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S L Goldenberg

Publications and source records attributed to S L Goldenberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Retroperitoneal lymphadenectomy for post-chemotherapy residual masses: is a modified dissection and resection of residual masses sufficient?

OBJECTIVE: To determine if post-chemotherapy retroperitoneal lymphadenectomy for residual masses can be limited to resection of the residual masses and a modified template dissection, without loss of therapeutic efficacy. PATIENTS AND METHODS: Between 1985 and 1995, 50 patients underwent one of three types of retroperitoneal lymphadenectomy for a residual mass after cisplatin-based chemotherapy for stages II and III testicular non-seminomatous germ cell tumour. The pre-operative imaging, operative record and pathology reports were reviewed to determine the location of the residual masses and whether tumour, defined as teratoma or viable carcinoma, was within the boundaries of the modified template and/or residual masses. The median (range) follow-up was 56 (1-140) months. RESULTS: Of 39 patients undergoing a bilateral dissection, one (2.6%) with a left testicular cancer had teratoma identified outside the boundaries of the modified template and the residual masses. The nine patients who underwent resection of residual masses and a modified-template dissection were relapse-free at a median follow-up of 55 months. One of two patients undergoing resection of residual mass alone had two recurrences arising from incomplete resection. Four of eight patients undergoing a modified dissection retained ejaculation, compared with seven of 25 (28%) undergoing a non-nerve sparing bilateral dissection. CONCLUSION: This retrospective study suggests that in patients whose tumour markers become normal and have a residual mass after chemotherapy, residual masses can be resected with a modified-template dissection with no significant risk of leaving tumour in the retroperitoneum.

Adolescent↗
PubMed1998

Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence.

PURPOSE: During a prospective cohort study to determine the effectiveness of and adverse effects associated with transurethral collagen injection for treatment of stress urinary incontinence in women, we observed 3 cases of delayed allergic reaction at the skin test site associated with arthralgia. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. Adverse effects were documented by a third party at each followup. RESULTS: Delayed reaction at the skin test site occurred in 3 patients (0.9%), and was associated with arthralgias in 2. CONCLUSIONS: The incidence and systemic nature of this type of reaction suggest that gluteraldehyde cross-linked collagen injection is not as innocuous as previously believed. Patients should be counseled regarding the unknown long-term outcome of this complication. Before treatment clinicians should consider double skin testing.

Adult↗
PubMed1998

Intermittent androgen suppression for prostate cancer: rationale and clinical experience.

The rationale behind intermittent androgen suppression (IAS) is based on: (1) observations that androgen ablation is palliative, not curative, in most patients with prostate cancer, and that quality of life must be considered; (2) the assumption that immediate androgen ablation is superior to delayed therapy in improving survival; (3) the hypothesis that if tumour cells surviving androgen withdrawal are forced into a normal pathway of differentiation by androgen replacement, then apoptotic potential might be restored and progression to androgen independence delayed. Several centres have now tested the feasibility of IAS therapy in non-randomized groups of prostate cancer patients using serum of prostate-specific antigen levels as trigger points. Clinical data suggest that prostate cancer is amenable to control by IAS and offers clinicians an opportunity to improve patients' quality of life by balancing the benefits of immediate androgen ablation (delayed progression and prolonged survival) while reducing treatment-related side effects and expense. Whether time to progression and survival is affected in a beneficial or adverse way is being studied in randomized, prospective protocols.

Androgen Antagonists↗
PubMed1998

Complications of periurethral collagen injection for stress urinary incontinence.

PURPOSE: Periurethral collagen injection has been advocated as a safe and effective method of treatment for stress urinary incontinence. This study was conducted to determine the complications associated with transurethral collagen injection for treatment of stress urinary incontinence in women. We report the incidence and management of adverse effects. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing, and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. A third party documented adverse effects at each followup. RESULTS: De novo urinary urgency with incontinence was the most frequent and serious complication, occurring in 12.6% of patients, and in many the symptoms were irreversible. Hematuria (5% of patients) and urinary retention (1.9%) were short-lived and resolved spontaneously. Delayed reaction at the skin test site occurred in 0.9% of the patients (3) and was associated with arthralgias in 2. CONCLUSIONS: Contrary to previous reports that periurethral collagen injection is complication-free, we found an overall incidence of 20% risk of complications in any given individual.

Biocompatible Materials↗
PubMed1998

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group.

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.

Adenocarcinoma↗
PubMed1997

Neoadjuvant androgen deprivation therapy before radical prostatectomy: who is unlikely to benefit?

