James England

Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases

Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR‐1 and VEGFR‐2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves’ disease, 10 follicular adenoma, 8 Hashimotos thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0–3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimotos thyroiditis and Graves’ disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves’ disease was less than other pathologies (P < 0.05). VEGFR‐1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR‐1 and VEGFR‐2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up‐regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology.

Somatostatin receptor expression in thyroid disease

Somatostatin analogues are commercially available and used for the management of acromegaly and neuroendocrine tumours, but the expression of the receptors as a target in thyroid disease has not been explored. To assess somatostatin (SST) and somatostatin receptor (SSTR1‐5) expression in both normal and thyroid disorders, as a potential target for somatostatin analogue therapy, 67 thyroid tissue specimens were reviewed: 12 differentiated thyroid carcinomas, 14 follicular adenomas, 17 multinodular goitres, 14 Graves disease, 10 Hashimotos thyroiditis specimens and five normal thyroids. Tissue was immunostained for SST and SSTR1‐5. Positivity and the degree of positivity were recorded by double‐blinded observers. Somatostatin receptor expression was highly expressed in normal tissue for SSTR1, 3, 4 and 5 (5 of 5, 4 of 5, 4 of 5 and 5 of 5 respectively) whilst SST and SSTR 2a and b were not expressed at all. The commonest receptor expressed for all pathological subtypes grouped together was SSTR2b (63 specimens). The commonest receptors expressed in differentiated thyroid cancer were SSTR5 (11 of 12 specimens) and SSTR2b (10 of 12 specimens). The commonest receptor expressed in benign disease was SSTR2b (53 of 55 specimens). SSTR5 was significantly under‐expressed in Graves disease (P < 0.05). This study illustrates that SSTR 1, 3, 4 and 5 are highly expressed in normal, benign and malignant thyroid tissue. SSTR 2a and 2b appear absent in normal tissue and present in benign and malignant thyroid tissue (P < 0.02). This suggests that focussed SSTR2 treatment may be a potential therapeutic target.

Post-thyroidectomy haemorrhage in a tertiary centre. Analysis of 1,280 operations and comparison to the BAETS audit 2012.

Haemorrhage following thyroid surgery is an uncommon, but potentially lethal complication, occurring in approximately 1% of all procedures, according to the data submitted to the most recent audit, performed in 2012, by the British Association of Endocrine and Thyroid Surgeons (BAETS). The BAETS audit contains data from 18 904 thyroid operations submitted by surgeons across the UK. Over 50% of thyroid surgery is performed for benign disease including colloid goitre and Graves’ disease, with total thyroidectomy being the mainstay of surgical treatment in thyrotoxicosis. In recent years, there has been a move towards day surgery, with some patients staying in hospital for less than 24 h. Increasingly,patientsundergoinghemithyroidectomyarebeing discharged on the day of surgery. Hospital Episode Statistics (HES) data suggest that 310 hemithyroidectomies, thyroid lobectomies and partial thyroidectomies were performed during the time period analysed in 2013–14. In 2011–12, the number of procedures listed above was 296, but this is much higher than figures from 2005–6when only 53 procedures were performed as a daycase. Treatment for hypocalcaemia is the predominant reason for inpatient stay over and above 24 h. Multivariate analysis of outcomes performed with BAETS data shows that haemorrhage is more common with increasing age and with extent of resection, referred to as ‘laterality’ in the BAETS audit. Histology is also not significantly associated with an increased risk of haemorrhage according to BAETS audit data. The lead author performs in excess of 130 thyroid operations in a calendar year at Hull and East Yorkshire (HEY) NHS Trust, and referrals are received from a large area encompassing East Yorkshire, Humberside and North Lincolnshire. A joint clinic involving endocrinologists and otorhinolaryngologists ensures that patients from the catchment area are managed centrally. Thyroidectomy is offered as a potential first-line treatment for Graves’ disease alongside medical management with carbimazole, propylthiouracil or radioiodine, in line with ATA guidelines. A significant number of patients with Graves’ disease, in the absence of clinical necessity, opt for surgical management as first line. Lugol’s iodine was used preoperatively for all toxic thyroidectomies prior to 2008 in this case series, but was subsequently only used in patients with uncontrolled thyrotoxicosis after 2008. Preoperatively, patients are not routinely given chemoprophylaxis for venous thromboembolism. A standard operative technique has been utilised throughout. A skin incision is made low in the neck, without prior infiltration with local anaesthetic or vasoconstriction. Monopolar haemostasis is used up to the level of the strap muscles. Bipolar diathermy is used thereafter, typically at 20J. No ties or haemostatic clips are used other than in the ligation and division of large vessels. Ultrasonic haemostatic devices and nerve monitoring devices are not used. Head-down, valsalva haemostatic checks are performed at the completion of the operation in all patients. Hydrocellulose haemostatic adjuncts are reserved for massive multinodular goitres and rarely used. The strap muscles are apposed, but not closed along their length, with a single interrupted midline vicryl suture, followed by a continuous subplatysmal vicryl suture.Clips areused to close the skin, with a drain inserted only in cases of toxic thyroidectomy. The senior surgeon remains present throughout the operation, haemostatic checks, wound closure and recovery. Postoperatively, hemithyroidectomy patients may be discharged on the day of surgery, with total thyroidectomy patients typically staying for 24 h for postoperative hypocalcaemia monitoring. Clips are removed after 48 h.

Effect on mortality of elective parathyroid surgery in one hundred and three patients with chronic kidney disease: our experience.

three patients with chronic kidney disease: our experience Sylvester, D.,* Srivastava, R.,* Lamplugh, A., Allgar, V., Snowden, C., Bhandari, S. & England, J.* *Department of Otolaryngology, Castle Hill Hospital, Cottingham, Department of Renal Medicine, Hull Royal Infirmary, Hull, Department of Health Sciences, The University of York, Heslington, York, Department of Anaesthesia, Castle Hill Hospital, Cottingham, UK

Parathyroid Ectopia-Development of a Surgical Algorithm

Objective: Study the incidence of ectopic parathyroid adenomata from a single surgical series and devise a surgical algorithm from the results to follow when an adenoma cannot initially be located. Method: Retrospective review of a prospectively collected senior author’s (RJAE) database of 357 patients who underwent parathyroidectomy between June 2001 and February 2008. From the database, an ordered surgical protocol has been developed for the location of both ectopic superior and inferior parathyroid adenomata in order of incidence. Results: Parathyroid ectopia occurs in approximately 10% of cases of hyperparathyroidism. It is more common in superior than inferior parathyroid glands. The most common superior location is the left retroesophageal position, and the most common inferior location is within the left thymic remnant. Conclusion: Prospective data collection and subsequent analysis can lead to the development of a systematic surgical protocol to aid the location of ectopic enlarged parathyroid glands in the surgical management of hyperparathyroidism.

Predicting Thyroxine Requirements After Total Thyroidectomy

and 95% confidence intervals were obtained using unconditional logistic regression analysis. RESULTS: A total of 30 with oral cancer and 30 controls were genotyped for SNP. The data indicated that the homozygous variant genotype (AA) was associated with a significantly increased oral cancer risk. However, the individuals with heterozygous genotype (TA) were not associated with oral cancer risk. CONCLUSION: This is the first epidemiological study to report significant associations between Aurora-A [F31I] SNP and oral cancer risk.