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J Brantley Thrasher

Publications and source records attributed to J Brantley Thrasher.

33 records · Page 2Linked to original sources
PubMed2004

Complications of androgen deprivation therapy for prostate cancer.

PURPOSE OF REVIEW: Androgen deprivation as a form of treatment for prostate cancer has been used for decades. Within the last decade, however, there has been a significant increase in its use. Therefore, it is incumbent upon the physician to be familiar with the side effects associated with this treatment. RECENT FINDINGS: Some of the side effects such as osteoporosis, changes in lipid profiles, and anemia may have significant morbidity associated with them, while other side effects such as impotence, decreased libido, fatigue, and hot flashes primarily affect the patient's quality of life. Prevention strategies and treatments exist for many of these side effects. SUMMARY: This review will update physicians treating patients with androgen deprivation therapy on the side effects associated with this treatment. Once physicians are aware of the potential side effects, they can educate patients on what to expect when starting androgen deprivation therapy. More importantly, physicians can now prevent some of these complications prior to their occurrence, and when these complications occur they have knowledge of the latest treatments.

Androgen Antagonists↗
PubMed2004

Direct gastrointestinal toxicity of flutamide: comparison of irradiated and nonirradiated cases.

PURPOSE: Gastrointestinal (GI) side effects of flutamide in cases treated for advanced prostate cancer are well documented. Proposed mechanisms for these side effects include increased serum blood levels, direct vehicle effects and/or local toxicity. If local toxicity, the focus of this study, mediates GI side effects of flutamide then cases exposed to external beam radiation (XRT) should have more symptoms. We hypothesize that GI side effects of flutamide are not a direct local toxic effect resulting in a similar side effect profile for irradiated and nonirradiated cases. Thus, the present study compares GI effects of flutamide in irradiated and nonirradiated cases. MATERIALS AND METHODS: We identified 106 of 440 cases from a prior flutamide dose comparison study as having undergone XRT (56 cases) or radical prostatectomy (50 patients). The prevalence of GI side effects (abdominal pain/distention, diarrhea, constipation, nausea/vomiting and anorexia) was tallied for each treatment group and/or dosing regimen, 250 mg every 8 hours or 500 mg daily. Chi-square analysis with Yates' correction was performed for statistical analysis. RESULTS: The overall prevalence in 106 cases of GI side effects with flutamide was 22%. Treatment specific differences revealed no differences between the XRT and radical prostatectomy groups at 21% and 22%, respectively. Furthermore, independent analysis of treatment groups for each distinct side effect and dosing regimen did not identify significant differences. CONCLUSIONS: Irradiated cases are not at greater risk for the development of GI side effects from flutamide, suggesting that drug induced local toxicity does not mediate GI distress.

Aged↗
PubMed2004

Complications of androgen deprivation therapy: prevention and treatment.

Androgen deprivation, as a form of treatment for prostate cancer, has been used for decades. Within the last decade, however, its use has increased significantly. Therefore, it is incumbent upon the physician to be familiar with the side effects associated with this treatment. Some of these side effects (eg, osteoporosis, changes in lipid profiles, and anemia) may be associated with significant morbidity, whereas others (eg, impotence, decreased libido, fatigue, and hot flashes) primarily affect the patient's quality of life. Prevention strategies and treatments exist for many of these side effects. In addition, alternative forms of antiandrogen therapy such as intermittent hormone ablation and antiandrogen monotherapy may be effective, with the added benefit of minimizing side effects. This review focuses on the wide range of side effects associated with androgen ablation as well as preventive and treatment strategies.

Androgen Antagonists↗
PubMed2003

Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy.

