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This meta-analysis aims to evaluate the long-term survival and prognostic factors in patients with metastatic small intestine neuroendocrine tumors (siNETs). Patients with siNETs usually present with advanced disease, limiting curative treatment options. The overall survival seems favorable compared to other cancers, but differences in terminology, lack of consistent coding, conflicting results from smaller cohorts, and recent developments of new treatment options make (reliable) survival data difficult to achieve. Nevertheless, accurate survival data are essential for many facets of health care. A systematic literature search was performed using MEDLINE®(PubMed), EMBASE®, Web of Science, and Cochrane Library up to June 30, 2021. Studies were included if the overall survival data in patients with metastatic siNETs were reported. The results were pooled in a random-effects meta-analysis and are reported as hazard ratios and 95% CIs. Subgroup analyses and meta-regression were performed to assess the observed heterogeneity and the impact of important prognostic factors. After screening 9065 abstracts, there were 23 studies, published between 1995 and 2021, that met the inclusion criteria, with a total of 8636 patients. The weighted 5- and 10-year overall survival was 67 and 37%, respectively. Meta-regression identified younger age and primary tumor resection to be associated with better prognosis. Subgroup analyses showed similar results. This study confirms that in an advanced, metastatic setting, the weighted 5- and 10-year overall survival reveal a favorable prognosis, improving over the last few decades. Meta-regression showed that age at diagnosis is an important prognostic factor.

Purpose This study aims to compare posterior retroperitoneal laparoscopic adrenalectomy (PRLA) and laparoscopic transperitoneal adrenalectomy (LTA) in adults using pan-European data as conflicting results have been published regarding length of hospital stay, institutional volume, and morbidity. Methods This retrospective cohort study analyzed data from the surgical registry EUROCRINE®. All patients undergoing PRLA and TLA for adrenal tumours and registered between 2015 and 2020 were included and compared for morbidity, length of hospital stay, and conversion to open surgery. Results A total of 2,660 patients from 11 different countries and 69 different hospitals were analyzed and 1,696 LTA were compared to 964 PRLA. Length of hospital stay was shorter after RPLA, with less patients (N=434, 45.5%, vs N=1094, 65.0%, p) staying more than 2 days. In total, 96 patients (3.6%) developed a complication Clavien-Dindo grade 2 or higher. No statistical difference was found between both study groups. After propensity score matching, length of hospital stay was shorter after PRLA (>2 days 45.2% vs 63.0%, p). After multivariable logistic regression, factors associated with morbidity were age (OR 1.03), male sex (OR 1.52), and conversion to open surgery (OR 5.73). Conclusion This study presents the largest retrospective observational analysis comparing LTA and PRLA. Our findings confirm the shorter length of hospital stay after PRLA. Both techniques are safe leading to comparable morbidity and conversion rates.

Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring.Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score.PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p 0.001), preoperative catecholamine level (p 0.001), open surgery (p 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CIThe derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Background. Post-operative hypocalcemia remains the most frequent complication after total thyroidectomy. Recently, autofluorescence imaging was introduced to detect parathyroid glands early during dissection. Aim. We aimed to check the feasibility of autofluorescence regarding the number of parathyroid glands visualised and the risk of post-operative hypocalcemia. Methods. In a prospectively gathered cohort of patients undergoing thyroid surgery, we describe the risk of hypocalcemia in relation to the number of parathyroid glands visualised during surgery (and the risk reported in the scientific literature) and the feasibility to obtain an autofluorescence of the parathyroid glands. Results. From 2010 to 2019, 1083 patients were referred for total thyroidectomy in our tertiary referral centre for endocrine surgery, of which, 40 consecutive cases were operated using autofluorescence. Among the autofluorescence group, 14 (35.0%) had all 4 parathyroid glands visualised, compared to 147 (14.1%) in the other patients, without differences in the number of parathyroid glands reimplanted. No permanent hypocalcemia occurred in the autofluorescence group and 17.5% temporary hypoparathyroidism, compared to 3.1% and 31.9% among the other patients, and 4% (95% confidence interval [CI] 3–5%) and 19% (95% CI 15–24%) in the literature. Conclusion. Autofluorescence imaging provides reliable real-time visualisation at any point during thyroid surgery and helps to identify the parathyroid glands before detection with the naked eye. To date, it cannot be used as a standard technique and does not replace meticulous dissection. To become a useful adjunct in peroperative parathyroid management, large multicentre studies need to establish a potential clinical benefit of this novel technique.

