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Martha K Terris

Publications and source records attributed to Martha K Terris.

At least 19 recordsLinked to original sources
PubMed2026

Oncogenic PIK3CA reprograms glutamine metabolism to drive bladder cancer progression.

BACKGROUND: Genomic analysis has revealed that approximately 40% of bladder cancer (BLCA) tumors harbor alterations in the PI3K/AKT pathway, with PIK3CA mutations occurring in 15-25% of cases. PIK3CA, which encodes the catalytic p110α subunit of PI3K, plays a critical role in regulating cell survival, proliferation, and metabolism. However, the metabolic and functional consequences of PIK3CA mutations in BLCA remain poorly defined. METHODS: To investigate the role of PIK3CA mutations in BLCA, we performed targeted sequencing on tumors from patients, identifying recurrent alterations. Using CRISPR/Cas9 knock-in models in SCaBER and UM-UC-3 cell lines, we introduced the PIK3CA E545K mutation to study its effects. We conducted transcriptomic profiling, targeted metabolomics, and stable isotope tracing to assess metabolic reprogramming. Functional assays measured proliferation, mitochondrial complex I activity, and glutaminolysis. Orthotopic xenografts in mice were used to evaluate in vivo tumor growth and metabolism. RESULTS: PIK3CA mutations were present in 20% of cases, consistent with TCGA data. The E545K and E545Q hotspots accounted for 70% of these mutations. PIK3CA E545K strongly activated PI3K/AKT signaling. Transcriptomic analysis revealed enrichment of OXPHOS, fatty acid metabolism, and mTORC1 signaling. Metabolomics indicated changes in TCA cycle metabolites and enhanced reductive carboxylation of glutamine to citrate, driving fatty acid synthesis. Mutant cells showed increased expression of GLS1 and FASN, higher proliferation rates, and elevated mitochondrial complex I activity. In vivo, PIK3CA-mutant xenografts displayed significantly increased tumor growth. CONCLUSION: PIK3CA mutations are frequent drivers of metabolic reprogramming in BLCA, leading to increased glutamine flux, elevated OXPHOS activity, and enhanced fatty acid synthesis, all of which contribute to tumor progression. These findings provide the first comprehensive evidence that PIK3CA-driven metabolic alterations are both biomarkers of aggressive disease and actionable therapeutic targets. The efficacy of PI3Kα inhibition in combination with metabolic targets may support its potential in precision medicine for PIK3CA-mutant BLCA and highlights the value of integrating metabolic biomarkers into treatment strategies for advanced BLCA.

Journal Article↗
PubMed2005

Body mass index as a predictor of prostate cancer: development versus detection on biopsy.

OBJECTIVES: To determine whether obesity is biologically associated with an increased risk of prostate cancer development, especially aggressive disease and to explore whether a bias may exist in our ability to detect these cancers in obese patients. METHODS: We evaluated the association of body mass index (BMI) with prostate cancer, biopsy Gleason sum, and amount of cancer using logistic and linear regression analyses adjusting for age at biopsy, race, prostate-specific antigen level, digital rectal examination findings, and prostate volume among 787 consecutive men undergoing prostate biopsy between 1998 and 2002 at an equal-access medical center. RESULTS: Men with a higher BMI were younger (P < 0.001), had lower prostate-specific antigen concentrations (P = 0.02), fewer abnormal digital rectal examination findings (P = 0.02), and larger prostate volumes (P < 0.001). After adjusting for age, no overall association was found between BMI and the odds of being diagnosed with cancer (P trend = 0.89), although overweight and mild obesity were inversely associated with the diagnosis of cancer. After multivariable adjustment, a higher BMI was associated with an increased odds of being diagnosed with prostate cancer (P trend = 0.007). Among men diagnosed with cancer, and after multivariable adjustment, a higher BMI was associated with a similar percentage of biopsy tissue with cancer (P trend = 0.23), but with greater odds of a high Gleason sum (P trend = 0.004). CONCLUSIONS: After taking into account the clinical characteristics that influence the likelihood of finding an existent cancer, a higher BMI was positively associated with being diagnosed with prostate cancer. Also, among the men with cancer, a higher BMI increased the odds of high-grade disease. These findings suggest that obesity may be biologically associated with prostate cancer development and, in particular, with high-grade disease.

