PCSK9 inhibition protects mice from food allergy.

The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema. Furthermore, specific PCSK9 inhibition during the elicitation steps of allergic process was sufficient to ensure anti-allergic effects in mice. Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.

Amiodarone-induced thyrotoxicosis: Should surgery be considered?

Amiodarone is the most widely prescribed antiarrhythmic drug worldwide, but induces thyrotoxicosis or hypothyroidism in 15 to 20% of patients. Hyperthyroidism is less frequent than hypothyroidism, and two types of thyrotoxicosis are distinguished according to presence of underlying thyroid disease. Diagnosis is made in case of low TSH and high levels of T3 and T4. Initial treatment is based on anti-thyroid drugs and/or glucocorticoids. Some patients do not respond to medication, which increases the time spent with hyperthyroidism. A long interval between diagnosis and euthyroidism and low left ventricular ejection fraction (LVEF) are predictive of major adverse cardiovascular events. Here, after describing the current state of knowledge of amiodarone-induced thyrotoxicosis, we analyze the literature on the impact of surgery. We suggest that early surgery should be the first option in case of ineffective medical treatment or LVEF<40%. In expert centers, surgical morbidity is no longer different than in other indications for thyroidectomy.

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.

Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy improves lipid and glucose homeostasis in ob/ob mice.

OBJECTIVE: The objective of this study was to compare the general and metabolic impact of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) with Roux-en-Y gastric bypass (RYGB) in an obese (ob/ob) mouse model. METHODS: 10-week-old male ob/ob mice underwent either SADI-S, RYGB, or laparotomy surgery (Sham group). General and metabolic parameters were assessed during a 5-week period thereafter. RESULTS: SADI-S induced a deeper weight loss ([mean ± SEM] -41.2% ± 3.3%) than RYGB (-5.6% ± 3.5%, p < 0.001) compared with the Sham group (+6.3% ± 1.0%, p < 0.05). A significant food restriction was observed after SADI-S only (-31%, 117.4 ± 10.3 g vs. 170.2 ± 5.2 g of food at day 35 in Sham group mice, p < 0.001). Random-fed glycemia and glucose tolerance were more improved after SADI-S than RYGB. SADI-S decreased plasma cholesterol concentration by 60% (0.49 ± 0.04 g/L vs. 1.40 ± 0.10 g/L in the Sham group at day 35, p < 0.01), significantly more than RYGB (1.04 ± 0.14 g/L, p = 0.018). Plasma sitosterol/cholesterol and campesterol/cholesterol ratios were decreased after SADI-S, suggesting a reduced intestinal cholesterol absorption. SADI-S increased exogenous plasma cholesterol-D7 clearance and fecal elimination, also indicating an increased plasma cholesterol excretion. Studying a pair-fed group demonstrated that calorie restriction alone did not explain the beneficial impact of SADI-S. CONCLUSIONS: SADI-S is associated with a greater improvement in lipid and glucose homeostasis than RYGB in ob/ob mice.

Do men improve their bone mineral density 1 year after parathyroidectomy for primary hyperparathyroidism? Results of a prospective study.

BACKGROUND: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. METHODS: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. RESULTS: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). CONCLUSION: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

CONTEXT: Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. OBJECTIVE: To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. DESIGN: In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. SETTING: Referral center. PATIENTS: A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: BMD change between before and 1 year after parathyroidectomy. RESULTS: Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. CONCLUSION: Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Mortality After Total Thyroidectomy for Amiodarone-Induced Thyrotoxicosis According to Left Ventricular Ejection Fraction.