Purpose Surgery remains the only permanent treatment option for primary hyperparathyroidism (pHPT). To date, the number of long-term outcome studies of parathyroidectomy is limited. This study aims to compare different surgical approaches and evaluate the importance of preoperative localization imaging in the treatment of pHPT. Methods All 200 consecutive patients with a parathyroidectomy for sporadic pHPT without planned concomitant surgery between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were enrolled. All patients underwent at least two preoperative localization imaging studies (neck ultrasound, CT, SPECT, and/or Sestamibi scintigraphy) of the parathyroid glands. The main outcomes were the (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve palsy, return to theater for bleeding, and wound morbidity). Results Most patients were referred with concordant positive imaging (82%, n =164). Only nine patients (4.5%) had double negative imaging, not revealing a possible adenoma. The remaining 27 (13.5%) were referred with discordant imaging. Parathyroidectomy was performed via traditional cervicotomy (30%), mini-open approach (39.5%), or endoscopic approach (30.5%). Morbidity was low with no persistent hypocalcemia, one return to theater for bleeding, and no 30-day mortality. In the concordant imaging population, 13 patients (8%) had multiglandular disease. Overall, 97.5% was considered cured. Long-term recurrence was 12% with a minimal follow-up of 5 years. Conclusion This consecutive, single-surgeon, single-center cohort with extensive data collection and long-term follow-up confirms the safety and excellent cured proportions of minimally invasive parathyroidectomy. Disease recurrence becomes more important long after surgery.

Background In search of an ideal cosmesis, transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has recently been introduced to avoid a visible scar. Although ambulatory thyroid surgery is considered safe in carefully selected patients, this remains unclear for TOETVA. Methods All consecutive adult patients who underwent ambulatory TOETVA or open thyroid surgery at a French university hospital were prospectively enrolled from 12/2020 until 11/2021. The primary outcome was postoperative morbidity (recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, wound morbidity, or hospital readmission). The secondary outcome was quality of life (QoL), measured by a survey including a validated questionnaire (SF-12) and a modified thyroid surgery questionnaire six weeks after surgery. Results Throughout the study period, 374 patients underwent a unilateral lobectomy or isthmectomy in ambulatory setting, of which 34 (9%) as TOETVA (including 21 (62%) for a possible malignancy). In the TOETVA group, younger age (median 40 (IQR 35-50) vs. 51 (40-60) years, P < 0.001) and lower BMI (median 23.1 (20.9-25.4) vs. 24.9 (22.1-28.9) kg/m(2), P = 0.001) were noted. No cases were converted to open cervicotomy. TOETVA was at least as good as open cervicotomy with nil versus four (1%) re-interventions for bleeding, one temporary (5%) versus 13 (4%) (temporary) RLN palsies, and one (

Background Patients with small intestinal neuroendocrine tumours (siNETs) usually present with advanced disease. Primary tumour resection without curative intent is controversial in patients with metastatic siNETs. The aim of this meta-analysis was to investigate survival after primary tumour resection without curative intent compared with no resection in patients with metastatic siNETs. Methods A systematic literature search was performed, using MEDLINE® (PubMed), Embase®, Web of Science, and the Cochrane Library up to 25 February 2021. Studies were included if survival after primary tumour resection versus no resection in patients with metastatic siNETs was reported. Results were pooled in a random-effects meta-analysis, and are reported as hazard ratios (HRs) with 95 per cent confidence intervals. Sensitivity analyses were undertaken to enable comment on the impact of important confounders. Results After screening 3659 abstracts, 16 studies, published between 1992 and 2021, met the inclusion criteria, with a total of 9428 patients. Thirteen studies reported HRs adjusted for important confounders and were included in the meta-analysis. Median overall survival was 112 (i.q.r. 82–134) months in the primary tumour resection group compared with 60 (74–88) months in the group without resection. Five-year overall survival rates were 74 (i.q.r. 67–77) and 44 (34–45) per cent respectively. Primary tumour resection was associated with improved survival compared with no resection (HR 0.55, 95 per cent c.i. 0.47 to 0.66). This effect remained in sensitivity analyses. Conclusion Primary tumour resection is associated with increased survival in patients with advanced, metastatic siNETs, even after adjusting for important confounders.

