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ABSTRACT: High-grade prostatic intraepithelial neoplasia (HGPIN) is an intracellular proliferation of ductal epithelial cells. On its own, the presence of HGPIN does not warrant active intervention. In contrast, intraductal carcinoma of prostate and prostatic ductal adenocarcinoma of prostate are markers of aggressive prostatic adenocarcinoma. The presence of even small foci of these tumours on biopsy warrants immediate intervention, even in the absence of demonstrable invasive disease. This second part of the review of in situ epithelial proliferations of the prostate looks at these conditions in more detail.
BJU International 12/2012; 110 Suppl 4:22-4. · 2.84 Impact Factor
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ABSTRACT: What's known on the subject? and What does the study add? The risk of developing aggressive prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. An earlier study by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer showed that BRCA2 mutation carriers displayed a loss of heterozygosity (LOH) within their prostate cancer tissue in the majority of cases, thus implying that the prostate cancer in these men occurred as a result of LOH for BRCA2. High grade prostatic intraepithelial neoplasia (HGPIN) has been considered a precursor to prostate adenocarcinoma in some, but not all, cases of prostate adenocarcinoma. The study found that there was no LOH for BRCA2 in HGPIN. From this small cohort of BRCA2-positive men, we suggest HGPIN is not necessarily a precursor to their prostate cancer development. The presence of HGPIN in a TRUS biopsy in these men at risk of high risk disease is not an indication for prostatectomy. OBJECTIVES: • To determine if high grade prostatic intraepithelial neoplasia (HGPIN), which is considered a precursor to the development of prostate adenocarcinoma, displays the same genetic hallmarks as adenocarcinoma. • To identify, using molecular genetic techniques, if HGPIN is a precursor of tumour development and progression in men carrying a pathogenic germline mutation in BRCA2. PATIENTS AND METHODS: • Ten participants from the Kathleen Cuningham Consortium for Research into Familial Breast Cancer cohort of high-risk breast cancer families were identified, with (i) a diagnosis of aggressive prostate cancer and presence of HGPIN, (ii) a pathogenic BRCA2 mutation, and (iii) access to archival prostate tissue specimens. • Loss of heterozygosity (LOH) at the BRCA2 gene was examined using mutation-specific PCR and sequencing of DNA from laser microdissected HGPIN. RESULTS: • Within this cohort of 10 pathogenic BRCA2 carriers, no patient displayed LOH at the mutation locus within HGPIN, irrespective of whether or not corresponding adenocarcinoma DNA displayed LOH. CONCLUSIONS: • Although HGPIN is considered a precursor to cancer, as no LOH was observed, this assay does not provide a genetic marker that may be considered a positive predictor of tumorigenesis in BRCA2 carriers. • In this group of high-risk men, early screening via prostate-specific antigen testing, rectal examination and prostate biopsy may be prudent to permit the detection and the optimum clinical management of prostate cancer.
BJU International 10/2012; · 2.84 Impact Factor
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Joe H Chang,
Daryl Lim Joon,
Sze Ting Lee,
Sylvia J Gong,
Nigel J Anderson,
Andrew M Scott,
Ian D Davis, David Clouston,
Damien Bolton,
Christopher S Hamilton,
Vincent Khoo
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ABSTRACT: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using (11)C-choline positron emission tomography PET scans in patients with localized prostate cancer.
This was an RT planning study of 8 patients with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans.
All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans.
IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.
International journal of radiation oncology, biology, physics 05/2012; 83(5):e691-6. · 4.59 Impact Factor
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ABSTRACT: What's known on the subject? and What does the study add? In the era of extended biopsy sampling of the prostate, multifocal high-grade prostatic intraepithelial neoplasia (HGPIN) is associated with a significantly higher rate of cancer diagnosis than unifocal HGPIN or a benign diagnosis. In addition, the cancers that are subsequently diagnosed in men with HGPIN on their initial biopsy tend to be smaller, lower grade and more commonly organ-confined. This has led to a reappraisal of the need and timing of repeat biopsies. The present paper provides a series of recommendations on the optimal timing of repeat biopsies in men with HGPIN on biopsy, based on the current available evidence. This is the first of a two part series reviewing the nature and clinical significance of in situ cellular proliferations in the prostate gland. This first part examines prostatic intraepithelial neoplasia (PIN), while the second part in the next supplement discusses intraductal carcinoma and ductal adenocarcinoma of the prostate. PIN is a precursor lesion in the development of some forms of adenocarcinoma of the prostate. In the 1990 s, high-grade PIN (HGPIN) on biopsy was a significant predictor of carcinoma, but this was due to incomplete sampling with sextant biopsies. With more extensive sampling in the last decade, the likelihood of identifying cancer after a diagnosis of HGPIN is not significantly different from a benign diagnosis. In several recent studies, it is now recognised that multifocal HGPIN is a better predictor of cancer than unifocal HGPIN. Most cases of cancer will be detected in the vicinity of the HGPIN, but up to 40% of cancers will occur in different sextants. In assessing potential markers for carcinoma in men with HGPIN on biopsy, α-methylacyl coenzyme-A racemase (AMACR) has emerged as a promising diagnostic tool. HGPIN with strong staining for AMACR is associated with a higher rate of cancer detection in subsequent biopsies compared with AMACR-negative HGPIN. Also, AMACR positivity in HGPIN is more commonly seen adjacent to carcinoma, and this may provide guidance as to the site of future biopsies.
