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Biomedical subjects

W A See

Publications and source records attributed to W A See.

At least 37 records · Page 2Linked to original sources

Laparoscopic pelvic lymph node dissection following definitive radiotherapy for carcinoma of the prostate.

PURPOSE: Laparoscopic pelvic lymph node dissection is an effective and minimally invasive approach to the clinical staging of adenocarcinoma of the prostate. We report our experience with this technique in patients in whom full course pelvic radiotherapy had failed and who were being considered for salvage local therapy. MATERIALS AND METHODS: In 14 patients disease was staged by transperitoneal laparoscopic pelvic lymph node dissection performed for persistent adenocarcinoma of the prostate at least 20 months (average 49.5) following external beam radiotherapy and/or brachytherapy. All patients were healthy, had no evidence of metastatic disease and were considered to be candidates for salvage therapy. RESULTS: A total of 13 patients underwent successful laparoscopic pelvic lymph node dissection while 1 sustained an enterotomy requiring conversion to open surgery. The normal surgical planes were more difficult to dissect, with the obturator lymph node packets appearing smaller and more fibrotic than in nonirradiated patients, yielding an average of 7.1 total nodes. Average operative time was 167 minutes and postoperative hospitalization was comparable to reported series of nonirradiated patients. Four patients (28%) with metastatic pelvic lymph nodes underwent subsequent orchiectomy. Nine patients with negative lymph nodes underwent ultrasound guided transperineal placement of radioactive gold or palladium seeds. One patient underwent salvage radical retropubic prostatectomy. CONCLUSIONS: Laparoscopic pelvic lymph node dissection following full course pelvic irradiation is technically feasible, albeit more difficult than in nonirradiated patients. This approach appears to be an excellent minimally invasive technique for the clinical restaging of persistent adenocarcinoma of the prostate in patients being considered for salvage therapy.

Adenocarcinoma↗

Transurethral bladder tumor resection alters fibronectin expression in transitional carcinoma cell lines.

PURPOSE: To examine the effect of TGF beta 1 and post-transurethral resection of bladder tumor (TURBT) urine on fibronectin (FN) expression by transitional carcinoma (TCC) cell lines. MATERIALS AND METHODS: Northern analysis and rtPCR for mRNA transcripts, in combination with ELISA and immunohistochemistry for protein, were used to quantify the effect of TGF beta 1 and post-TURBT urine on cellular expression of FN in two TCC lines, 253J and 647V. The TGF beta 1-dependent nature of the response seen in post-TURBT urine was confirmed using exogenous TGF beta 1 or blocking antibodies to TGF beta 1. Active and latent levels of TGFb1 were measured in post-TURBT urine and urine "spiked" cell culture media. RESULTS: Baseline FN expression was low in the poorly differentiated, metastatic 253J line and high in the moderately differentiated 647V line. TGF beta 1 and post-TURBT urine increased FN expression at both the mRNA and protein levels in the 253J line. Anti-TGF beta 1 antibodies inhibited the effect of post-TURBT urine on FN expression in 253J cells. High levels of TGF beta 1 decreased FN expression in 647V cells. Only latent TGF beta 1 was present in samples of urine and media. CONCLUSIONS: FN production in low expressing TCC lines can be augmented by exogenous TGF beta 1. TURBT increases latent urinary TGF beta 1 which in turn affects TCC FN expression. Altered tumor expression of FN following TURBT may influence the effectiveness of intravesical BCG.

Carcinoma, Transitional Cell↗

Prognostic implications of extracapsular extension of lymph node metastases in prostate cancer.

We performed a retrospective review of surgical pathology specimens and clinical data for all patients with node-positive prostate cancer diagnosed in our institutions between 1985 and 1994. We used adjusted actuarial survival analyses and univariate and multivariate analyses to evaluate the clinical significance of extracapsular perinodal tumor extension. Sixty patients with histologically confirmed prostate cancer metastatic to regional lymph nodes were reviewed. Forty-two patients (70%) had evidence of extracapsular extension of the tumor into perinodal tissue. The 5-year adjusted cumulative survival rates for patients with extracapsular nodal extension was 54.6%, compared with 71.4% for patients with histologically confined nodal metastases (P < .05). Univariate and multivariate analyses revealed the presence of extracapsular nodal tumor extension to be an independent predictor of patient survival. In this study, only the histologic grade (Gleason score) of the primary tumor was a stronger predictive factor. These data suggest that histologic evidence of extracapsular tumor extension from lymph node metastases into perinodal tissue might be an important prognostic factor in patients with node-positive adenocarcinoma of the prostate. Development of a pathologic substage to include this feature might be warranted.

