Intraoperative nerve monitoring in thyroid surgery: analysis of United Kingdom registry of endocrine and thyroid surgery database.

BACKGROUND: Intraoperative nerve monitoring (IONM) is used increasingly in thyroid surgery to prevent recurrent laryngeal nerve (RLN) injury, despite lack of definitive evidence. This study analysed the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS) to investigate whether IONM reduced the incidence of RLN injury. METHODS: UKRETS data were extracted on 28 July 2018. Factors related to risk of RLN palsy, such as age, sex, retrosternal goitre, reoperation, use of energy devices, extent of surgery, nodal dissection and IONM, were analysed. Data with missing entries for these risk factors were excluded. Outcomes of patients who had preoperative and postoperative laryngoscopy were analysed. RESULTS: RLN palsy occurred in 4.9 per cent of thyroidectomies. The palsy was temporary in 64.6 per cent and persistent in 35.4 per cent of patients. In multivariable analysis, IONM reduced the risk of RLN palsy (odds ratio (OR) 0.63, 95 per cent confidence interval (CI) 0.54 to 0.74, P < 0.001) and persistent nerve palsy (OR 0.47, 0.37 to 0.61, P < 0.001). Outpatient laryngoscopy was also associated with a reduced incidence of RLN palsy (OR 0.50, 0.37 to 0.67, P < 0.001). Bilateral RLN palsy occurred in 0.3 per cent. Reoperation (OR 12.30, 2.90 to 52.10, P = 0.001) and total thyroidectomy (OR 6.52, 1.50 to 27.80; P = 0.010) were significantly associated with bilateral RLN palsy. CONCLUSION: The use of IONM is associated with a decreased risk of RLN injury in thyroidectomy. These results based on analysis of UKRETS data support the routine use of RLN monitoring in thyroid surgery.

Post-thyroidectomy bleeding: analysis of risk factors from a national registry.

BACKGROUND: Post-thyroidectomy haemorrhage occurs in 1-2 per cent of patients, one-quarter requiring bedside clot evacuation. Owing to the risk of life-threatening haemorrhage, previous British Association of Endocrine and Thyroid Surgeons (BAETS) guidance has been that day-case thyroidectomy could not be endorsed. This study aimed to review the best currently available UK data to evaluate a recent change in this recommendation. METHODS: The UK Registry of Endocrine and Thyroid Surgery was analysed to determine the incidence of and risk factors for post-thyroidectomy haemorrhage from 2004 to 2018. RESULTS: Reoperation for bleeding occurred in 1.2 per cent (449 of 39 014) of all thyroidectomies. In multivariable analysis male sex, increasing age, redo surgery, retrosternal goitre and total thyroidectomy were significantly correlated with an increased risk of reoperation for bleeding, and surgeon monthly thyroidectomy rate correlated with a decreased risk. Estimation of variation in bleeding risk from these predictors gave low pseudo-R2 values, suggesting that bleeding is unpredictable. Reoperation for bleeding occurred in 0.9 per cent (217 of 24 700) of hemithyroidectomies, with male sex, increasing age, decreasing surgeon volume and redo surgery being risk factors. The mortality rate following thyroidectomy was 0.1 per cent (23 of 38 740). In a multivariable model including reoperation for bleeding node dissection and age were significant risk factors for mortality. CONCLUSION: The highest risk for bleeding occurred following total thyroidectomy in men, but overall bleeding was unpredictable. In hemithyroidectomy increasing surgeon thyroidectomy volume reduces bleeding risk. This analysis supports the revised BAETS recommendation to restrict day-case thyroid surgery to hemithyroidectomy performed by high-volume surgeons, with caution in the elderly, men, patients with retrosternal goitres, and those undergoing redo surgery.