OBJECTIVE: To report cardiac outcomes after total thyroidectomy for amiodarone-induced thyrotoxicosis according to the baseline left ventricular ejection fraction in a tertiary referral center. STUDY DESIGN: Retrospective, monocentric. SETTING: The tertiary health care system. METHODS: Patients who underwent total thyroidectomy for amiodarone-induced thyrotoxicosis between 2010 and 2020 with age >18 and available preoperative left ventricular ejection fraction were included in this study. Patients were dichotomized into: group 1 with left ventricular ejection fraction ≥40% (mildly reduced/normal ejection fraction), and group 2 with left ventricular ejection fraction <40% (reduced ejection fraction). RESULTS: There were 34 patients in group 1 and 17 to group 2. The latter were younger (median 58.4 [Q1-Q3 48.0-64.9] vs. 69.8 years in group 1 [59.8-78.3], p = .0035) and they presented more cardiomyopathy (58.8 vs. 26.5%, p = .030). Overall, the median time until surgery referral was 3.1 [1.9-7.1] months and 47.1% underwent surgery after restoration of euthyroidism. Surgical complications accounted for 7.8%. In group 2, the median left ventricular ejection fraction was significantly improved after surgery (22.5 [20.0-25.0] vs. 29.0% [25.3-45.5], p = .0078). Five-year cardiac mortality was significantly higher in group 2 (p < .0001): 47.0% died of cardiac causes versus 2.9% in group 1. A baseline left ventricular ejection fraction <40% and a longer time until surgery referral were significantly associated with cardiac mortality (multivariable Cox regression analysis, p = .015 and .020, respectively). CONCLUSION: These results reinforce the idea that surgery, if chosen, should be performed quickly in patients with left ventricular ejection fraction <40%.

Suture versus open mesh repair for small umbilical hernia: Results of a propensity-matched cohort study.

BACKGROUND: The objective was to compare the outcomes of open mesh repair versus suture repair for small (≤1 cm in diameter) umbilical hernia. The primary endpoint was the 30-day outcomes including pain, and secondary endpoints were the 2-year outcomes including recurrences and patient-reported outcomes. METHODS: This propensity-matched, multicenter study was carried out on data collected prospectively in the Hernia-Club database between 2011 and 2021. A total of 590 mesh repairs and 590 suture repairs were propensity score matched (age, sex, body mass index) at a ratio of 1:1. Postoperative pain was assessed using the Verbal Rating Scale-4 and 0‒10 Numerical Rating Scale-11. RESULTS: Mesh insertion was intraperitoneal in 331 patients (56.1%), extraperitoneal in 249 (42.2%), and onlay in 10 (1.7%). The rate of 30-day complications and Numerical Rating Scale-11 pain scores on postoperative days 8 and 30 were similar between the groups, including surgical site occurrences (2.2 vs 1.4% after suture repair). At 1 month, postoperative discomfort (sensation of something different from before) was significantly (P < .0001) more frequent after mesh repair, whereas the rate of relevant (moderate or severe) pain (mesh repair: 1.1% vs suture repair: 2.6%) and the distribution of Numerical Rating Scale-11 scores did not differ between the groups. At the 2-year follow-up, mesh repair patients had fewer reoperated recurrences (0.2% vs 1.7%; P = .035) and no more pain or discomfort than suture repair patients. CONCLUSION: Both techniques are effective and safe. Mesh repair is likely to reduce the rate of recurrences. Concerns about postoperative pain and infection might not prevent the use of mesh in smallest umbilical hernias.

Prevention of hypocalcemia and hypoparathyroidism after total thyroidectomy. Recommendations of the Francophone Association of Endocrine Surgery (AFCE) with the French Society of Endocrinology (SFE) and the French Society of Nuclear Medicine (SFMN).

Postoperative hypoparathyroidism, resulting from removal and/or devascularization of one or more parathyroid glands, is a feared complication of total thyroidectomy. Two forms, which are distinguished by their frequency, their time to onset and their duration as well as by their presentation, must be individualized: early postoperative hypocalcemia, often secondary to early hypoparathyroidism is a frequent and often transient situation occurring within the first days after surgery; permanent hypoparathyroidism, which is rarer, manifests when parathyroid function remains impaired for more than six months after surgery. Because of their severity, these conditions must be known and ideally prevented during total thyroidectomy. The objective of this article is to provide surgeons with practical recommendations for the prevention, diagnosis, and treatment of hypoparathyroidism after total thyroidectomy. These recommendations, which are the fruit of a medico-surgical consensus, were developed by the Francophone Association of Endocrine Surgery (AFCE), the French Society of Endocrinology (SFE) and the French Society of Nuclear Medicine and Molecular Imaging. (SFMN). The content, grade and level of evidence for each recommendation was decided after consultation within a panel of experts, based on an analysis of recent literature.

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.

Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy Model in Mice.