Adenocarcinoma↗

Disease-free and overall survival after cryosurgical monotherapy for clinical stages B and C carcinoma of the prostate: a 20-year followup.

PURPOSE: We attempt to provide insight into the historical efficacy of cryosurgical monotherapy for prostate carcinoma through a single institution, retrospective, long-term followup. MATERIALS AND METHODS: From 1973 to 1977, 66 men underwent cryosurgical monotherapy for prostate carcinoma. Patient charts were reviewed to determine age, clinical stage, tumor grade, and progression-free, overall and cause specific survival status. RESULTS: Of 51 patients 47 to 81 years old (mean age 67.2) with clinically localized carcinoma 11 had clinical stage B and 40 had stage C disease. Tumor grade was well differentiated in 11 cases, moderately differentiated in 26, poorly differentiated in 11 and undetermined in 3. Recurrence was documented in 40 of the 51 men (78.4%) as local in 34 and unspecified in 6. Following recurrence all patients were treated with adjuvant therapy. All but 2 patients were followed until death with a mean followup of 93.7 months. Of the 51 men 24 (47.1%) died of disease and 17 (33.3%) died of an unspecified cause. Kaplan-Meier analysis demonstrated median overall progression-free survival of 34 months and median overall survival of 75 months. Median progression-free survival by grade was 34 months for well differentiated, 36 for moderately differentiated and 14 for poorly differentiated disease (p = 0.0288), and 57 for stage B and 30 for stage C disease (p = 0.0377). Median overall survival by grade was 114 months for well differentiated, 80 for moderately differentiated and 82 for poorly differentiated disease (p = 0.4437), and 60 months for stage B and 78.5 for stage C disease (p = 0.4915). CONCLUSIONS: As performed in this series cryosurgery was poorly effective for local control of prostatic carcinoma. Stage and grade correlated with the duration of tumor response but not with overall survival.

Aged↗

Brachytherapy and continuous infusion 5-fluorouracil for treatment of locally advanced, lymph node negative, prostate cancer: a phase I trial.

BACKGROUND: 5-fluorouracil (5-FU) is a known radiosensitizer that enhances efficacy, in vivo and in vitro, when administered during radiotherapy. The following study was performed to evaluate the toxicity of continuous infusion 5-FU administered concomitant with brachytherapy in patients with locally advanced prostate cancer. METHODS: Over a 26-month period, a total of 25 patients with newly diagnosed, locally advanced prostate cancer underwent radioactive gold (Au198) brachytherapy. Twenty-four of 25 patients were surgically staged and confirmed node negative. Au198 seed placement was performed transperineally under fluoroscopic and ultrasonographic guidance using an average of 195 mCi of Au198. Within 4 hours after seed placement, 25 patients received 5-FU administered as a continuous infusion over 4 days, at 1 of 8 dose levels ranging from 200-1100 mg/m2/day. Patients had clinical follow-up for a minimum of 1 year. Decreases in serum prostate specific antigen (PSA) and prostate volume (normalized to pretreatment values) were determined at 12 months. RESULTS: 5-FU associated toxicity was negligible, with Grade 1 nausea in four patients and no Grade 2 or higher toxicity. No unique locoregional toxicity was noted. At 12 months after treatment, PSA values decreased on average to 16.4% of pretreatment values. Twelve-month prostate volumes decreased to 55% of the pretreatment values. CONCLUSIONS: These findings suggest that continuous infusion 5-FU can be administered safely concomitant with brachytherapy at doses up to 1100 mg/m2 per day for 4 days.

Aged↗

Paclitaxel in advanced urothelial carcinoma: its role in patients with renal insufficiency and as salvage therapy.

PURPOSE: We evaluated the role of paclitaxel in patients with advanced urothelial carcinoma and renal insufficiency or as second line therapy for metastatic disease. MATERIALS AND METHODS: Nine patients with advanced urothelial carcinoma received 175 to 250 mg./m2. paclitaxel intravenously as a 24-hour infusion. Six patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl. (range 1.9 to 3.2) and 3 with normal renal function were treated after disease progression following 1 to 2 prior chemotherapy regimens. RESULTS: Of 9 patients 5 (56%) achieved a partial response, including 4 of 6 with renal insufficiency. Toxicity was primarily hematological with 4 patients experiencing febrile neutropenia. There was no adverse impact on renal function. CONCLUSIONS: Paclitaxel as a single agent represents an effective therapeutic alternative for patients with advanced transitional cell carcinoma of the urothelium and renal insufficiency precluding cisplatin or gallium nitrate based chemotherapy. Additionally, paclitaxel appears to be effective in patients in whom prior cisplatin based therapy failed.

Adult↗

Peritoneal venous shunting for the treatment of lymphatic ascites following retroperitoneal lymph node dissection.