A Review of Parathyroid Surgery for Primary Hyperparathyroidism from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: The United Kingdom Registry of Endocrine and Thyroid Surgeons is a national database holding details on > 28,000 parathyroidectomies. METHODS: An extract (2004-2017) of the database was analysed to investigate the reported efficacy, safety and use of intra-operative surgical adjuncts in targeted parathyroidectomy (tPTx) and bilateral neck exploration (BNE) for adult, first-time primary hyperparathyroidism (PHPT). RESULTS: 50.9% of 21,738 cases underwent tPTx. Excellent short-term (median follow-up 35 days) post-operative normocalcaemia rates were reported overall (tPTx 96.6%, BNE 94.5%, p < 0.05) and in image-positive cases (tPTx 96.7%, BNE 96%, p < 0.05). Intra-operative PTH improved overall normocalcaemia rates (tPTx 97.8% vs 96.3%, BNE 95% vs 94.4%: both p < 0.05). Intra-operative nerve monitoring reduced vocal cord (VC) dysfunction in image-positive tPTx, but not in BNE (97.8% vs 93.2%, p < 0.05). Complications were higher following BNE (7.4% vs 3.8%, p < 0.05), especially hypocalcaemia (5.3% vs 2%, p < 0.05). There was no difference in rates of subjective dysphonia following tPTx or BNE (2.4% vs 2.3%, p > 0.05), nor any difference in VC dysfunction when formally examined (4.9% vs 4.1%, p > 0.05). CONCLUSIONS: In image-positive, first time, adult PHPT cases, tPTx is as safe and effective as BNE, with both achieving excellent short-term results with minimal complications.

Reduced exertion high-intensity interval training (REHIT) in an adult with Cystic Fibrosis: A mixed-methods case study.

Although aerobic capacity has been identified as an important predictor of mortality in Cystic Fibrosis (CF) individuals, many remain insufficiently active. As a 'lack of time' is a commonly cited barrier to exercise, reduced-exertion high-intensity interval training (REHIT) may provide a truly time-effective method to increase aerobic capacity. Six-weeks of REHIT in a CF individual was assessed by a cardiopulmonary exercise test (CPET) and individual perceptions described using a self-report narrative. Peak oxygen uptake ( V ˙ O2peak) increased by 6% whilst pulmonary function remained unchanged. Qualitative data indicated social support and low-time commitment positively influenced adherence with fatigue and lack of enjoyment noted as a significant barriers. REHIT was demonstrated as a viable, manageable option for a CF individual with moderate-severe pulmonary limitation. Further research is needed to determine the efficacy of REHIT in a large representative sample to ascertain whether it represents an alternative treatment strategy.

Calcitonin-negative medullary thyroid carcinoma: the 'triple-negative' phenotype.

Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterised by classic medullary thyroid carcinoma morphology without raised serum calcitonin. A 24-year-old woman presented with a slow-growing, right-sided neck swelling. She underwent an ultrasound scan, cytopathological and histopathological examination, and tests for alternative diagnoses. The ultrasound showed a heterogeneous, hyperechoic nodule in the right thyroid lobe. Serum calcitonin was normal. Cytopathology and histopathology showed typical medullary thyroid carcinoma morphology but without calcitonin upon immunostaining and mRNA in situ hybridisation. A 'triple-negative' calcitonin-negative medullary thyroid carcinoma was diagnosed. A completion thyroidectomy with bilateral central lymph node dissection was performed. The patient remains well three-years post-surgery. When cytopathology suggests a medullary thyroid carcinoma, serum calcitonin, pro-calcitonin, carcinoembryonic antigen and calcitonin-gene-related peptide should be measured to identify cases of calcitonin-negative medullary thyroid carcinoma. They should also be measured post-treatment for monitoring purposes. This will aid future calcitonin-negative medullary thyroid carcinoma diagnoses and will inform prognostic stratification and influence treatment decisions.

Effect of surgeons' annual operative volume on the risk of permanent Hypoparathyroidism, recurrent laryngeal nerve palsy and Haematoma following thyroidectomy: analysis of United Kingdom registry of endocrine and thyroid surgery (UKRETS).