OBJECTIVES: To define the utility of bone scan and computed tomography (CT) in the evaluation of patients with biochemical recurrence after radical prostatectomy. METHODS: A retrospective analysis of the Center for Prostate Disease Research database was undertaken to identify patients who underwent radical prostatectomy between 1989 and 1998. Patients who developed biochemical recurrence (two prostate-specific antigen [PSA] levels greater than 0.2 ng/mL) and underwent either bone scan or CT within 3 years of this recurrence were selected for analysis. The preoperative clinical parameters, pathologic findings, serum PSA levels, follow-up data, and radiographic results were reviewed. RESULTS: One hundred thirty-two patients with biochemical recurrence and a bone scan or CT scan were identified. Of the 127 bone scans, 12 (9.4%) were positive. The patients with true-positive bone scans had an average PSA at the time of the bone scan of 61.3 +/- 71.2 ng/mL (range 1.3 to 123). Their PSA velocities, calculated from the PSA levels determined immediately before the radiographic studies, averaged 22.1 +/- 24.7 ng/mL/mo (range 0.14 to 60.0). Only 2 patients with a positive bone scan had a PSA velocity of less than 0.5 ng/mL/mo. Of the 86 CT scans, 12 (14.0%) were positive. On logistic regression analysis, PSA and PSA velocity predicted the bone scan result (P <0.001 each) and PSA velocity predicted the CT scan result (P = 0.047). CONCLUSIONS: Patients with biochemical recurrence after radical prostatectomy have a low probability of a positive bone scan (9.4%) or a positive CT scan (14.0%) within 3 years of biochemical recurrence. Most patients with a positive bone scan have a high PSA level and a high PSA velocity (greater than 0.5 ng/mL/mo).

Bone Neoplasms↗
PubMed2003

Androgen stimulates matrix metalloproteinase-2 expression in human prostate cancer.

Prostate growth and differentiation is androgen dependent, and increased expression of matrix metalloproteinase 2 (MMP-2) has been found in more aggressive prostate cancers. As part of our efforts to elucidate the mechanisms responsible for prostate cancer progression, we evaluated the MMP-2 expression after androgen stimulation in human prostate cancer LNCaP and LAPC-4 cells, which express a functional androgen receptor. Treatment of the cells with a synthetic androgen R1881 resulted in an increase of pro-MMP-2 expression assessed by Western blot and gelatinolytic zymography in both cell lines. R1881-stimulated pro-MMP-2 expression occurred in a dose-dependent manner, which was completely abrogated in the presence of the nonsteroid androgen antagonist bicalutamide. In accordance with the protein expression, MMP-2 promoter activity was also increased by R1881 in a cell-based luciferase reporter assay. However, R1881 treatment did not significantly affect either the pro-MMP-9 expression or its promoter activity. Although we observed an appearance of active form of MMP-2, its activator MT1-MMP was not changed after R1881 treatment. Pretreatment of the cells with inhibitors of RNA transcription, actinomycin D, or protein translation, cycloheximide, significantly suppressed R1881-induced pro-MMP-2 expression in LNCaP cells, indicating that androgen stimulates pro-MMP-2 gene expression. In addition, phosphatidylinositol 3'-kinase inhibitor, LY294002 or wortmannin, strongly inhibited R1881-induced pro-MMP-2 expression. Finally, R1881-enhanced LNCaP cell migration was clearly suppressed by LY294002 or the MMP-2 inhibitor OA-Hy in an in vitro migration assay. In conclusion, our data demonstrated that androgen stimulates pro-MMP-2 expression in LNCaP cells via phosphatidylinositol 3'-kinase-dependent androgen receptor transactivation.

Cell Movement↗
PubMed2003

Selenium concentration in the prostate.

Samples of healthy tissue were taken from each of six prostatectomy specimens (55-72 yr), digested with acids, and analyzed for selenium by atomic fluorescence spectroscopy. The concentrations for five specimens were 1.32 +/- 0.09 microg Se/g dry wt (range 1.24-1.42) and 0.213 +/- 0.012 microg Se/g wet wt (range 0.200-0.229). The other specimen, from a 58-yr-old man who was the only one within this study to take a 200-microg Se/d dietary supplement, contained 2.72 microg Se/g dry wt and 0.421 microg Se/g wet wt.

Aged↗
PubMed2003

Complications of androgen-deprivation therapy for prostate cancer.

