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.

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.

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.

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.

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.

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.

The effect of four interventions on the informational content of histopathology reports of resected colorectal carcinomas.

AIM: To investigate the effect of different interventions on the inclusion of data items in the histopathology reports of resected colorectal carcinomas. STUDY POPULATION: 272 routine histopathology reports on colorectal carcinomas from the department of histopathology, Royal Hallamshire Hospital, Sheffield. METHODS: The presence or absence of 10 specific data items was recorded for each report. The reports were divided into five audit periods. In the initial period reports were generated using free text with no agreed guidelines. In period 2, text guidelines had been issued; in period 3, flow diagram guidelines had been issued; and in periods 4 and 5, template proformas were attached to each specimen request form. RESULTS: All interventions produced some increase in inclusion rate for some features, but only with the introduction of template proformas did these rates approach 100% for all data items. Inclusion rates were 100% for all items in all cases reported using a proforma. In the final audit period 96% of specimens were reported using proformas. CONCLUSIONS: Template proformas produce a high rate of inclusion of data items in reports of colorectal carcinoma resection specimens.

Lymphocytic gastritis and coeliac disease: evidence of a positive association.

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.

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.

Effect of host Lewis and ABO blood group antigen expression on Helicobacter pylori colonisation density and the consequent inflammatory response.

The Lewis(b) blood group antigen has been implicated as a putative receptor for Helicobacter pylori in the gastric mucosa. Furthermore, an increased prevalence of duodenal ulcer was found in non-secretors and it has been suggested that secretor status may influence bacterial colonisation density. Other investigators have hypothesised that severity of antral gastritis may be related to colonisation density of the bacterium alone, and that a critical bacterial load is necessary for the development of duodenal ulcer. Our objectives were to investigate whether a relationship existed between host Lewis and ABO blood group phenotype and prevalence of H. pylori infection. In addition we investigated whether bacterial colonisation density and the ensuing inflammatory response was influenced by secretor status and ABO blood group phenotype. The Lewis and ABO blood group phenotype of 207 patients undergoing upper endoscopy was determined. Of these, 136 were secretors and 62 were nonsecretors. Forty-five percent of patients were infected with H. pylori. No significant association was found between H. pylori infection and expression of Lewis(a) or Lewis(b) blood group antigen. The mean histological density of H. pylori was 1.8 +/- 0.2 among non-secretors and 1.51 +/- 0.13 among secretors (P = 0.209), with a mean grade of lymphocytic infiltration significantly greater in H. pylori-infected non-secretors (2.23 +/- 0.123 vs 1.8 +/- 0.074; P = 0.003). In addition, blood group O non-secretors had a significantly higher grade of lymphocyte infiltration of their gastric mucosa compared to non-O non-secretors (2.53 +/- 0.133 vs 1.93 +/- 0.181, P = 0.027). These results suggest that although no in vivo relationship exists between H. pylori and preferential adhesion to the putative Lewis(b) receptor, bacterial colonisation and the ensuing inflammatory response may be influenced at least in part by host expression of ABO and Lewisa blood group antigens.

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.

Primary small intestinal tumours: increased incidence of lymphoma and improved survival.

Small intestinal malignancies are rare and may have a delayed presentation owing to insidious growth. We have reviewed the case notes of 25 patients presenting with primary small bowel tumours over a 10-year period. Abdominal pain, weight loss and vomiting were the most common symptoms. The median duration of symptoms was 6 months. Physical examination was normal in 24% of patients. An abdominal mass was present in 46% of cases. Emergency laparotomy was undertaken in 28% of patients. Lymphomas were identified in 72% and adenocarcinomas were present in 16%. The predominance of small bowel lymphoma is an unusual finding and may be related to the high incidence of coeliac disease in the region. The median survival in the lymphoma group was 36 months, which compares favourably with reported series.

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.

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.

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.

[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.

Communication intervention for persons with severe and profound disabilities.

Traditionally, communication interventionists focused on teaching a beginning repertoire of communicative behavior, once learners with severe to profound disabilities had emitted intentional behavior. Increasingly, interventionists are recognizing that valuable opportunities may be lost if intervention does not begin at an earlier point. In part, intervention strategies at increasingly earlier points have resulted from a prevailing change from semantically-focused intervention logic to pragmatic, interaction-focused intervention logic. At the same time that intervention content has increasingly focused on pragmatics, there has been a wealth of information addressing the social functions served by repertoires of simple idiosyncratic (as well as socially unacceptable) behavior. The increasing availability of augmentative and alternative communicative options has provided an extensive array of motorically simple strategies to exert significant control and influence over one's environment. We have long since passed the need to demonstrate that persons with severe disabilities can be taught a repertoire of communicative functions. However, we have not been as successful in demonstrating that the communicative behavior taught is well maintained solely in the presence of natural maintaining contingencies. Nor have we adequately demonstrated that established repertoires are sufficiently generalized. Most recently, interventionists have begun to focus on more efficient strategies to use in the selection of the most critical teaching instances to teach a new communicative response. Additionally, interventionists are considering response efficiency as an important variable in determining the likelihood that a learner will choose to emit members of his or her communicative repertoire. There appears to be a consensus among those who currently serve individuals with severe disabilities that inclusion represents an attainable objective for students with even the most severe disabilities. Unfortunately, it is not clear that either special or regular educators are being adequately prepared to accomplish included placements. There remains a significant need to recognize those aspects of best practice which must be further explored in regular education settings. What once were considered best practice methods may not meet the test of social validity and be considered best practices in regular classrooms. The vast majority of intervention research has selected a fairly narrow communicative form or function to teach. Increasingly, information on maintenance and generalization is considered. However, often the periods sampled postacquisition are very modest. Among the plethora of available communication intervention curricula, there are virtually none that have taken a learner from a point of engaging in no intentional communicative behavior to the establishment of an effusive repertoire of communicative functions and corresponding vocabulary.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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.