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Biomedical subjects

Eric Wallen

Publications and source records attributed to Eric Wallen.

7 recordsLinked to original sources

Phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy.

OBJECTIVES: Recent evidence has shown that cyclooxygenase-2 (COX-2) inhibitors have potent antitumor activity in prostate cancer both in vitro and in vivo. However, human trials are absent. This study evaluated the efficacy of the COX-2 inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer after radiation therapy (X-ray therapy or XRT) or radical prostatectomy. METHODS: Forty patients who had biochemical relapse after XRT or radical prostatectomy were treated with celecoxib 400 mg twice per day. Follow-up PSA levels were obtained at 3, 6, 12, and 18 months and subsequently every 6 months thereafter. Data were evaluated by calculating PSA doubling times and by calculating the slope of the curve of log(PSA) versus time to assess rate of PSA increase before and after celecoxib treatment for each patient. RESULTS: Thirty-six of 40 (90%) patients had a slowing effect on their rate of PSA after 3 months, including 11 of 40 with a decline and 8 of 40 with stabilization of PSA. Short-term responses at 3 months continued at 6, 12, 18 months. Comparison of rate of PSA increase before versus after celecoxib treatment showed significant flattening of slope of log(PSA) versus time from pretreatment for each of the time points. There was no significant change in testosterone levels, suggesting an androgen-independent mechanism. CONCLUSIONS: COX-2 inhibitors may have an effect on serum PSA levels in patients with biochemical progression after XRT or radical prostatectomy. These results suggest that COX-2 inhibitors may help delay or prevent disease progression in these patients and thereby help extend the time until androgen deprivation therapy.

Aged↗

Large presacral schwannoma after radical prostatectomy.

A 56-year-old man presented with long-standing, mild urinary frequency 6 years after radical prostatectomy. Pathologic assessment showed presence of organ confined prostate cancer (pT2a), Gleason 6 (3+3). Since the time of surgery, PSA level was undetectable and the patient remained without evidence of recurrent disease. However, digital rectal examination revealed the presence of a very large mass palpable on the anterior rectal wall. Therefore, the patient underwent abdominal/pelvic MRI which demonstrated presence of a solid, well-circumscribed pelvic mass extending from the level of the sacrum posteriorly to the anterior abdominal wall. Histologic examination of percutaneous biopsy of the mass was suggestive of schwannoma. The patient underwent laparotomic excision of the mass, which was confirmed to be a schwannoma, with its characteristic slender spill cells and elongate nuclei. No intra-operative complication was reported. The patient has no evidence of recurrence with complete resolution of urinary symptom one year after surgery.

Biopsy↗

Virtual pyeloscopy using volumetric depth peeling.

RATIONALE AND OBJECTIVES: The aim of the study is to test a new volume-rendering method, volumetric depth peeling (VDP), for use in virtual pyeloscopy. MATERIALS AND METHODS: VDP was applied to axial contrast-enhanced source computed tomographic (CT) images and coronal reformatted maximum intensity projections of three contrast-filled gloves containing objects of varying density. Similar renderings were performed on CT urograms performed to evaluate hematuria (n = 20). Renderings were assessed for anatomic appearance of ureters and specific calyces in comparison with source images. RESULTS: Objects of soft-tissue and calcific density ranging in size from 4 to 20 mm were identified by using VDP within the glove phantoms. Normal and deformed renal calyces were well visualized by using VDP; however, two stones were not identified. The minimal ureteral width that could be visualized was 3 mm. CONCLUSION: VDP may be a useful technique for virtual pyeloscopy providing that a robust and user-friendly computer interface can be developed.

Endoscopy↗

Characterization of biochemical recurrence after radical prostatectomy.

BACKGROUND: This study sought to characterize the variables that predict postoperative prostate-specific antigen doubling time (PSADT) and biochemical recurrence time (RT) in patients who have failed radical prostatectomy (RP). METHODS: A total of 477 patients underwent RP at our institution for clinically localized prostate cancer. Of these patients, 64 (13.4%) demonstrated evidence of postoperative biochemical failure. PSADT and biochemical RT were calculated for all patients. PSADT and RT were correlated with clinical variables including preoperative PSA level, patient age, race, prostate weight and with pathologic characteristics of the operative specimen using uni- and multivariate analyses. In addition, PSADT and RT were also correlated with each other and with the time to postoperative adjuvant therapy. RESULTS: Median postoperative PSADT for patients who recurred after radical prostatectomy was 9.7 months. Postoperative PSADT was predicted by lymph node involvement (p < 0.001) and Gleason grade (p = 0.06). Rapid PSADT also correlated with institution of postoperative adjuvant therapy (p = 0.003). Median biochemical RT for all patients was 6.7 months. Gleason grade and pathologic stage were found to be predictors of RT (p < 0.002). Postoperative PSADT did not correlate with RT (r = 0.08; p = 0.53). PSADT and RT were not different between Caucasian- versus African-Americans. CONCLUSIONS: These results serve to better characterize our cohort of patients who have evidence of biochemical recurrence after radical prostatectomy. Aggressiveness of recurrent disease (i.e. PSADT) seems to be predicted by lymph node involvement and higher pathologic grade. Furthermore, the lack of correlation of RT and PSADT suggests that early recurrences are not necessarily aggressive tumors: conversely, aggressive recurrences may occur at any point in the postoperative period. This information may aid in the postoperative treatment of recurrent disease and help to better define those patients who are at higher risk for developing clinical recurrence and who would benefit from greater vigilance during the postoperative period.

