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Stewart C.J.R.,King Edward Memorial Hospital | Mccluggage W.G.,Belfast Health and Social Care Trust

Invasion is a defining feature of malignancy, but the mechanisms of invasion in many common cancers, including gynaecological malignancies, remain unclear. However, it has been proposed that malignant cells may usurp a normal embryological process, epithelial-mesenchymal transition (EMT), as a means of acquiring migratory capacity. The synergistic role of the tumour microenvironment in EMT induction has also been explored and helps to explain the spatially restricted distribution of EMT at the deep tumour margin (invasive front). Furthermore, tumour cells undergoing EMT may acquire cancer stem cell characteristics, and this may be relevant to the entire metastatic process and to tumour recurrence and treatment failure. Nevertheless, doubts persist regarding the role of EMT in malignant progression in vivo, partly because few studies have correlated molecular and histological alterations in clinical pathology specimens. In the current review we summarize the evidence for EMT in the common gynaecological epithelial malignancies, and discuss the morphological and immunohistochemical changes occurring at the invasive tumour front that may represent EMT-like processes. The possibility that carcinosarcomas represent a variant type of EMT with 'fixed' mesenchymal differentiation is also considered. Diagnostic histopathologists are ideally placed to critically evaluate the role of EMT in gynaecological and other types of malignancy. © 2012 Blackwell Publishing Limited. Source

Raha S.,P D Hinduja Hospital | Shah U.,King Edward Memorial Hospital | Udani V.,P D Hinduja Hospital
Epilepsy and Behavior

Aim: The aims of this study were to assess the cognitive and behavioral problems of patients with Epilepsy with Electrical Status Epilepticus in slow sleep (ESES) and related syndromes and to review their EEG (electroencephalography) findings and treatment options. Results: Fourteen patients with ESES were evaluated and treated in 2010. Nine children had continuous spike and wave during slow-wave sleep (CSWS)/ESES syndrome, 3 had Atypical BECTS (benign epilepsy with centrotemporal spikes), 1 had Opercular syndrome, and 1 had Landau-Kleffner syndrome. The duration of ESES ranged from 6 to 52. months. Eleven (91%) children had behavioral issues, most prominent being hyperactivity. Seven of the 13 children (53%) showed evidence of borderline to moderate cognitive impairment. A total of 28 EEG findings of ESES were analyzed for SWI (spike-wave index). Antiepileptic drugs received by the patients included valproate, clobazam, levetiracetam, and others. Eleven patients had been treated with oral steroids and it was found to be efficacious in seven (63%). Conclusion: Disabilities caused by ESES affect multiple domains. Patients with an SWI > 50% should be followed up frequently with neuropsychological assessments. Steroids appear to be effective, although there is a need to standardize the dose and duration of treatment. © 2012 Elsevier Inc. Source

Stewart C.J.R.,King Edward Memorial Hospital | Leung Y.C.,University of Western Australia | Whitehouse A.,Sullivan Nicolaides Pathology

Aims: To determine the frequency and distribution of Fallopian tube involvement in patients with ovarian metastases of non-gynaecological origin. Methods and results: All Fallopian tube tissue was processed for histological examination in a consecutive series of 31 patients with ovarian metastases of non-gynaecological origin. The most common primary sites were appendix (n=10) colon (n=7), stomach (n=6) and breast (n=4). Twenty cases (65%) showed at least one type of tubal spread. Mural involvement was most common (14 cases) but serosal, intra-vascular, intra-epithelial and intra-lumenal spread were also identified in 12, 9, 8 and 11 cases respectively. Intra-epithelial involvement was restricted to the fimbrial epithelium and mimicked tubal carcinoma in situ (CIS) architecturally. Pagetoid invasion was noted in two of the cases. Conclusions: The Fallopian tubes are commonly involved in patients who have neoplasms metastatic to the ovaries. Metastases may show a CIS-like pattern of intra-epithelial spread and therefore small serous CIS-type lesions may not represent proof of tubal tumour origin in patients who have high-stage pelvic serous carcinomas. The frequency of intra-lumenal tumour cells supports transtubal spread as a likely mechanism for mucosal involvement by metastatic tumours involving the lower genital tract. © 2012 Blackwell Publishing Ltd. Source

Shah N.S.,King Edward Memorial Hospital
Advances in Experimental Medicine and Biology

Abstract Triple-A syndrome is characterized by triad of adrenocorticotrophic hormone (ACTH)- resistant adrenal insufficiency, alacrimia and achalasia cardia. It is a rare disease and inherited by autosomal recessive pattern. Allgrove syndrome is characterized by mutation(s) in AAAS gene, located on chromosome 12q13, that codes for ALADIN protein. Most mutations produce a truncated protein, although missense and point-mutations have also been reported. Some patients with Triple-A syndrome may not have mutations in AAAS gene; in those there is no specific genotype-phenotype correlation. Although alacrimia is not the usual presenting manifestation, probably it is the earliest and most consistent feature. Achalasia cardia and adrenal insufficiency are the early and usual presenting manifestations. Neurological features appear at later age and autonomic manifestations are the most common neurological disorder. Polyneuropathy, amyotrophy, optic atrophy are the other common neurological problems. Alacrimia is diagnosed by Schirmer's test while ahalasia cardia and adrenal insufficiency are best diagnosed by esophageal monometry and ACTH stimulated cortisol levels respectively. Alacrimia is treated with artificial tears while achalasia cardia with either pneumatic dilatation or Heller's myotomy. Adrenal insufficiency is treated with glucocorticoid and if necessary mineralocorticoid replacement. © 2010 Landes Bioscience and Springer Science+Business Media. Source

Little L.,King Edward Memorial Hospital | Stewart C.J.R.,King Edward Memorial Hospital
Modern Pathology

It may be difficult to distinguish reactive glandular lesions from adenocarcinoma in situ of the uterine cervix, and although several immunohistochemical markers have established value in this diagnostic setting, none is completely reliable. We have noted that neoplastic endocervical lesions often show loss of nuclear cyclin D1 expression in contrast to benign glandular cells. Therefore, we investigated cyclin D1 staining in a series of 64 cervical biopsy specimens including examples of normal and reactive endocervical epithelium, adenocarcinoma in situ, stratified mucin-producing intraepithelial lesions, and invasive adenocarcinoma. Thirteen specimens also included a component of high-grade cervical squamous intraepithelial neoplasia. Normal endocervical epithelium usually expressed cyclin D1, although staining was typically focal, and there was increased immunoreactivity in reactive and metaplastic glandular cells including tubo-endometrioid metaplasia. In contrast, most cases of adenocarcinoma in situ were completely negative and, therefore, cyclin D1 staining distinguished benign from neoplastic epithelial cells. Although focal cyclin D1 expression was observed in 5/19 cases of adenocarcinoma in situ, the staining was associated with more marked cytological atypia precluding confusion with a reactive process. The invasive adenocarcinomas were mainly negative for cyclin D1. However, focal staining was observed in 10/19 cases and was mainly restricted to cells at the deep tumor margin, or to small infiltrative glands and detached cell clusters within the stroma. In conclusion, cyclin D1 can be included within an immunohistochemical panel to aid in the distinction between reactive cervical glandular lesions and adenocarcinoma in situ. The localized distribution of staining within invasive lesions suggests that cyclin D1 up-regulation has a specific role during the progression of some endocervical adenocarcinomas. © 2010 USCAP, Inc. All rights reserved. Source

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