With the increasing indications for the use of androgen-deprivation therapy in the treatment of men with prostate cancer, side effects of the therapy deserve greater attention. Side effects such as hot flashes, decreased libido, decreased sexual function, and fatigue primarily affect the patients quality of life. Other side effects such as osteoporosis and changes in lipid profiles may also affect the patients overall health. Treatments such as estrogen, megestrol acetate, antidepressants, and bisphosphonates are useful in the management of many of the deleterious side effects of androgen deprivation. In addition, alternative management strategies such as intermittent androgen ablation and antiandrogen monotherapy may be useful in minimizing side effects caused by androgen ablation. Patients and physicians should be well aware of the potential side effects of androgen-deprivation therapy as well as the preventive and treatment strategies for these side effects in order to improve patients quality of life and health.

Androgen Antagonists↗
PubMed2003

Glycogen synthase kinase-3beta suppression eliminates tumor necrosis factor-related apoptosis-inducing ligand resistance in prostate cancer.

Prostate cancer is a major health threat for American men. Therefore, the development of effective therapeutic options is an urgent issue for prostate cancer treatment. In this study, we evaluated the effect of glycogen synthase kinase-3beta (GSK-3beta) suppression on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human prostate cancer cell lines. In the presence of lithium chloride (LiCl) or SB216763, the GSK-3beta inhibitors, TRAIL-induced cell death was dramatically enhanced, and the enhanced cell death was an augmented apoptotic response evidenced by increased Annexin V labeling and caspase-3 activation. GSK-3beta gene silencing mediated by a small interference RNA (siRNA) duplex also sensitized the cells to TRAIL, confirming the specificity of GSK-3beta suppression. Importantly, TRAIL stimulation increased GSK-3beta tyrosine phosphorylation at Y216, suggesting that GSK-3beta is activated by TRAIL. Furthermore, TRAIL sensitization was associated with increased proteolytic procession of caspase-8 and its downstream target BID, and z-IETD-FMK, the inhibitor specific to active caspase-8 totally blocked LiCl-induced TRAIL sensitization. Finally, Trichodion, a potent nuclear factor-kappaB (NF-kappaB) inhibitor, could not affect LiCl-induced TRAIL sensitization, although GSK-3beta inhibitors significantly blocked TRAIL-reduced NF-kappaB activity in prostate cancer cells. These results indicate that GSK-3beta suppression sensitizes prostate cancer cells to TRAIL-induced apoptosis that is dependent on caspase-8 activities but independent of NF-kappaB activation, and suggest that a mechanism involving GSK-3beta activation may be responsible for TRAIL resistance in prostate cancer cells.

Apoptosis↗
PubMed2002

Ejaculatory function in stage T1 nonseminomatous germ cell tumors: retroperitoneal lymph node dissection versus surveillance--a decision analysis.

PURPOSE: Ejaculatory function remains a major concern for patients with low stage nonseminomatous germ cell tumors of the testis. Whereas, it has been extensively studied in patients undergoing retroperitoneal lymph node dissection, preservation of ejaculatory function on surveillance protocols has not been studied. To compare ejaculatory function for surveillance protocols to primary retroperitoneal lymph node dissection appropriately, we constructed a decision analysis model mimicking the standard treatment algorithm for stage 1 nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: The primary clinical payoff for this study is ejaculatory function. Based on this model, we established that a primary nerve sparing retroperitoneal dissection must be performed with a 96.8% ejaculatory function rate to be recommended as the appropriate therapy. However, if a highly skilled surgeon routinely performs post-chemotherapy dissection with an ejaculatory function rate of 69.2% or greater, surveillance should be offered as the primary treatment modality. This result simply demonstrates a high skill level to allow the surgeon to salvage ejaculatory function in post-chemotherapy retroperitoneal lymph node dissection settings. If this level cannot be achieved, primary retroperitoneal lymph node dissection is the best choice. If we account for a 10% loss of ejaculatory function from primary chemotherapy, the minimum ejaculatory function rate for primary retroperitoneal dissection decreases to 95.7%. RESULTS: In the post-chemotherapy setting an 85.7% ejaculatory function rate must be achieved for surveillance to be considered the optimal choice. Clearly, less surgical rigor is needed with a primary retroperitoneal lymph node dissection when correcting for the effects of chemotherapy on ejaculatory function. Despite this fact, 1-way sensitivity analysis revealed that our model is insensitive to the ejaculatory function effects of chemotherapy. Furthermore, if the likelihood of recurrence on surveillance is greater than 16%, primary nerve sparing retroperitoneal lymph node dissection should again be recommended. CONCLUSIONS: Thus, to maximize ejaculatory function for patients with stage 1 nonseminomatous germ cell tumor a nerve sparing primary retroperitoneal lymph node dissection should always be performed, unless the likelihood of recurrence on surveillance is low or the surgical skill level allows for a highly successful post chemotherapy nerve sparing dissection.

