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.

Metachronous testicular teratoma, testicular seminoma and papillary thyroid carcinoma occurring in a single individual: a report of two unrelated cases.

We describe two unrelated men who both developed teratomas in one testis followed by seminomas in the contralateral testis followed by papillary thyroid carcinomas. Neither man had a family history of cancers. Although random occurrence is possible, genetic predisposition and/or environmental influence would seem a likely explanation for this previously unreported combination of tumours.

How is adrenocortical cancer being managed in the UK?

INTRODUCTION: Adrenocortical carcinomas are rare. This case series is reported to give an overview of how adrenocortical carcinoma is currently managed in the UK. PATIENTS AND METHODS: A retrospective review was made of case notes from patients with adrenocortical carcinomas presenting to the authors (TWJL, RDB, BJH, and DS-C) over the past 10 years in Newcastle, Sheffield and Cardiff. RESULTS: Newcastle treated twelve, Sheffield eleven and Cardiff seven cases. The median follow-up was 25.5 months (range, 1-102 months). All tumours were greater than 5 cm in diameter. The majority presented with symptoms of hormone excess. Adrenalectomy was performed in 83% - this was radical in 30% and followed by excision of recurrence in 13%. Adjuvant mitotane was given in 64% of patients, in combination with cytotoxic chemotherapy in 20%. One-third of patients did not receive any adjuvant therapy. There was no significant difference in survival between the three centres. The majority of patients (57%) died during the period of follow-up of this study. The median survival was 37 months (range, 2-102 months). CONCLUSIONS: The size of tumour, stage and mode of presentation, age and overall survival of patients in this study are comparable to published series of adrenocortical carcinomas from major endocrine surgical centres world-wide. Despite controversies about benefits, adjuvant mitotane was used in the majority of cases, whereas cytotoxic chemotherapy was only used in the minority. The exact role of adjuvant therapy in the management of adrenocortical carcinoma is not as well established as for other more common malignancies. Establishing a database for adrenocortical carcinomas in the UK would contribute to our understanding of the management of this disease.

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.

Impact of standardised reporting in adrenocortical carcinoma: a single centre clinicopathological review.

AIMS: Structured multicentre efforts are needed if the prognosis of adrenocortical carcinoma (ACC) is to be improved. Data collection may be enhanced through standardised histopathological reporting using criteria such as the recently published Royal College of Pathologists' (UK) minimum dataset (MDS). This study aimed to perform a clinicopathological review of the adult patients treated at the Royal Victoria Infirmary, Newcastle upon Tyne, in the 10 years preceding the MDS. METHODS: Case records were examined for all patients diagnosed with ACC between 1996 and 2006. Pathology was reviewed and compared with the Royal College of Pathologists' MDS along with the original reports. A systematic evaluation of Ki-67 immunolabelling was also performed. RESULTS: Eleven patients with ACC were diagnosed and treated. Histopathological reporting according to the MDS identified more features of malignancy than in the original reports (8.5+/-1.2 versus 5.1+/-0.8, p<0.02). The median number of microscopic criteria of malignancy was 7 (range 5-10), with > or =5 features occurring in all cases. The most commonly observed features of malignancy were diffuse architecture, <25% clear cells, confluent necrosis, abnormal mitoses and mitotic count > or =6 per 50 high-power fields. Capsular invasion and > or =8 MDS criteria of malignancy were associated with a worse outcome (each p<0.01). Median Ki-67 index was 19.0% (range 3.7-44.1%) and was not apparently related to survival. CONCLUSIONS: Standardised criteria for histopathological reporting of ACC will improve the accuracy of data for cancer registration and may also assist in individual patient stratification. An elevated Ki-67 index is a feature of ACC, although it does not appear to predict individual patient survival.

Primary squamous cell carcinoma of the thyroid gland: a case report and role of radiotherapy.

Primary squamous cell carcinoma is an extremely rare tumour of the thyroid gland. A case of an elderly lady who was diagnosed to have primary squamous cell carcinoma of the thyroid gland is presented and the role of radiotherapy is discussed.

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.

Surgeon's approach to the thyroid gland: surgical anatomy and the importance of technique.

The cornerstone of safe and effective thyroid surgery is thorough training in and understanding of thyroid anatomy and pathology. With appropriate techniques, total thyroid lobectomy and total thyroidectomy (which should be considered simply as a bilateral total thyroid lobectomy performed during the same operation) can be undertaken with minimal risk of damage to the recurrent laryngeal nerves, the external branches of the superior laryngeal nerves, and the parathyroid glands. Safe surgery requires a specific operative plan, progressing in a series of logical, orderly, anatomically based steps. Exposure of the thyroid gland is followed by careful dissection of the superior pole, utilizing the avascular plane between the superior pole and the cricothyroid muscle to identify and preserve the external branch of the superior laryngeal nerve. Medial retraction of the gland then allows dissection of the lateral aspect of the thyroid lobe. Protection of the recurrent laryngeal nerves and preservation of the blood supply to the parathyroid glands is best achieved by "capsular dissection," ligating the tertiary branches of the inferior thyroid artery on the gland surface. If a parathyroid gland cannot be preserved or becomes ischemic after dissection of its vascular pedicle, it should be immediately minced and autotransplanted into the ipsilateral sternocleidomastoid muscle. The current evolution of outpatient or short-stay thyroidectomy emphasizes the need to avoid complications by utilizing meticulous surgical technique. Minimally invasive thyroidectomy utilizing endoscopic techniques may also affect the practice of thyroid surgery. Even so, understanding the surgical anatomy of the thyroid gland and its possible variations is paramount to safe and effective surgery.

