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Papers by David Paulson

Commentary on: “Remote Cerebellar Hemorrhage after Revision Lumbar Spine Surgery”

Global Spine Journal, 2015

Technical Note – Lateral Approach to the Lumbar Spine for the Removal of Interbody Cages

Cureus, 2015

Revision surgery to address the migration or fracture of a lumbar interbody cage can be technical... more Revision surgery to address the migration or fracture of a lumbar interbody cage can be technically challenging. Scar tissue and fibrosis, among other anatomic barriers, can make removal of the cage a complicated procedure, potentially increasing postoperative pain as well as the probability of neurologic deficits. Use of the lateral surgical technique for removal of the cage can avoid these potential complications. In this case report, we describe the removal of interbody cages through a lateral approach in three patients without the necessity of additional posterior hardware revision.

Complications of therapy for testicular cancer

The Journal of Urology, 1989

Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 ... more Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.

Neurosurgery Simulation in Residency Training

Neurosurgery, 2013

The effort required to introduce simulation in neurosurgery academic programs and the benefits pe... more The effort required to introduce simulation in neurosurgery academic programs and the benefits perceived by residents have not been systematically assessed. To create a neurosurgery simulation curriculum encompassing basic and advanced skills, cadaveric dissection, cranial and spine surgery simulation, and endovascular and computerized haptic training. A curriculum with 68 core exercises per academic year was distributed in individualized sets of 30 simulations to 6 neurosurgery residents. The total number of procedures completed during the academic year was set to 180. The curriculum includes 79 simulations with physical models, 57 cadaver dissections, and 44 haptic/computerized sessions. Likert-type evaluations regarding self-perceived performance were completed after each exercise. Subject identification was blinded to junior (postgraduate years 1-3) or senior resident (postgraduate years 4-6). Wilcoxon rank testing was used to detect differences within and between groups. One hundred eighty procedures and surveys were analyzed. Junior residents reported proficiency improvements in 82% of simulations performed (P < .001). Senior residents reported improvement in 42.5% of simulations (P < .001). Cadaver simulations accrued the highest reported benefit (71.5%; P < .001), followed by physical simulators (63.8%; P < .001) and haptic/computerized (59.1; P < .001). Initial cost is 341,978.00,with341,978.00, with 341,978.00,with27,876.36 for annual operational expenses. The systematic implementation of a simulation curriculum in a neurosurgery training program is feasible, is favorably regarded, and has a positive impact on trainees of all levels, particularly in junior years. All simulation forms, cadaver, physical, and haptic/computerized, have a role in different stages of learning and should be considered in the development of an educational simulation program.

Heat shock protein 70 (HSP70) does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-β1

Anticancer Research, 2001

Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta s... more Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta signaling pathways while heat shock protein 70 (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the interrelationship between TGF-beta and HSP70 signaling is still unknown. DU-145 prostate cancer cells were treated with 40 pM and 200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2 and p38) were analyzed by Western blot at each time-point. TGF-beta1 inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1 accumulation in the cell cycle was observed in a dose-dependent manner after 24 hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1 treatment. These data suggest that HSP70 does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.

Testicular seminoma revisited: Time for a multimodal therapeutic approach

World Journal of Urology, 1984

Urology, 1976

An aggressive approach in this systemic disease appears to be warranted.

A review: prostate monoclonal antibodies � the magic bullet

World Journal of Urology, Nov 30, 1986

Impact of pelvic lymphadenectomy in patients with prostatic adenocarcinoma

Urology, 1981

The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy w... more The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy were compared with that of 29 males receiving radical without lymphadenectomy. The adverse survival impact of positive pelvic nodes and the impact of pelvic lymphadenectomy are discussed.

Vincristine, bleomycin, methotrexate, 5-fluorouracil, and prednisone in metastatic, hormonally unresponsive prostatic adenocarcinoma☆

Urology, 1981

Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chem... more Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chemotherapy program using bleomycin, 5-fluorouracil, methotrexate, vincristine, and prednisone. Analysis of survival curves indicated that deletion of an alkylating agent from this five-drug program reduced survival when patients with equal risk factors were compared. Bleomycin was poorly tolerated by this aged population.

Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement

Prostate Cancer and Prostatic Diseases, 2007

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radic... more The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Radical Surgery Versus Radiation Therapy in Early Prostatic Carcinoma

Patients with organ-confined prostatic cancer, as determined by digital examination, bone scans a... more Patients with organ-confined prostatic cancer, as determined by digital examination, bone scans and serum acid phosphatase determination, were randomized to radical prostatectomy or external-beam radiation therapy. With respect to first evidence of treatment failure, there was a significant difference in favor of the patients who had surgical treatment. In the patients given radiotherapy there was no essential difference in time to failure as compared with comparable patients in two recent observation-only trials on record.

Immediate Adjuvant Chemotherapy versus Observation with Treatment at Relapse in Pathological Stage II Testicular Cancer

New England Journal of Medicine, 1987

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study ... more Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Cancer Immunol Immunother, 1984

The a-Pro 13-secreting hybridoma was produced by immunizing mice with an equal mixture of PC-3, D... more The a-Pro 13-secreting hybridoma was produced by immunizing mice with an equal mixture of PC-3, DU145, and LNCaP established prostatic carcinoma cell lines. The specificity of a-Pro 13 monocIonal antibody was evaluated by the criteria of differential binding to cultured cells; differential binding to extracts of malignant prostate, nonmalignant prostate, and malignant and nonmalignant tissues of various histiotypes in solid phase radioimmun6assay; and by immunoperoxidase staining of primary surgical tissues of varied histiotypes. The data generated by multiple assay investigation indicate that a-Pro 13 exhibits preferential binding to the ductal epithelium of prostate tissue; immunoperoxidase evaluation indicates a considerable heterogeneity of staining of ductal epithelial cells. The most prevalent cross-reactivity of a-Pro 13 monoclonal antibody with non-prostate tissue occurs with blood vessel endothelium of restricted tissues. Electrophoretic analysis of immunoprecipitates from radioiodinated prostatic tumor extracts indicates that the molecule recogn&ed by a-Pro 13 is of 120,000 dalton apparent nonreduced molecular weight. Under reducing conditions, the antigen (p40) consists of a major component of 40,000 dalton apparent MW and a minor component of 17,000 dalton MW. p40 has an isoelectric point of 3.5-4.5. The antigen is intrinsically st¢.ble on the PC-3 cell surface; its release into spent culture medium is negligible, p40 is also stable upon complexation with a-Pro 13 antibody in that it is not shed from the cell surface as an immune complex nor is it endocytosed to any extent as an immune complex.

p53 Immunohistochemical and Genetic Alterations are Associated at High Incidence with Post-Irradiated Locally Persistent Prostate Carcinoma

The Journal of Urology, 1996

Several reports have shown that cells with p53 mutations display increased resistance to ionizing... more Several reports have shown that cells with p53 mutations display increased resistance to ionizing radiation, a treatment often used clinically for localized prostate carcinoma. Totals of 18 post-irradiated locally recurrent prostatic carcinoma specimens and 25 (no radiation) stage D1 node-positive (TxN+MO) primary prostatic carcinoma specimens were tested for p53 immunoreactivity by immunohistochemistry. Of the 18 post-radiation locally recurrent prostatic carcinomas 10 were further analyzed by single strand conformational polymorphism to assess the validity of using this immunohistochemistry approach in irradiated tissue for detecting p53 alterations. Specimens showing p53 alterations by single strand conformational polymorphism were subjected to nucleotide sequence analysis or tested for loss of heterozygosity at a locus within the p53 gene. Of the 25 stage TxN+MO prostatic carcinomas without radiation 5 (20%) were immunoreactive (consistent with the reported incidence of positive immunoreactivity in clinical/surgical stage TxN+MO primary prostatic carcinomas). In contrast, 13 of 18 post-radiation locally recurrent prostatic carcinoma specimens (72%) were immunoreactive. Multivariate logistic regression analysis showed no dependence of p53 immunoreactivity to grade, stage or androgen status in the post-radiation locally recurrent prostatic carcinoma group, while 8 of 10 hormone naive prostatic carcinoma specimens (80%) were immunoreactive. The temporal relationship between p53 alterations and radiotherapy was assessed. Pre-irradiation prostatic carcinomas available from 5 patients with immunoreactive post-radiation locally recurrent disease were analyzed and all were immunoreactive. p53 Alteration in localized prostatic carcinoma is uncommon. Our study confirms others in that even aggressive locally advanced nonirradiated primaries (stage TxN+MO) contain only 20% incidence of p53 alterations. However, our study demonstrates that p53 alterations are found in the preponderant majority of post-radiation locally recurrent prostatic carcinoma specimens. Limited evaluation of pretreatment prostatic carcinoma biopsies uniformly documented the presence of p53 alterations before ionizing radiation, thereby demonstrating that p53 alteration was already present and was not radiation-induced or only correlated with late stage disease. This finding suggests a potential for p53 immunoreactivity to be used as a pretreatment marker that might predict local treatment failure with ionizing radiation. Large scale prospective trials would appear warranted to evaluate conclusively the potential prognostic applicability of p53 pre-screening before enrollment in definitive radiotherapy.