Adult↗
PubMed2002

Long-term complications related to the modified Indiana pouch.

OBJECTIVES: To describe a single-institution, single-surgeon experience with 125 modified Indiana pouches performed during a period of 14 years and their long-term complications. The modified Indiana pouch is a widely accepted and often used form of continent urinary diversion. Few studies have established the long-term complication rates associated with the procedure. METHODS: A retrospective chart review of 129 modified Indiana pouches constructed from March 1985 to August 1998 was performed, and the long-term complications and reoperation rates were tabulated. RESULTS: Complete information was obtained for 125 of the 129 charts, with a mean follow-up of 41.1 months (range 3 to 127). Complications occurred in 112 patients (89.6%; several patients had more than one complication), with a mean onset of 20.4 months (range 1 to 125) postoperatively. Seventy-three complications (58.4%) were due to the efferent limb, of which incontinence (defined as any leakage) was the most common (35 [28.0%]), followed by stomal stenosis in 19 (15.2%) and difficult catheterization in 12 (9.6%). Of the 26 pouch-related problems (21.8%) that occurred, the most common were stones in 13 (10.4%), perioperative leaks in 5 (4.0%), and perforations in 4 (3.2%). Ureteral anastomotic strictures were seen in 9 (7.2%). Other complications included gallstones in 32 (25.6%), kidney stones in 8 (6.4%), and small bowel obstruction in 6 (4.8%). Reoperation was performed in 65 patients (52.0%; several patients with more than one reoperation). Twenty-six (20.8%) of the patients required an open operation, and 39 (31.2%) received minimally invasive (percutaneous, endoscopic, extracorporeal shock wave lithotripsy) procedures. Sixty percent of the reoperations were minimally invasive. Reoperation was due to stomal stenosis in 18 (14.4%), pouch stones in 13 (10.4%), ureteral strictures in 9 (7.2%), and parastomal hernias in 6 (4.8%). Small bowel obstruction required reoperation in 5 patients (4.0%). CONCLUSIONS: In our experience, long-term complications of the modified Indiana pouch were mostly related to the efferent limb, and reoperations were usually due to stomal stenosis. Our data suggest that with longer follow-up, the complication and reoperation rates of the modified Indiana pouch appear to be higher than previously reported.

Constriction, Pathologic↗
PubMed2002

The role of soy phytoestrogens in prostate cancer.

Epidemiological data of phytoestrogens and prostate cancer strongly supports the cancer protective effects of isoflavones found in soy products. Inhibition of cell proliferation via hormone-dependent and hormone-independent mechanisms by soy phytochemicals has been studied extensively in cell culture and animal studies. Herein, we review the current literature on the epidemiology and effects of two soy phytoestrogens, genistein and daidzein, and would stress the need for controlled human trials to assess the true preventive and therapeutic effects of these compounds.

Animals↗
PubMed2002

Multi-institutional experience with buccal mucosa onlay urethroplasty for bulbar urethral reconstruction.