Aged↗
PubMed2005

Prostate biopsy volume indices do not predict for significant Gleason upgrading.

Significant discordance exists between biopsy and matched prostatectomy grades. This study tests the hypothesis that surrogate tumor volume indices available from biopsies could yield an improved prediction of the underlying pathologic Gleason grade. Records of 124 patients who underwent radical prostatectomy were reviewed. Biopsies were characterized by primary and secondary Gleason grade, number of positive cores, and linear tumor length. Surgical specimens were characterized by primary and secondary Gleason grade, organ-confined disease, seminal vesicle invasion, and margins. Biochemical failure (BF) was defined by a postoperative prostate-specific antigen >0.05 ng/mL. There were 28 patients (24%) who experienced biochemical failure. On multivariate analysis, only the pathologic Gleason sum (P = 0.012) and the cumulative tumor length (P = 0.050) were independently associated with BF, and only the cumulative tumor length was associated with nonorgan-confined disease (P = 0.034). For patients with a cumulative tumor length >10 mm, 49% (18 of 37) had nonorgan-confined disease and 37% (13 of 35) had BF compared with 29% (25 of 87) and 19% (15 of 80), respectively, if they had cumulative tumor length < or =10 mm (P <0.034). Overall, an exact match was seen in 39% of biopsy Gleason grades, whereas 21% were downgraded by 1 or more points, and 41% were upgraded by 1 or more points. On univariate or multivariate analysis, none of the biopsy surrogate volume indices examined achieved significance or suggested a trend in predicting for a clinically meaningful grade change. Although indices of tumor volume from prostate needle biopsies independently predict for organ-confined disease and BF after prostatectomy, none predicted for a clinically significant upgrading or downgrading of biopsies. This suggests that the correlation that exists between such volume surrogates and outcomes after surgery reflect tumor volume effects only, independently of any possible association between tumor volume and Gleason grade.

Adenocarcinoma↗
PubMed2005

Status of women in urology: based on a report to the Society of University Urologists.

PURPOSE: Written responses from American trained women in urological surgery were obtained to evaluate practice patterns, career choices and workplace satisfaction. MATERIALS AND METHODS: A 3-page unblinded questionnaire was mailed in March 2003 to American trained women in urological surgery available through the databases of the Society of Women in Urology with subsequent statistical analysis. RESULTS: The response rate was 60% but inclusive of all women in current academic practice in the United States. A total of 61% reported working 51 or more hours a week whereas 2% have left practice due to retirement or medical infirmity. There were 41% who had completed fellowships including 87% reporting active practice within their subspecialty, whereas 62% of fellowship trained surgeons remained in an academic practice. Among United States women in academic urological practice, academic progression has occurred in a third of this cohort. CONCLUSIONS: Threats to successful practice, consistent with other workplace surveys of physicians and professional women including gender based role limitation and inadequate mentoring, were commonly reported. These correctable workplace deficiencies represent an opportunity for American urology to enhance the professional workplace for all urologists regardless of gender.

Female↗
PubMed2005

Primary care providers' attitudes toward prostate cancer risk factors at a Veterans Affairs health care facility.

OBJECTIVE: We asked what factors influence primary care providers' decision to screen patients for prostate cancer. METHODS: A survey completed by 175 Veterans Affairs primary care providers queried whether patient anxiety, family history, race, and other assorted risk factors increased their likelihood of screening for prostate cancer. Subsequent questions assessed the degree to which various factors, such as age, comorbidities, and lack of interest, decreased their likelihood of screening. RESULTS: The African American race increased the tendency for screening for 84.6%, followed by a family history of prostate cancer for 73.3%. Life expectancy of less than 5 years substantially decreased the tendency to screen for only 42.3%. Only 28% thought that age of more than 75 years was a deterrent to screening. CONCLUSIONS: Veterans Affairs primary care providers recognize the need to aggressively screen African Americans and men with a family history of prostate cancer. However, they often screen men with a limited life expectancy or advanced age.