Obesity is a major health issue worldwide. As a response, bariatric surgeries have emerged to treat obesity and its related comorbidities (e.g., diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, cardiovascular events, and cancers) through restrictive and malabsorptive mechanisms. Understanding the mechanisms by which these procedures allow such improvements often require their transposition into animals, especially in mice, because of the ease of generating genetically modified animals. Recently, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has emerged as a procedure that uses both restrictive and malabsorptive effects, which is being used as an alternative to gastric bypass in case of major obesity. Thus far, this procedure has been associated with strong metabolic improvements, which has led to a marked increase in its use in daily clinical practice. However, the mechanisms underlying these metabolic effects have been poorly studied as a result of a lack of animal models. In this article, we present a reliable and reproducible model of SADI-S in mice, with a special focus on perioperative management. The description and use of this new rodent model will be helpful for the scientific community to better understand the molecular, metabolic, and structural changes induced by the SADI-S and to better define the surgical indications for clinical practice.

Effects of parathyroidectomy on kidney function in patients with primary hyperparathyroidism: Results of a prospective study.

BACKGROUND: Altered glomerular filtration rate is a controversial indication for parathyroidectomy in patients with primary hyperparathyroidism. The objective of this study was to evaluate the estimated glomerular filtration rate change 12 months after parathyroidectomy for primary hyperparathyroidism according to preoperative kidney function. METHOD: Patients who underwent parathyroidectomy for primary hyperparathyroidism between 2016 and 2021 (n = 381) were enrolled in a monocentric prospective cohort. Patients without 1-year follow-up or with missing data were excluded (n = 135, 35%). Patients were dichotomized according to their baseline estimated glomerular filtration rate: <60 mL/min (group 1) and ≥60 mL/min (group 2). Parameters were measured before and then at 6 and 12 months after parathyroidectomy. RESULTS: Out of 246 included patients, 27 (11%) were assigned to group 1 and 219 (89%) to group 2. The mean baseline estimated glomerular filtration rate was 46.8 ± 11.5 and 87.3 ± 14.7 mL/min in groups 1 and 2, respectively. Group 1 patients were older (P = .0006) and had a higher median serum parathyroid hormone level (P = .021). At 6 months postoperative, 224 patients (91%) were normocalcemic. The estimated glomerular filtration rate raw change after parathyroidectomy was significantly higher in group 1 than in group 2 (4.2 ± 7.8 vs -2.2 ± 9.1 mL/min, P = .0004). In group 1, 13/27 patients (48%) improved their chronic kidney disease stage after parathyroidectomy, including 6/13 (46%) with postoperative estimated glomerular filtration rate ≥60 mL/min, whereas 2/27 (7%) worsened. The baseline estimated glomerular filtration rate <60 mL/min and elevated serum calcium level were associated with postoperative estimated glomerular filtration rate improvement in multivariable analysis (P = .0023 and .039, respectively). CONCLUSION: Parathyroidectomy for primary hyperparathyroidism is more likely to improve kidney function in patients with preoperative estimated glomerular filtration rate <60 mL/min. These results strengthen the current guidelines for surgery.

SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Surgical treatment.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French-speaking Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the surgical management of thyroid nodules.

Calcium homeostasis and hyperparathyroidism: Nephrologic and endocrinologic points of view.

Parathyroid hormone (PTH) is a hypercalcemic hormone acting on kidneys, bone and intestine. PTH promotes calcium release from the bone, renal calcium reabsorption and phosphate excretion, and conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D-3. Hyperparathyroidism consists in PTH elevation, which may be adapted (secondary hyperparathyroidism) or non-adapted to calcemia levels (primary hyperparathyroidism, familial hypercalcemia/hypocalciuria, tertiary hyperparathyroidism). Primary hyperparathyroidism (PHP) features hypercalcemia and elevated or inappropriate PTH elevation. PHP may be revealed by biological abnormalities such as hypercalcemia and can be accompanied by renal complications (hypercalciuria, nephrolithiasis, nephrocalcinosis) and/or osteoporosis. However, it can also be normocalcemic and calcium loading will be necessary to diagnosis it. The differential diagnosis of PHP is familial hypocalciuric hypercalcemia (FHH), a dominant autosomal disease implicating a calcium sensing receptor-inactivating mutation. It impairs parathyroid cell sensitivity to calcemia elevation and thus induces excessive PTH stimulation, leading to hypercalcemia. Secondary HP (SHP) consists in PTH elevation secondary to a stimulus that needs to be corrected. 25 OHvitD deficiency, kidney failure, renal hypercalciuria, malabsorption and some drugs can induce SHP. Tertiary HP (THP) consists in autonomous PTH secretion by the parathyroid glands after prolonged stimulation under SHP, of whatever cause. This parathyroid autonomy results from the polyclonal hyperplasia observed in SHP progressing toward monoclonal nodular proliferation, leading to nodular hyperplasia or parathyroid adenoma (or, exceptionally, carcinoma), with reduced expression of CaSR and vitamin D receptor. In patients under dialysis, the frontier between SHP and THP is a matter of debate. This review will focus on the pathophysiology of calcium, diagnosis, and management of hyperparathyroidism.