PURPOSE: Categorize data to investigate the surgeon volume outcome relationship in thyroidectomies. Determine the evidence base for recommending a minimum number of thyroidectomies performed per year to maintain surgical competency. METHODS: Data on thyroid operations in the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS) from 01/09/2010 to 31/08/2016 was analysed. The primary outcome measure was permanent hypoparathyroidism (PH). Recurrent laryngeal nerve palsy (RLN) and post-operative haematoma were also examined. Exclusion criteria included patient age > 85 or < 18 years, and surgeons contributing <10 operations. Data analysis was performed using general additive models and mixed effect logistic regression for PH and binary logistic regression for others. RESULTS: For PH 10313 bilateral thyroid operations were analysed. The Annual rate (AR, p = 0.012) and nodal dissection (P < 10-7) were significant factors. 25,038 thyroidectomies were analysed to investigate the effect of surgeon Volume on RLN palsy and haematoma. Age, retrosternal goitre, routine laryngoscopy, re-operation, nodal Dissection, bilateral thyroidectomy, RLN monitoring and surgeon volume were significantly associated with RLN palsy. Post-operative haematoma showed no significant correlation to surgeon volume. Categorisation of AR showed that PH and RLN palsy rates declined in surgeons performing >50 cases/year to a minimum of 3% and 2.6% respectively in highest volume AR group (>100 cases/year). CONCLUSION: Surgeon annual operative volume is a factor in determining outcome from thyroid surgery. Results are limited by a high proportion of missing data, which could potentially bias the outcome, but tentatively suggests the minimum recommended number of thyroid operations / year should be 50 cases.

Correlation of surgeon-performed parathyroid ultrasound with the Perrier classification and gland weight.

BACKGROUND: Ultrasound localisation of parathyroid glands correlates with gland weight. We hypothesise that gland identification is also dependent on anatomical location. Perrier et al. have described a uniform and reliable nomenclature for parathyroid locations. We aimed to correlate surgeon-performed ultrasound (SUS) with intra-operative Perrier classification and gland weight. METHODS: Review of a prospectively maintained single operator SUS database of 194 patients referred with non-familial primary hyperparathyroidism (PHPT) at a tertiary centre between 2010 and 2015. Patients underwent MIBI localisation as well as on table SUS. Intra-operative pathological gland locations were classified according to the Perrier nomenclature. RESULTS: Mean weight of pathological glands found and missed by SUS was 1.07 ± 0.1 g and 0.48 ± 0.08 g respectively (p = 0.0001, unpaired t test). The weight of glands identified was greater than that of missed glands for each of the Perrier locations (p < 0.001, Mann-Whitney). The proportion of pathological glands found at each Perrier location varied significantly (p < 0.0001, Chi Square); so we find proportionally more B-, D-, E- and F-type glands and miss more A- and C-type glands. The median weight of glands missed on SUS varied significantly across the Perrier groups (Kruskal-Wallis, p = 0.0034) and suggests that SUS can miss quite large glands (> 0.5 g) in locations B, C and F; whereas missed glands in locations A, D and E were all small (< 0.5 g). CONCLUSION: Whilst gland identification correlates well with gland weight, anatomical location has a significant impact on failure of localisation irrespective of gland weight. For the surgeon operating on PHPT patients with negative US localisation, particular attention should be paid to locations C, D and A as these are the sites where pathological glands are most often missed on pre-operative US.

Hypoxia Increases Thyroid Cancer Stem Cell-Enriched Side Population.

INTRODUCTION: Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC). METHODOLOGY: We have isolated thyroid CSC from a papillary thyroid cancer-derived cell line (BCPAP) and an anaplastic thyroid cancer-derived cell line (SW1736) as side population (SP) cells (a putative stem cell population) and treated them with cobalt chloride (II) to induce hypoxia. RESULTS AND DISCUSSION: We observed an increase in the SP of cells within the thyroid cancer cell lines following induction of hypoxia.

Short and long-term cosmesis of cervical thyroidectomy scars.

Introduction Multiple surgical approaches to the thyroid gland have been described via cervical or extracervical routes. Improved cosmesis, patient satisfaction, reduced pain (procedure dependent) and early discharge have all been reported for minimally invasive approaches with similar safety profiles and long-term outcomes to conventional surgery. This review summarises the current evidence base for improved cosmesis with minimally invasive cervical approaches to the thyroid gland compared with conventional surgery. Methods A systematic review was undertaken. The MEDLINE(®), Embase™ and Cochrane databases were searched for relevant articles. Results A total of 57 papers thyroid papers were identified. Of those, 20 reported some form of cosmetic outcome assessment. There were 6 randomised controlled trials with 412 patients (evidence level 2B), 7 cohort studies with 3,073 patients (level 3B) and 7 non-comparative case series with 1,575 patients (level 4). There was significant heterogeneity between studies in terms of wound closure technique, timing of scar assessment and scar assessment scales (validated and non-validated). Most studies performed early scar assessments, some using non-validated scar assessment tools. Conclusions Assessment of cosmesis is complex and requires rigorous methodology. Evidence from healing/remodelling studies suggests scar maturation is a long-term process. This calls into question the value of early scar assessment. Current evidence does not support minimally invasive surgical approaches to the thyroid gland if improved long-term cosmesis is the goal.

