The role of surveillance for small renal masses.
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Aged↗
Biomedical subjects
Michael A S Jewett
Publications and source records attributed to Michael A S Jewett.
Variants of the hK2 protein gene (KLK2) are associated with serum hK2 levels and predict the presence of prostate cancer at biopsy.
PURPOSE: Increased levels of serum human kallikrein-2 (hK2) and an hK2 gene (KLK2) variant are positively associated for prostate cancer, but the relationships between them remain unclear. We examined five variants of the KLK2 gene to further define its relevance to prostate cancer susceptibility and hK2 levels. EXPERIMENTAL DESIGN: We genotyped 645 men with biopsy-proven prostate cancer (cases) and 606 males with biopsies negative for prostate cancer (controls) for five additional single nucleotide polymorphisms (SNP) across the KLK2 gene and also tested for serum hK2 levels. These SNPs were identified from sequencing the KLK2 gene among 20 patients with aggressive prostate cancer. Odds ratios (OR) for prostate cancer detection and haplotype analysis were done. RESULTS: Among the SNPs studied, the A allele of the KLK2-SNP1 (G>A, rs2664155) and the T allele of the KLK2-SNP5 (C>T, rs198977) polymorphisms showed positive associations with prostate cancer, adjusted ORs for KLK2-SNP1 AG and AA genotypes being 1.4 [95% confidence interval (95% CI), 1.2-1.8; P=0.002] and for KLK2-SNP5 TT or CT genotypes being 1.3 (95% CI, 1.1-1.6; P=0.05). Haplotype analyses also revealed a significant association between prostate cancer and the haplotype containing both risk alleles (ACCTT), OR being 5.1 (95% CI, 1.6-6.5; P=0.005). Analysis of serum hK2 revealed hK2 levels to be significantly increased in association with KLK2-SNP1 AA and AG risk genotypes compared with the GG genotype (P=0.001) and also in association with the ACCTT risk haplotype compared with the most common non-risk haplotype (P=0.05). CONCLUSIONS: These findings suggest a role for the KLK2 gene in prostate cancer susceptibility and imply that this role may be realized at least in part by the induction of increases in hK2 production.
Adenocarcinoma↗
VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail.
The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.
Cadherins↗
Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.
A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
Chromosome Mapping↗
Variability in size measurement of renal masses smaller than 4 cm on computerized tomography.
PURPOSE: We assessed the degree of interobserver and intra-observer variability in the size measurement of small renal tumors with computerized tomography. MATERIALS AND METHODS: A total of 29 renal masses from 21 patients were reviewed independently by 3 radiologists on computerized tomography performed with 5 mm collimation and a reconstruction interval of 2.5 mm. Measurements were made of the largest axial dimension (X), perpendicular axial dimension (Y) and slice direction (Z) with double reads performed in a subset of patients. The predicted 95% CI was calculated for each measure, assuming different readers and the same reader. RESULTS: The predicted error bounds for a single renal mass measurement in the X axis were +/-3.1 mm when considering multiple readers and +/-2.3 mm for a single reader. In the X axis 78 of the 87 measurements (90%) were within 2 mm of the average measure. Smaller variances in measurements were seen with single reader repeat measurements than with multiple readers. Highest variances were seen in the Z axis. Measurements of volume and cross-sectional area showed a higher degree of variance. CONCLUSIONS: When comparing independent computerized tomography readings done with 5 mm collimation and a 2.5 mm reconstruction interval, a size change in the largest axial dimension of a renal mass of less than 3.1 mm between different radiologists and less than 2.3 mm for the same radiologist should be viewed with caution because it is within the range of measurement variability.
Carcinoma, Renal Cell↗
Prevention and management of osteoporosis in men receiving androgen deprivation therapy: a survey of urologists and radiation oncologists.
