Linear IgA disease associated with ulcerative colitis: the role of surgery.

The association of linear IgA disease (LAD) with ulcerative colitis (UC) is well documented. One hypothesis for the association proposes immune exposure to autoantigens present in the colon, and subsequent targeting of these autoantigens in the skin. There are variable reports on the effect of bowel surgery on skin disease in such patients. We report a patient with LAD and UC who required colectomy to control her UC, but whose skin disease failed to resolve following surgery. A literature review revealed that in reported cases of this association, proctocolectomy has resulted in remission of skin disease in all cases where it has been performed, in contrast to variable results seen in cases where colectomy alone was performed.

The surgical management of Spitz naevi and atypical spitzoid neoplasms: A review of the literature.

Melanocytic lesions with spitzoid differentiation represent a difficult management paradigm. Spitzoid lesions form a spectrum of distinct entities encompassing Spitz naevi, atypical Spitz naevi and spitzoid melanoma which range from benign to malignant. Differentiation between benign and malignant lesions can be challenging making surgical management difficult. In this article we highlight clinical conundrums regarding Spitz naevi. We review the literature in terms of the newer histological tools available to more explicitly classify these lesions which may have an impact on the clinical care that these patients receive. The article also examines the controversy which surrounds the role of sentinel lymph node biopsy (SLNB) and completion lymph node dissection in the management of melanocytic proliferations with Spitz differentiation.

Acute ischaemic colitis in a young woman.

Although rare in young patients, acute ischaemic colitis can have devastating consequences. We detail the presentation and clinical course of a severe, progressive case of this disease related temporally to the recent ingestion of a sibutramine-containing herbal slimming agent procured on-line without prescription or medical indication in a young female that ultimately required emergency laparoscopic total colectomy with end ileostomy to prevent end organ failure.

PEA3/ETV4-related transcription factors coupled with active ERK signalling are associated with poor prognosis in gastric adenocarcinoma.

BACKGROUND: Transcription factors often play important roles in tumourigenesis. Members of the PEA3 subfamily of ETS-domain transcription factors fulfil such a role and have been associated with tumour metastasis in several different cancers. Moreover, the activity of the PEA3 subfamily transcription factors is potentiated by Ras-ERK pathway signalling, which is itself often deregulated in tumour cells. METHODS: Immunohistochemical patterns of PEA3 expression and active ERK signalling were analysed and mRNA expression levels of PEA3, ER81, MMP-1 and MMP-7 were determined in gastric adenocarcinoma samples. RESULTS: Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in gastric adenocarcinomas. PEA3 is upregulated at the protein level in gastric adenocarcinomas and both PEA3/ETV4 and ER81/ETV1 are upregulated at the mRNA level in gastric adenocarcinoma tissues. This increased expression correlates with the expression of a target gene associated with metastasis, MMP-1. Enhanced ERK signalling is also more prevalent in late-stage gastric adenocarcinomas, and the co-association of ERK signalling and PEA3 expression also occurs in late-stage gastric adenocarcinomas. Furthermore, the co-association of ERK signalling and PEA3 expression correlates with decreased survival rates. CONCLUSIONS: This study shows that members of the PEA3 subfamily of transcription factors are upregulated in gastric adenocarcinomas and that the simultaneous upregulation of PEA3 expression and ERK pathway signalling is indicative of late-stage disease and a poor survival prognosis.

Analysis of trends and seasonal variation in primary cutaneous melanoma: an Irish study.

A seasonal variation in the presentation of cutaneous melanoma has been documented in several studies. We performed a retrospective review of primary cutaneous melanomas (n = 263) from our institution to examine whether the seasonal patterns of presentation noted in the literature would be similar in Ireland, a climate with low ambient sunshine. A summer : winter ratio was determined for age, gender, subtype, location and Breslow thickness. We found an increase in total numbers of melanomas, particularly in men. The summer : winter ratio was 2.39 for all patients (95% CI 1.60-3.57, P < 0.001), with seasonal variations noted for location, thickness and subtype (excluding lentigo). Melanomas presenting over the summer tended towards a greater Breslow thickness than did those presenting in winter. This subclassification of primary cutaneous melanoma with summer : winter ratios based on patient and tumour characteristics gave remarkably similar results to previously published reports, notwithstanding the low levels of annual ambient sunshine in Ireland.