PURPOSE: Buccal mucosa has been advocated as an ideal graft material for urethral reconstruction. We report our multicenter experience with buccal mucosa ventral onlay urethroplasty for complex bulbar urethral reconstruction in adults. MATERIALS AND METHODS: A retrospective analysis of patients who had undergone buccal onlay urethroplasty at 4 military medical treatment facilities participating in the Uniformed Services Urology Research Group was performed. The database generated included demographic data, genitourinary history, preoperative symptoms (American Urological Association symptom score), preoperative urinary flow rate, stricture length and operative statistics. Postoperative followup data included symptom score, flow rate, retrograde urethrogram results, and complications. RESULTS: A total of 53 patients (average age 32 years, range 17 to 64) underwent buccal mucosa graft urethroplasty between January, 1996 and March, 1998 for refractory strictures. Sixteen patients had undergone an average of 2.2 prior endoscopic procedures (range 1 to 7). Average stricture length was 3.6 plus or minus standard deviation 1.8 cm. (range 2 to 7.5) as measured on preoperative retrograde urethrogram. Followup averaged 25 months (range 11 to 40 months). Average symptom scores decreased from 21.2 (range 14 to 33) preoperatively to 5.4 (range 3 to 8) postoperatively (p <0.001). Average peak urinary flow rates increased from 7.9 preoperatively to 30.1 ml. per second postoperatively (p <0.001). Postoperative retrograde urethrograms were available for 34 patients and were normal in 24. The overall complication rate was 5.4%. Three patients required endoscopic incisions. One patient has a recurrent narrowing and treatment is considered a failure. There were 4 sacculations (7.5%) and 6 narrowings, 3 of which required further treatment. Of the patients 50 required no additional procedures (94.3%). CONCLUSIONS: Buccal mucosa grafts used as a ventral onlay for bulbar urethral reconstruction yield reproducibly excellent results with minimal morbidity and low complication rates. Longer followup will be required to confirm the durability of our results.

Adolescent↗
PubMedDate not supplied

Case selection and outcome of radical perineal prostatectomy in localized prostate cancer.

Radical prostatectomy continues to play a central role in the management of localized prostate cancer. The majority of patients diagnosed with prostate cancer will undergo radical prostatectomy. A decrease in the morbidity of this surgical procedure has been accomplished through an improved understanding of pelvic anatomy and a greater understanding of the natural history of prostate cancer. Recently, minimally invasive techniques have been applied to radical prostatectomy (laparoscopic prostatectomy) in order to further decrease the morbidity of this operation. What remains to be determined is whether this approach confers the same long term surgical outcomes as the open approach. One method which offers known long term outcomes coupled with decreased morbidity is the radical perineal prostatectomy. The purpose of this paper is to review the criteria for patient selection as well as outcomes of the radical perineal prostatectomy.

Journal Article↗
PubMedDate not supplied

Differential expression of neuropilin-1 in malignant and benign prostatic stromal tissue.

Neuropilin-1 (NRP-1), a co-receptor for VEGF165, is overexpressed in various prostate cancer cell lines and in advanced prostate tumors. However, distribution of the NRP-1 in prostate tumors has not yet been evaluated. Using immunohistochemical analysis, we evaluated 21 archival prostate tumors and 5 benign glands for the expression of NRP-1. In addition, we utilized a quantitative RT-PCR method to examine mRNA expression in 9 additional prostate tumors obtained from radical prostatectomy specimens and compared this expression to the adjacent normal tissue. The RT-PCR analyses demonstrated overexpression of NRP-1 mRNA in malignant tissue samples by 10.0-fold as compared to adjacent normal tissue. By immunohistochemistry, NRP-1 protein was undetected or minimally detected in the epithelial tumor cells. However, NRP-1 immuno-reaction was detected in the surrounding tumor stroma. Variable immuno-reaction for NRP-1 was also seen in the adjacent normal tumor stroma and the stroma of the benign prostate samples. These observations suggest that neuropilin-1 is expressed in the prostatic stromal cells, not epithelial tumor cells, and this expression is significantly increased in the malignant phenotype.

Aged↗