Operative management of primary hyperparathyroidism in Europe.

BACKGROUND: Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. METHODS: Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. RESULTS: A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. CONCLUSION: This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.

24-hour Urine Calcium Predicts Reduced Fracture Incidence and Improved BMD After Surgery for Primary Hyperparathyroidism.

CONTEXT: Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with impact on fracture incidence and bone mineral density after surgery have not been firmly established. OBJECTIVE: To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT). DESIGN: Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register. SETTING: Tertiary referral center. PATIENTS OR OTHER PARTICIPANTS: 709 patients with successful parathyroidectomy for pHPT, and 2,112 controls matched on sex, age, and municipality were included in the study. MAIN OUTCOME MEASURES: Fracture incidence, absolute change and ≥2.77% increase in bone mineral density of femoral neck, L2-L4 and distal third of radius at 1-year follow-up. RESULTS: Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (IRR for the highest tertile 220- mg/d 0.29, CI 95% 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin and adenoma weight were all associated with bone mineral density recovery after surgery. CONCLUSIONS: 24-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT.

Effect of thyroid hormone replacement therapy on mortality rate in patients undergoing total or hemithyroidectomy for benign multinodular goitre.

BACKGROUND: Thyroid surgery for benign non-toxic nodular goitre is a common endocrine surgical procedure. It is not known whether thyroid hormone replacement therapy following surgery for benign thyroid disease influences mortality or morbidity rates. METHODS: A retrospective observational study was conducted using national registries in Sweden. Overall mortality and morbidity rates were compared for patients with or without thyroid hormone replacement therapy in patients operated on with hemithyroidectomy or total thyroidectomy for a diagnosis of benign non-toxic nodular goitre. RESULTS: Between 1 July 2006 and 31 December 2017, 5573 patients were included, 1644 (29.5%) patients were operated on with total thyroidectomy and 3929 patients with hemithyroidectomy. In the hemithyroidectomy group, 1369 (34.8%) patients were prescribed thyroid hormone replacement therapy in the follow-up. The patients who underwent hemithyroidectomy and did not use thyroid hormone replacement therapy in the follow-up had a standard mortality ratio of 1.31 (95% confidence interval, 1.09-1.54). The mortality ratio was not increased in patients who underwent total thyroidectomy or hemithyroidectomy and used thyroid hormone replacement therapy. The risk of death analysed by multivariable Cox regression for patients operated on with hemithyroidectomy without later thyroid hormone replacement therapy, adjusted for age and sex, showed an increased hazard ratio of 1.65 (1.19-2.30) compared with hemithyroidectomy with hormone replacement therapy. CONCLUSION: Patients subjected to hemithyroidectomy without later hormone replacement therapy had a 30% higher risk of death compared with the normal Swedish population and a 65% increased risk of death compared with patients undergoing hemithyroidectomy with postoperative hormone replacement therapy.

Clinical use of an emergency manual by resuscitation teams and impact on performance in the emergency department: a prospective mixed-methods study protocol.

INTRODUCTION: Simulation-based studies indicate that crisis checklist use improves management of patients with critical conditions in the emergency department (ED). An interview-based study suggests that use of an emergency manual (EM)-a collection of crisis checklists-improves management of clinical perioperative crises. There is a need for in-depth prospective studies of EM use during clinical practice, evaluating when and how EMs are used and impact on patient management. METHODS AND ANALYSIS: This 6-month long study prospectively evaluates a digital EM during management of priority 1 patients in the Skåne University Hospital at Lund's ED. Resuscitation teams are encouraged to use the EM after a management plan has been derived ('Do-Confirm'). The documenting nurse activates and reads from the EM, and checklists are displayed on a large screen visible to all team members. Whether the EM is activated, and which sections are displayed, are automatically recorded. Interventions performed thanks to Do-Confirm EM use are registered by the nurse. Fifty cases featuring such interventions are reviewed by specialists in emergency medicine blinded to whether the interventions were performed prior to or after EM use. All interventions are graded as indicated, of neutral relevance or not indicated. The primary outcome measures are the proportions of interventions performed thanks to Do-Confirm EM use graded as indicated, of neutral relevance, and not indicated. A secondary outcome measure is the team's subjective evaluation of the EM's value on a Likert scale of 1-6. Team members can report events related to EM use, and information from these events is extracted through structured interviews. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority (Dnr 2022-01896-01). Results will be published in a peer-reviewed journal and abstracts submitted to national and international conferences to disseminate our findings. TRIAL REGISTRATION NUMBER: NCT05649891.

Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

BACKGROUND: Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. METHODS: This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. RESULTS: Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. CONCLUSION: The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

Role of hospital and patient factors in the outcome of reoperations for primary hyperparathyroidism: a retrospective multicenter cohort study.

BACKGROUND: There are few data on outcomes after reintervention for persistent or recurrent primary hyperparathyroidism (PHPT). The authors hypothesized that the variation in outcomes at the hospital level after reoperation would be significant. After accounting for this variability, some patient-level clinical criteria could be identified to help inform treatment decisions in this patient population. The aim of this study was to determine whether there is significant variation in outcomes after reoperation for PHPT between hospitals (hospital-level analysis) and identify clinical factors (patient-level analysis) that influence postoperative outcomes. MATERIALS AND METHODS: This retrospective multicenter cohort study was performed using the Eurocrine registry. Data from 11 countries and 76 hospitals from January 2015 to October 2020 were extracted. A generalized linear mixed model was used to assess the variation in outcomes at the hospital level and to identify risk factors of postoperative outcomes at the patient level. The primary endpoint (textbook outcome) was achieved when all six of the following postoperative conditions were met: no hypocalcemia or persistent hypercalcemia, no laryngeal nerve injury, no negative exploration, no normal parathyroid gland only on histopathology, and no postoperative death. RESULTS: Among 13 593 patients who underwent parathyroidectomy for PHPT, 617 (4.5%) underwent reoperative parathyroidectomy. At follow-up, 231 patients (37.4%) were hypocalcemic, 346 (56.1%) were normocalcemic without treatment, and 40 (6.5%) had persistent hypercalcemia. Textbook outcomes were achieved in 321 (52.0%) patients. The hospital-level variation in textbook outcome rates was significant ( P <0.001), and this variation could explain 29.1% of the observed outcomes. The criterion that remained significant after controlling for inter-hospital variation was 'a single lesion on sestamibi scan or positron emission tomography (PET) imaging' (odds ratio 2.08, 95% confidence interval 1.24-3.48; P =0.005). CONCLUSION: Outcomes after reoperation are significantly associated with hospital-related factors. A 'single lesion observed on preoperative sestamibi scan or PET' appears relevant to select patients before reoperation.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Visuospatial ability is associated to 2D laparoscopic simulator performance amongst surgical residents.

Background: The technical skills of a surgeon influence surgical outcome. Testing technical aptitude at point of recruitment of surgical residents is only conducted in a few countries. This study investigated the impact of visuospatial ability (VSA), background factors, and manual dexterity on performance in two different laparoscopic surgical simulators amongst applicants and 1st year surgical residents. Method: Applicants from general surgery, pediatric surgery, and urology were included from seven hospitals in Sweden between 2017 and 2021. Some 73 applicants were invited and 50 completed. Participants filled out a background form, and were tested for manual dexterity, and visuospatial ability. Two laparoscopic simulators were used, one 2D video box trainer and one 3D Virtual Reality Simulator. Results: A significant association was found between the visuospatial ability test and 2D video box laparoscopic performance (95 % CI: 1.028-1.2, p-value <0.01). For every point on the visuospatial test the odds of accomplishing the task increased by 11 %. No association was found between VSA and performance in a laparoscopic VR simulator using 3D vision. No other background factors were associated with performance in the two laparoscopic simulators. Conclusion: Visuospatial ability in applicants to surgical residency positions is associated to performance in a 2D video box trainer. Knowledge of a resident's visuospatial ability can be used to tailor individualized laparoscopic training programs, and in the future might function as a selection tool concerning laparoscopic ability. Key message: Visuospatial ability differs greatly amongst applicants for surgical residency and is associated to laparoscopic simulator performance. Testing applicants' visuospatial ability could possibly be used to tailor individualized laparoscopic training programs or in the future as a selection tool concerning laparoscopic ability.