Thyroid Stem Cells: Concept and Clinical Implications

Thyroid pathology is the commonest endocrine surgical problem encountered. However, the study of thyroid stem cells is relatively new in the field of stem cell research. Since the identification of thyroid stem cells in 1992, research interest in this area has been increasing mainly based on furthering our knowledge of the biology of these important cells that are thought to be responsible for tumourigenesis and propagation of cancers. This article reviews the current science and biology of thyroid stem cells and summarizes their potential role in the general management of thyroid disorders.

Accuracy of a multidisciplinary team-led discussion in predicting postmastectomy radiotherapy.

INTRODUCTION: Immediate breast reconstruction (IBR) is performed increasingly following mastectomy for breast cancer. The literature suggests higher reconstructive failure and poorer cosmesis in the subgroup of patients receiving postmastectomy radiotherapy (PMRT) following IBR. We set out to determine the accuracy of a multidisciplinary team (MDT) discussion in predicting PMRT. METHODS: Preoperative MDT discussions were recorded prospectively over a 12-month period (from February 2011) in a symptomatic breast unit. The estimated need for PMRT was stratified into 'PMRT not required', 'PMRT possibly required', 'PMRT probably required' and 'PMRT required' groups. RESULTS: Of 156 referrals included in the study, 76 patients (49%) underwent mastectomy: 61 simple mastectomy, 10 skin sparing mastectomy (SSM) and delayed-immediate breast reconstruction, 3 SSM and implant-based IBR, and 2 mastectomy IBR with an autologous flap. The IBR rate was therefore 19.7%. The proportion of patients who received PMRT was 14% (3/21) in the 'PMRT not required', 30% (7/23) in the 'PMRT possibly required', 65% (9/14) in the 'PMRT probably required' and 94% (17/18) in the 'PMRT required' groups. Assigning a linear numerical score (1-4) to these groups (higher score representing greater likelihood of receiving PMRT), the predicted need for PMRT correlated with the proportion of patients who ultimately received PMRT (linear regression r(2)=0.98, p=0.01). CONCLUSIONS: This study has examined the factors influencing MDT discussions regarding IBR, demonstrating that the MDT is reasonably accurate at predicting need for PMRT. Whether such accuracy is clinically adequate and/or reproducible across units is debatable.

Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Confidence interval: 56-88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children. METHODS: A prospective, double-blind, placebo controlled multi-centered trial in South Africa and Malawi randomly assigned infants in a 1:1:1 ratio to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. RESULTS: 1339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1-83%). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. CONCLUSION: Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children.

The impact of surgeon-based ultrasonography for parathyroid disease on a British endocrine surgical practice.

INTRODUCTION: Surgeon-based ultrasonography (SUS) for parathyroid disease has not been widely adopted by British endocrine surgeons despite reports worldwide of accuracy in parathyroid localisation equivalent or superior to radiology-based ultrasonography (RUS). The aim of this study was to determine whether SUS might benefit parathyroid surgical practice in a British endocrine unit. METHODS: Following an audit to establish the accuracy of RUS and technetium sestamibi (MIBI) in 54 patients, the accuracy of parathyroid localisation by SUS and RUS was compared prospectively with operative findings in 65 patients undergoing surgery for primary hyperparathyroidism (pHPT). RESULTS: The sensitivity of RUS (40%) was below and MIBI (57%) was within the range of published results in the audit phase. The sensitivity (64%), negative predictive value (86%) and accuracy (86%) of SUS were significantly greater than RUS (37%, 77% and 78% respectively). SUS significantly increased the concordance of parathyroid localisation with MIBI (58% versus 32% with RUS). CONCLUSIONS: SUS improves parathyroid localisation in a British endocrine surgical practice. It is a useful adjunct to parathyroid practice, particularly in centres without a dedicated parathyroid radiologist, and enables more patients with pHPT to benefit from minimally invasive surgery.