BJU International 04/2012; 109 Suppl 3:22-6. · 2.84 Impact Factor
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Cancer Prevention Research 07/2011; 4:1002-1010. · 4.91 Impact Factor
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ABSTRACT: The role of a germ-line BRCA2 mutation in the development of prostate cancer is established, but the clinical presentation linked to outcome for this group of men has not been well described. A total of 148 men from 1,423 families were ascertained from the kConFab consortium. Each participant met the following criteria: (i) a verified case of prostate cancer; (ii) confirmed as either a carrier or noncarrier of a family-specific BRCA pathogenic mutation; (iii) comprehensive clinical and treatment data were available. Clinical data were linked to treatment received and overall survival was analyzed by Kaplan-Meier. Prostate cancer in men from breast cancer-prone families has a high risk of disease progression, irrespective of mutation status. BRCA2 mutation carriers have an increased risk of death and prostate cancer-related death [HR (95% CI) 4.5 (2.12-9.52), P = 8.9 × 10(-5)] by comparison with noncarriers. Serum PSA readings taken prior to diagnosis in 90% of all men, age adjusted, were above clinical significance. Following D'Amico risk stratification, 77.5% of BRCA2 mutation carriers and 58.7% of noncarriers had high-risk disease. BRCA2 mutation status was also an independent prognostic indicator of overall survival. Furthermore, there was a poor overall survival outcome for both the BRCA2 mutation carriers and noncarriers given curative-intent treatment. All men in breast cancer-prone families are at risk of developing aggressive prostate cancer. This information is significant and should be included in discussions with genetic counselors and medical professionals when discussing prostate cancer treatment options for men in these families, irrespective of mutation status.
Cancer Prevention Research 07/2011; 4(7):1002-10. · 4.91 Impact Factor
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ABSTRACT: To evaluate the accuracy of (11)C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition.
Eight men with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy were studied. Several methods were used to contour the DIL on the PET scans: visual, PET Edge, Region Grow, absolute standardised uptake value (SUV) thresholds and percentage of maximum SUV thresholds. Prostatectomy specimens were sliced in the transverse plane and DILs were delineated on these by a pathologist. These were then compared with the PET scans. The accuracy of correlation was assessed by the Dice similarity coefficient (DSC) and the Youden index.
The contouring method resulting in both the highest DSC and the highest Youden index was 60% of the maximum SUV (SUV(60%)), with values of 0.64 and 0.51, respectively. However SUV(60%) was not statistically significantly better than all of the other methods by either measure.
Although not statistically significant, SUV(60%) resulted in the best correlation between (11)C-choline PET and pathology amongst all the methods studied. The degree of correlation shown here is consistent with previous studies that have justified using imaging for DIL radiotherapy target volume definition.
Radiotherapy and Oncology 05/2011; 99(2):187-92. · 5.58 Impact Factor
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ABSTRACT: This is a case report of a 12 year old girl who presented with a rare condition in paediatrics, transitional cell carcinoma of the bladder. It is important because it is readily treated by endoscopic means if diagnosed early. Potential aetiologies for this unusual condition are explored.
Journal of Paediatrics and Child Health 12/2007; 43(11):773-5. · 1.28 Impact Factor
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ABSTRACT: The recommended treatment for a focal mass in the head of the pancreas is pancreaticoduodenectomy. Preoperative biopsy is not advised in patients who are candidates for resection because of the documented risk of tumour dissemination along the needle tract and significant false negative results.1 Autoimmune pancreatitis is a relatively uncommon condition that can present as a pancreatic mass and mimic malignancy. It may respond to glucocorticoid therapy, and further assessment of such treatment is indicated.2 Such experience will only accumulate if wider knowledge of this condition leads to clinical suspicion.
ANZ Journal of Surgery 07/2002; 72(6):450-2. · 1.25 Impact Factor