Context Preoperative localization studies are standard practice in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT). The most common modalities are neck ultrasound (US) and sestamibi scanning. However, the nature of pHPT is changing, with imaging increasingly yielding negative results. Numerous studies suggest unlocalized disease is associated with poor outcomes, calling into question whether such patients are best treated conservatively. Objective This study aims to correlate parathyroidectomy outcomes with preoperative imaging in a single, high-volume institution. Methods Data from a prospectively maintained departmental database of operations performed from 2017 to 2019 were analyzed. All patients undergoing first-time surgery for sporadic pHPT were included. Data collected included patient demographics, preoperative imaging, surgical strategy, and postoperative outcomes. Results A total of 609 consecutive parathyroidectomies were included, with a median age of 59 years (range 20-87 years). The all-comer cure rate was 97.5%; this was 97.9% in dual localized patients (those with positive US and sestamibi), compared to 95.8% in the dual unlocalized group (those with negative US and sestamibi) (P = 0.33). Unilateral neck exploration was the chosen approach in 59.9% of patients with double-positive imaging and 5.7% of patients with double-negative imaging (otherwise, bilateral parathyroid visualization was performed). There was no significant difference in postoperative complications between patients undergoing unilateral or bilateral neck exploration. Conclusions Patients with negative preoperative imaging who undergo parathyroidectomy are cured in almost 96% of cases, compared to 98% when the disease is localized. This difference does not reach statistical or clinical significance. These findings therefore support current recommendations that all patients with pHPT who are likely to benefit from operative intervention should be considered for parathyroidectomy, irrespective of preoperative imaging findings.

Hobnail variant of papillary thyroid carcinoma (HVPTC), also designated as a micropapillary variant, is a rare but aggressive variant of PTC, representing2% of all PTC. It was adopted in the newest World Health Organization classification. HVPTC is strongly associated with higher mortality in comparison to classic PTC and a high propensity for disease progression. This paper aimed to investigate the clinical course, cytological and histopathological features, and mutational profile of the hobnail variant from a unique case.A case of a 38-year-old female patient with HVPTC is presented. Total thyroidectomy with central and bilateral, lateral lymphadenectomy was performed. The clinical course showed aggressive features, as lymph node metastasis and extrathyroidal extension were present at the presentation. Molecular and immunohistochemical features are addressed along with a review of the literature.The cytological examination of FNA was in consonance with published literature. The cells showed hobnail features in several segments of both thyroidal lobes on histological examination. The tumour displayed a typical BRAF mutation and Gly12Ala mutation in the KRAS gene, previously not associated with PTC.We aimed to highlight the aggressive, clinicopathological features of this high-risk variant. We emphasise the need to evaluate suspicious thyroid nodules as an adequate diagnosis can prevent delayed therapy. It directly impacts the tumour's stage and prognosis. In fine-needle aspiration cytology showing papillary architecture carcinomas, HVPTC has to be part of the differential diagnosis.

Background Postoperative hypocalcaemia, recurrent laryngeal nerve palsy and postoperative bleeding are the most frequent postoperative complications after thyroid surgery, and therefore often used as quality indicators of thyroid surgery. We aimed to assess postoperative morbidity in a high-volume endocrine surgery unit, and to detect which factors are associated with higher risks. Methods Prospective surgical cohort in a high-volume tertiary referral centre for endocrine surgery in xxx. The first 1500 patients operated with hemi or total thyroidectomy during 2010–2019 were included. Postoperative hypocalcaemia, recurrent laryngeal nerve palsy and postoperative bleeding were assessed in relation to pre- and peri-operative characteristics using multivariable logistic regression analyses, expressed as odds ratios and 95% confidence intervals. Results Overall, 1043 patients (69.5%) received a total thyroidectomy and 457 (30.5%) a hemithyroidectomy. Permanent hypocalcaemia occurred in 3.1%, permanent recurrent laryngeal nerve palsy in 1.8% and surgical reintervention for bleeding in 2.6%. Younger age, female sex and cancer were risk factors for permanent hypocalcaemia. No clear risk factors could be identified for permanent nerve palsy. Female sex, high body mass index and heavier thyroids were protective against postoperative bleeding after total thyroidectomy. Conclusions Surgical experience in endocrine surgery seems beneficial for clinical outcomes and contributes to organizational efficiency. A low complication risk can be obtained by trained high-volume endocrine surgeons, yet the risk is not negligible.

Multinodular goiter associated with preoperative vocal cord palsy is usually indicative of invasive thyroid malignancy. However, benign thyroid disease may also lead to vocal cord paralysis.We present a case of a 63-year old woman with a two-month history of hoarseness, loss of vocal pitch, difficulties with swallowing and shortness of breath. Preoperative flexible fiberoptic laryngoscopy showed a left vocal cord paralysis. Left hemithyroidectomy with isthmectomy under intraoperative neuromonitoring for multinodular goiter was performed. Intra-operatively, both ipsilateral recurrent laryngeal nerve (RLN) and vagal nerve (VN) were identified and preserved. Follow-up laryngoscopy 5 weeks postoperatively showed complete recovery of the left vocal cord movement.Intuitively, surgeons may assume that preservation of a palsied RLN in patients with preexisting vocal cord paralysis is not meaningful. However, patients with RLN palsy associated with benign thyroid disease can experience full recovery after surgery.Multinodular goiter associated with preoperative vocal cord paralysis should be managed with extreme caution and use of intra-operative neuromonitoring. The existing probability of intra-operative recovery of a preoperative RLN palsy underlines the importance of preserving the affected RLN during surgery for benign thyroid disease.