OBJECTIVE: To determine which patients undergoing radical prostatectomy for localized cancer are unlikely to benefit from neoadjuvant androgen withdrawal therapy. PATIENTS AND METHODS: Over a 5-year period, 173 patients underwent radical retropubic prostatectomy: 87 patients received no pre-operative androgen withdrawal therapy, for whom the clinical stages were T1b (17 patients), T1c (3), T2a (31) and T2b/c (36). Pre-operative prostate biopsies contained well-differentiated cancer in 43 and moderately differentiated cancer in 44 patients. Serum prostate-specific antigen (PSA) ranged from 0.4 ng/mL to 110.1 ng/mL (median 5.0). The presence of extracapsular disease, positive surgical margins and seminal vesicle involvement were correlated with pre-operative PSA, PSA density (PSAD), the natural logarithm of PSA [In(PSA)], biopsy grade, clinical stage, and sparing of neurovascular bundles. RESULTS: Patients with a PSA < or = 4.0 ng/mL had a rate of extracapsular disease and positive margins of 8.3% and none had seminal vesicle invasion; corresponding rates for patients with a PSA > 4.0 ng/mL were 57%, 51% and 12%, respectively. Multivariate analysis revealed In(PSA) to be the best predictor of extracapsular disease (P < < 0.001), margin positivity (P < < 0.001) and seminal vesicle invasion (P = 0.0019). CONCLUSIONS: These results suggest that in patients who have clinically localized, well or moderately differentiated prostate cancer, a PSA < or = 4.0 ng/mL is predictive for organ-confined disease. This group is unlikely to benefit from neoadjuvant androgen deprivation. Ln(PSA) may be able to improve the accuracy of mathematical multivariate models predicting the presence of extracapsular disease or margin positivity, but this will require verification in larger population-based studies.

Aged↗
PubMed1997

Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model.

PURPOSE: The role of neoadjuvant androgen withdrawal before radical prostatectomy continues to be defined and remains investigational. It is unknown whether decreases in positive margin rates will translate into lower biochemical and local recurrence rates until long-term followup is available. We determined whether local recurrence rates after tumor excision were less with neoadjuvant compared to adjuvant androgen ablation in the Shionogi tumor model. Androgen withdrawal in this model triggers apoptosis and complete tumor regression but rapidly growing androgen independent tumors inevitably recur after 1 month. Conceptually, the ideal time for excision is after maximal castration induced tumor involution but before outgrowth of androgen resistant clones. MATERIALS AND METHODS: Shionogi tumors were allowed to grow to 1 to 2 gm. before mice were randomly assigned to group 1-tumor excision with wide margins and castration at tumor recurrence and group 2-neoadjuvant castration for 10 days followed by wide excision of the regressed tumor. RESULTS: Tumors recurred locally in 87% of group 1 mice after a median of 17 days (range 6 to 24) and all regressed completely with adjuvant castration. However, androgen independent tumors recurred in 92% of mice after a median of 36 days. In group 2 androgen independent disease recurred in 44% of mice after a median of 40 days. Tumor-free survival was significantly greater in group 2 than in group 1 (56 versus 20%, respectively, p <0.05). Inked surgical resection margins were positive in two-thirds of group 1 and one-third of group 2 mice. CONCLUSIONS: Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.

Animals↗
PubMed1996

Intermittent androgen suppression delays progression to androgen-independent regulation of prostate-specific antigen gene in the LNCaP prostate tumour model.

In most patients with prostate cancer, continuous androgen suppression (CAS) therapy causes tumour regression and an accompanying decrease in serum prostate specific antigen (PSA). However, with tumour progression, regulation of both tumour growth and PSA gene expression becomes androgen-independent. Because androgen resistance develops, in part, from adaptive cell survival mechanisms activated by androgen withdrawal, we hypothesize that intermittent re-exposure to androgens may prolong time to androgen-independent progression. The objective of this study was to determine whether intermittent androgen suppression (IAS) could delay the onset of androgen-independent PSA gene regulation in LNCaP prostate tumour model when compared to CAS. Five or six cycles of IAS were possible before progression developed. IAS prolonged time to androgen-independent PSA gene regulation from an average of 26 days in CAS to 77 days in IAS. Serum PSA increased above pre-castrate levels in all mice treated with CAS by 28 days post-castration, but remained below pre-castrate levels in 75% of IAS-treated mice by 60 days post-castration. By 15 weeks post-castration, serum PSA levels increased 7-fold above pre-castrate levels in CAS-treated mice compared to 1.9-fold increase in IAS-treated mice. PSA mRNA expression levels highly correlated with serum PSA levels in both groups. Maintenance of androgen dependency through IAS may be due to androgen-induced differentiation and/or down-regulation of androgen-suppressed gene expression.