Adult↗
PubMed2004

Biochemical outcome after radical prostatectomy among men with normal preoperative serum prostate-specific antigen levels.

BACKGROUND: Recent studies have shown that a significant number of men with normal prostate-specific antigen (PSA) levels have prostate carcinoma. Whether malignancies in such men are associated with better outcomes is unclear. The authors compared the risk of biochemical failure after radical prostatectomy (RP) between men with normal PSA levels and men with elevated PSA levels. METHODS: Data were examined from 1582 men who underwent RP between 1988 and 2002 at 1 of 5 equal-access medical centers. Patients were segregated into groups based on serum PSA levels (with stratification according to age-specific reference ranges). Clinical and pathologic characteristics and biochemical outcome data were compared across groups using analyses of variance, log-rank tests, and Cox proportional hazards analysis. RESULTS: Men who had normal PSA levels had significantly fewer high-grade tumors compared with men who had higher PSA levels (P < 0.001). The former group had a significantly decreased incidence of positive surgical margins, extracapsular disease, seminal vesicle invasion, and lymph node involvement (P < 0.001). On multivariate analysis, only serum PSA level (P < 0.001) and biopsy Gleason score (P < 0.001) predicted the time to disease recurrence. When only men with serum PSA levels < 10 ng/mL were examined, PSA level treated as a continuous variable remained a significant predictor of time to biochemical failure (P = 0.02). CONCLUSIONS: Men who had normal PSA levels had significantly fewer high-grade tumors and significantly better biochemical outcomes after undergoing RP compared with men who had elevated PSA levels. Overall, men with normal PSA levels who undergo RP represent a favorable risk group.

Aged↗
PubMed2004

Predictors of prostate-specific antigen progression among men with seminal vesicle invasion at the time of radical prostatectomy.

BACKGROUND: Seminal vesicle (SV) invasion at the time of radical prostatectomy (RP) generally is considered to be indicative of poor outcome. The authors examined whether there was a subset of men with SV invasion who had long-term prostate-specific antigen (PSA) progression-free survival. METHODS: Data were examined from 1687 men who underwent RP between 1988 and 2002 at 5 equal-access medical centers. Patients were grouped based on the presence or absence of SV invasion at the time of RP. Clinical and pathologic variables as well as biochemical outcome data were compared across the groups using rank-sum, chi-square, and log-rank tests. Multivariate Cox proportional hazards analysis was used to determine the significant predictors of time to PSA failure among men with SV invasion. RESULTS: Men with SV invasion had significantly higher PSA values, higher clinical stage, higher grade tumors, and were more likely to have concomitant extracapsular extension or a positive surgical margin. The 5-year PSA progression-free rates for men who had SV invasion was 36%, compared with 70% among men who had no SV invasion. Among men who had SV invasion, using multivariate analysis, only age (P = 0.023), pathologic Gleason score (P = 0.041), and surgical margin status (P = 0.019) were found to be independent predictors of PSA failure. By combining significant prognostic variables, the authors identified a subset of men with SV invasion, low-grade tumors (Gleason score 2-6), and negative surgical margins who had a 5-year PSA progression-free rate of 69%. Men with SV invasion, Gleason scores 2-6 tumors, negative surgical margins, and age > or = 60 years (n = 11; 8%) had a 5-year PSA progression-free rate of 100%. CONCLUSIONS: Although the majority of men with SV invasion have high-grade disease and a short time to biochemical failure, the authors identified a subset of men with low-grade disease, negative surgical margins, and older age who, despite SV invasion, had an extremely favorable clinical course. Thus, SV invasion does not uniformly suggest an unfavorable prognosis. prognosis.