We report a case of refractory lymphatic ascites following retroperitoneal lymph node dissection and venacavectomy. Placement of a Denver peritoneal venous shunt resulted in resolution of the ascites and marked improvement in the patient's nutritional parameters. Shunt occlusion 2 months following placement demonstrated no recurrence of the ascites. This technique may prove useful in the management of lymphatic ascites associated with radical retroperitoneal surgery.

Adult↗

Oral bropirimine immunotherapy of carcinoma in situ of the bladder: results of a phase II trial.

OBJECTIVES: Bropirimine is an orally administered immunostimulant that has been shown to have activity against carcinoma in situ (CIS) of the bladder. To further assess this potential activity, bropirimine was administered to 42 patients for bladder CIS in a Phase II trial. METHODS: Patients were treated with bropirimine 3.0 g/day by mouth for 3 consecutive days each week up to 1 year. Cystoscopy with biopsies and bladder wash cytology were performed quarterly. RESULTS: Twenty (61%) of 33 evaluable patients converted malignant biopsies and bladder wash cytology to negative, including 6 (50%) of 12 who failed prior bacillus Calmette-Guérin (BCG) immunotherapy, 14 (67%) of 21 who had not received prior BCG therapy, and 12 (80%) of 15 with primary CIS. Median response duration exceeds 21 months. Four of the 20 responders did have a papillary tumor recurrence at 3 to 15 months, all Stage Ta or T1. Mild toxicity (grade I or II) suggestive to interferon induction or administration occurred in one third of patients. Headache, transient hepatic enzyme elevations, skin rash, and arthralgias each occurred in 5% to 14% of the patients, with nausea or emesis in 21%. Grade 1 tachycardia/palpitations or chest pain each were noted in 5%. CONCLUSIONS: Oral bropirimine can induce remission of bladder CIS with acceptable toxicity at 3.0 g/day. Bropirimine may be a valuable alternative to cystectomy for some failures of BCG therapy and may have the potential to replace BCG as front-line therapy because of its ease of administration.

Adjuvants, Immunologic↗

Incidence and management of testicular carcinoma metastatic to the neck.

PURPOSE: We evaluated the incidence and impact on outcome of neck metastasis in germ cell carcinoma. MATERIALS AND METHODS: A retrospective, institutional analysis of patients who presented with germ cell neoplasms was performed. RESULTS: During an 11-year period 7 of 155 patients (4.5%) with testis cancer had neck metastasis. The incidence of neck metastasis strongly correlated with disease stage. Selective neck dissection in 3 patients with post-chemotherapy residual neck masses demonstrated teratomatous elements in 2, with scar and necrosis in 1. CONCLUSIONS: Post-chemotherapy neck masses should be treated by definitive surgery for local disease control and to eliminate the possibility of residual neoplastic or teratomatous elements.

Adult↗

Diversity and modulation of plasminogen activator activity in human prostate carcinoma cell lines.

Baseline cellular plasminogen activator (PA) activity, and the cellular proteins responsible for variations in PA activity were evaluated in three human prostate carcinoma cell lines. Net PA activity in the cell lines PC-3, DU-145, and LNCaP was measured using a plasminogen-dependent fibrin lysis assay. These three cell lines were then analyzed to determine the specific protein(s) responsible for differences in PA activity. mRNA and protein levels of cellular urinary PA (uPA), tissue PA (tPA), PA inhibitor 1 (PAI1), PA inhibitor 2 (PAI2), and uPA receptor (uPAr) were measured using Northern analysis and ELISA assays. Net cellular PA activity in the three cell lines varied over a 3-fold range (PC3 > DU145 >> LNCaP). Net PA activity in the fibrinolysis assay demonstrated a direct correlation with mRNA transcript levels of uPA, tPA, PAI1, and uPAr (PC-3 > DU-145 > LNCaP). uPA protein was identified in both the PC-3 and the DU-145 lines. tPA, PAI1, and PAI2 proteins were identified only in PC-3 cells. In general, cellular protein levels correlated with mRNA levels. These findings demonstrate that prostate carcinoma cell lines vary in their net PA activity. This variability results from both qualitative and quantitative differences in the cellular expression of PA regulatory proteins.

Blotting, Northern↗

Histopathological features and p53 nuclear protein staining as predictors of survival and tumor recurrence in patients with transitional cell carcinoma of the renal pelvis.

