Lipophilic statins merit additional study for breast cancer chemoprevention.
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Breast Neoplasms↗
Biomedical subjects
Bruce Trock
Publications and source records attributed to Bruce Trock.
Intraoperative conversion of laparoscopic partial nephrectomy.
PURPOSE: To assess the incidence of conversion from laparoscopic partial nephrectomy (LPN) to open surgery or laparoscopic radical nephrectomy (LRN) when liberal selection criteria are utilized. PATIENTS AND METHODS: A retrospective review of medical records was done for all patients scheduled for LPN at our institution from January 2000 through March 2004. The preoperative risk factors, intraoperative course, and pathologic outcomes of patients who were converted to LRN were compared with those of the cohort of patients who underwent LPN as originally scheduled. RESULTS: Among the 257 operations that started as LPN, 35 (13.6%) were converted to LRN and 4 (1.6%) to open surgery. Age, tumor size, operating time, and hypertension were significantly higher in patients requiring conversion in than those who underwent completed LPN. Patients over the age of 70 had a 3.8-fold higher risk of requiring conversion, and, independent of age, patients with tumor>4.0 cm had a 4-fold increase in the likelihood of conversion to LRN. CONCLUSION: Of the preoperatively determined factors compared across the cohort of patients who underwent LPN and the cohort of patients converted to LRN, only tumor size and patient age were predictive of an increased risk of conversion. Other variables, including sex, side of affected kidney, clinical stage, ASA score, comorbidity with hypertension or diabetes mellitus, and surgeon were not significant in predicting conversion.
Adult↗
Racial differences in prognostic value of adult height for biochemical progression following radical prostatectomy.
PURPOSE: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. EXPERIMENTAL DESIGN: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. RESULTS: Taller men (>175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stage T(1) disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (< or =175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (P(interaction) = 0.05). CONCLUSIONS: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor-binding protein-3 concentrations among Black men may be involved.
Aged↗
Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy.
PURPOSE: Hypermethylation of the CpG island at the promoter region of the pi-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated circulating cell-free DNA GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. EXPERIMENTAL DESIGN: Prostate cancer DNA GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a data set of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering prostate-specific antigen (PSA) recurrence (median, 2 years) and 55 men who were free of disease at last follow-up (median, 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. RESULTS: Circulating cell-free DNA with GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (P = 0.003). In the matched data set, eight men (15%) who developed PSA recurrence were positive for DNA with GSTP1 CpG hypermethylation, whereas no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test, chi(2) = 6.1, P = 0.01). In a multivariable analysis that accounted for recognized prognostic factors, the presence of serum DNA with GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (hazard ratio, 4.4; 95% confidence interval, 2.2, 8.8; P < 0.001). CONCLUSION: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.
Adult↗
Multidrug resistance/P-glycoprotein and breast cancer: review and meta-analysis.
Previously untreated breast cancer is relatively sensitive to a range of anticancer drugs. However, exposure to these drugs is often followed by acquisition of multidrug resistance, which is associated with a significantly worse outcome. One of the more widely studied mechanisms of drug resistance is the function of P-glycoprotein (P-gp), a membrane transporter with a wide range of substrates, including several anticancer agents, and a member of the ATP-binding cassette superfamily of proteins. A review of the published literature indicates that P-gp expression is detected in a significant percentage of breast cancers. Moreover, P-gp expression is increased after exposure to chemotherapeutic drugs (particularly those known to be P-gp substrates), and correlates with a worse response to treatment, especially when detected following treatment, in both the adjuvant and neoadjuvant settings. Consequently, P-gp represents a potential biomarker of drug resistance. However, a direct role of P-gp as a cause of clinical drug resistance has not been adequately tested in breast cancer. Future studies aimed at validating the mechanistic role of P-gp should include trials of multidrug resistance reversal using P-gp-specific inhibitors and relating results to the levels of P-gp expression. Future studies should also take into account the potentially multifactorial nature of multidrug resistance.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Prediction of extraprostatic extension in the neurovascular bundle based on prostate needle biopsy pathology, serum prostate specific antigen and digital rectal examination.
PURPOSE: There are few studies on predictors of extraprostatic extension (EPE) in the region of the neurovascular bundle (NVB). We investigated whether clinical information and prostate biopsy data could predict EPE of clinical localized prostate cancer. MATERIALS AND METHODS: Through a retrospective analysis of the pathology database we identified 2,660 cases of clinically localized prostate cancer treated with radical retropubic prostatectomy without preoperative adjuvant therapy at The Johns Hopkins Hospital. The study sample involved a total of 3,006 lobes with prostate cancer including 2,070 with organ confined disease, 620 with EPE in the NVB at the posterolateral edge of the prostate and 316 with EPE in a region other than the NVB (EPE elsewhere). Through univariate and multivariate logistic regression analysis we determined whether patient age, year of surgery, serum prostate specific antigen, digital rectal examination, biopsy highest Gleason score, perineural invasion, percent of side specific biopsy cores with cancer, percent of each core involved with cancer and the maximum percent of a core involved with cancer was predictive of EPE in the NVB. RESULTS: Prostate specific antigen (10 or greater vs less than 10), biopsy Gleason score (7 or greater vs 6 or less), digital rectal examination (abnormal vs normal), percent of side specific cores with tumor (greater than 33.3% vs 33.3% or less) and average percent involvement of each positive core (greater than 20% vs 20% or less) were all found to be statistically significant independent predictors of NVB penetration in multivariate analysis. The generated model stratifies each of these variables into high and low risk. The probability of EPE in the NVB was less than 10% in cases with 1 or fewer of the higher risk variables and was 10% or greater in cases with more than 1 of the higher risk variables. CONCLUSIONS: The model generated in this study allows for the preoperative identification of patients with 10% or greater probability of EPE in the NVB. Our algorithm will help provide objective parameters that aid in the decision to spare the NVB safely.