Aged↗
PubMed2004

Prostate cancer diagnosed in spinal cord-injured patients is more commonly advanced stage than in able-bodied patients.

OBJECTIVES: To determine the incidence and characteristics of prostate cancer in men with spinal cord injury (SCI). Little is known about the characteristics of prostate cancer in men with SCI, because prostate cancer screening is not aggressively performed in this population. METHODS: In one fiscal year, 648 men with SCI older than age 50 years were actively enrolled with the SCI service, 20,949 able-bodied men older than age 50 years were actively enrolled in the outpatient clinic database, and 945 patients with prostate cancer were in the cancer registry at our facility. These three databases were cross-referenced for prostate cancer diagnosis and stage and compared with the presence of SCI. RESULTS: Of the 648 patients with SCI, 12 patients with a prostate cancer diagnosis that preceded their injury were excluded. Of the remaining 636 patients, 11 (1.7%) had been diagnosed with prostate cancer since their injury. In contrast, of the 20,949 able-bodied men older than age 50 years seen at our facility in fiscal year 1999, 919 (4.4%) had prostate cancer. Of the patients with SCI and prostate cancer, 7 (63.6%) had locally advanced (Stage T3) or metastatic prostate cancer compared with 267 (29.1%) in the able-bodied population (P = 0.012). CONCLUSIONS: Although the proportion of patients with a prostate cancer diagnosis was greater in the able-bodied patients, the prostate cancer detected in the patients with SCI tended to be of a more advanced stage and grade. The difference was likely a result of the decreased use of prostate cancer screening in this population.

Adenocarcinoma↗
PubMed2004

Do younger men have better biochemical outcomes after radical prostatectomy?

OBJECTIVES: To examine the relationship between age and biochemical failure after radical prostatectomy (RP), controlling for the year of surgery. Prior studies have suggested that younger men have lower prostate-specific antigen recurrence rates after RP, although none of the prior studies had controlled for the year of surgery. METHODS: We examined the data from 1753 men treated with RP between 1988 and 2002 at five equal access medical centers. We compared age, as a categorical variable according to decade of life (50 years old or younger, 51 to 60, 61 to 70, and older than 70 years), with the clinical and pathologic variables at RP, as well as the time to biochemical recurrence, using a multivariate Cox proportional hazards model. RESULTS: Age was significantly related to the year of surgery, with the more recently treated patients being younger than less recently treated patients (P <0.001). After controlling for the year of surgery, the younger men had smaller prostates, fewer high-grade tumors on biopsy, and less lymph node metastasis, but a greater percentage of cores with cancer. On multivariate analysis, men 50 years old or younger had significantly lower recurrence rates than did the older men. Moreover, men older than 70 years had significantly greater prostate-specific antigen failure rates than men aged 51 to 70 years or men aged 50 years or younger. CONCLUSIONS: The average age of men undergoing RP has decreased with time. Independent of this, young men have more favorable outcomes after RP than older men. Continued screening to detect prostate cancer among younger men when it is most curable appears warranted.

Adenocarcinoma↗
PubMed2004

Continuous, noninvasive, and localized microvascular tissue oximetry using visible light spectroscopy.

BACKGROUND: The authors evaluated the ability of visible light spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (StO2) in small, thin tissue volumes. METHODS: In pigs, StO2 was measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%), and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation). RESULTS: In pigs, normoxic StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2 (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia). CONCLUSIONS: VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.

Animals↗
PubMed2004

Preoperative model for predicting prostate specific antigen recurrence after radical prostatectomy using percent of biopsy tissue with cancer, biopsy Gleason grade and serum prostate specific antigen.

