Biomedical subjects

Matthew E Nielsen

Publications and source records attributed to Matthew E Nielsen.

11 recordsLinked to original sources

PubMed2006

Advanced age is associated with poorer bladder cancer-specific survival in patients treated with radical cystectomy.

OBJECTIVE: Bladder cancer (BCa) is a disease of older persons, the incidence of which is expected to increase as the population ages. There is controversy, however, regarding the outcomes of radical cystectomy (RC), the gold standard treatment of high-risk BCa, in patients of advanced chronological age. The aim of our study was to assess the impact of patient age on pathological characteristics and recurrence-free and disease-specific survival following RC. METHODS: The records of 888 consecutive patients who underwent RC for transitional cell carcinoma (TCC) were reviewed. Age at RC was analyzed both as a continuous (yr) and categorical (< or =60 yr old, n=240; 60.1-70 yr old, n=331; 70.1-80 yr old, n=266; >80 yr old, n=51) variable. Logistic regression and survival analyses were performed. RESULTS: Higher age at RC, analyzed as a continuous or categorical variable, was associated with extravesical disease and pathological upstaging (all p<0.02). Older patients were less likely to receive postoperative chemotherapy (< or =60 yr: 32% vs. >80 yr: 14%, p=0.008). In both pre- and postoperative multivariate models, higher age at RC as a categorical variable was associated with BCa-specific survival (p<0.05). Patients >80 yr old had a significantly greater risk of disease recurrence than patients aged < or =60 yr (p<0.05). CONCLUSION: Greater patient age at the time of RC for BCa is independently associated with adverse outcomes. Better understanding of factors associated with postoperative outcomes in this growing segment of the population is necessary. Prospective corroboration and further refinement of similar analyses in other large datasets is needed.

Adult↗

PubMed2006

Toward critical evaluation of the role(s) of molecular biomarkers in the management of bladder cancer.

Among genitourinary malignancies, bladder cancer is a common, potentially dangerous and exceedingly costly disease entity. Predicated on substantial gains in our understanding of the natural history and molecular biology of bladder cancer, recent years have seen an explosion of new applied technologies to aid clinicians in the management of bladder cancer. Herein we present a systematic overview of general conceptual issues and specific strategies of potential relevance to the clinical evaluation of patients with bladder cancer. A number of basic epidemiological issues provide the relevant background within which we should consider candidate biomarkers. Within this framework, we highlight a number of important recent research findings representative of the large number of candidate bladder cancer biomarkers that have emerged. With several markers already having obtained regulatory approval for clinical use, this topic is of clear relevance not only to researchers but also to the practicing physician. Bladder cancer is a common, costly, and potentially dangerous disease with the opportunity for significant technological inroads in the area of applied biomarkers. An appreciation of basic epidemiological considerations informs our consideration of the state of the art and identifies specific strategies amenable to further innovation.

Antibodies, Monoclonal↗

PubMed2006

High pressure surgery.

Explore the source record for details and available documents.

Anterior Compartment Syndrome↗

PubMed2006

Black race does not independently predict adverse outcome following radical retropubic prostatectomy at a tertiary referral center.

PURPOSE: There is controversy in the literature as to whether black race is associated with poorer oncological outcomes among men undergoing radical prostatectomy for clinically localized prostate cancer. To address this issue we examined the outcomes of a cohort of black and white men treated by multiple surgeons at our institution. MATERIALS AND METHODS: The study population consisted of 4,962 white and 326 black men treated with anatomical radical retropubic prostatectomy between 1988 and 2004 by 10 different surgeons at the Johns Hopkins Hospital, a tertiary care referral center. We evaluated the association between race and adverse pathological features, and biochemical progression. RESULTS: Black men had significantly higher preoperative serum prostate specific antigen (mean 7.2 vs 6.0 ng/ml, p <0.001), body mass index (median 27.4 vs 26.3 kg/m, p <0.001) and incidence of higher grade disease (Gleason sum 4 + 3 or greater) on prostate biopsy (17% vs 14%, p = 0.011). After adjustment for multiple clinical variables there was no statistically significant association between race and the adverse pathological characteristics of high grade disease, positive surgical margins, extraprostatic extension or seminal vesicle invasion. Black race was associated with a significantly increased risk of biochemical progression on univariate analysis (HR 1.52, 95% CI 1.16-2.00, p = 0.002). However, after adjusting for clinical and pathological characteristics, black race was not an independent predictor of biochemical progression (HR 1.09, 95% CI 0.81-1.45, p = 0.578). CONCLUSIONS: Black men were more likely to be obese and present with adverse preoperative clinical features at a younger age, and have a higher rate of biochemical progression. However, on multivariate analysis black race was not an independent predictor of adverse pathological outcome or biochemical recurrence. Further efforts are needed to detect prostate cancer earlier among black men.

Adenocarcinoma↗

PubMed2006

Percutaneous renal cryoablation.

