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Papillary thyroid carcinoma (PTC) is frequently multifocal (mPTC), with synchronous tumour foci often showing varied morphology. The genetic mechanisms underlying the development of multiple and histologically diverse tumour foci remain uncertain. Different tumour foci might develop either through intrathyroidal dissemination of a single malignant clone, with morphotype differentiation occurring as a result of subclonal progression, or they may stem from independent transformational events involving multiple progenitor clones. To determine the clonal derivation of multiple tumour foci and to map their clonal relationships and genetic progression in mPTC, we evaluated genome-wide allelic imbalances (AI) and BRAF V600 E mutation status in 55 synchronous tumour foci from 18 mPTC patients. For apparently monoclonal tumours, we calculated the probabilities of monoclonal derivation and used phylogenetic analysis to model clonal evolution. Genome-wide allelotyping and BRAF mutation analysis showed genetic alterations consistent with monoclonal origin in 83% of cases, mostly with evidence of subclonal evolution. BRAF V600 E mutations were early events during clonal evolution of most, but not all cases. MPTC with morphologically diverse tumour foci also arose through monoclonal derivation in 75% of cases, demonstrating that morphotype-determining genetic changes can be acquired during clonal diversification, subsequent to the spread of the original malignant progenitor clone. In 17% of patients, discordant AI or BRAF V600 E profiles implied that mPTCs can occasionally develop from distinct transformation events. This study suggests that mPTC originates usually from neoplastic transformation and subsequent intrathyroidal spread of a single malignant progenitor clone. Clonal progression and morphotype differentiation occur through progressive acquisition of genetic alterations subsequent to the initial intra-glandular spread. In monoclonal BRAF V600 E-positive mPTCs, BRAF V600 E is not always present in all tumour foci, indicating that other tumour-genetic factors in the primary progenitor clone can also trigger PTC neoplastic transformation. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Allele frequency distributions of the HLA-DRB1 and HLA-DQB1 genes were investigated in four Pacific Islands populations from the Cook Islands, Samoa, Tokelau and Tonga. Limited diversity was observed for both the HLA-DRB1 and HLA-DQB1 loci. Five HLA-DRB1 alleles were observed to be the most frequent amongst all the studied Pacific Islands populations. They were: HLA-DRB1*0403, HLA-DRB1*08032, HLA-DRB1*09012, HLA-DRB1*11011 and HLA-DRB1*1201. Cook Islanders had the largest number of low frequency DRB1 alleles followed by Samoans, Tokelauans and Tongans, most of which may be attributed to reported non-Polynesian admixture. The most frequently observed DQB1 alleles in the four studied Pacific Islands populations were those of the DQ3 subgroup of alleles HLA-DQB1*03011, HLA-DQB1*0302 and HLA-DQB1*03032 as well as HLA-DQB1*05031 and HLA-DQB1*06011. Cook Islanders had the highest number of rare HLA-DQB1 alleles, the distibution being similar to that of the HLA-DRB1 allele. While, in general, the values of homozygosity for DRB1 and DQB1 were observed to be lower then expected under neutrality, a statistical significance was observed in Tongans, Samoans and Tokelauans for the DQB1 locus and in Tongans for the DRB1 locus. Differences were observed between allele frequency distributions for Tokelauans compared to the other three populations. This was also demonstrated by principal component analysis of DRB1 and DQB1 allele frequencies, which separated the Tokelauan population from Cook Islanders, Tongans and Samoans. Tongans and Samoans were separate from the other Polynesian populations in the phylogenetic trees. Observed allele and haplotype frequencies were found to be in agreement with previously published HLA-DRB and HLA-DQB Polynesian data. [ABSTRACT FROM AUTHOR]