Simple Summary This review reflects on health economic considerations associated with the increasing diagnosis and treatment of differentiated thyroid cancer. Analysis of different relevant health economic topics, such as overdiagnosis, overtreatment, surgical costs, and costs of follow-up are being addressed. Several unanswered research questions such as optimising molecular markers for diagnosis, active surveillance of primary tumours, and improved risk stratification and survivorship care all influence future healthcare expenditures. Abstract The incidence of differentiated thyroid cancer (DTC) is rising, mainly because of an increased detection of asymptomatic thyroid nodularity revealed by the liberal use of thyroid ultrasound. This review aims to reflect on the health economic considerations associated with the increasing diagnosis and treatment of DTC. Overdiagnosis and the resulting overtreatment have led to more surgical procedures, increasing health care and patients’ costs, and a large pool of community-dwelling thyroid cancer follow-up patients. Additionally, the cost of thyroid surgery seems to increase year on year even when inflation is taken into account. The increased healthcare costs and spending have placed significant pressure to identify potential factors associated with these increased costs. Some truly ground-breaking work in health economics has been undertaken, but more cost-effectiveness studies and micro-cost analyses are required to evaluate expenses and guide future solutions.

An effective method for controlling haemostasis during open thyroidectomy procedures is crucial because of the high risks of haemorrhage and neck haematoma. This study aimed to demonstrate the efficacy of the integrated ultrasonic/bipolar Thunderbeat™ for this procedure. This retrospective non-inferiority study compared the Thunderbeat™ and the ultrasonic Harmonic Focus® devices in 761 consecutive patients receiving a partial or total open thyroidectomy (with or without neck dissection). The main outcomes were duration of surgery, blood loss, and length of hospitalisation. Secondary outcomes were occurrence of hypocalcaemia, recurrent nerve paralysis, or other post-operative complications. A non-inferiority logistic regression approach was used to evaluate primary outcomes, adjusting for age, gender, body mass index, type of surgery, anaesthesiology score, and indication (benign or malign). The data demonstrated that the Thunderbeat was non-inferior to the Focus in terms of duration of surgery, blood loss, and length of hospital stay. Furthermore, subgroup analyses showed non-inferiority of the Thunderbeat for partial thyroidectomy (all three outcomes), total thyroidectomy (duration of surgery and length of hospitalisation), and total thyroidectomy with neck dissection (length of hospitalisation). In terms of recurrent nerve paralysis and post-operative complications, the Thunderbeat performed at least as well as the Focus; however, no conclusions could be drawn regarding the occurrence of post-operative hypocalcaemia. In a cohort of patients that underwent partial or total thyroidectomy, the Thunderbeat appeared to be at least as good as the Harmonic Focus.

International audience; Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders for which parathyroidectomy is the most effective therapy. Until late 1970s, the standard approach to parathyroidectomy was a four-gland exploration using a large skin incision. However, 80 to 85 percent of cases of PHPT are caused by a single adenoma. As such, the concept of performing a bilateral exploration in order to visualize all four glands has been argued to be excessive since in the majority of cases, there is only one abnormal gland. Focused exploration (one gland) is currently the standard technique for parathyroidectomy worldwide. Despite a rapid acceptance of minimally invasive approaches in most endocrine surgery centers, the use of an endoscope with or without the use of a robotic system to perform parathyroidectomy remains controversial. The goal of this study was to review current available data about surgical approaches using an endoscope with or without the use of a robotic system in the management of patients with PHPT. For conventional endoscopic and video assisted parathyroidectomy, several comparative studies have demonstrated some advantages in terms of reduced postoperative pain, better cosmetic results and higher patient satisfaction compared to open non-endoscopic minimally invasive parathyroidectomy. Robot-assisted transaxillary parathyroidectomy has the advantage of leaving no scar in the neck but its role has not yet been delineated clearly given the limited number of published series. Subjective postoperative cosmetic evaluation is good by concealing the scar in the axilla or infraclavicular area. However, this approach is associated with more extensive dissection than during conventional open or endoscopic neck access surgical procedures. Patients with true ectopic mediastinal parathyroid glands are good candidates for conventional or robot-assisted thoracoscopic approaches because these glands are in remote and narrow anatomical locations.