Androgens↗
PubMed1996

Low-dose cyproterone acetate plus mini-dose diethylstilbestrol--a protocol for reversible medical castration.

OBJECTIVES: To determine whether a low dose of cyproterone acetate (CPA) (50 mg twice a day) with minidose diethylstilbesterol (DES) is efficacious in rapidly reducing and maintaining serum testosterone at less than 10% of pretreatment level and whether the effect is reversible upon cessation of therapy. METHODS: Data were collected prospectively on 62 subjects, aged 50 to 90 years (mean 69) with histologically confirmed prostate cancer and normal serum testosterone levels. Treatment was initiated with CPA 50 mg twice a day plus DES 0.11 mg once a day, both administered orally, and continued or 6 months unless discontinued for reasons unrelated to the study. Subsequent management was at the discretion of the investigator/managing physician. Treatment was discontinued with determination of at least one follow-up testosterone level in 28 patients. RESULTS: Mean pretreatment testosterone level was 13.8 nmol/L (range 4.5 to 46.6, median 14.0, 95% confidence interval [CI] 12.0 to 15.0). Testosterone dropped to a mean of 0.6 nmol/L (range 0.1 to 2.2, median 0.5, 95% CI 0.4 to 0.6) by first follow-up (usually 1 month) in all patients (P <0.001) and remained at this level as long as treatment continued. Testosterone normalized in all subjects whose treatment was discontinued. Side effects were minimal. CONCLUSIONS: An oral dosage of CPA of 50 mg twice a day in combination with a mini-dose of DES results in rapid and reversible reduction in serum testosterone to castrate levels. This regimen minimizes morbidity and monetary costs of therapy and allows the implementation of novel treatment approaches such as intermittent or neoadjuvant withdrawal therapy.

Aged↗
PubMed1996

Ability of serum prostate-specific antigen levels to predict normal bone scans in patients with newly diagnosed prostate cancer.

OBJECTIVES: To determine whether pretreatment serum prostate-specific antigen (PSA) levels in newly diagnosed prostate cancer patients can identify a group with a low probability of osseous metastasis and safely eliminate the need for a bone scan as a routine part of the staging evaluation. METHODS: We retrospectively reviewed 683 patients with prostate cancer between 1990 and 1993. Patients with prior therapy or serum PSA levels obtained longer than 3 months prior to bone scan were excluded. Bone scans were reviewed by two nuclear medicine physicians with a third deciding equivocal cases. RESULTS: Only 6% of 490 evaluable patients had a positive bone scan on initial evaluation. Scans were positive in 0 of 290 (0%) with PSA levels below 10 micrograms/L, 4 of 88 (4.5%) with PSA levels between 10 and 20 micrograms/L, and 24 of 112 (21%) with PSA levels above 20 micrograms/L. Although the risk of a positive bone scan increased with increasing PSA levels, PSA is a poor positive predictor of positive bone scans. The risk of a positive bone scan was 8% (5 of 64 patients) when PSA was between 20 and 50 micrograms/L, and increased to 40% (19 of 48 patients) for PSA levels greater than 50 micrograms/L. In contrast, serum PSA levels below 10 micrograms/L are strong negative predictors of positive bone scans, with no positive scans in 290 patients with PSA levels below 10 micrograms/L. Although the risk of a positive bone scan increased with increasing stage and grade, tumor stage and grade were poor negative predictors of positive bone scans. Up to 4% of patients with clinically confined or well-differentiated to moderately differentiated tumors had positive scans. Scans were positive in 12% of poorly differentiated tumors, but all these patients had PSA levels above 10 micrograms/L. CONCLUSIONS: Our data support the elimination of routine bone scintigraphy in patients with newly diagnosed prostate cancer and PSA levels below 10 micrograms/L. Bone scans are indicated when PSA levels are above 10 micrograms/L, or with T3 or poorly differentiated disease.

Adult↗
PubMed1996

Characterization of 5alpha-reductase gene expression in stroma and epithelium of human prostate.