A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

Nephrogenic systemic fibrosis.

Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland's experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition.

Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phospho-isoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelial-mesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelial-mesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer.

Mycobacterium marinum infection complicating Crohn's disease, treated with infliximab.

Tumour necrosis factor-alpha inhibitors including infliximab are often used to treat a number of recalcitrant medical conditions. These agents are increasingly associated with infections, particularly mycobacterial infections. We report sporotrichoid spread of Mycobacterium marinum in a 37-year-old woman with Crohn's disease, who had been receiving infliximab infusions for 2 years. An infection had spread up the right leg, after she had been swimming on holiday in the Canary Islands. M. marinum was cultured from the lesions and also identified by PCR on formalin-fixed tissue. To our knowledge, this is the first report of M. marinum occurring in a patient receiving infliximab.

Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer.

The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management.

Telomerase activity in proximal and distal gastric neoplastic and preneoplastic lesions using immunohistochemical detection of hTERT.

BACKGROUND: The incidence of distal (corpus and antrum) gastric adenocarcinoma is decreasing with a simultaneous increase in incidence of proximal (cardia) adenocarcinoma. Epidemiological studies suggest that they may represent different diseases but corroborative molecular data are scarce. Intestinal metaplasia may have a lower malignant potential in the proximal stomach but regardless of the locations, its specificity as a predictor of carcinoma is low. AIMS: The aim of this study was to establish whether human telomerase reverse transcriptase expression differs at various points in proximal versus distal gastric carcinogenesis and to test the utility of human telomerase reverse transcriptase expression as a marker of cancer risk in intestinal metaplasia. MATERIAL AND METHODS: Wax-embedded tissue from proximal and distal stomach including normal mucosa (n=86), intestinal metaplasia (n=83) and carcinoma (n=101) were used and slides were immunostained for human telomerase reverse transcriptase and pRb and scored semi-quantitatively. RESULTS: The results showed that in both proximal and distal stomach, human telomerase reverse transcriptase expression rates increased from normal mucosa to cancer. High rates of human telomerase reverse transcriptase expression were seen in the proliferative zones of glands in intestinal metaplasia. In both the locations, loss of pRb expression correlated with higher human telomerase reverse transcriptase expression. CONCLUSIONS: In conclusion, telomerase activity appears to be an early event in both proximal and distal gastric carcinogenesis and human telomerase reverse transcriptase is expressed in intestinal metaplasia. Telomerase re-expression may be facilitated by pRb inactivation.

Miniature tissue microarrays for HercepTest standardisation and analysis.

AIMS: To assess the practicality of using a miniature tissue microarray (TMA) with several examples of each HercepTest score from 0 to 3+ as a control for routine HercepTest immunohistochemistry. METHODS: A TMA was constructed from in house cases of breast cancer where HercepTest on the whole sections showed scores 0, 1+, 2+, or 3+. The TMA, which measured 5 x 5 mm, was designed with four rows (each representing scores 0, 1+, 2+, and 3+), with five 0.6 mm cores from separate cases. In all, 20 individual cases were represented and the TMA took less than one hour to construct. Fifty sequential 4 microm sections were cut from the TMA to maximise the number of available sections. They were stored at 4 degrees C for 1-270 days and when a case needed HercepTest staining the section was added to the TMA tissue control slide. RESULTS: All slides contained tissue spots and immunohistochemical staining was consistent throughout the time period. CONCLUSIONS: The miniature TMA with examples of all HercepTest scores described here is an ideal tissue control and can be used as a visual reference for scoring a case. Slides stored at 4 degrees C could be used for up to 270 days.

Cytokeratin 7/20 and mucin expression patterns in oesophageal, cardia and distal gastric adenocarcinomas.

AIMS: The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ. METHODS AND RESULTS: Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage. CONCLUSIONS: CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.