Objective To determine the clinical significance of nondiagnostic small acini showing cellular atypia (atypical small acinar proliferation) in prostatic biopsies of patients with clinical findings suggestive of malignancy. Patients and methods Of 331 patients who underwent thin-core biopsy of the prostate over a 30-month period, 21 (6.3%) had atypical histological features, and of these 17 underwent repeat biopsy. In addition, a further 20 patients with normal histology underwent repeat biopsy for persistent abnormal clinical findings. The incidence and Gleason score of carcinomas subsequently diagnosed in the two groups were compared. The predictive significance of patient age, prostate specific antigen (PSA) level and digital rectal examination (DRE) findings were compared between both patient groups, those in each group subsequently found to have carcinoma, and between patients with malignant or normal repeat biopsies who had either atypical or normal initial biopsies. Results Nine patients with atypical histology and four with normal histology on initial biopsy were found to have carcinoma on subsequent biopsy (P = 0.036). The site of carcinoma diagnosed in the repeat biopsy frequently differed from that of the initial atypical biopsy. The Gleason primary pattern was not significantly different between the groups. Neither patient age, PSA level nor DRE findings differed between patients with initial normal or atypical biopsy, or in these groups for those in whom carcinoma was subsequently diagnosed. These clinical features did not distinguish between those with carcinoma or normal findings on repeat biopsy who had an initial atypical biopsy, while only PSA level varied significantly in patients with normal or malignant repeat biopsy in the group with an initial normal biopsy. Conclusion The presence of atypia on initial biopsy is a strong predictor of malignancy in subsequent biopsy specimens. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between tumour vascularity and patient survival in a series of clear-cell renal cell carcinoma (RCC), which often metastasizes via the vascular route and frequently has a prominent vascular network. Materials and methods Vessels were labelled in sections from 150 cases of clear cell RCC by factor VIII immunohistochemistry. The mean microvessel density (MMD), expressed as the number of vessels per 10 high-power fields (HPFs, ×400, aggregate field area 1.452 mm2 ) and tumour microvessel area (TMA), expressed as the percentage of the total tumour area within 10 HPFs, were measured for each case. The relationship between MMD and TMA, tumour stage and grade, and patient survival over a 5-year follow-up was determined. Results Tumour MMD ranged from 1 to 238 vessels per HPF, while the TMA was 1.2-60.8%. There was a weak but significant difference for MMD between tumour grades ( P<0.01) and stages ( P<0.05). There was no significant association between TMA and either tumour stage or grade. Division of cases according to MMD ≤40 and >40 per HPF showed a significant difference in survival curves between both groups, with a higher MMD being associated with longer patient survival. The significant association between MMD and survival was retained for stage 3 tumours only when cases were stratified according to Robson's stage at presentation. TMA did not correlate with survival. Conclusions The assessment of tumour vascularity is of prognostic significance for clear cell RCC. The significant inverse relationship between MMD and patient survival suggests that for tumours with a poor prognosis, decreased MMD is associated with tumour fibrosis and the development of large diameter vascular channels. [ABSTRACT FROM AUTHOR]

Objective To evaluate occupational risk factors for renal cell carcinoma. Subjects and methods A case control design was employed using data reported to the New Zealand Cancer Registry from 1978 to 1986 inclusive. The occupational risk for renal cell carcinoma was derived by comparison with the occupation of cases of non-urinary tract malignancy reported to the Registry over the same period. Results An active occupational code was derived for 86.2% of all cases and 98.9% (710) of male cases. In a series of case-control studies for selected occupational groups, adjusting for patient age and smoking history, a significantly increased relative risk for the development of renal cell carcinoma among firefighters (RR 4.89, 95% CI 2.47-8.93) and painters (RR 1.79, 95% CI 1.31-3.44) was demonstrated. Conclusion The data suggest that both firefighters and painters may be at an increased risk of developing renal cell carcinoma, which is likely to be of significance as both occupational groups are frequently exposed to known carcinogens. [ABSTRACT FROM AUTHOR]

Between 1960 and 1986, 177 cases of Wilms' tumour were reported to the New Zealand National Cancer Registry. There was an equal sex distribution and 93.2% of patients were in the paediatric age group with a mean age of 3.4 years. The mean symptom interval was 2.0 months and the majority of patients presented with localised disease, although the incidence of advanced disease was greater than that reported from other series. The 5-year survival rate for all cases was 52.5%. Data were divided into patients presenting before and after the publication of the first National Wilms'Tumour Study (NWTS) in the United States in 1976. In patients presenting after 1976 the diagnosis was based on histology in 100%, compared to 58.6% in patients before 1977. Treatment was considered curative in a greater proportion of the post-1976 group. Treatment modalities reflected the recommendations of the NWTS and the 5-year survival rate of this group was 78.3%, this being similar to that reported from the NWTS. Multivariate analysis showed patient age, symptom interval, tumour stage and treatment (pre- and post-NWTS) to be independent predictors of survival. [ABSTRACT FROM AUTHOR]

