Correlation between adenoma detection rate and polyp detection rate at endoscopy in a non-screening population.

It is understood that colorectal adenomas progress to colonic adenocarcinoma. Adenoma detection rate (ADR) at endoscopy has been used as a key performance indicator at endoscopy and is inversely associated with diagnosis of interval colorectal cancer. As most endoscopy reporting systems do not routinely incorporate histological assessment, ADR reporting is a cumbersome task. Polyp Detection Rate (PDR) has therefore been adopted as a surrogate marker for ADR. A prospectively maintained database of colonoscopies performed between July 2015 and July 2017 was analysed. This was cross referenced with a histological database. Statistical analysis was performed using IBM SPSS, version 24. Inferential procedures employed included the Pearson's correlation coefficient (r) and Binomial logistic regression. Of 2964 procedures performed by 8 endoscopists, overall PDR was 27% and ADR was 19%. The PDR, ADR, adenoma to polyp detection rate quotient (APDRQ) and estimated ADR (PDR x APDRQ group average = 0.72) was calculated for each individual. There was a strong positive linear correlation between PDR and ADR,r(8) = 0.734, p = 0.038 and between PDR and estimated ADR, r(8) = 0.998, p < 0.001. Adenoma detection rate strongly correlated with estimated ADR, r(8) = 0.720, p = 0.044. With the exclusion of a moderate outlier, these correlations increased in both strength and significance. There was a stronger correlation between PDR and ADR,r(7) = 0.921, p = 0.003 and between ADR and estimated ADR, r(7) = 0.928, p = 0.003.

Distance as a Barrier to Melanoma Care

Aim Our aim was to review cases of melanoma diagnosed histologically in UHK in 2016 and to compare them to cases of melanoma nationally and in Kerry. Methods For each patient we recorded age, Breslow depth, and shortest distance to travel by car and travelling time (without traffic) to the South Infirmary Victoria University Hospital (SIVUH) from their primary residence (calculated using Google maps™ (2018)). Results 20 cases of invasive melanoma were diagnosed in UHK in 2016. Of the 20 cases, 9 (45%) presented at a very advanced stage with a Breslow depth of greater than 4mm. A further 7 (35%) cases had a depth of 1.5-4mm. These patients with invasive melanoma had a mean age of 72.5 (±15). The mean shortest distance to travel from the patient's primary residence to the SIVUH was 114.8km (±15.5) taking an average of 102 minutes (±14.6) by car. Conclusion Cases of melanoma diagnosed locally in UHK presented at an advanced stage compared to the national average. We suspect that the long distances to travel to the SIVUH pigmented lesion clinic is a barrier for these patients.

Ecological character displacement alters the outcome of priority effects during community assembly.

Character displacement may facilitate species coexistence through niche partitioning. However, the degree to which character displacement influences broader patterns of community assembly is unclear. Here, we capitalize on a natural experiment of community assembly on the oceanic island of Bermuda. Over the past century, three species of ecologically similar but distantly related Anolis lizards have been introduced to Bermuda where no Anolis has ever naturally existed. The Jamaican anole (A. grahami) arrived first in 1905 and dispersed rapidly across the island. Five decades later, the Antiguan anole (A. leachii) and the Barbadian anole (A. extremus) were introduced to independent locations. In 1991, A. leachii and A. extremus were observed to nearly meet at a contact zone, but not yet to coexist. We record that subsequent range expansion at this contact zone has been asymmetrical; A. leachii invaded the range of A. extremus, but reciprocal invasion by A. extremus has not occurred. When in allopatry in Bermuda, both species occupy identical ecological space. However, A. leachii underwent rapid ecological character displacement to use arboreal habitat when invading the range of A. extremus. These findings highlight how character displacement may influence the process of dispersal and drive patterns of coexistence and community assembly.

Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma.