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.

Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism.

Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT. Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded. Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001). Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors' improvements on cardiovascular events.

Are the relative benefits of open versus laparoscopic intraperitoneal mesh repair of umbilical hernias dependent on the diameter of the defect?

BACKGROUND: The aim of this study was to assess whether the respective values of open and laparoscopic intraperitoneal repairs of umbilical hernias are related to the European Hernia Society diameter of defects. METHODS: This registry-based study compared the early and 2-year outcomes of 776 open versus 1,019 consecutive laparoscopic intraperitoneal repairs performed from 2011 to 2019. RESULTS: Intraperitoneal mesh repair, either laparoscopic or open, was found to be a safe procedure at the 2-year follow-up. The incidence of reoperated bowel obstructions was 0.3%. Compared with the open group: (1) postoperative surgical site occurrences in small (<2 cm) or medium (2-4 cm) hernias (0.3% vs 2.4%; P = .041; 1.4% vs 5.9%; P = .0002); (2) recurrence rates in large (≥4 cm) umbilical hernias (0.0% vs 8.6%; P = .0195); and (3) cumulative reoperation rates (0.9% vs 2.2%; P = .021) were significantly better in the laparoscopic group. Conversely, the rate of early pain on day 1 and 1 month postsurgery was higher in the laparoscopic group, for all hernia sizes (P < .001). The rate of moderate or severe chronic pain at 2 years was significantly higher in the laparoscopic group (8.1% vs 2.4%; P = .049) for small hernias. CONCLUSION: The respective benefit to drawback ratios for open versus laparoscopic intraperitoneal repairs were related to the European Hernia Society diameter of hernia defect. In medium-large hernias, the benefits of laparoscopic repair overrode its drawbacks. In small hernias, the low recurrence rate, reduced early and chronic pain, and better rate of ambulatory surgery suggest there is still a place for open repair.

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.

Impact on sleeve gastrectomy in patients with esophageal motor disorder.

BACKGROUND: Gastroesophageal reflux disease (GERD) and esophageal motor disorders (EMD) are frequent conditions among patients with obesity. The effects of sleeve gastrectomy (SG) on esophageal function can worsen GERD, but little is known about its effects on EMD and the consequences of preexisting EMD on GERD after SG. OBJECTIVES: To study the postoperative outcomes of SG in a population of patients displaying preexisting EMD. SETTING: University Hospital, France. METHODS: Patients with EMD confirmed by high-resolution manometry who underwent a laparoscopic SG between 2010 and 2019 were retrospectively included in this monocenter study. GERD symptoms and high-resolution manometry results were recorded before surgery and during follow-up. Conversion to gastric bypass were also recorded. RESULTS: Thirty-seven patients were included. Mean age was 52.6 ± 12.9 years. Most patients were female (70%). EMD were achalasia (19% of patients), hypercontractile (22%), hypocontractile (30%) and nutcracker esophagus (22%), and ineffective esophageal motility (8%). GERD symptoms were present in 10 patients (27%) preoperatively and 18 (49%) postoperatively. Achalasia was not resolved after SG and was constantly associated with disabling food blockage or GERD symptoms after surgery, and 3 of 4 patients with nutcracker esophagus had postoperative GERD symptoms and underwent gastric bypass. CONCLUSIONS: This study is the largest to describe the course of GERD and EMD after SG in patients displaying preoperative EMD. Achalasia and nutcracker esophagus are associated with poorer postoperative outcomes, and another procedure such as a gastric bypass should be performed.