Biopsy, Needle↗
A pilot study to establish a clinical model to perform phase II studies of breast cancer chemopreventive agents in women at high risk with biomarkers as surrogate endpoints for activity.
PURPOSE: Use of surrogate end point biomarkers in phase II trials may help select agents that appear to have activity and might be evaluated in future phase III definitive trials of breast cancer prevention. We performed a pilot clinical trial to establish the logistics for a clinical model to perform phase II studies of breast cancer chemopreventive agents in women at high risk with novel imaging techniques and candidate surrogate end point biomarkers for activity. We chose tamoxifen to establish proof of principal with a known effective agent. EXPERIMENTAL DESIGN: Women at a high risk of developing a new breast cancer and for whom tamoxifen was recommended were eligible. The women underwent baseline and 3 and 6 months mammogram and magnetic resonance imaging (MRI) of one breast to identify areas of water-like intensity (epithelial) and to determine the changes over time and MRI-directed core breast biopsies of these areas for surrogate end point biomarkers analysis. RESULTS: From August 1999 to March 2001, 26 women underwent baseline imaging and core biopsies. Sixteen women took tamoxifen and 10 chose not to. Overall, 79% of the samples contained glandular tissue evaluable for histology, but only 66% of the samples were evaluable for marker analysis. Only 12 patients had specimens with glandular tissue sufficient for marker analysis both at baseline and in at least one follow-up. Because of the small number of women with matched samples, marker analysis was not informative. CONCLUSIONS: This study shows the feasibility of obtaining serial core breast biopsies from women at a high risk of developing a new breast cancer. Patient participation in this model is satisfactory, and such a model may provide indication of drug activity. MRI-directed biopsy did not provide a high yield of evaluable samples, and additional work on adequate collection of epithelial tissue for surrogate end point biomarker analysis is thus necessary.
Adult↗
Preoperative somatic symptoms are associated with disease progression in patients with bladder carcinoma after cystectomy.
BACKGROUND: A link between patient psychologic factors and bladder carcinoma outcome has not been demonstrated. The purpose of the current study was to assess the association of psychologic factors measured preoperatively with bladder carcinoma progression after cystectomy. METHODS: The Brief Symptom Inventory (BSI)-18 was administered prospectively to 65 patients with clinically localized bladder carcinoma before surgery. The BSI-18 measures distress in three specific domains-depression, anxiety, and somatization (i.e., distress due to somatic symptoms)-as well as general distress. Preoperative BSI-18 scores, tumor pathologic stage, and certain clinical variables were compared with disease status. Disease progression was defined as the development of either local disease recurrence or distant metastasis. Univariate and multivariate Cox proportional hazards models were constructed for statistical analysis. RESULTS: Of the 65 patients, 49 (79.4%) had no evidence of disease, 4 (6.2%) had local disease recurrence, and 12 (18.5%) had metastatic disease at last follow-up. The mean follow-up time was 1.3 years and did not differ significantly between survival outcomes (P = 0.577). Both tumor pathologic stage and preoperative somatic distress scores were associated with time to disease progression by univariate analysis (P = 0.038 and P = 0.055, respectively). After adjusting for tumor pathologic stage, a somatic distress score of > or = 2.00 was a significant predictor of disease progression (P = 0.044, hazard ratio = 3.31, 95% confidence interval = 1.03-10.60). Patient age, gender, reconstruction type, and BSI-18 scores for depression, anxiety, and general distress were not significantly associated with disease outcome. CONCLUSIONS: The authors found no correlation between psychologic symptoms measured preoperatively (i.e., depression, anxiety, and general distress) and bladder carcinoma progression. However, they reported an association between somatic symptoms and cancer outcome. If confirmed by other studies, these results may have important implications for the diagnosis, staging, and potential treatment of patients with bladder carcinoma.
Aged↗
A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia.