Reduced fracture incidence in patients having surgery for primary hyperparathyroidism.

OBJECTIVE: The indication of surgery in primary hyperparathyroidism has been controversial, as many patients experience mild disease. The primary aim was to evaluate fracture incidence in a contemporary population-based cohort of patients having surgery for primary hyperparathyroidism. The secondary aim was to investigate whether preoperative serum calcium, adenoma weight or multiglandular disease influence fracture incidence. DESIGN: A retrospective cohort study with population controls. Primary outcomes, defined by discharge diagnoses and prescriptions, were any fracture and fragility fracture, secondary outcomes were multiple fractures anytime and osteoporosis. Subjects were followed 10 years pre- and up to 10 years postoperatively (or 31 December 2015). Multiple events per subject were allowed. Fracture incidence rate ratios (IRRs) for patients pre- and postoperatively were tabulated and evaluated with mixed-effects Poisson regression. Secondary outcomes were evaluated using conditional logistic regression. PATIENTS: A Swedish nationwide cohort of patients having surgery for primary hyperparathyroidism (n = 5009) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery between 2003 and 2013 was matched with population controls (n = 14,983). Data were cross-linked with Statistics Sweden and the National Board of Health and Welfare. MEASUREMENTS: Preoperative serum calcium and adenoma weight at pathological examination. RESULTS: Patients had an increased incidence rate of any fracture preoperatively, IRR 1.27 (95% confidence interval: 1.11-1.46), highest in the last year before surgery. Fracture incidence was not increased postoperatively. Serum calcium, adenoma weight and multiglandular disease were not associated with fracture incidence. CONCLUSIONS: Fracture incidence is higher in patients with primary hyperparathyroidism but is normalized after surgery.

Impediments to and impact of checklists on performance of emergency interventions in primary care: an in situ simulation-based randomized controlled trial.

OBJECTIVE: Medical crises occur rather seldom in the primary care setting, but when they do, initial management impacts on morbidity and mortality. Factors that impede the performance of emergency interventions in primary care have not been studied through in-situ simulation. Checklists reportedly improve crisis management. DESIGN: This randomized controlled trial evaluated emergency intervention performance during two scenarios (hypoglycemia-coma and anaphylaxis-cardiac arrest) simulated at primary care centers, and whether checklist access improved performance. SETTING: Twenty-two primary care centers in Southern Sweden participated in the study. SUBJECTS: A total of 347 personnel performed 100 simulations, 45 with and 55 without checklist access. MAIN OUTCOME MEASURES: Time and impediments to performance of five emergency interventions in each scenario. RESULTS: On 28 of the 37 occasions when the adrenalin auto-injector was employed, the administration technique was incorrect. In 9 of 49 scenarios, teams had trouble locating the 30% glucose solution. Median time to supplemental oxygen administration during the first scenario was 186 s compared with 96 s during the second scenario (p < 0.001). Checklist access had no significant impact on time to performance of emergency interventions, aside from shorter time to adequate glucose or glucagon administration (median times 632 s with, 756 s without checklist access; p = 0.03). CONCLUSION: Unfamiliarity with local emergency equipment impedes the performance of emergency interventions during crises simulated in the primary care setting. Simply providing checklist access does not improve the performance of emergency interventions.KEY POINTSLittle is known about the factors that affect the performance of emergency interventions in the primary care setting.Unfamiliarity with local emergency equipment impedes the performance of emergency interventions during crises simulated in the primary care setting.Simply providing crisis checklist access does not improve the performance of emergency interventions in the primary care setting.

Different approaches to selection of surgical trainees in the European Union.