PURPOSE: We developed a preoperative model to risk stratify patients for prostate specific antigen (PSA) failure following radical prostatectomy (RP) and identify those at high risk who would be potential candidates for neoadjuvant clinical trials. MATERIALS AND METHODS: A retrospective survey of 459 patients from the SEARCH Database treated with RP between 1990 and 2002 was done. Multivariate analysis was used to compare the preoperative variables of patient age, race, PSA, biopsy Gleason score, clinical stage and percent of prostate needle biopsy tissue with cancer for the ability to predict time to PSA recurrence following RP. Significant independent predictors were combined to create a novel risk grouping model. RESULTS: On multivariate analysis biopsy Gleason score (p < 0.001), percent of biopsy tissue with cancer (p < 0.001) and serum PSA (p = 0.001) were the only significant independent predictors of PSA failure. Combining these 3 significant predictors of PSA failure using previously published cutoff points for each variable generated a 4 tier preoperative model for predicting biochemical failure following RP (HR 1.91 for each 1 risk category increase, CI 1.62 to 2.26, p < 0.001). The model further stratified patients who were already stratified into low, intermediate and high risk groups based on a previously described model using PSA, biopsy Gleason score and clinical stage. A simplified table was developed to predict the risk of biochemical recurrence within 2 years following surgery, as stratified by percent of tissue with cancer, PSA and biopsy Gleason score. CONCLUSIONS: A combination of serum PSA, biopsy Gleason score and percent of prostate biopsy tissue with cancer define a new preoperative model for predicting PSA failure following RP. This model further stratified patients who were already stratified based on PSA, biopsy Gleason score and clinical stage, and it can be used preoperatively to identify patients at high risk who would be candidates for neoadjuvant clinical trials. Using this model an easy to use table was developed to predict preoperatively the 2-year risk of PSA recurrence following RP.

Biopsy↗
PubMed2004

Lower body mass index is associated with a higher prostate cancer detection rate and less favorable pathological features in a biopsy population.

PURPOSE: Body mass index (BMI), calculated as weight in kg divided by the square of height in m, is used as an indicator of obesity. We assessed the relationship between BMI, and prostate cancer detection rates and biopsy features in a referral based biopsy population. MATERIALS AND METHODS: A total of 787 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen (PSA) greater than 4 ng/ml underwent systematic prostate biopsy. Three standard categories of BMI were considered, namely normal-less than 25, overweight-25 to 29.9 and obese-30 or greater kg/m. The presence or absence of cancer, percent of core involvement and tumor grade were correlated with BMI. Additional analyses controlled for patient age, PSA and prostate volume. RESULTS: For the entire population detection rates were highest in the normal BMI group compared to the overweight or obese group (52% vs 37% vs 42%, p = 0.0026). When stratified by age, this observation was true for men younger than 70 years (49% vs 32% vs 37%, p = 0.0042) but not for men 70 years or older. When only patients with PSA 10 ng/ml or less were considered, detection rates were highest in the normal BMI group (44% vs 28% vs 36%, p = 0.0061). This observation also persisted in patients younger than 70 years with PSA 10 ng/ml or less, or when only patients younger than 70 years with a total prostate volume of less than 50 cc were included. Of patients with cancer those with a normal BMI had a greater length of needle core involvement on biopsy. CONCLUSIONS: Normal BMI correlates with a higher cancer detection rate and larger cancers in men undergoing prostate biopsy.

Aged↗
PubMed2004

Obesity and biochemical outcome following radical prostatectomy for organ confined disease with negative surgical margins.

