Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to ...predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).
Previous studies have shown that the percentage of high grade prostatic adenocarcinoma (Gleason patterns 4 and 5) in a biopsy correlates with outcome parameters. It has also been shown that the ...percentage Gleason pattern 4/5 tumour correlates with biochemical failure and overall survival. There are little data relating to the prognostic significance of quantifying the percentage of Gleason pattern 5 in isolation. We investigated the prognostic predictive value of quantifying the percentage of Gleason pattern 5 tumour in needle biopsies from a series of 196 cases of Gleason score 4+5=9 prostate adenocarcinoma from patients who had also undergone radical prostatectomy. Division of cases according to the percentage of Gleason pattern 5 present (based upon the core with the highest grade) and analysing these with tumour grouped as Gleason score 4+5 with <5% pattern 5 (GS 4+5 <5%), Gleason score 4+5 with 5–20% pattern 5 (GS 4+5 5–20%) and Gleason score 4+5 with 21–49% pattern 5 (GS 4+5 21–49%) showed no difference in outcome determined as time interval to prostate specific antigen biochemical failure. The results showed that each of the subgroups of GS 4+5 tumours had a significantly shorter biochemical recurrence-free survival than for a control group of 179 patients with Gleason score 4+3=7 (GS 4+3) cancer. Similar results were obtained when grading was based upon percentage of Gleason pattern 5 present in all the cores taken from the same patient (case-based grade). Adverse findings at radical prostatectomy showed each of the subgroups of GS 4+5 tumours to have a higher incidence of extraprostatic extension and seminal vesicle invasion than the GS 4+3 group of controls. Further, the differences in incidence between each of the subgroups were not significant for either extraprostatic extension or seminal vesicle invasion. These observations applied to both the highest core-based grade and the case-based grade. Our study has shown that any proportion of Gleason pattern 5 tumour in a needle biopsy is associated with a worse prognosis when compared to GS4+3 tumours and that these results are similar for grading that is core- or case-based.
The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal ...neoplasia, which has a tumour category of ‘tumours that are molecularly defined’. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.
Infiltration of the prostatic ducts by prostatic adenocarcinoma occurs relatively frequently, being most commonly associated with high grade disease. It is now recognised that intraductal carcinoma ...of the prostate (IDCP) has an associated poor prognosis and this is reflected in its histological, molecular and immunohistochemical features. The current recommendation of the World Health Organization is that IDCP not be taken into consideration when grading prostate adenocarcinoma. It is apparent that Gleason did not differentiate between IDCP and stromal invasive carcinoma when developing and validating his grading system, and recent studies suggest that the incorporation of IDCP grading into the overall grading of the specimen provides additional prognostic information.
Separation and attachment lines are topologically significant curves that exist on 2D surfaces in 3D vector fields. Two algorithms are presented, one point-based and one element-based, that extract ...separation and attachment lines using eigenvalue analysis of a locally linear function. Unlike prior techniques based on piecewise numerical integration, these algorithms use robust analytical tests that can be applied independently to any point in a vector field. The feature extraction is fully automatic and suited to the analysis of large-scale numerical simulations. The strengths and weaknesses of the two algorithms are evaluated using analytic vector fields and also results from computational fluid dynamics (CFD) simulations. We show that both algorithms detect open separation lines-a type of separation that is not captured by conventional vector field topology algorithms.
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.
Background. Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral ...prophylactic oophorectomy as a risk-reducing option.
Case. We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation.
Conclusions. This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.
Streak lines and particle traces are effective visualization techniques for studying unsteady fluid flows. For real time applications, accuracy is often sacrificed to achieve interactive frame rates. ...Physical space particle tracing algorithms produce the most accurate results although they are usually too expensive for interactive applications. An efficient physical space algorithm is presented which was developed for interactive investigation and visualization of large, unsteady, aeronautical simulations. Performance has been increased by applying tetrahedral decomposition to speed up point location and velocity interpolation in curvilinear grids. Preliminary results from batch computations showed that this approach was up to six times faster than the most common algorithm which uses the Newton-Raphson method and trilinear interpolation. Results presented show that the tetrahedral approach also permits interactive computation and visualization of unsteady particle traces. Statistics are given for frame rates and computation times on single and multiprocessors. The benefits of interactive feature detection in unsteady flows are also demonstrated.