There is evidence that carcinoma in situ (CIS) is the precursor of invasive urothelial carcinoma, a tumour characterized by frequent gene promoter methylation. The timing of altered DNA methylation is unknown in this pathway. Here we investigate gene methylation in 196 consecutive samples of normal urothelium, CIS, and tumours from 104 patients with both CIS and invasive urothelial carcinoma using quantitative methyl-sensitive polymerase chain reaction for six genes (p16, p14, E-cadherin, RARbeta2, RASSF1a, and GSTP1). Control normal urothelial samples from 15 patients with no history of urothelial carcinoma were also analysed. Immunohistochemistry established the expression of well-characterized CIS markers p53 and cytokeratin 20. Promoter methylation occurred frequently in both normal urothelium and CIS samples from patients with urothelial carcinoma, and increased with progression from normal to invasive urothelial carcinoma, at both specific loci (chi2 test: E-cadherin, p=0.0001; RASSF1a, p=0.003, RARbeta2, p=0.007, p16, p=0.024) and in general (methylation indices [t-test, p<0.0001]). Methylation was associated with cytokeratin 20 expression (t-test, p=0.004) and poor prognosis, and with increased progression to tumour death in patients whose CIS samples showed methylation, in comparison with those without methylation (log rank p<0.03). Promoter methylation occurs early in the urothelial carcinogenic pathway and appears to be a good biomarker of the invasive urothelial carcinoma phenotype.

Activated eosinophils in nasal polyps: a comparison of asthmatic and non-asthmatic patients.

OBJECTIVES: There is a recognized clinical association between nasal polyps and asthma. Nasal polyps and the airways of asthmatic patients demonstrate marked eosinophilia suggesting that this inflammatory cell may have a key role to play in both conditions. The objective of this study was to determine whether nasal polyps from patients with asthma had a greater density of activated eosinophils than patients with no associated respiratory disease. DESIGN: Archived specimens were retrieved from patients who had undergone nasal polyp surgery and their case notes reviewed. Activated eosinophils were identified using immunohistochemistry for a monoclonal antibody to secreted eosinophil cationic protein (EG2). SETTING: Teaching hospital otolaryngology unit. PARTICIPANTS: Consecutive patients who had undergone nasal polyp surgery in 1994 were recruited. The diagnosis of asthma was based on a documented physician diagnosis and appropriate drug treatment. Twenty-four asthmatic and 35 non-asthmatic patients were studied. MAIN OUTCOME MEASURES: Eosinophil density was measured using a standardized counting technique. RESULTS: Asthmatic patients were significantly more likely to have had previous polyp surgery (chi-square test: P < 0.05). Areas of intense eosinophilia were identified in all samples. There was a significant greater degree of activated eosinophilia in the asthmatic patients (t-test: P < 0.05). CONCLUSIONS: We have demonstrated a higher number of previous operations in asthmatic patients, and also a greater degree of activated eosinophilia in asthmatic polyps compared with non-asthmatics. This would suggest that eosinophil activity has a role to play in the pathogenesis of nasal polyps.

Fine needle aspiration cytology in the management of a parotid mass: a two centre retrospective study.

OBJECTIVES: There is a diversity of opinion regarding the role of fine needle aspiration cytology (FNAC) in the pre-operative evaluation of the parotid mass. This study further investigates the role of FNAC from the standpoint of the clinician attempting to resolve one or more clinical issues. METHODS: A retrospective study conducted at two UK Hospitals with no overlap of cytopathologists or surgeons. Patients undergoing parotidectomy at each institution were identified from Pathology department databases. The definitive histopathological diagnosis was compared with any pre-operative FNAC diagnosis. Cytology results were classified as suggestive, non-diagnostic, sampling error, or misleading. SETTING: The study was conducted in a District General Hospital and a University Teaching Hospital providing secondary care for each community. RESULTS: For the University Teaching Hospital the sensitivity in distinguishing malignant from benign disease was 79% (95% CI 61-97%) with a specificity 84% (95% CI 73-95%). However, three of eight patients with a primary parotid salivary gland malignancy were reported as having benign disease on FNAC. For the participating District General Hospital the sensitivity in distinguishing malignant from benign disease was 38% (95% CI 13-63%) and specificity 95% (95% CI 73-95%). CONCLUSIONS: Fine needle aspiration cytology does not reliably distinguish a benign from a malignant primary salivary gland neoplasm in the participating institutions. Where clinical teams use FNAC in an attempt to resolve this clinical problem, the results should be interpreted with caution and an ongoing audit of performance is required.

A fatal case of disseminated zygomycosis associated with the use of blood glucose self-monitoring equipment.

We report a fatal case of disseminated zygomycosis due to Cunninghamella bertholletiae in a 68-year-old man with myelodysplasia and type II diabetes mellitus, receiving desferrioxamine therapy for iron overload secondary to multiple transfusions. It is thought that he acquired the infection through the use of blood glucose self-monitoring equipment.