- The measurement of urinary flow rate by uroflowmetry and its relationship to voided volume and age have been extensively studied. It is well recognised that some men void with abdominal straining, but any effect of this on the urinary flow rate is usually not taken into account in urological practice. The aim of this study was to determine whether abdominal straining had any significant influence on the urinary flow rate. Three male volunteers performed multiple voidings either with or without abdominal straining. Statistical transformation of the data and the use of co-variant analysis allowed a comparison between 'normal' or passive voiding and voiding with abdominal straining. The results showed that abdominal straining caused a significant improvement in both the average and maximum urinary flow rate. If the effect of abdominal straining is not taken into account during the interpretation of uroflowmetry results, incorrect conclusions may be made which could influence subsequent management. It is suggested that the method of voiding should be standardised by instructing patients, if possible, to avoid abdominal straining during uroflowmetry assessment. [ABSTRACT FROM AUTHOR]

- Levels of volatile N-nitrosamines were measured in 10 brands of latex and 2 brands of silicone catheters using high performance liquid chromatography. The cytotoxicity of catheters from identical batches was determined by measuring the inhibitory effect of catheter extracts on the uptake of 3H-labelled thymidine into L-929 fibroblasts in culture (IC50). The most frequently encountered nitrosamines were N-nitrosodi-n-butylamine and N-nitrosodiethylamine. Total N-nitrosamine levels in excess of 100 ng/g were found in 6 of the 16 catheters tested. When compared with the cytotoxicity of the catheters a significant correlation was found, with increasing nitrosamine content being associated with greater cytotoxicity. In view of the reported toxic and carcinogenic effects of these compounds it is suggested that the nitrosamine content of catheters be routinely monitored and safe regulatory limits be imposed. [ABSTRACT FROM AUTHOR]

- The hydrogel-coated urinary catheter is a novel formulation in which the coating hydrogel polymer is claimed to reduce the level of cytotoxicity frequently associated with the use of latex catheters. This study was undertaken to measure cytotoxicity using in vivo techniques. Twelve first generation and 5 second generation hydrogel-coated latex catheters were evaluated in vivo using canine urethras. The results showed all catheters to cause minimal inflammatory changes of the urethral mucosa (toxicity score 0-1.2/6). [ABSTRACT FROM AUTHOR]

Objective: To determine whether serum antioxidant capacity measured by the electrochemical technique of cyclic voltammetry (CV) could resolve differences in severity of the inflammatory disease acute pancreatitis. Methods: Experimental animal study using male Wistar rats. Group 1 (baseline), immediate euthanasia with no surgical interventions; Group 2 (sham), identical surgical procedures to the pancreatitis groups but no intraductal infusion; Groups 3–5, acute pancreatitis induced by intraductal infusion of 3%, 4% or 5% sodium taurocholate respectively. Terminal blood and pancreatic tissue samples for CV, biochemistry and histology were collected at 12 h (Groups 2–5). Results: There was a significant positive correlation of the first serum cyclic voltametric peak current maxima (CVi1) with pancreatic histological severity (Spearman r = 0.51, p = 0.007) as well as with a number of other markers of systemic disease severity, notably bicarbonate (r =−0.57, p = 0.002), base excess (r =−0.65, p < 0.001) urea (r =−0.68, p < 0.001) and calcium (r =−0.60, p = 0.008). CVi1 was superior at indicating the severity of the disease state compared to a standard method of total antioxidant capacity measurement. Conclusions: CV was found to be a simple, technique that could differentiate between the physiological and histological severities of acute pancreatitis. Further clinical studies are now justified to determine if point-of-care CV offers prognostic and treatment-monitoring advantages for severe acute inflammatory illnesses within the critical care setting. [ABSTRACT FROM AUTHOR]

Discusses the immunohistochemical evidence of mesothelial cell origin for a series of paratesticular adenomatoid tumors. Immunohistochemical phenotypic profile of the epithelioid component of acinar and solid adenomatoid tumors; Description of calretinin staining of the tumor; Nature of the stromal compartment.