Percutaneous renal cryoablation (PRC) has been gaining acceptance as a minimally invasive option for the treatment of patients with solid renal masses. Herein, we reviewed the historical development of PRC, relevant contemporary clinical data, and future directions of percutaneous approaches to renal masses. Early experience suggests that PRC has the potential to offer an alternative treatment for patients with small renal masses, with the advantages of decreased treatment-associated morbidity and spared renal function. Ultrasound, computed tomography, magnetic resonance imaging, and positron-emission tomography have all been explored as potential solutions to the challenges of image guidance and follow-up; distinct advantages and disadvantages of each are reviewed here. Encouraging early results regarding oncologic efficacy, rate of complications, and overall costs support the continued evaluation of PRC. Longer-term oncologic follow-up is essential if the potential application of this minimally-invasive technique to a broader spectrum of patients with renal masses is to be determined.

Cryosurgery↗

PubMed2006

Insight on pathogenesis of varicoceles: relationship of varicocele and body mass index.

OBJECTIVES: Varicoceles, present in 15% to 20% of men, are the most common abnormal finding among men presenting with infertility, yet controversy exists regarding their etiology. Anecdotal experience suggests that varicoceles are more prevalent in lean men, supporting the "nutcracker" effect of the superior mesenteric artery compressing the left renal vein over the aorta. We examined this hypothesis in a large adult population. METHODS: A total of 2106 men were evaluated for infertility or erectile dysfunction from 1990 to 1996. The men were examined for the presence and severity of a varicocele. The association between age, height, body mass index, year of evaluation, and reason for consultation and the presence and severity of a varicocele was examined using logistic regression analysis. RESULTS: The mean age was 47 years (range 18 to 85), and the median body mass index was 26.4 kg/m2 (range 15.4 to 53.3). A varicocele was present in 398 men (18.9%). Stratified by grade, 59 (14.8%) were grade III, 155 (38.9%) were grade II, and 184 (46.2%) were grade I. The prevalence of varicoceles in the erectile dysfunction group (12.7%) was significantly less (P <0.001) than in the infertile group (32.2%). Multivariate logistic regression analysis revealed a statistically significant inverse relationship between body mass index and the presence of a varicocele. CONCLUSIONS: Varicoceles were less likely to be diagnosed among obese men. Although this suggests that the "nutcracker" phenomenon or other biophysical effects of increased adiposity may play a role in the pathogenesis, other factors could not be excluded as contributing to our findings.

Adolescent↗

PubMed2006

Urinary markers in the detection of bladder cancer: what's new?

PURPOSE OF REVIEW: Bladder cancer is one of the most common genitourinary malignancies and is a potentially life-threatening diagnosis. For many patients, however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly, and invasive surveillance for recurrent and/or progressive disease. In the context of relative limitations of the current standard of cystoscopy and cytology, there has been burgeoning activity in the development of novel molecular urine-based markers for bladder cancer detection. RECENT FINDINGS: A large number of candidate bladder cancer biomarkers have emerged as our understanding of the molecular pathogenesis of the disease has evolved. Many of these are in the relatively earlier phases of development but several have received the approval of the United States Food and Drug Administration for clinical use and are already being applied to patients in clinical practice. SUMMARY: Urine-based markers for bladder cancer detection represent an area of substantial innovation and discovery with potentially profound scientific, clinical, and economic implications. As more of these tests become standardized and undergo evaluation in large multicenter trials, it is conceivable that a novel marker or panel of markers will emerge as a major enhancement to the current standard of care.

Biomarkers, Tumor↗

PubMed2006

Assessment of gefitinib- and CI-1040-mediated changes in epidermal growth factor receptor signaling in HuCCT-1 human cholangiocarcinoma by serial fine needle aspiration.

One specific limitation to the clinical development of targeted cancer therapeutics is the lack of well-validated pharmacodynamic markers. Such tools might conceivably provide a framework within which to better evaluate the selection of specific molecules as therapeutic targets. Nevertheless, the practical application of this hypothesis in clinical development remains elusive. In this study, we present a minimally invasive pharmacodynamic assay for monitoring therapy-mediated changes in the activity of target signaling pathways by using fine needle aspiration (FNA) samples and quantitative ELISA methods. To this end, we used the HuCCT-1 cholangiocarcinoma cell line treated with gefitinib (ZD1839, Iressa), a selective blocker of the epidermal growth factor receptor (EGFR), and CI-1040, a selective inhibitor of the mitogen extracellular regulated kinase [mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase 1/2]. HuCCT-1 cells were resistant to gefitinib and CI-1040 alone but susceptible to the combination of these drugs in vitro and in vivo. This effect was associated with a greater inhibition of ERK1/2 activation, a downstream mediator in the EGFR-mitogen-activated protein/ERK kinase pathway. Using this model, we sought to assess whether FNA-obtained tumor biopsies could be used to measure signaling pathway activation. Cellular extracts prepared from FNA samples yielded adequately cellular, high-quality samples to assess therapy-mediated changes in EGFR and ERK1/2 phosphorylation by Western blotting and quantitative ELISA assays. Treatment with gefitinib alone effectively inhibited EGFR activation but failed to block ERK1/2 phosphorylation and tumor growth. Blocking was achieved by the addition of CI-1040 to the treatment regimen. These results show that the combination of serial FNA sampling with highly sensitive quantitative ELISA assays permits assessment of therapy-mediated changes in signaling pathways, which correlate well with antitumor effects. This assay is simple to implement and broadly applicable to diverse tumor types in clinical studies with cancer patients and may be useful in the development of targeted anticancer agents.