OBJECTIVES: To determine the current practice of clinicians in the diagnosis and management of osteoporosis among men taking androgen deprivation therapy (ADT), because ADT leads to decreased bone mineral density (BMD) and fractures. METHODS: We sent out a survey to Canadian urologists and radiation oncologists. The survey included questions about BMD testing, treatment practices, referral patterns, and risk of osteoporosis. RESULTS: The surveys were returned by 170 of 294 respondents (response rate 58%). Few respondents would obtain a baseline BMD in patients starting ADT. Forty percent would order a repeat BMD test after starting ADT if the baseline BMD were normal or unknown, but more than two thirds would if the baseline BMD showed osteoporosis. In men with a normal BMD starting ADT, respondents recommended weight-bearing exercises (58%), calcium (50%), vitamin D (47%), and bisphosphonate (6%) supplements. In men with osteoporosis at baseline, the use of nonprescription therapies increased slightly and bisphosphonate use increased to 44%. If osteoporosis were diagnosed, 11% would treat the patient themselves. The estimated risk of developing osteoporosis within 1 year of starting ADT with a normal baseline BMD ranged from 0% to 90% (median 20%). CONCLUSIONS: To our knowledge, this is the first survey of its kind. The key findings included that few physicians would order a baseline BMD test, would prescribe bisphosphonates for prevention but almost one half would consider bisphosphonates to treat established osteoporosis, and wide variations exist in the practice patterns and risk perception surrounding ADT-related osteoporosis. Evidence-based guidelines are needed to help physicians deal effectively with osteoporosis prevention and management among men taking ADT.
Androgen Antagonists↗
An efficient solution to the retained Foley catheter.
The most common cause of a retained Foley catheter is failure of the balloon to deflate. If noninvasive means are unsuccessful, balloon puncture is required. We present a safe and efficient technique using flexible video cystoscopy for balloon puncture and removal of any free fragments formed.
Aged↗
Making sense of prostate specific antigen: improving its predictive value in patients undergoing prostate biopsy.
PURPOSE: The clinical usefulness of PSA for prostate cancer screening is unclear, although the test remains in common use. New methods to interpret PSA are needed. MATERIALS AND METHODS: We examined a cohort of 2,637 men who underwent prostate biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for prostate cancer, including patient age, ethnicity, family history of prostate cancer, previous negative biopsy, voiding symptoms and prostate volume, we developed risk groups for prostate cancer using recursive partitioning modeling independent of PSA or DRE. We then compared prostate cancer probabilities by PSA ranges by risk group. RESULTS: Of the 2,637 men 1,282 (48.6%) had prostate cancer. Age, ethnicity, family history, previous negative biopsy and prostate volume were predictive for cancer. We constructed 6 risk groups by combining these factors and created tables to assign patients to these groups. Independent of PSA and DRE the probability of cancer ranged from 15% in patients in group 1 to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk group prostate cancer probabilities were refined from 0% to 100%. Patients in the higher risk groups also had higher grade cancer (p <0.0001). CONCLUSIONS: We generated 6 risk groups based on simple risk factors for prostate cancer. When used in the right context and patient, PSA is highly accurate for predicting prostate cancer and permitting rational decision making in patients with abnormal PSA.
Adult↗
Evidence for a biopsy derived grade artifact among larger prostate glands.
PURPOSE: The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. MATERIALS AND METHODS: We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS: Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. CONCLUSIONS: These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.
Adult↗
Upper tract urothelial carcinoma.
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Carcinoma, Transitional Cell↗
A novel serum marker, total prostate secretory protein of 94 amino acids, improves prostate cancer detection and helps identify high grade cancers at diagnosis.
PURPOSE: New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals. MATERIALS AND METHODS: We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer. RESULTS: Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p <0.0001). The adjusted odds ratios for the presence of prostate cancer for patients with the lowest quartile of PSP94, compared to patients in the highest quartile was 2.70 (95% CI 1.8 - 4.0, p <0.0001). Among a subgroup of 649 men in whom PSA had a low predictive value (PSA less than 20 ng/ml, normal DRE and less than 70 years), 260 (40.1%) were found to have cancer. In this subgroup total PSP94 levels helped discriminate between patients with high grade disease (Gleason score 8 or more, median 1.90 ng/ml), moderate grade disease (Gleason score 7, median 2.34 ng/ml) and low grade disease (Gleason score 6 or less, median 2.60 ng/ml, p = 0.007). PSA and the FTPSA were not able to distinguish between patients with different grades in this group. CONCLUSIONS: Patients with low total PSP94 levels had a high probability for having prostate cancer detected at biopsy. The total PSP94 level was able to help identify patients with high grade disease among a subset of patients in whom PSA and FTPSA are least informative.
