to HC as microadenoma (grade I) in 117 cases (57.9%), macroadenoma in 59 (29.2%) with 20 HC grade II and 39 HC grades III-IV and unspecified in 26 (12.8%). They were prolactinomas in 92 cases (45.5%) and non-secreting in 73 (36.1%). After a median follow-up of 3 years among the 137 patients with HC grades I-II, 4 patients (2.9%) presented tumour progression. CONCLUSION: PAs in patients with MEN1 are less aggressive than previously thought. Tumour progression is rare with a standard of care monitoring and treatment, especially in related patients who mostly present non-secreting microadenoma. MRI monitoring for asymptomatic MEN1 patients should be reduced accordingly.

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.

Head-to-Head Comparison of 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT in Patients With Midgut Neuroendocrine Tumors.

PURPOSE: The aim of this study was to compare retrospectively 18F-DOPA PET/CT versus 68Ga-DOTANOC PET/CT in a group of patients affected by midgut NET. PATIENTS AND METHODS: Patients with histologically proven grade 1 or grade 2 midgut NET were explored after injection of 150 MBq of 68Ga-DOTANOC and 210 MBq of 18F-DOPA. The PET/CTs were analyzed visually and semiquantitatively at the patient level, regional level (7 defined regions), and lesion level (maximum of 5 lesions/organ). The criterion standard was determined on the basis of histology and imaging follow-up. RESULTS: Thirty patients (17 males and 13 females; median age, 63.5 years [37-82 years]) were included. Both PET/CTs were negative in 3 patients and positive in 25 patients. PET/CTs were discordant in 2 patients, with 18F-DOPA positive and 68Ga-DOTANOC negative. 18F-DOPA PET/CT detected more involved regions and more metastatic lesions than 68Ga-DOTANOC PET/CT in 6 (20%) and 10 (33.3%) patients, respectively. Of the 81 confirmed affected regions, 77 (95%) were detected by 18F-DOPA PET/CT and 71 (87.7%) by 68Ga-DOTANOC PET/CT (P < 0.0001). 18F-DOPA PET/CT detected significantly more lesions (211/221) than 68Ga-DOTANOC PET/CT (195/221), corresponding to a sensitivity of 95.5% and 88.2%, respectively (P < 0.0001). Tumor-to-background ratios were more favorable in liver for 18F-DOPA than for 68Ga-DOTANOC. Interestingly, a correlation was found between 18F-DOPA SUVmax and tumor burden and especially with the number of regions involved by the disease (P = 0.019). CONCLUSIONS: 18F-DOPA PET/CT is superior to 68Ga-DOTANOC PET/CT for the detection of lesions, and when available, this tracer may be recommended as the first-line examination for an accurate staging of midgut NET.

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.

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.

Glycaemic control influences the relationship between plasma PCSK9 and LDL cholesterol in type 1 diabetes.

Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a critical regulator of LDL cholesterol metabolism. Little is known, however, about the regulation of PCSK9 in patients with type 1 diabetes (T1D). In the present study, we aimed to determine the relationship between circulating PCSK9 and metabolic variables in T1D. Plasma PCSK9 levels were measured in 195 people with T1D (mean age 38.8 years, mean diabetes duration 17.2 years, mean glycated haemoglobin [HbA1c] 8.3%), who were free of any lipid-lowering agent. Plasma PCSK9 was positively correlated with LDL cholesterol (P = .0007), triglycerides (P = .004), apolipoprotein B (P = .005), HbA1c (P = .003), systolic (P = .003) and diastolic (P = .001) blood pressure and body mass index (0.02). In multivariate analysis, PCSK9 concentration was independently associated with HbA1c (P = .02) and LDL cholesterol (P = .03). After classifying patients according to HbA1c tertile, the correlation between PCSK9 and LDL cholesterol was only observed in the highest tertile (P = .0006; Rho = 0.43), whereas no correlation was found in the lowest and intermediate tertiles. This study suggests that good glycaemic control abolishes the positive relationship between PCSK9 and LDL cholesterol in patients with T1D; however, the underlying molecular mechanisms remain to be established.

Laparoscopic Gastric Banding in Obese Patients with Sleep Apnea: A 3-Year Controlled Study and Follow-up After 10 Years.

BACKGROUND: The purpose of this study was to compare the effects of intensive nutritional care (INC) and laparoscopic adjustable gastric banding (LAGB) on nocturnal non-invasive ventilation (NIV) requirement in obese patients using short-, medium-, and long-term follow-up data. METHODS: This prospective randomized controlled trial included obese patients with obstructive sleep apnea (OSA) treated by NIV. Patients were randomized to the INC and LAGB groups. The primary endpoint was the theoretical rate of weaning from NIV at years 1 and 3. Data were also collected from patients 10 years after randomization. RESULTS: Sixty-three patients were randomized. The rate of weaning from NIV did not differ significantly between the LAGB and INC groups at year 1 (35 vs. 13%) or year 3 (14 vs. 21%). Percentages of excess weight loss were greater in the LAGB group than in the INC group at years 1 (33 vs. 15%, p = 0.002) and 3 (27 vs. 8%, p = 0.014). Decreases in the apnea-hypopnea index were observed in the LAGB group from baseline to year 1 (-44%, p = 0.001) and from baseline to year 3 (-26%, p = 0.044). After 10 years, the weaning rate was low and similar between groups. CONCLUSION: LAGB was not superior to INC for weaning from NIV at 1 and 3 years in obese patients with OSA.

Management of thyroid nodules incidentally discovered on MIBI scanning for primary hyperparathyroidism.

INTRODUCTION: Parathyroid sestamibi scan is routinely performed before parathyroid surgery. A large number of thyroid cancers take up 99mTc-sestamibi (MIBI). Since 2001, thyroid nodules discovered on sestamibi, nodules >2 cm, and/or with suspicious criteria were resected. The aim of this study was to evaluate the results of this policy. METHODS: All patients operated on for hyperparathyroidism, with a MIBI and cervical ultrasonography (US) with a thyroid resection for nodule, were retrospectively included. RESULTS: From 2001 to 2013, 685 patients were operated on for hyperparathyroidism. Some 137 (85 % females) had both preoperative MIBI and cervical US and a thyroid resection. The mean age was 63.2 ± 12.8 years. Sixty-three patients had a total thyroidectomy and 74 a lobectomy. Thirty-six patients had a thyroid cancer. The median size of cancers was 6.5 mm (0.3-22 mm), and 23 (16.7 %) patients had microcarcinoma. Among the 137 patients, 44 (32 %) had a MIBI+ nodule including 22 cancers. Sixty-one percent of malignant nodules were MIBI+ (22/36). The median size of MIBI+ cancers was 15 mm (9-22 mm) versus 2 mm (0.3-17 mm) for MIBI- cancers (p = 0.03). Twenty-two percent of benign nodules were MIBI+ (22/101). Finally, the sensitivity, specificity, positive predictive value, and negative predictive value of MIBI were 61, 78, 50, and 85 %, respectively. CONCLUSION: Thyroid nodules incidentally discovered on MIBI in hyperparathyroidism patients should be resected.