Animals↗

PubMed2005

Systematic detection and repair of subclinical inguinal hernias at radical retropubic prostatectomy.

OBJECTIVES: Inguinal hernias occur in 15% of men within 1 to 2 years after radical retropubic prostatectomy (RRP). This suggests that many of these hernias may have been present at surgery, but not diagnosed. Beginning in September 2001, all patients undergoing RRP were carefully examined intraoperatively for the presence of a hernia or a dilated internal inguinal ring. In this study we define the frequency of inguinal hernias detected at RRP and the durability of repair. METHODS: Between September 2001 and December 2004, 430 patients underwent RRP by one surgeon. Hernias, detected in 142 men (33%), were repaired preperitoneally: direct hernias were repaired with mesh and indirect hernias with 2-0 Prolene suture. The patients were followed up for an average of 19 months (range 9 to 36). Information on postoperative hernia status was available for 315 men (73.3%). RESULTS: Of the 430 patients, 142 (33%) had hernias repaired at RRP. Of these hernias, 32% were right sided, 28% left sided, and 40% bilateral; 34% were direct hernias and 66% indirect. Of the 142 patients who underwent intraoperative hernia repair, 95 (67%) had follow-up data, and 5 (5.3%) of that group developed a hernia postoperatively. None of the hernias repaired at RRP recurred. Recurrent hernias on the side of the repair occurred in 3.1%. CONCLUSIONS: Incidental inguinal hernias were commonly found (33%) at RRP. Two thirds of the defects detected were indirect. Clinical recurrence after repair was rare.

Hernia, Inguinal↗

PubMed2005

Obesity and risk of biochemical progression following radical prostatectomy at a tertiary care referral center.

PURPOSE: We have previously reported that obesity is an independent predictor of biochemical progression after radical prostatectomy (RP) in men treated by a single surgeon at our institution. We sought to validate or refute these findings using data on men treated by multiple other surgeons at our institution. MATERIALS AND METHODS: The study population consisted of 2,796 men treated with anatomical radical RP between 1988 and 2004 by 1 of 17 surgeons at our institution, a tertiary care referral center. We evaluated the association between body mass index (BMI), and adverse pathological features and biochemical progression. RESULTS: On multivariate analysis increased BMI was associated with high grade disease in the RP specimen (p = 0.03), positive surgical margins (p <0.001), extraprostatic extension (p <0.001) and lymph node metastasis (p = 0.01) but not with seminal vesicle invasion (p = 0.59). After multivariate adjustment for preoperative clinical characteristics increased BMI was significantly associated with an increased risk of biochemical progression (p <0.001), which was somewhat but not completely attenuated by further adjusting for RP specimen pathological features (p = 0.03). Adjustment for surgeon did not affect these results. CONCLUSIONS: In men undergoing RP increased BMI was associated with adverse pathological features and a greater risk of biochemical progression. These findings together with the results of several recently published series collectively provide strong evidence that obese men undergoing RP are more likely to have aggressive prostate cancer.

Aged↗

PubMed2005

Obesity and capsular incision at the time of open retropubic radical prostatectomy.

PURPOSE: The goal of radical prostatectomy (RP) is complete removal of the intact prostate. Obese men can represent a technical challenge. However, to our knowledge objective data linking obesity with technically inferior surgery are lacking. Therefore, we examined the association between body mass index (BMI) and capsular incision at RP as a surrogate of a poor technical operation in men treated for prostate cancer by several high volume surgeons at a center of excellence. MATERIALS AND METHODS: The study population consisted of 7,027 men treated with anatomical retropubic RP between 1996 and 2004 by 7 high volume surgeons. We evaluated the association between BMI and capsular incision using logistic regression, adjusting for clinical and pathological variables, and for the surgeon. RESULTS: Overall capsular incision was noted in 4.6% of all RP specimens. After adjustment for preoperative prostate specific antigen, patient race, height, year of surgery, clinical stage, pathological Gleason sum, prostate weight, extraprostatic extension and seminal vesicle invasion increased BMI was associated with increased odds of capsular incision (p trend = 0.005). After further adjustment for surgeon mild obesity was associated with 30% increased odds of capsular incision (OR 1.30, 95% CI 0.92 to 1.83), while moderate and severe obesity was associated with 57% increased odds of capsular incision (OR 1.57, 95% CI 0.82 to 3.00) relative to normal weight men (p trend = 0.06). CONCLUSIONS: In a study of more than 7,000 men treated by 7 experienced surgeons BMI was positively related to capsular incision. This suggests that open retropubic RP is technically more difficult in obese men, which results in a greater likelihood of a less than technically ideal operation. Although this may be predicted to have a negative impact on disease-free survival outcomes in obese men, it is unlikely to alone explain the worse outcomes in obese men noted in previous RP series.

Aged↗