BACKGROUND: There is an increasing global interest in selection processes for candidates to surgical training. The aim of the present study is to compare selection processes to specialist surgeon training in the European Union (EU). A secondary goal is to provide guidance for evidence-based methods by a proposed minimum standard that would align countries within the EU. METHODS: Publications and grey literature describing selection strategies were sought. Correspondence with Union Européenne des Médecins Specialists (UEMS) Section of Surgery delegates was undertaken to solicit current information on national selection processes. Content analysis of 13 semi-structured interviews with experienced Swedish surgeons on the selection process. Two field trips to Ireland, a country with a centralized selection process were conducted. Based on collated information typical cases of selection in a centralized and decentralized setting, Ireland and Sweden, are described and compared. RESULTS: A multitude of methods for selection to surgical training programs were documented in the 27 investigated countries, ranging from locally run processes with unstructured interviews to national systems for selection of trainees with elaborate structured interviews, and non-technical and technical skills assessments. Associated with the difference between centralized and decentralized selection systems is whether surgical training is primarily governed by an employment or educational logic. Ireland had the most centralized and elaborate system, conducting a double selection process using evidence-based methods along an educational logic. On the opposite end of the scale Sweden has a decentralized, local selection process with a paucity of evidence-based methods, no national guidelines and operates along an employment logic, and Spain that rely solely on examination tests to rank candidates. CONCLUSION: The studied European countries all have different processes for selection of surgical trainees and the use of evidence-based methods for selection is variable despite similar educational systems. Selection in decentralized systems is currently often conducted non-transparent and subjectively. A suggested improvement towards an evidence-based framework for selection applicable in centralized and decentralized systems as well as educational and employer logics is suggested.

Impact of Adrenalectomy on Morbidity in Patients with Non-Functioning Adrenal Cortical Tumours, Mild Hypercortisolism and Cushing's Syndrome as Assessed by National and Quality Registries.

BACKGROUND: The impact of adrenalectomy on morbidity in patients with mild hypercortisolism and non-functioning adrenocortical adenoma is unclear. The present study evaluated morbidity before and after adrenalectomy in patients with benign adrenocortical tumour with Cushing´s syndrome (CS), autonomous cortisol secretion (ACS) and non-functioning adrenocortical adenoma as assessed by national and quality registries. METHODS: Patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) 2009-2017 with CS, ACS or non-functioning adrenocortical adenoma, were included in this retrospective study and analysed with age- and sex-matched controls, 1:3. Morbidity associated with CS was assessed pre- and postoperatively by analysing data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. RESULTS: Some 271 patients were included, CS (127), ACS (45) and non-functioning adrenocortical adenoma (99), with 813 matched controls. The frequency of hypertension was almost 50% in all tumour groups. Antihypertensive medication preoperatively was more frequent in all tumour groups compared with controls. No preoperative differences in medication were detected between patients with CS and ACS. A decrease in the use of hypertensive drugs was noticed annually for all patient groups after adrenalectomy. CONCLUSIONS: Hypertension is common in patients with benign adrenocortical tumours regardless of cortisol hypersecretion. The use of antihypertensive drugs in patients with CS, ACS and non-functioning adrenocortical adenoma was reduced after adrenalectomy. These findings highlight the need for a randomized controlled trial to investigate the impact of adrenalectomy on morbidity in patients with mild hypercortisolism.

Medical crisis checklists in the emergency department: a simulation-based multi-institutional randomised controlled trial.