PURPOSE: We have previously shown that men with a body mass index (BMI) greater than 35 kg/m2 had higher rates of positive surgical margins and significantly higher biochemical recurrence rates following radical prostatectomy (RP). To determine whether the higher prostate specific antigen (PSA) recurrence rates were due solely to the higher positive margin rate, we examined whether obesity was an independent predictor of biochemical failure among men with negative surgical margins. MATERIALS AND METHODS: We examined data from 1,250 men treated with RP between 1988 and 2003 at 5 equal access medical centers, of whom 731 had pathologically organ confined disease and negative surgical margins. Multivariate Cox proportional hazards analysis was used to determine if BMI was a significant independent predictor of biochemical recurrence. RESULTS: Mean BMI significantly increased over time (p = 0.010). Black men were significantly more likely to be obese than white or nonwhite-nonblack men. After controlling for all preoperative characteristics, body mass index was a significant predictor of biochemical failure with moderately and severely obese men (BMI 35 kg/m2 or greater) having greater than a 4-fold increased risk of PSA failure (p = 0.035). After controlling for the higher pathological Gleason grades among obese men, body mass index remained a significant predictor of biochemical failure with moderately and severely obese men (BMI 35 kg/m2 or greater) having nearly a 4-fold increased risk for PSA failure (p = 0.036). CONCLUSIONS: BMI 35 kg/m2 or greater was associated with higher grade tumors and worse outcome following RP in a cohort of men with favorable pathological findings. Thus, surgical technique (margin status) cannot fully explain the worse outcomes among obese men, suggesting that obesity may be associated with a biologically more aggressive form of prostate cancer.

Black or African American↗
PubMed2003

Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital database study group.

PURPOSE: Given the limited information regarding the impact of obesity on treatment outcomes for prostate cancer, we sought to examine the relationship between body mass index (BMI) and cancer control after radical prostatectomy (RP). PATIENTS AND METHODS: We compared clinicopathologic and biochemical outcome information across BMI groups from 1,106 men treated with RP between 1988 and 2002. Multivariate analysis was used to determine if BMI significantly predicted adverse pathology or biochemical recurrence. RESULTS: Obesity was related to year of surgery (P <.001) and race (P <.001), with black men having the highest obesity rates. Obese patients had higher biopsy and pathologic grade tumors (P <.001). On multivariate analysis, BMI > or = 35 kg/m(2) was associated with a trend for higher rates of positive surgical margins (P =.008). Overweight patients (BMI, 25 to 30 kg/m(2)) had a significantly decreased risk of seminal vesicle invasion (P =.039). After controlling for all preoperative clinical variables including year of surgery, BMI > or = 35 kg/m(2) significantly predicted biochemical failure after RP (P =.002). After controlling for surgical margin status, BMI > or = 35 kg/m(2) remained a significant predictor of biochemical failure (P =.012). There was a trend for BMI > or = 35 kg/m(2) to be associated with higher failure rates than BMI between 30 and 35 kg/m(2) (P =.053). CONCLUSION: The percentage of obese men undergoing RP in our data set doubled in the last 10 years. Obesity was associated with higher-grade tumors, a trend toward increased risk of positive surgical margins, and higher biochemical failure rates among men treated with RP. A BMI > or = 35 kg/m(2) was associated with a higher risk of failure than a BMI between 30 and 35 kg/m(2).

Black People↗
PubMed2003

The percentage of prostate needle biopsy cores with carcinoma from the more involved side of the biopsy as a predictor of prostate specific antigen recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

