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.

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.

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.

Long-term studies of the juxtaglomerular apparatus in young microalbuminuric type 1 diabetic patients.

AIM: To determine the long-term changes of the juxtaglomerular apparatus in incipient diabetic nephropathy. METHODS: Three renal needle biopsies were performed on 15 young type I diabetic patients with microalbuminuria; at baseline and after an average of 2.4 and 8.2 years. Using light microscopy, 1 microm serial sections of the plastic-embedded biopsies were investigated and volumes of the juxtaglomerular apparatus and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were measured. RESULTS: From baseline to second follow-up there was a significant decrease in JGA relative to glomerular volume. There was an increase in luminal area of the efferent arteriole which was paralleled by (non-significant) changes in the afferent arteriole. CONCLUSION: Over a period of 8.2 years JGA size remained stable, but decreased relative to glomerular size. Also, an increase in luminal area was noted in efferent arterioles. This may be due to increased single nephron blood flow secondary to nephron loss.

Renal arterioles in patients with type I diabetes and microalbuminuria before and after treatment with antihypertensive drugs.

Antihypertensive drugs can slow or even reverse the progression of diabetic nephropathy at the microalbuminuric stage. This study was performed to obtain quantitative data on changes in the renal arterioles in a follow-up study. Twelve patients with type I diabetes and with microalbuminuria were allocated to treatment for 3 years with either an ACE inhibitor (group I, 6 patients) or a beta blocker (group II, 6 patients). Baseline and follow-up renal needle biopsy specimens were taken and serially sectioned at 1 microm for light microscopy, enabling identification of arterioles as afferent or efferent. Thin sections for electron microscopy were made at 50-microm intervals, and micrographs were taken of arteriolar profiles. Matrix volume fraction of the media and a calculated matrix thickness were obtained. At baseline, structural parameters were higher than normal values. At follow-up all patients were normoalbuminuric. Both groups showed only minor changes in arteriolar structures over 3 years. In the afferent arterioles in group II there was a significant increase in the matrix volume fraction of the media, and there was a tendency to an increase in matrix thickness in both groups. In the efferent arterioles there were no significant changes in parameters. There were no differences between the two groups in arteriolar structural changes from baseline to follow-up. Thus, this study shows a slight but significant matrix accumulation in the afferent arterioles during treatment with antihypertensive drugs. This may have implications for the progression to overt nephropathy, which indicates a need for more long-term studies of treatment with antihypertensive drugs in incipient nephropathy in type I diabetes.

Enlargement of the juxtaglomerular apparatus in insulin-dependent diabetes mellitus patients with microalbuminuria.

Kidney biopsies from 15 insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria were investigated to obtain quantitative data on the juxtaglomerular apparatus. The IDDM patients were young and normotensive with a mean duration of microalbuminuria of 2 years. Eight healthy kidney donors served as controls. Measurements taken by light microscopy, using 1-microm serial sections of epon blocks, included volumes of the juxtaglomerular apparatus and of glomeruli, areas of the macula densa and luminal area of the juxtaglomerular (afferent and efferent) arterioles at the level of the glomerular vascular pole. The volume of the juxtaglomerular apparatus was significantly larger in the IDDM group than in controls [6.08 (2.96-18.8) 10(4) microm3 vs 3.48 (1.84-5.21) 10(4) microm3, P=0.003, median and (range)], as was the volume of the juxtaglomerular apparatus relative to glomerular volume [1.89(1.28-4.21)% vs 1.48 (1.13-1.71)%, P=0.004]. The area of the macula densa was also larger in the IDDM patients (1370 microm2 vs 937 microm2, P=0.03). Luminal areas of the afferent and efferent arterioles and the ratio between them did not differ significantly between the two groups. In conclusion, the juxtaglomerular apparatus is enlarged more than would be expected from the glomerular hypertrophy in IDDM patients with microalbuminuria.

Chronic osteomyelitis mimicking sarcoma.

This report describes a rare case of chronic osteomyelitis in a 60 year old man mimicking a soft tissue sarcoma. Chronic osteomyelitis is an infrequent cause of a soft tissue mass and is usually diagnosed clinically by a combination of radiology and microbiology. Rarely, COM can mimic a primary bony neoplasm, but this is the first reported case where it mimicked a soft tissue sarcoma. The clinical, radiological, and histological appearances of this case will be discussed.

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.

The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria. Effect of antihypertensive treatment.

BACKGROUND: Our goal was to investigate the effect of antihypertensive drugs on the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with microalbuminuria. METHODS: Twelve patients were allocated to treatment with either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a beta-receptor blocker (group 2, six subjects). A comparable group of nine patients without antihypertensive treatment provided reference values (group 3, nine subjects). Renal biopsies were taken at baseline and after a median of 40 months (groups 1 and 2) and 30 months (group 3). Using light microscopy with 1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were obtained. RESULTS: A significant decrease of the volume of the JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding glomerulus (P=0.0005) was noted in the reference group only. Negative correlations existed between the increase in the luminal area of the afferent arteriole and mean diastolic blood pressure in the study period in group 1 (P=0.024) and group 2 (P=0.032). CONCLUSIONS: Our results showed that a decrease in the size of the JGA is offset by antihypertensives. The negative correlation between the change in the luminal area of the afferent arteriole and mean diastolic blood pressure in groups 1 and 2 suggest that renal protection in antihypertensive treatment may be through a better constriction of the afferent arteriole protecting the glomerulus from systemic blood pressure.

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.