BACKGROUND: Studies carried out in simulated environments suggest that checklists improve the management of surgical and intensive care crises. Whether checklists improve the management of medical crises simulated in actual emergency departments (EDs) is unknown. METHODS: Eight crises (anaphylactic shock, life-threatening asthma exacerbation, haemorrhagic shock from upper gastrointestinal bleeding, septic shock, calcium channel blocker poisoning, tricyclic antidepressant poisoning, status epilepticus, increased intracranial pressure) were simulated twice (once with and once without checklist access) in each of four EDs-of which two belong to an academic centre-and managed by resuscitation teams during their clinical shifts. A checklist for each crisis listing emergency interventions was derived from current authoritative sources. Checklists were displayed on a screen visible to all team members. Crisis and checklist access were allocated according to permuted block randomisation. No team member managed the same crisis more than once. The primary outcome measure was the percentage of indicated emergency interventions performed. RESULTS: A total of 138 participants composing 41 resuscitation teams performed 76 simulations (38 with and 38 without checklist access) including 631 interventions. Median percentage of interventions performed was 38.8% (95% CI 35% to 46%) without checklist access and 85.7% (95% CI 80% to 88%) with checklist access (p=7.5×10-8). The benefit of checklist access was similar in the four EDs and independent of senior physician and senior nurse experience, type of crisis and use of usual cognitive aids. On a Likert scale of 1-6, most participants agreed (gave a score of 5 or 6) with the statement 'I would use the checklist if I got a similar case in reality'. CONCLUSION: In this multi-institution study, checklists markedly improved local resuscitation teams' management of medical crises simulated in situ, and most personnel reported that they would use the checklists if they had a similar case in reality.

Complications of surgery for gastro-entero-pancreatic neuroendocrine neoplasias.

PURPOSE: Surgery is recommended for most patients with gastro-entero-pancreatic neuroendocrine neoplasias (GEP-NENs). Rates of complications and perioperative mortality have been reported in few mostly retrospective single-center series, but there has been no detailed analysis on risk factors for perioperative complications and mortality to date. METHODS: Data of patients with GEP-NENs operated between January 2015 and September 2018 were retrieved from EUROCRINE©, a European online endocrine surgical quality registry, and analyzed regarding rate and risk factors of surgical complications. Risk factors were assessed by logistic regression. RESULTS: Some 376 patients (211 female, 167 male; age median 63, range 15-89 years) were included. Most NENs were located in the small intestine (SI) (n = 132) or pancreas (n = 111), the rest in the stomach (n = 34), duodenum (n = 30), appendix (n = 30), colon, and rectum (n = 22), or with unknown primary (n = 15). Of the tumors, 320 (85.1%) were well or moderately differentiated, and 147 (39.1%) of the patients had distant metastases at the time of operation. Severe complications (Dindo-Clavien ≥ 3) occurred in 56 (14.9%) patients, and 4 (1.1%) patients died perioperatively. Severe complications were more frequent in surgery for duodenopancreatic NENs (n = 31; 22.0%) compared with SI-NENs (n = 15; 11.4%) (p = 0.014), in patients with lymph node metastases operated with curative aim of surgery (n = 24; 21.4%) versus non-metastasized tumors or palliative surgery (n = 32; 12.1%) (p = 0.020), and in functioning tumors (n = 20; 23.0%) versus non-functioning tumors (n = 30; 13.5%) (p = 0.042). Complication rates were not significantly associated with tumor stage or grade. CONCLUSIONS: Severe complications are frequent in GEP-NEN surgery. Besides duodenopancreatic tumor location, curative resection of nodal metastases and functioning tumors are risk factors for complications.

Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines.

Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.

Sentinel Lymph Node Biopsy in Thyroid Cancer.

BACKGROUND: Prophylactic central neck dissection in patients with papillary thyroid carcinoma is controversial. Sentinel node biopsy might be an adjunct to optimize surgical treatment for these patients. Earlier studies reported inconsistent detection rates and diagnostic value of this technique, and the role of sentinel lymph node biopsy in thyroid cancer needs to be established. PATIENTS AND METHODS: During a single-center prospective interventional study between 2010 and 2017, sentinel lymph node biopsy using 99mTc-nanocolloidal albumin tracer was performed on patients undergoing thyroid surgery for suspected thyroid cancer by fine needle aspiration cytology. All eligible patients without clinical lymph node involvement were invited to participate. Central neck dissection was performed on all patients after the detection of sentinel lymph nodes. RESULTS: Ninety-six patients participated in the study. The detection rates of the sentinel node were 67% and 45% by scintigraphy and intraoperative gamma probe, respectively. The detection rate was not associated with Bethesda score, malignancy, or presence of lymph node metastases. Sensitivity, negative predictive value, and accuracy were 80%, 97%, and 98%, respectively, for the sentinel node to represent the status of lymph node metastasis in the central neck compartment. The false negative rate was 20%. CONCLUSION: Sentinel lymph node biopsy had a low detection rate and only moderate sensitivity in patients with suspected thyroid carcinoma and is not a useful adjunct to surgery in the context of current treatment concepts.

