Biomedical subjects

Peter W Nichols

Publications and source records attributed to Peter W Nichols.

8 recordsLinked to original sources

PubMed2005

Prescription drug use and risk of acute myeloid leukemia by French-American-British subtype: results from a Los Angeles County case-control study.

Chemotherapy is a well-established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population-based Los Angeles County study in which 299 matched case-control pairs had complete data on prescription drug use and 88% of cases were subtyped according to the French-American-British (FAB) criteria. Cases were diagnosed between 1987 and 1994. Prescription nonsteroidal anti-inflammatory drug (NSAID) use for at least 4 weeks in the 2 to 10 years before diagnosis was associated with decreased risk (odds ratio = 0.5, 95% confidence interval=0.3, 1.0; p=0.04) with dose-response most evident for FAB subtype M2 (OR = 0.6, CI: 0.1, 2.9 for duration < or =6 months; OR = 0.2, CI: 0.0, 1.6 for >6 months). For subtype M4, ORs increased with increasing duration of benzodiazepine use in the 2 to 10 years before diagnosis (OR = 1.5, CI: 0.3, 9.0 for < or =6 months vs. OR = 5.0, CI: 0.6, 42.8 for >6 months). These results suggest that prescription drugs other than chemotherapy may have FAB subtype-specific effects on AML risk.

Adult↗

PubMed2005

Ethnic differences in neuroendocrine cell expression in normal human prostatic tissue.

OBJECTIVES: To determine whether any differences exist in neuroendocrine (NE) cell differentiation in normal prostates among various ethnic groups because the incidence and mortality from prostate cancer vary across racial groups. METHODS: Archived paraffin-embedded prostate samples not containing any malignancy were obtained from cystoprostatectomy specimens. Prostatic tissue was obtained from 15 African Americans, 13 Hispanics, 15 Asians, and 16 whites. NE cells were identified based on immunoreactivity for chromogranin A. The mean number of NE cells per high power field (HPF) for each patient was determined using a visual quantitative method by two observers who were unaware of the race of the patients. RESULTS: The geometric mean number of NE cells was 6.1/HPF for Asians, 5.6/HPF for whites, 4.0/HPF for Hispanics, and 0.7/HPF for African Americans. A highly significant difference was observed in the distribution of NE cells between African Americans and each of the other races (P < or =0.003). A trend toward greater NE expression was noted in Asians and whites compared with Hispanics; however, this difference did not reach statistical significance. CONCLUSIONS: We found a fivefold to eightfold difference in the distribution of NE cells in the normal prostates of African-American men compared with that of other races. The comparatively low NE cell expression in African-American men may play a role in the greater rate of prostate carcinogenesis seen in this ethnic group.

Black or African American↗

PubMed2005

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience.

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.

Adult↗

PubMed2005

Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy.

PURPOSE: We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI. RESULTS: Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival. CONCLUSIONS: Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.

Adult↗

PubMed2004

Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients.

PURPOSE: There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments. EXPERIMENTAL DESIGN: We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients. RESULTS: The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals. CONCLUSIONS: Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.

Adult↗

PubMed2004

Alcohol consumption and risk of adult-onset acute myeloid leukemia: results from a Los Angeles County case-control study.

Few studies have examined the role of alcohol consumption in risk of adult acute myeloid leukemia (AML). Two previous case-control studies resulted in inconsistent findings. We report data from a Los Angeles County population-based case-control study in which 164 matched case-control pairs were asked about lifetime history of alcohol consumption and 136 cases were subtyped according to the French-American-British (FAB) criteria. Estimated categorical odds ratios (OR) adjusted for smoking and education were suggestive of a possible protective effect but trend tests were non-significant. Analyses by FAB subtype did not reveal subtype-specific associations but generally suffered from lack of power. Larger studies are needed to more thoroughly investigate the relationship between alcohol consumption and AML risk.

Acute Disease↗

PubMed2004

Prognosis of seminal vesicle involvement by transitional cell carcinoma of the bladder.

PURPOSE: Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy. MATERIALS AND METHODS: From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots. RESULTS: There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p <0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status. CONCLUSIONS: Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

Adult↗

PubMed2002

Smoking and risk of acute myeloid leukemia: results from a Los Angeles County case-control study.

Acute myelogenous leukemia (AML) is a heterogeneous disease with distinct histologic subtypes likely to have distinct risk factors. The authors examined smoking and the risk of adult AML by French-American-British (FAB) subtype in a Los Angeles County, California, population-based case-control study of 412 cases diagnosed between 1987 and 1994 and 412 matched controls. Consistent with previous studies, smoking was not a substantial risk factor for AML overall (odds ratio (OR) = 1.2, 95% confidence interval (CI): 0.9, 1.6). However, increased risk was observed for FAB subtype M2 (OR = 2.3, 95% CI: 1.1, 4.4), particularly for subjects aged 60-75 years (OR = 3.3, 95% CI: 1.1, 10.0). For M2, significant dose-response was associated with total years smoked (p = 0.02), cigarettes per day (p = 0.007), and product filter status (filtered vs. nonfiltered; p = 0.03). The authors estimate that 42% (standard error = 13%) of M2 cases are attributable to smoking. There were no or weak associations between smoking and increased AML risk for other FAB subtypes. The finding by this study of an association between smoking and FAB subtype M2 confirms a previously published report and suggests that earlier findings of no or weak smoking-AML associations may have been due to lack of subtype-specific analysis.

Acute Disease↗