[Promoter methylation and microsatellite mutation reveals the clonal relationship of multiple urothelial carcinomas with mutator phenotype]. / Promotor-hypermethylierung und Mikrosatelliten-Instabilität in multifokalen Urothelkarzinomen mit Mutator-Phänotyp.

AIMS: The clonality of multiple urothelial carcinomas (UC) is subject to debate and affects treatment. Evidence derived from X-chromosome mosaicism and patterns of molecular alterations supports both a mono- and polyclonal relationship. In contrast to most UC, tumours with the mutator phenotype have frequent mutations in repetitive sequences (MSI) and promoter methylation. The aim of this study was to investigate the clonality of multifocal UC with MSI. METHODS: We have screened 400 UC for MSI and found it to occur in 1% of bladder and 15% of upper tract UC. Of these, 9 patients, whose tumours had MSI, developed or presented with multiple UC. A total of 32 UC (occurring over 0-6 years, 2-12 TCC per patient), 2 cases of CIS and 9 normal urothelial samples were screened for MSI at 17 loci and aberrant promoter methylation at 7 genes. RESULTS: In 8 of 9 patients, the pattern of microsatellite mutation and promoter methylation suggested that the multiple tumours had a clonal origin. Patterns of aberrant methylation in multiple tumours were more similar than microsatellite mutations, suggesting an earlier carcinogenic timing. MSI and promoter methylation were present in macroscopically normal urothelium from these patients. CONCLUSIONS: Aberrant promoter methylation occurs before microsatellite alteration in UC with mutator phenotype. The majority of recurrent UC with MSI are monoclonal in origin and macroscopically normal urothelium harbours multiple molecular abnormalities. Thus, at the time of apparently successful treatment, there is molecular evidence of residual tumour that subsequently develops into recurrent disease.

Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: a pilot study.

OBJECTIVES: Serum prostate-specific antigen measurements are widely used for the early detection of prostate cancer but lack specificity, thus warranting the search for additional biomarkers. METHODS: Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis was used to investigate the protein profiles of voided urine after prostatic massage from 6 patients with histologically confirmed prostate cancer and 6 age-matched patients with benign prostatic hyperplasia. RESULTS: The median number of protein spots per gel was lower in the urine from the patients with cancer (median 143 spots, range 118 to 163) than in the urine from those with benign prostatic hyperplasia (median 154 spots, range 142 to 209), although the difference was not statistically significant. MALDI-TOF-MS analysis identified six commonly expressed proteins: alpha-enolase, isocitrate dehydrogenase, beta-2-microglobulin, alpha-1-microglobulin, complex-forming glycoprotein HC, and PRO2044. Of the five protein spots seen in a subset of patients with cancer, one was identified as calgranulin B/MRP-14. Immunohistochemical staining of prostatic tissue showed greater expression of calgranulin B/MRP-14 in 2 of 7 well-differentiated, 1 of 12 moderately differentiated, and 0 of 8 poorly differentiated tumors relative to adjacent benign tissue; expression of calgranulin A/MRP-8, a heterodermic binding partner of calgranulin B/MRP-14, was absent. CONCLUSIONS: The role of urinary calgranulin B/MRP-14 as a potential novel marker for prostate cancer needs additional investigation.

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non-asthmatic patients.

The cause of nasal polyps remains unknown, although there is a well-recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty-four asthmatic and 35 non-asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.

Audit of clinical and histological prognostic factors in primary invasive squamous cell carcinoma of the skin: assessment in a minimum 5 year follow-up study after conventional excisional surgery.

In an attempt to evaluate the prognostic factors for primary squamous cell carcinoma of the skin treated by conventional surgery, a 6 year (1990-1995) cohort comprising 171 patients was analysed. Of these 171 patients, 157 were confirmed as having been treated for invasive squamous cell carcinoma, of whom 64 (41%) died within 5 years of treatment from causes other than squamous cell carcinoma, and were therefore defined as indeterminate. The remaining 93 patients were determinate patients; 85 lived without recurrence or metastasis for at least 5 years after treatment, and eight died of their disease. Comparing the groups who were alive or had died of disease at 5 year follow-up, the tumour diameter and tumour thickness were significantly greater in the eight patients who died (P = 0.02 and P = 0.0057, respectively) but there were no significant differences between the two groups with regard to age, deep resection margin clearance, lateral epidermal resection margin clearance, lymphocyte response or degree of tumour differentiation. This study defines the 5 year follow-up outcome following conventional surgery for squamous cell carcinoma of the skin, related to histological parameters, which, if routinely reported, would allow valid comparisons to be made between differing primary therapies.

