Acute hypercortisolism: what can the surgeon offer?

Rapid onset or acute hypercortisolism is a rare critical illness requiring emergency management. The majority of patients will have underlying malignancy with surgery an obvious choice in the minority with resectable disease. For those with unresectable disease, medical management alone has been the traditional approach. However, this often proves inadequate raising interest in the role of surgery as palliation in this setting. Patient selection, timing of surgery and optimal surgical technique are areas of current controversy with little literature available to provide answers. Decisions regarding management of patients with acute hypercortisolism are complex, and these patients are best managed in a subspecialized setting.

Radioactive seed localization compared with wire-guided localization of non-palpable breast carcinoma in breast conservation surgery- the first experience in the United Kingdom.

OBJECTIVE: In the UK, guidewires have traditionally been used for localization of non-palpable breast lesions in patients undergoing breast conservation surgery (BCS). Radioactive seed localization (RSL) using Iodine-125 seeds is an alternative localization method and involves inserting a titanium capsule, containing radioactive Iodine-125, into the breast lesion. We aim to demonstrate feasibility of RSL compared with guidewire-localization (GWL) for BCS in the UK. METHODS: Data were collected on 100 patients with non-palpable unifocal invasive carcinoma of the breast undergoing GWL WLE prior to the introduction of RSL and the first 100 patients treated with RSL WLE. Statistical comparisons were made using Χ2-squared analysis or unpaired two-sample t-test. Significance was determined to be at p ≤ 0.05. RESULTS: Mean total tumour size was 19.44 mm (range: 5-55) in the GWL group and 18.61 mm (range: 3.8-59) in the RSL group (p = 0.548), while mean total specimen excision weight was significantly lower in the RSL group; 31.55 g (range: 4.5-112) vs 37.42 g (range: 7.8-157.1) (p = 0.018). Although 15 patients had inadequate surgical resection margins in the GWL group compared the 13 in the RSL group (15 vs 13%, respectively, p = 0.684), 10 of the patients in the GWL group had invasive carcinoma present resulting in at least one positive margin compared with only 3 patients in the RSL group (10 vs 3%, respectively, p = 0.045). CONCLUSION: In this study, RSL is shown to be non-inferior to the use of GWL for non-palpable carcinoma in patients undergoing BCS and we suggest that it could be introduced successfully in other breast units. Advances in knowledge: Here we have demonstrated the use of RSL localization results in significant lower weight resection specimens of breast carcinoma when compared with a matched group using GWL, without any significant differences in oncological outcome between the groups.

Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy.

OBJECTIVES: Minichromosome maintenance protein 2 (Mcm-2) is essential for DNA replication and serves as a useful biomarker of cell-cycle state in human tissue samples. Ki-67 is an established proliferation marker. Because Mcm-2 expression has not previously been assessed in thyroid tissue, the aim of this study was to assess the expression of both proteins in a range of thyroid lesions to determine their potential value as preoperative markers of thyroid malignancy. METHODS: Mcm-2 and Ki-67 protein expression were assessed by immunohistochemistry in formalin-fixed, paraffin-embedded thyroid tissues from 128 patients with histologic diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 22), follicular adenoma (n = 33), and dominant nodules of multinodular goitre (n = 35). RESULTS: Mcm-2 and Ki-67-labeling indices (LIs) were both higher in follicular and papillary carcinomas than in follicular adenomas or dominant nodules. The Ki-67 LI discriminated better between follicular carcinomas and follicular adenomas (P < .0001) than Mcm-2 (P = .0273). However, the Mcm-2 and Ki-67 LIs overlapped widely between the four histologic groups, and the expression of these proteins was also noted to be heterogenous within these lesions. CONCLUSION: Neither Mcm-2 or Ki-67 can currently be reliably applied as preoperative markers to distinguish benign from malignant thyroid lesions.

Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasia.

We report what we believe to be the first case of a patient with multiple endocrine neoplasia type 2A (MEN 2A) and renal dysplasia associated with an RET 634 mutation. The proband presented at the age of 29 with medullary thyroid carcinoma (MTC), bilateral pheochromocytomas, and primary hyperparathyroidism. Screening of family members identified the syndrome in his father. Both the proband and his father carry RET 634 germline mutation resulting in cysteine to arginine amino acid substitution. The proband had a left nephrectomy at the age of 10 years. Histologic examination of the resected kidney revealed severe dysplasia. His father had normal renal tract on ultrasonography. The proband's clinical presentation was unusual, and initially thought to be an atypical pneumonia. Surgical management after pharmacologic alpha- and beta-blockage consisted of bilateral adrenalectomy, total thyroidectomy, and subtotal parathyroidectomy as a single procedure.

Estrogen regulates vesicle trafficking gene expression in EFF-3, EFM-19 and MCF-7 breast cancer cells.

Estrogens are critical mediators of breast tumorigenesis. This occurs via the action of estrogens on the estrogen receptor (ER), which regulates the transcriptome of breast cancer cells. Despite the long history of the search for estrogen-regulated genes in breast cancer, knowledge of the E2-regulated transcriptome and its effects is incomplete. We used Affymetrix GeneChips to profile the effects of estradiol on the expression of genes in EFF-3, EFM-19 and MCF-7 cells. In addition to many well-characterized estrogen-regulated genes, this identified a novel group of genes that have roles in vesicle trafficking, including exocytosis. Recent evidence in the literature supports a role for vesicle trafficking in tumorigenesis. We focused on five genes (SYTL5, RAB27B, SNX24, GALNT4 and SLC12A2/NKCC1/BSC2) and confirmed their estrogen-regulation using quantitative real-time PCR (qPCR). qPCR also demonstrated that these five genes were expressed in invasive breast carcinoma tissue. Immunohistochemistry showed expression of SYTL5 in cells of normal breast ductal epithelium, ductal carcinoma in-situ (DCIS) and invasive breast carcinoma. The results suggest that a significant effect of estrogens is to regulate the expression of genes that affect diverse aspects of vesicle trafficking including exocytosis.