PURPOSE: Efficient strategies to screen promising agents in early phase development are essential for rapid progress in breast cancer chemoprevention. We report our experience with the natural compound perillyl alcohol (POH) administered in a short-term surrogate end point biomarker (SEB) protocol, using the "window" between diagnostic and definitive surgery. EXPERIMENTAL DESIGN: Eligible patients included those with a diagnosis of atypical ductal hyperplasia, ductal carcinoma in situ, lobular carcinoma in situ, or invasive carcinoma (<3 cm in size) that required further surgery. Thirty-seven of 267 women screened were enrolled in the study (14%). Five women received single-dose POH (1.5 g/m2) 2 days before surgery, 16 received escalating doses of POH (1.2 g/m2 to 4.8 g/m2/day) for 2 days before surgery, and 16 served as untreated controls. Exploratory SEB analysis [estrogen receptor, progesterone receptor, proliferation, apoptosis, M6P/insulin-like growth factor (IGF)-2R, IGF1, IGF2 and transforming growth factor beta] was conducted before and after POH. RESULTS: Only a small portion of the population screened entered the study. Reasons for nonparticipation included protocol ineligibility, conflict of timing of surgery, miscellaneous logistical reasons, or patient's choice. POH administration was well tolerated and did not interfere with surgical management. The power to observe changes in candidate SEB was diminished by a 44% incidence of cases in which the index lesion was not present in the definitive surgical specimen. CONCLUSIONS: Preoperative POH exposure was safe and suitable for a more definitive phase II SEB study. Further investigations must overcome logistical obstacles to accrual, and they must focus on approaches to maximize tissue collection and to incorporate genomic analysis of target lesions.
Aged↗
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↗
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↗
Evaluation of water jet morcellation as an alternative to hand morcellation of renal tissue ablation during laparoscopic nephrectomy: an in vitro study.
OBJECTIVES: To evaluate the feasibility and safety of morcellation with a new prototype device that uses high-pressure water flow as a cutting/ablating tool and compare it with standard manual morcellation. METHODS: Ten porcine kidneys were morcellated with the new water jet device and ten with conventional manual morcellation. Morcellation in all cases was performed in commercially available entrapment bags. The two groups were evaluated for morcellation time, fragment size, and perforation rates (macroscopic and microscopic). RESULTS: The kidney size in both groups was similar. Morcellation was significantly (P <0.0001) faster in the water jet morcellator group than in the hand morcellation group (5.6 versus 11.9 minutes). The macroscopic evaluation after filling the entrapment bags with normal saline revealed 4 (40%) and 2 (20%) pinhole perforations in the water jet and hand morcellation groups, respectively. The microscopic evaluation revealed an 80% perforation rate in the water jet group and a 20% rate in the hand morcellator group. The size of the resulting fragments in the water jet group was not available, because the morcellated kidney was transformed in a semiliquid form. Therefore, cytology evaluation of the tissue was not possible. CONCLUSIONS: Water jet technology can be used to morcellate renal porcine tissue effectively. It is faster, but the problems of safety and histologic evaluation must be solved before this promising technology can be used in a clinical setting.
Animals↗
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↗
Assessment of perioperative psychological distress in patients undergoing radical cystectomy for bladder cancer.
PURPOSE: Despite a recent growth in our understanding of the impact of psychosocial factors on the outcome of patients with cancer there is still relatively little known about the effect of these issues on patients with genitourinary malignancies. We determined the prevalence of psychological distress in patients with bladder cancer prior to and following radical cystectomy. MATERIALS AND METHODS: A total of 74 consecutive patients with clinically organ confined bladder cancer were prospectively surveyed preoperatively using the Basic Symptom Inventory-18, a validated instrument that measures the psychological domains of general distress, anxiety, depression and somatization. Of the initial 74 patients 62 were available for postoperative assessment 1 month following cystectomy. Preoperative and postoperative distress scores were evaluated with respect to age, sex, marital status, type of surgical reconstruction and tumor stage. RESULTS: The preoperative prevalence of psychological distress in patients diagnosed with bladder cancer was 45% and it remained somewhat increased at 34% approximately 4 weeks after cystectomy. Demographic factors such as gender, age, and marital status were not significantly associated with the overall prevalence of distress. In the entire study group there was a statistically significant decrease in general distress (p = 0.028), depression (p = 0.034) and anxiety (p = 0.0004) from the preoperative to the postoperative assessments. Pathological stage was significantly associated with post-cystectomy anxiety (p = 0.040) and general distress (p = 0.042). CONCLUSIONS: Our findings indicate that a large proportion of patients with bladder cancer undergoing radical cystectomy experience psychological distress during the perioperative period. The identification of psychological distress in this population has the potential to influence health related quality of life as well as recovery in all individuals with bladder cancer.
Adult↗
Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.
It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.
Animals↗
Prevalence of Plasmodium falciparum infection in pregnant Cameroonian women.
Between 1995 and 1998, a longitudinal study was conducted at 2 health centers in Cameroon to determine the prevalence of Plasmodium falciparum infection in pregnant women. There were 520 pregnant women enrolled at a rural clinic in the village of Etoa and 199 enrolled at the Biyem Assi Clinic in the city of Yaounde. In Etoa, pregnant women were younger, fewer took prophylaxis, and malaria prevalence was higher compared with pregnant women in the Biyem Assi Clinic. The prevalence of malaria infection peaked during the fourth month of pregnancy at both sites. Age was identified as a major risk factor because women < or = 20 years old were 1.8 and 3.4 times more likely to have malaria infection than women > 20 years old at Etoa and the Biyem Assi Clinic after adjusting for gravidae and other factors. The use of chemoprophylaxis and seasonality did not have a major effect.
Adolescent↗