Morbidity in patients with permanent hypoparathyroidism after total thyroidectomy.

BACKGROUND: Permanent hypoparathyroidism is common after thyroidectomy. The present study evaluated the risk for morbidity in patients operated with total thyroidectomy with and without permanent hypoparathyroidism. METHODS: Data was retrieved from the Scandinavian Quality Register for Thyroid, Parathyroid, and Adrenal Surgery and cross-linked with the Swedish National Prescription Registry for Pharmaceuticals, the National Data Inpatient Registry, and Causes of Death Registry. Patients with benign thyroid disease were included. Permanent hypoparathyroidism was defined as treatment with active vitamin D for more than 6 months after thyroidectomy. Analyzed morbidity was evaluated by multivariable Cox's regression analysis and presented as hazard ratio and 95% confidence interval. RESULTS: There were 4,828 patients. The mean (standard deviation) follow-up was 4.5 (2.4) years. Some 239 (5.0 %) patients were medicated for permanent hypoparathyroidism. Patients with permanent hypoparathyroidism had an increased risk for renal insufficiency, hazard ratio 4.88 (2.00-11.95), and an increased risk for any malignancy, hazard ratio 2.15 (1.08-4.27). Patients with permanent hypoparathyroidism and known cardiovascular disease at the time of thyroidectomy had an increased risk for cardiovascular events during follow-up, hazard ratio 1.88 (1.02-3.47). CONCLUSION: Patients with permanent hypoparathyroidism after total thyroidectomy have an increased risk of long-term morbidity. These results are a cause of great concern.

Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery: A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents.

BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Health-related quality of life in patients undergoing adrenalectomy: report from a Swedish National Audit.

PURPOSE: The aim of the study was to examine subjective health-related quality of life (HRQoL) in patients undergoing adrenalectomy. METHODS: The study included patients scheduled for adrenalectomy 2014-2017 after giving informed consent. The SF-36 questionnaire was administrated before operation and 1 year postoperatively. Results were compared with published normative values in Sweden. RESULTS: Some 50 patients were included. SF-36 scores for the whole cohort improved significantly after adrenalectomy in all dimensions except for bodily pain. Compared with the general Swedish population, the patients reported a significantly reduced HRQoL before and after adrenalectomy in all domains except for bodily pain postoperatively. Patients with benign functional tumours had lower HRQoL in physical domains before adrenalectomy than patients with benign non-functional tumours; Physical Component Summary (PCS), median 33.1 (range 17.1-62.9) vs. 44.2 (20.0-66.5), p = 0.018. Postoperatively, HRQoL was similar in the two groups of patients. Patients with benign functional tumours reported significantly improved HRQoL in all dimensions after adrenalectomy: PCS 33.1 (17.1-62.9) preoperatively vs. 47.6 (19.8-57.3) postoperatively, p = 0.005; Mental Component Summary (MCS) 33.8 (11.8-62.0) preoperatively vs. 52.7 (16.4-59.8) postoperatively, p = 0.004. These improvements were not seen in patients with benign non-functional or malignant tumours. Patients with malignant tumours reported no difference in SF-36 scores before or after adrenalectomy compared with patients with benign non-functional tumours. CONCLUSIONS: Adrenalectomy improved HRQoL in patients with benign functional tumours. Adrenalectomy did not improve HRQoL in patients with benign non-functional tumours or in patients with malignant tumours.