PURPOSE: We determine which histopathological features are predictive of recurrence and cause-specific survival in renal pelvic transitional cell carcinoma. MATERIALS AND METHODS: Univariant and multivariant analysis was done on material from 67 patients. RESULTS: Univariate and multivariate analysis identified lamina propria invasion, grade 3 tumors and capillary-lymphatic invasion as predictors of disease-specific survival. Multicentric disease was the sole independent predictor of recurrence. Multicentric disease and lamina propria invasion were independent predictors of recurrence-free survival. Also, p53 over-expression was not statistically associated with any of the studied prognostic factors. CONCLUSIONS: Histopathological features remain the cornerstone of prognostic assessment for renal pelvic transitional cell carcinoma.

Adult↗

An outcome study of patient-controlled morphine analgesia, with or without ketorolac, following radical retropubic prostatectomy.

PURPOSE: We compared the effects of postoperative pain control strategies on recovery after radical retropubic prostatectomy. MATERIALS AND METHODS: The results in 22 consecutive patients who underwent radical retropubic prostatectomy between 1993 and 1994 were evaluated. Pain control was achieved using morphine patient-controlled analgesia in 11 patients or nonsteroidal anti-inflammatory ketorolac in 11. Outcome measures were compared between the 2 groups. RESULTS: The interval to return of bowel function, length of hospitalization and total hospital costs were significantly decreased in the ketorolac treated patients. CONCLUSIONS: Pain control with ketorolac affords excellent analgesia while allowing for earlier recovery of bowel function, shorter hospitalization and lower overall costs in patients undergoing radical retropubic prostatectomy.

Aged↗

Regulation of plasminogen activator activity in transitional carcinoma cell lines by wound site growth factors.

The effect of two growth factors ellicited in response to surgical woundings (transforming growth factor alpha [TGF alpha] and beta 1) on the regulation of cellular plasminogen activator activity (PAA) in human transitional carcinoma cell lines, with differing baseline PAA (253J--high; 647V--low), was studied. mRNA transcript levels of PA regulatory proteins in both cell lines were responsive to TGF alpha and TGF beta 1. However, both the magnitude and nature of the response differed markedly between the two lines. TGF alpha increased uPA transcript levels in both cell lines in a dose-dependent fashion. In the case of uPA receptor, exogenous TGF alpha concentrations which increased receptor levels over fivefold in the 253J line had no effect on this transcript in the 647V line. This differential responsiveness was even more pronounced for TGF beta 1. TGF beta 1 appeared to increase uPA transcript in the 253J line in a dose dependent manner while decreasing transcript levels in the 647V line. uPAr mRNA in 253J cells increased over a 19-fold range in response to TGF beta 1 while this same transcript was decreased 14-fold in 647V cells. The most pronounced effect of TGF beta 1 was seen on PAI1 transcript levels in the 253J line. This transcript increased in a concentration dependent fashion from non-detectable levels. These findings demonstrate that growth factors ellicited by surgical wounding may alter the biology of neoplastic cells. Both the growth factor milieu, and intrinsic cellular regulatory mechanism, appear important in determing net PAA in transitional carcinoma cell lines.

Carcinoma, Transitional Cell↗

Urological laparoscopic practice patterns 1 year after formal training.

The long-term impact of laparoscopic training on urological surgical practice patterns is unclear. We assessed urologist practice patterns 1 year subsequent to a formal training course in urological laparoscopic surgery. Results were compared to findings from an identical study performed 3 months following training. On 5 dates between January and October 1991, a total of 163 urologists participated in a 2-day, university sponsored, laparoscopic surgery training seminar. At 3 months and 1 year following the course, participants were mailed a 20-question survey inquiring as to the interval laparoscopic experience. Multiple questions were designed for later correlation with participant use of laparoscopic surgery. Totals of 105 and 128 course participants (64% and 78.5%) responded to the questionnaire at 3 and 12 months, respectively. No significant differences in 3-month and 12-month demographics were demonstrated with respect to practice setting, practice focus or percentage undergoing additional training. Significant increases were noted between 3 and 12 months in the number of candidates identified per month (1.5 versus 2.4), proportion of surgical case load taken by laparoscopy (2.6% versus 4.1%), number of laparoscopic patient inquiries per month (0.25 versus 1.0) and number of laparoscopies performed per month (0.55 versus 0.78). Additional post-course training was significantly correlated with clinical use at 3 and 12 months. Of the 105 and 108 respondents 64 (61%) and 83 (65%) had engaged in some form of additional training by 3 months and 1 year after the course, respectively. Additional training as well as performance of laparoscopy proved to be independent of practice setting or practice focus at 3 and 12 months. Those who attended the course with a partner were significantly more likely to have performed laparoscopy at 1 year than those who attended alone. At 12 months following course completion 66% of the respondents believed that the year of laparoscopic experience was sufficient to maintain skills. This survey suggests that laparoscopic techniques are being used consistently by urologists subsequent to formal laparoscopic training courses.

Education, Medical, Continuing↗