BACKGROUND: The authors previously found that, although the total percentage of prostate needle biopsy cores with carcinoma was a significant predictor of prostate specific antigen (PSA) failure among men undergoing radical prostatectomy (RP), there was a trend toward a lower risk of recurrence in patients with positive bilateral biopsies, suggesting that high-volume, unilateral disease was a worse predictor of outcome than an equivalent number of positive cores distributed over two lobes. In the current study, the authors sought to compare the total percentage of cores with carcinoma directly with the percentage of cores from the more involved or dominant side of the prostate with carcinoma for their ability to predict outcome among men who underwent RP. METHODS: A retrospective survey of 535 patients from the Shared Equal Access Regional Cancer Hospital database who underwent RP at 4 different equal-access medical centers between 1988 and 2002 was undertaken. The total percentage of cores positive was compared with the percentage of cores positive from the dominant and nondominant sides for their ability to predict biochemical recurrence after RP. The best predictor then was compared with the standard clinical variables PSA, biopsy Gleason score, and clinical stage in terms of ability to predict time to PSA recurrence after RP using multivariate analysis. RESULTS: The adverse pathologic features of positive surgical margins and extracapsular extension were significantly more likely to be ipsilateral to the dominant side on the prostate biopsy. The percentage of cores positive from the dominant side provided slightly better prediction (concordance index [C] = 0.636) for PSA failure than the total percentage of cores positive (C = 0.596) and markedly better than the percentage of cores from the nondominant side (C = 0.509). Cutoff points for percentage of cores positive from the dominant side were identified (< 34%, 34-67%, and > 67%) that provided significant risk stratification for PSA failure (P < 0.001). On multivariate analysis, the percentage of cores positive from the dominant side was the strongest independent predictor of PSA recurrence (P < 0.001). Biopsy Gleason score (P = 0.017) also was a significant, independent predictor of recurrence. There was a trend, which did not reach statistical significance, toward an association between greater PSA values and biochemical failure (P = 0.052). Combining the PSA level, biopsy Gleason score, and percentage of cores positive from the dominant side of the prostate resulted in a model that provided a high degree of prediction for PSA failure (C = 0.671). CONCLUSIONS: The percentage of cores positive from the dominant side of the prostate was a slightly better predictor of PSA recurrence than was the total percentage of cores positive. Using the percentage of cores from the dominant side along with the PSA level and the biopsy Gleason score provided significant risk stratification for PSA failure.

Aged↗
PubMed2003

The effect of contrast material on transitional cell carcinoma viability.

In this study, increasing contrast concentration and/or exposure time decreased the growth and adherence of transitional cell carcinoma cells. Similarly, several authors have shown that the toxicity of contrast material to vascular endothelial cells in culture is related to concentration and time of exposure; this toxicity is minimized if non-ionic, low osmolar contrast is utilized. Identical trends of increasing toxicity with increasing osmolality have been documented with kidney cell lines, vascular smooth muscle cells, myocardial cells, neural cells, human fibroblasts, rat mesenchymal cells, and rat hepatocytes. The toxicity of contrast material in malignant cells (human cervical carcinoma cell lines and prostate cancer cell lines) has also been documented. Factors other than direct cellular toxicity may also affect the ability of malignant transitional cells transported with contrast material to implant on other sites in the collecting system. Zhan et al have evaluated neutrophil adhesion to contrast-exposed vascular endothelial cells. These authors observed increasing cellular adhesion with decreasing contrast dose. This was not related to osmolality as there was no similar endothelial adhesion activation with equal osmolality solutions of non-contrast solutions. The authors felt that contrast material, therefore, caused some form of modulation of cell adhesion molecules. This theory is supported by research by Owens et al that shows increases in the adhesive properties of endothelial cells to platelets after contrast exposure, and Rasmussen et al who found decreased granulocyte adherence with contrast exposure. In our study, transitional cell carcinoma cultures were placed on a collagen substrate to encourage adherence. There was an increasing number of non-adherent cells with increasing contrast concentration and exposure time, which suggests an effect of the contrast on cellular adhesion as well (Table 1). Potier et al found that rat mesangial cells were more sensitive to the cytotoxic effects of contrast agents than the less differentiated human fibroblasts were. This might suggest that the more poorly-differentiated transitional cell carcinoma cells would not be as sensitive to contrast material as low-grade tumors. However, we did not observe any differences in the responses of high- versus low-grade transitional cell tumors to exposure to contrast material. Intravenous contrast administration can lead to multiple adverse reactions, such as cardiotoxicy, nephrotoxicy, and hemodynamic toxicity. This makes non-ionic, low-osmolality agents preferable to ionic, high-osmolality agents. However, direct introduction of material into the urinary collecting system for the evaluation of transitional cell carcinoma may be less prone to seeding of viable malignant cells if ionic, high-osmolar contrast agents are utilized. Additional considerations include potential masking of very small filling defects in the upper urinary tract through opacification with extremely concentrated contrast material. Also, cytologic abnormalities are worsened by exposure to ionic, high-osmolar contrast agents, thus, any specimens for cytologic analysis should be collected prior to utilization of any contrast agents.

Aged↗