Offline telepathology diagnosis of colorectal polyps: a study of interobserver agreement and comparison with glass slide diagnoses.

BACKGROUND/AIMS: Technological advances have produced telepathology systems with high quality colour images and reasonable transmission times. Most applications of telepathology have centred on the remote diagnosis of frozen sections or remote real time expert opinions. This study investigates the reproducibility and accuracy of offline telepathology as a primary diagnostic medium for routine histopathology specimens. METHODS: One hundred colorectal polyps (50 hyperplastic, 50 adenomatous) were presented in a randomised order to five histopathologists as offline images on a telepathology workstation. Six images of each case were used: the slide label, a low power scan of all material on the slide, and four higher magnification views. The times taken to prepare the images, and to make the diagnoses, were recorded. Interobserver agreement was measured with kappa statistics and compared with the glass slide diagnoses. RESULTS: The kappa statistics for the interobserver agreement on the telepathology images lay in the range of 0.90-1.00, which is interpreted as excellent agreement, and were significantly higher than those for the glass slide diagnoses (range, 0.84-0.98; p = 0.001). The median time taken to capture the images for a case was 210 seconds. The median time taken to make a diagnosis from the telepathology images was five seconds, which was significantly shorter than for the glass slide diagnoses (median, 13 seconds; p < 0.0005). CONCLUSIONS: Offline telepathology has the potential to be a primary diagnostic medium for routine histopathology with a high degree of reproducibility and short diagnosis times. Further studies are required to validate offline telepathology for different types of specimens and different operators of the image capture system.

Hormone replacement therapy and the endometrium.

Modern hormone replacement therapy (HRT) regimens contain oestrogen and progestogen, given either in a cyclical or continuous combined manner. Most endometrial biopsies from women on sequential HRT show weak secretory features. Approximately 15% show proliferative activity, although this figure may be less if more than nine days of progestogen is given in each cycle. A small proportion will show an inactive or atrophic endometrium. Up to 50% of biopsies from women on continuous combined HRT contain minimal endometrial tissue for histopathological analysis: this correlates well with an atrophic endometrium with no appreciable pathology. Of the 50% with more substantial material, approximately one half will show endometrial atrophy, and one half will show weak secretory features. Proliferative, menstrual, and pseudodecidual changes are rare. Approximately 20% of women given unopposed oestrogen for one year develop endometrial hyperplasia. The relative risk of endometrial carcinoma is two to three. This is dramatically reduced by the addition of progestogen to the regimen, but cyclical progestogen as part of a sequential HRT regimen does not completely eliminate the risk of carcinoma. The prevalence of endometrial hyperplasia associated with sequential HRT is 5.4%, and that of atypical hyperplasia (endometrial intraepithelial neoplasia) is 0.7%. Continuous combined HRT is not associated with the development of hyperplasia or carcinoma, and may normalise the endometrium of women who have developed complex hyperplasia on sequential HRT. The probability of a histopathologist finding clinically relevant pathology in an endometrial biopsy specimen of a patient on HRT is low and is more likely to be a manifestation of pre-existing disease.

Precursor lesions of ovarian epithelial malignancy.

Most ovarian carcinomas arise from the mesothelial surface lining of the ovaries, or from invaginations of this lining into the superficial ovarian cortex to form cortical inclusion cysts. The native ovarian surface mesothelium is of an 'uncommitted' phenotype, and has potential to modulate to epithelial or mesenchymal phenotypes in response to signals such as those associated with ovulation. The exposure of the mesothelial lining of an inclusion cyst to the ovarian stromal microenvironment may be responsible for the phenotypic change to Müllerian epithelium so commonly seen in these cysts. Müllerian metaplasia is usually to a serous phenotype, and it is possible that undefined molecular events occurring in an inclusion cyst that has undergone Müllerian metaplasia may initiate neoplastic change in these cysts. This may be the developmental pathway of most invasive serous carcinomas. Occasional rare cases of ovarian intraepithelial neoplasia, manifested by epithelial atypia in an inclusion cyst or on the surface epithelium without invasive carcinoma, are identified histologically. Serous borderline tumours represent a separate category and in most cases probably do not progress to frank carcinoma. Mucinous carcinomas may in some cases have arisen from pre-existing benign and borderline mucinous tumours. Endometriosis of the ovary is associated with genetic abnormalities and is frequently found in association with clear cell and endometrioid carcinomas, suggesting that in many cases these latter two types of carcinoma may have arisen directly from endometriotic deposits. Ovaries removed prophylactically from women with a family history of ovarian carcinoma or with a mutation in one of the genes predisposing to ovarian carcinoma should be processed in their entirety, and examined closely not just for obviously neoplastic lesions, but also for more subtle morphological abnormalities of the surface epithelium or the epithelium lining cortical inclusion cysts.