Appendicitis and Meckel's diverticulum in a femoral hernia: simultaneous De Garengeot and Littre's hernia.

This report presents the case of a 73-year-old woman who was admitted with sepsis, cachexia and confusion secondary to a strangulated femoral hernia containing both the appendix (De Garengeot hernia) and a Meckel's diverticulum (Littre's hernia). She underwent successful operative management and was discharged from hospital on the 10th post-operative day. This is the first report in the literature of a combined De Garengeot and Littre's hernia within a femoral hernia sac.

The use of the harmonic scalpel in thyroidectomy: 'beyond the learning curve'.

INTRODUCTION: Safe and effective haemostasis in surgery is clearly essential, and in the neck where risks of airway compromise are also present any new technology that purports to offer advantages must be rigorously evaluated. We describe our experience with the use of the Harmonic Scalpel [Ethicon UK] in thyroidectomy. PATIENTS AND METHODS: A retrospective clinical review of 183 patients undergoing hemi or total thyroidectomies from 12 months prior to using the harmonic scalpel (2003; n = 77) and 12 months 'beyond the learning curve' (2006; n = 106). RESULTS: The results demonstrate that, once past the learning curve, the use of the harmonic scalpel during thyroidectomy significantly reduces operative time and postoperative hypocalcaemia, and is as safe as conventional surgery with regard to voice change and bleeding. CONCLUSIONS: The harmonic scalpel is as safe as conventional methods of haemostasis and operations using this technique are quicker once the need to have repetitive 'clip, cut and tie' routines is avoided.

The proliferative effects of 5-androstene-3 beta,17 beta-diol and 5 alpha-dihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines.

Epidemiological studies suggest that precursor steroids are implicated in the aetiology of breast cancer. However, our understanding of the role of precursor steroids in breast cancer is complicated by fact that there are many precursor steroids, which are metabolically inter-related and have divergent proliferative activities on the growth of breast cancer cell lines. In this study the proliferative affects of 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol, which may be considered true metabolites acting at a tissue level, on MCF7, T47D and MDAMB231 breast cancer cell lines have been examined by a flow cytometric technique. DNA cell cycle analysis demonstrates that 5-androstene-3 beta,17 beta-diol stimulates the proliferation of hormone-dependent cell lines at physiological levels by an oestrogen receptor mediated mechanism whereas 5 alpha-dihydrotestosterone does not affect the proliferation of MCF7 and T47D cell lines at physiological levels over short (48 h) incubations. Both 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol stimulate proliferation of hormone-dependent cell lines at pharmacological levels via and interaction with the oestrogen receptor. In long (6-9 days) incubations both 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol inhibit the 17 beta-oestradiol induced proliferation of MCF7 and T47D cell lines, however, 5 alpha-dihydrotestosterone inhibits while 5-androstene-3 beta,17 beta-diol stimulates basal proliferation. These cell line studies suggest a model for the role of precursor steroids in pre- and postmenopausal breast cancer.

Serum adrenal androgens in women with primary operable breast cancer and their relationship with age and body mass index.

Several studies have found elevated levels of adrenal androgens in postmenopausal women and depressed levels in premenopausal women with breast cancer, suggesting a role for adrenal androgens in the aetiology of breast cancer. We have measured serum dehydroepiandrosterone sulphate and androstenedione in 81 women with primary operable breast cancer and 62 age-matched controls. Results showed that serum levels of both adrenal androgens fell significantly with age in women with breast cancer (P=0.003). However, no relationship was observed between serum adrenal androgen levels and body mass index in either women with breast cancer or controls. Dehydroepiandrosterone sulphate levels were elevated in postmenopausal women with breast cancer compared to controls, and this was not due to preoperative stress. No differences were observed in androstenedione levels between premenopausal or postmenopausal women with breast cancer and controls, nor were dehydroepiandrostenedione sulphate levels significantly different between premenopausal women with breast cancer and controls. These results suggest that dehydroepiandrosterone sulphate has a role in the aetiology of postmenopausal breast cancer.