The expression of 5alpha-reductase type 1 and type 2 isoenzymes in hyperplastic human prostate tissue and several human prostate cell lines was investigated by Northern blot analyses, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme activity. Separation of stroma and epithelium was confirmed histologically and only preparations with no apparent contamination were employed in the subsequent studies. Poly(A)+ RNA was isolated from stromal and epithelial fractions and analysed by Northern blot and RT-PCR. Inhibition of epithelial and stromal 5alpha-reductase activities by 17beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5alpha-androstan- 3-one (4MA) was assessed using a range of concentrations between 10(-13) and 10(-5) M. Results from Northern blot analyses and RT-PCR showed that the prostate stroma expressed 5alpha-reductase type 1 and type 2 isoenzymes, whereas the prostate epithelium only expressed 5alpha-reductase type 1. This was consistent with biphasic inhibition of 5alpha-reductase activity by 4MA in stroma and monophasic inhibition in epithelium. Cultured epithelial cells derived from human prostate only expressed 5alpha-reductase type 1 and had Vmax and Km values that approximated the lower end of the range reported for surgically removed prostate epithelium. The foregoing data explains the disparate activities of 5alpha-reductase, previously reported, in stroma and epithelium. The differential localization of these isoenzymes in the prostate suggests that future therapy of androgen-sensitive disease may be more successful through the use of selective inhibitors of the different 5alpha-reductase isoenzymes.

Aged↗
PubMed1996

Effects of intermittent androgen suppression on the stem cell composition and the expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma.

The proportion of tumorigenic stem cells and the expression of the apoptosis-related gene, TRPM-2 (clusterin), were studied in populations of Shionogi carcinoma cells subjected to multiple cycles of androgen withdrawal and replacement (intermittent androgen suppression). The parent androgen-dependent cell line was initially transplanted into a male mouse which was castrated when the estimated weight of the resultant tumour became approximately 3 g. After the tumour had regressed to 40% or less of the original weight, it was transplanted into the next non-castrated male. This was repeated for four cycles of transplantation and castration-induced apoptosis before the tumour progressed to an androgen-independent state. The proportion of total stem cells in the tumour, as determined by in vivo limiting dilution assays in male mice, was constant during the first three cycles but increased 15-fold between the third and fourth cycles. In the parent androgen-dependent tumour before androgen ablation, the androgen-independent stem cell population formed 0.8% of the total stem cell compartment. After the fourth cycle this population increased to 47%; a population of similar size (33%, P = 0.8) was found in the androgen-independent recurrent form of the tumour induced by one-time castration. Whether androgen withdrawal therapy was intermittent or continuous, conversion to androgen independence thus occurred when one-third to one-half of the total stem cell compartment was populated by androgen-independent stem cells. The androgen-repressed TRPM-2 (clusterin) gene was actively expressed in regressing tumours after androgen ablation, and also became constitutively expressed in non-regressing tumours after the first and subsequent cycles of androgen withdrawal. Staining of cytoplasm and nuclei with anti-clusterin antibody was observed in androgen-dependent tumour cells after each cycle of intermittent androgen suppression; the nuclear staining was more intense in recurrent androgen-independent cells. The anomalous nuclear localization of clusterin, an anti-cytolytic TRPM-2 encoded protein, may serve to inhibit early events in the apoptotic process and thereby foster the generation and outgrowth of androgen-independent stem cells in an androgen-depleted environment.

Androgens↗
PubMed1996

Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.

PURPOSE: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining. MATERIALS AND METHODS: We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly. RESULTS: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy. CONCLUSIONS: Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.

Androgen Antagonists↗
PubMed1996

Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. Canadian Urologic Oncology Group.

PURPOSE: A prospective, multicenter, randomized study was done to test the hypothesis that neoadjuvant androgen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Observations were made of 213 patients randomized to undergo radical prostatectomy alone (101) or to receive a 12-week course of 300 mg. cyproterone acetate daily followed by surgery (112). Groups were similar at baseline in terms of clinical stage, serum prostate specific antigen and Gleason score. Of 192 patients available for efficacy analysis 9 had stage T1b, 8 stage T1c, 63 stage T2a, 36 stage T2b and 76 stage T2c disease. RESULTS: One or more positive surgical margins were found in 59 of 91 patients (64.8%) in the surgery only group compared to 28 of 101 (27.7%) in the cyproterone acetate group (p = 0.001). Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not (17.8 versus 47.8%, respectively, p < 0.0001). There was no statistically significant difference in surgical (p = 0.8645) or postoperative (p = 0.173) complications between the 2 groups. CONCLUSIONS: Neoadjuvant androgen withdrawal with a 12-week course of 300 mg. cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery. The impact on patient survival will be determined by long-term followup.