Adult↗
Testicular radiation for primary seminoma in a solitary testis.
Orchiectomy is the standard of care for patients with a second primary testicular tumor. We report a case of a man, with previous history of stage I left testicular germ cell tumor, who developed a contralateral seminoma and desired preservation of the remaining testis. Partial orchiectomy was not feasible due to tumor size and percutaneous needle biopsy revealed classical seminoma. He was treated with radiotherapy to the testis. Post treatment biopsy revealed no evidence of disease. At 32 months follow-up, he has not required androgen replacement. He has preservation of total testosterone level and libido.
Adult↗
Treatment of the inguinal regions in penile cancer: a review of the literature and treatment proposal.
Penile cancer is a rare malignancy affecting only 1 per 100,000 men in North America and Western Europe. Although the majority of men present with clinically negative inguinal lymph nodes, node positivity is associated with a very poor prognosis. Both the management of positive nodes, and the management of clinically negative nodes in intermediate- and high-risk patients remain controversial. Experience with penile cancer is often limited as even tertiary referral cancer centers may see only one or two such patients per year. The literature, which consists mainly of retrospective studies of patients treated over several decades, is not conclusive. We undertook a literature review to address this issue and to propose.
Humans↗
Nomogram prediction for prostate cancer and aggressive prostate cancer at time of biopsy: utilizing all risk factors and tumor markers for prostate cancer.
BACKGROUND: There is a large amount of confusion in interpreting prostate specific antigen (PSA) values for prostate cancer. More precise risk assessments for prostate cancer detection are needed for men faced with an abnormal PSA. METHODS: We studied a sample of 2,637 men who underwent a prostate biopsy for an abnormal digital rectal exam (DRE) or PSA. Using factors including age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA, we constructed nomograms to predict the probability of prostate cancer at biopsy. RESULTS: Of the 2,637 men, 1,282 men (48.6%) had prostate cancer detected. Age, ethnicity, family history of prostate cancer, a previous negative biopsy, prostate volume, DRE and PSA were all significant predictors of prostate cancer. Nomograms were constructed based on these factors to predict the risk of prostate cancer and of aggressive prostate cancer (defined as a Gleason Score 7 or more). The positive predictive value varied from 5% to 95% based on the nomograms. The nomograms were validated using bootstrapping methods and the expected and observed proportions were found to be highly concordant. CONCLUSIONS: For men with an abnormal PSA or DRE, the risk for prostate cancer can be accurately estimated using a nomogram based on age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA. This tool will aid physicians and patients in determining the need for prostate biopsy.
Adult↗
The concept and trajectory of "operative competence" in surgical training.
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Clinical Competence↗
The use of genetic markers to determine risk for prostate cancer at prostate biopsy.
PURPOSE: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam. EXPERIMENTAL DESIGN: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostate-specific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms. RESULTS: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with the TT genotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1 gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer. CONCLUSIONS: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.
Adenocarcinoma↗
The Y deletion gr/gr and susceptibility to testicular germ cell tumor.
Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region--known as the "gr/gr" deletion--has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.
Alleles↗
Management of stage T1 tumors of the bladder: International Consensus Panel.
The International Consensus Panel on T1 bladder tumors markers reviewed the subject from a clinical perspective. From diagnosis to treatment decisions, what are the important issues in the management of a new patient? The assessment of prognostic factors for progression requires optimal resection and documentation. The role of immediate adjuvant intravesical chemotherapy after resection remains controversial. How often should the upper tract be assessed for tumor recurrence? The decision on whether to attempt bladder conservation with intravesical therapy or to perform a cystectomy is the most difficult issue in the management of superficial bladder cancer today. Finally, what therapies exist if initial intravesical bacille Calmette-Guérin fails to eradicate the disease or prevent recurrence? The panel thoroughly explored all these subjects and has made recommendations with supporting evidence.
Algorithms↗