Aged↗

Erectile dysfunction and treatment of carcinoma of the prostate.

Prostate cancer is the leading malignancy in men in the United States and causes more than 60,000 deaths annually. Treatment of prostate cancer, whether it be with surgery, radiation therapy, cryotherapy, or medical treatment, is associated with significant life-altering morbidity. Incontinence and erectile dysfunction (ED) too often are sequelae of these treatment alternatives. ED can be a significant complication and can alter the life of the patient with prostate cancer and his partner. Newer modifications of the radical prostatectomy with nerve-sparing techniques are the cornerstone of erection preservation. Time following radical prostatectomy has been shown to increase erectile function such that more patients have functional erections at 3 years than 1 year after surgery. With the advent of phosphodiesterase-5 (PDE-5) inhibitors, many men can have improved functional erections and return to active coitus. Prevention of ED also is an important management technique. Evidence is gathering that prophylaxis with regular vasoactive injection or daily PDE-5 agents may be an integral part of preservation of corpus cavernosum smooth muscle function. Combination medical therapy and surgical penile prosthesis implantation also are options for patients who do not respond to oral PDE-5 inhibitors.

Aged↗

Partial nephrectomy with fibrin glue repair: measurement of vascular and pelvicaliceal hydrodynamic bond integrity in a live and abbatoir porcine model.

PURPOSE: Some of the challenges during partial nephrectomy include control of bleeding and repair of the pelvicaliceal system. Fibrin tissue sealants have recently been used to achieve hemostasis and collecting system closure in open and laparoscopic partial nephrectomy. However, there exist little data regarding the intrinsic strength of the bond, especially when applied to the vasculature and the urinary collecting system of the transected kidney. We examined the hydrodynamic bond integrity of a commercially available fibrin tissue sealant in a live porcine animal model undergoing partial nephrectomy. MATERIALS AND METHODS: Open partial nephrectomy was performed in 19 porcine renal units. Collecting system entry was confirmed by methylene blue instillation into the proximal ureter. Fibrin tissue sealant was used to repair 16 renal units, that is 8 kidneys hardened in vivo for 10 minutes and 8 hardened in vivo for 60 minutes. In an additional 3 renal units monopolar electrocautery was used to achieve hemostasis (no fibrin glue used). The strength of vasculature repair was performed by infusing saline into the renal artery (renal vein ligated) and measuring pressure at bond rupture. Similarly the integrity of pelvicaliceal repair was evaluated by retrograde infusion of saline into the collecting system via the proximal ureter and measurement of pressure at bond rupture. RESULTS: Fibrin tissue sealant was successful in achieving prompt hemostasis and it was subjectively superior to cautery alone with regard to bleeding control. Mean renal vascular and pelvicaliceal burst pressure for fibrin sealant treated kidneys was 378 (median 420) and 166 mm Hg (median 170), respectively. There was no significant difference in 10 vs 60-minute hardening times in treated kidneys. In comparison, vascular and pelvicaliceal burst pressure for nontreated (cautery alone) kidneys was 230 (median 220) and 87 mm Hg (median 90), respectively. CONCLUSIONS: Commercially available fibrin tissue sealants can provide supraphysiological renal parenchyma and collecting system sealing pressures after partial nephrectomy. This information supports the potential use of fibrin sealants during open and laparoscopic partial nephrectomy.

Abattoirs↗

Silencing of pi-class glutathione S-transferase in MDA PCa 2a and MDA PCa 2b cells.

BACKGROUND: Loss of expression of the glutathione S-transferase-pi (GSTP1) is the most common genetic alteration described in human prostate cancer, occurring in virtually all tumors regardless of grade or stage. Of the available human prostate cancer cell lines, only LNCaP mirrors this phenotype. We investigated whether the prostate cancer cell lines MDA PCa 2a and MDA PCa 2b share this phenotype. METHODS: GSTP1 protein and mRNA levels were assessed in the MDA PCa 2a and MDA PCa 2b cell lines by Western and Northern blot. DNA methylation was evaluated by Southern blot analysis of genomic DNA digested with the methylation-sensitive restriction enzymes BssHII, NotI, and SacII. Re-expression of GSTP1 was determined by RT-PCR following treatment with 5-azacytidine, a DNA methyltransferase inhibitor, and/or the histone deacetylase inhibitor trichostatin A (TSA). RESULTS: Like all human prostatic carcinomas in vivo, both the MDA PCa 2a and 2b cell lines lack protein and mRNA expression of GSTP1. This lack of expression is associated with methylation in the GSTP1 gene promoter. Treatment with the methyltransferase inhibitor 5-azacytidine resulted in re-expression of GSTP1. By itself, TSA did not result in re-expression of GSTP1, nor did it augment expression induced by 5-azacytidine. CONCLUSIONS: MDA PCa 2a and 2b appear to be useful models of human prostatic carcinoma in that they lack expression of GSTP1 due to gene silencing via promoter methylation. Inhibition of histone acetylation does not appear to affect GSTP1 expression.

DNA Methylation↗