Aged↗
PubMed1996

Optimal duration of neoadjuvant androgen withdrawal therapy before radical prostatectomy in clinically confined prostate cancer.

Experimental studies have shown that neoadjuvant androgen therapy dramatically reduces the rate of local recurrence after tumor excision. In the clinical setting, a 3-month course of neoadjuvant therapy before radical prostatectomy has been shown to significantly reduce positive margin rates, but follow-up is too short to assess the impact of such therapy on biochemical and clinical recurrence rates. A phase II study using an ultrasensitive assay showed that 8 months of neoadjuvant therapy were required before prostate-specific antigen (PSA) levels to reach their nadir in 84% of study participants. The positive margin rate in this study was substantially lower than those reported in the literature. Importantly, restaging of specimens after prostatic acid phosphatase (PAP) immunostaining did not upstage or increase positive margin rates. In addition, prolonged neoadjuvant therapy did not appear to result in progression of androgen-independent clones. A randomized phase III trial has been initiated to determine whether an 8-month course of neoadjuvant hormonal therapy is superior to a 3-month course in reducing positive margin rates and biochemical recurrences in patients with clinically confined prostate cancer.

Adult↗
PubMed1996

[Hormone release and intermittent hormonal therapy in the LN CaP model of human prostate cancer].

Androgen-independent progression invariably occurs following castration of patients with prostate cancer. Animal model data suggest that androgen resistance may result from adaptive cell survival mechanisms activated by androgen withdrawal. If this is true, then re-exposure to, or low levels of, androgens may suppress or downregulate these mechanisms. The objective of this study is to determine whether intermittent androgen suppression (IAS) delays the onset of nonandrogen-regulated PSA production in the LNCaP prostate tumour model, when compared to continuous androgen suppression (CAS). Serum PSA levels correlate highly with LNCaP tumour volume and decrease rapidly following castration; beginning 3-4 weeks post-castration LN CaP tumours become androgen-independent with respect to PSA gene expression and produce PSA in amounts similar to precastrate state. In this study, IAS-treated mice were implanted with testosterone pellets beginning two weeks post-castration; cycles of testosterone replacement for 1 week and withdrawal for 2 weeks were repeated until serum PSA levels no longer returned to baseline. IAS therapy prolonged time to androgen-independent PSA production 3-fold, from an average of 26 days in the CAS group to 77 days in the IAS group. Serum and LNCaP tumour mRNA PSA levels remained below precastrate levels by 60 days post-castration in 75% of the IAS group, while serum PSA in all mice in the CAS group exceeded precastrate PSA by 28 days post-castration. Following castration, serum PSA levels increased 9-fold faster with CAS compared to IAS therapy. Observations using IAS in the LNCaP tumour model suggest that the onset of androgen-independent PSA gene regulation is prolonged 3-fold, perhaps due to androgen-induced differentiation and/or downregulation of androgen-suppressed gene expression.

Androgens↗
PubMed1995

Malignant breast masses detected only by ultrasound. A retrospective review.

BACKGROUND: The authors attempted to appraise the ability of high resolution, real-time ultrasound to find malignant breast masses that are nonpalpable and undetectable by high quality mammography in women with radiographically dense breasts, who were referred because of palpable or mammographically detected lesions. METHODS: The records of breast ultrasound examinations of 12,706 women were retrospectively reviewed. All lesions were classified according to clinical and mammographic status as palpable or nonpalpable and as visible or nonvisible, respectively. Solid masses were sampled percutaneously by fine needle aspiration biopsy (FNAB) using ultrasound guidance and either were excised surgically or followed by sequential imaging. RESULTS: There were 1575 solid masses detected sonographically that were nonpalpable and nonvisible by mammography; percutaneous biopsies (FNABs) were performed on 279 of these. Cytologic interpretation was definitely malignant in 22, suspicious in 18 (6 confirmed cancers), and benign in 183 (no false negatives). Surgery confirmed malignancy in 44 of the 1575 solid masses (2.8%), including 16 in patients with multifocal cancers. CONCLUSIONS: Ultrasound can detect unsuspected, mammographically occult cancers in radiographically dense breasts and can alter treatment planning when a second cancer is found in a breast that otherwise was considered appropriate for conservative surgery. The authors recommend that any solid lesion detected incidentally during breast sonography either should be biopsied percutaneously under ultrasound guidance and/or closely followed with sequential scans.

Adult↗