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 Hashimoto's 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 Hashimoto's 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.

INTRODUCTIONOver the last two decades increasing numbers of surgical procedures have been performed on an outpatient basis. In 2000 the National Health Service in England set the target of performing 75% or more of all elective surgical procedures as day cases and in 2001 the British Association of Day Surgery added thyroidectomy to the list of day case procedures. However, same day discharge following thyroidectomies has been adopted by only a very small number of UK centres. The aim of this review was to establish the evidence base surrounding same day discharge thyroid surgery.METHODSThe British Association of Endocrine and Thyroid Surgeons commissioned the authors to perform a review of the best available evidence regarding day case thyroid surgery as a part of a consensus position to be adopted by the organisation. A MEDLINE® review of the English medical literature was performed and the relevant articles were collated and reviewed.RESULTSThere are limited comparative data on day case thyroid surgery. It is feasible and may save individual hospitals the cost of inpatient stay. However, the risk of airway compromising and life threatening post-operative bleeding remains a major concern since it is not possible to positively identify those patients most and least at risk of bleeding after thyroidectomy. It is estimated that half of all post-thyroidectomy bleeds would occur outside of the hospital environment if patients were discharged six hours after surgery.CONCLUSIONSSame day discharge in a UK setting cannot be endorsed. Any financial benefits may be outweighed by the exposure of patients to an increased risk of an adverse outcome. Consequently, 23-hour surgery is recommended.

The global incidence of thyroid cancer is increasing, and metastatic spread to the lymph nodes is common in papillary thyroid carcinoma. The metastatic course of thyroid carcinoma is an intricate process involving invasion, angiogenesis, cell trafficking, extravasation, organ specific homing, and growth. A key aspect in this process involves a multitude of interactions between chemokines and their receptors. Chemokines are a group of small proteins, which act to elicit normal physiologic and immune responses principally through recruitment of specific cell populations to the site of infection or malignancy. Thyroid cancer cells, like other tumors, possess the ability to corrupt the chemokine system to their advantage by altering cell movement into the tumor microenvironment and affecting all aspects of thyroid cancer progression.

BackgroundThough the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or ‘precision’ medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies.MethodsHuman thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 μm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting).ResultsMaintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p < 0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated on-chip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period.ConclusionsThe described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time.

The diagnostic role of intraoperative cytology (IC) has been demonstrated by many comparative studies. These studies have used sensitivity and specificity as statistical tools, based on binary principles. Statistical methods based on binary principles appear to be inappropriate for comparing anatomic pathology studies which involve significant human judgment with a range of subjective nonbinary result patterns. In this study, we applied the receiver operating characteristic (ROC) curve, which is based on probabilistic principles for the comparison of diagnostic accuracy with IC and frozen sections (FS). Seven observers studied a variable number of IC alone, FS alone, and IC/FS together from a pool of 446 specimens. The results were analyzed by ROC curve, using the MEDCALC software program (MedCalc Software, Mariakerke, Belgium). The accuracy with IC alone and FS alone was comparable. IC alone was diagnostic for many lesions, offering the choice of not freezing the tissue, and thus avoiding the introduction of artifacts. This strongly favors the routine practice of preparing IC during intraoperative consultation. Diagn. Cytopathol. 23:134–139, 2000. © 2000 Wiley‐Liss, Inc.