Insulinoma: a review of current management.

Insulinomas are a relatively rare tumour which occur predominantly in the pancreas. The majority of the tumours are benign, but have profound effects upon the patient. The diagnosis of insulinoma is often elusive, and the management may involve demanding surgery with a significant morbidity. In this review article, all clinical aspects of insulinomas are examined. Particular emphasis is placed on the myriad modes of presentation, and the methods used to localise the tumour pre-operatively. Medical, as well as surgical treatments are discussed and their role in the management of both malignant and benign tumours. Despite potential difficulties encountered in managing patients with this tumour, a large majority may be either cured or achieve useful palliation.

Inhibition of endothelial adhesion and invasion by breast carcinoma cells may contribute towards the anti-metastatic effects of tamoxifen.

The anti-metastatic actions of tamoxifen on the oestrogen receptor-(ER-) positive cell line, MCF-7 and Hs578T, which is ER-negative, were investigated by measuring changes in the tumour cell adherence to endothelium and invasion of Matrigel. The endothelial hybridoma EA.hy926 was grown to confluence on the bases of 96-well plates. Either tamoxifen, the pure ER antagonist ICI 182,780 or the control, phosphate-buffered saline (PBS), was added to each well in varying concentrations. Adhesion of tumour cells to the endothelium was then measured using an isotopic adhesion assay. Invasion was determined by measuring the number of cells passing across a Matrigel-coated filter with 8 microm diameter pores. After 24-h incubation, the number of cells which had invaded was determined by an XTT colorimetric assay. Tamoxifen and ICI 182,780 inhibited both adhesion to the model endothelium and Matrigel invasion of the ER-positive cell line at therapeutic concentrations (P<0.005). Neither compound, however, had an effect on the ER-negative cell line. This action of the ER antagonists may play a role in prolonging the disease-free survival seen in women with breast cancer who are treated with adjuvant tamoxifen.

The role of beta 1 integrins in adhesion of two breast carcinoma cell lines to a model endothelium.

Interactions between tumour cells and the endothelium are vital to the formation of haematogenous metastases. Binding to model endothelium of one oestrogen receptor positive breast carcinoma cell line (MCF-7) and one receptor negative line (HS578T) was examined in vitro together with endothelial retraction induced by these tumour cells. Adhesion was inhibited by monoclonal antibodies specific for the VLA integrins and by peptides containing the RGD motif which is commonly recognised as a ligand by the VLA adhesion molecules. However, binding of the two tumour cell lines was inhibited by monoclonal antibodies specific for different VLA molecules; anti-alpha 6 beta 1 inhibited MCF-7 adhesion but anti-alpha 5 beta 1 inhibited Hs578T. These results were consistent with flow cytometric quantification of the expression of these VLA integrins on the surfaces of the two tumour cell lines. Enzyme-linked immunosorbent assays (ELISA) demonstrated that laminin was present on the endothelial cell surface but collagen IV was absent. ELISA failed to detect increased exposure of the subendothelial matrix during the first hour after addition of either cancer cell type. This was supported by assays which demonstrated maintenance of the endothelial permeability barrier during this period. Slight endothelial retraction was detected within 2 hours of the addition of tumour cells. It is concluded that binding between tumour cells and confluent endothelium is inhibited by the blockade of adhesion molecules which are normally associated with interactions between the cell and the subendothelial matrix. Tumour cell to matrix interactions rather than direct tumour to endothelial cell adhesion may be the limiting step in tumour cell binding to the endothelium.

A standardized procedure for quantification of the Ames Salmonella/mammalian-microsome mutagenicity test.

Factors determining the precision and variability of the Ames Salmonella test for mutagenicity were investigated. The most important source of variability in the agar-overlay method was nonuniformity in the soft-agar layer thickness. Solution of this problem resulted from application of an agar-leveling table described in this paper. Several other procedural elements also contribute to improved precision, including temperature uniformity during incubation, incubation interval, consistency of plate agar volume, completeness of mixing the soft-agar overlay, peculiarities in the interaction of mutagens and mammalian liver microsomal extract (S9), and methods of storage and controls for tester strains. When these and other effects were well-controlled, variability of the test results was reduced from 200 or 300% to only +/- 10% or less. The significance of the factors affecting precision are discussed and an improved experimental protocol is presented.