What levels of agreement can be expected between histopathologists assigning cases to discrete nominal categories? A study of the diagnosis of hyperplastic and adenomatous colorectal polyps.

AIMS: To assess the levels of agreement between histopathologists for a two-class nominal categorization process--the discrimination between hyperplastic and adenomatous colorectal polyps. METHODS: Fifty hyperplastic and 50 adenomatous polyps received consecutively in the laboratory were categorized by nine histopathologists, and the level of agreement between all observers and the original diagnosis was assessed using kappa statistics. RESULTS: For the eight observers with 11 months or more experience in histopathology, there was a high level of agreement with kappa statistics ranging from 0.84 to 0.98. This process was performed rapidly with an average of 13 to 22 seconds spent on each case. One observer with only 6-weeks' experience of histopathology had a lower overall level of agreement with kappa statistics ranging from 0.46 to 0.54, but the performance on the later cases was much higher. CONCLUSIONS: The level of agreement in the distinction between hyperplastic and adenomatous colorectal polyps is high among histopathologists with at least moderate amounts of experience in histopathology. The one virtually naïve observer showed a marked learning response during the study without feedback on case outcome. This suggests that histopathologists are very reliable in assigning cases to distinct nominal categories and that learning of these processes occurs early in a histopathologist's career.

Necropsy diagnosis of myocarditis: a retrospective study using CD45RO immunohistochemistry.

AIM: To use CD45RO immunohistochemistry to investigate the numbers of T lymphocytes found in sections of myocardium from a routine necropsy series, and to determine the incidence of myocarditis in this series. METHODS: Myocardial sections from 163 routine hospital necropsies were stained with CD45RO and the numbers of positive lymphocytes/mm2 were counted. The results were correlated with the H/E opinion and the clinical context of the necropsy. RESULTS: Most (143) cases showed low numbers (0-3) of CD45RO positive lymphocytes/mm2. Fifteen cases showed 7-13 positive lymphocytes/mm2, comprising a wide variety of clinical conditions, generally with no specific cardiac pathology. Five cases showed 14 or more positive lymphocytes/mm2, comprising one case of active myocarditis, three cases of cardiac transplant rejection, and one post-transplant lymphoproliferative disorder, all conditions in which large numbers of lymphocytes would be expected. CONCLUSIONS: The incidence of myocarditis in our series was 0.6%. In most cases the normal myocardium has a low T lymphocyte count (0-3/mm2). In some cases immunohistochemistry shows more positive cells than would have been expected on light microscopy. Immunohistochemistry is a useful and reliable means of confirming a diagnosis of myocarditis. The results support the conclusion of the 1997 ISFC task force that 14 or more lymphocytes or macrophages/mm2 of myocardium in the appropriate clinical context is a reliable threshold for the diagnosis of chronic myocarditis.

Squamous cell carcinoma of the colon in an asbestos worker.

We report a case of squamous cell carcinoma of the colon in an asbestos worker. We speculate whether the asbestos exposure could have been causative and review the literature.

Microsatellite instability in sporadic colorectal carcinoma is not an indicator of prognosis.

Fifty sporadic colorectal carcinomas diagnosed in 1991 were analysed for microsatellite instability at four loci. Five of 50 (10 per cent) tumours showed replication errors (RERs) at two or more loci and were classed as RER-positive (RER+). A further five showed RERs at one locus only. A significant association (Fisher exact test) was found between RER+ tumours and location in the proximal colon, exophytic shape, size >5 cm, histological margin, lymphoid reaction, and near-diploid DNA content. There was no significant difference for age, sex, grade, mucin production, p53 protein overexpression or Duke's stage. There was no significant difference in survival as measured over a 60-month follow-up period. The findings, though limited by the small case numbers involved, show an association between RER positivity in sporadic colorectal tumours and certain clinico-pathological features. They do not suggest a better clinical outcome for sporadic RER+ tumours.