A Longitudinal Assessment of Bowel Related Symptoms and Fecal Incontinence Following Radical Perineal Prostatectomy

The Journal of Urology, 2003

Recent studies have suggested an increased incidence of fecal incontinence following radical peri... more Recent studies have suggested an increased incidence of fecal incontinence following radical perineal prostatectomy. We provide a prospective and longitudinal assessment of bowel related symptoms of patients undergoing radical perineal prostatectomy. A total of 78 patients who underwent radical perineal prostatectomy between January 1 and December 31, 2001 and had a minimal followup of 6 months were included in the analysis. Patient information was obtained from the chart and the bowel domain specific questions of a validated quality of life questionnaire, the Expanded Prostate Cancer Index Composite. The questionnaire was administered to the candidates preoperatively, at 4 weeks following surgery and subsequently at 3-months intervals. A mean bowel function, bother and summary health related quality of life score was calculated at each interval. The duration of new or worsened symptoms with respect to baseline was evaluated using Kaplan-Meier analysis. Symptoms of involuntary stool leakage and rectal urgency were reported by 11.5% (9 of 78) and 19.2% (15) of patients preoperatively. While all bowel related symptoms transiently increased following surgery, rectal urgency was the most persistent symptom, yet normalized in more than 90% of patients within 9 1/2 months. Compared to individual baseline 15.4%, 7.7%, 5.1% and 3.9% of patients reported worsened symptoms of fecal incontinence after 3, 6, 9 and 12 months, respectively. In the subset of 69 patients who denied preoperative fecal incontinence the incidence of involuntary stool leakage was 2.9% by 12 months following radical perineal prostatectomy. Of 10 patients 9 recovered individual health related quality of life score by 6 months after prostatectomy. Longitudinal assessment of self-reported questionnaire data suggests that fecal incontinence and bowel related symptoms are more prevalent following radical perineal prostatectomy compared to baseline, yet resolve in the majority of patients with time in the early postoperative period.

An in vitro assay was developed to measure the Chemother apeutic drug susceptibility of cells fro... more An in vitro assay was developed to measure the Chemother apeutic drug susceptibility of cells from human tumors. The assay utilized live cells, freshly isolated from tumor tissue, which were incubated for a short period in vitro. The drug- induced inhibition of incorporation of radiolabeled precursor into DNA, RNA, and protein was measured. The assay is sensitive to concentrations of

Ultrasound Determination of Prostate Volume: Comparison of Transrectal (Ellipsoid v Planimetry) and Suprapubic Methods

Journal of Endourology, 1991

Page 1. JOURNAL OF ENDOUROLOGY Volume 5, Number 3, 1991 Mary Ann Liebert, Inc., Publishers Ultras... more Page 1. JOURNAL OF ENDOUROLOGY Volume 5, Number 3, 1991 Mary Ann Liebert, Inc., Publishers Ultrasound Determination of Prostate Volume: Comparison of Transrectal (Ellipsoid Planimetry) and Suprapubic Methods ...

Treatment of metastatic endocrine-unresponsive carcinoma of the prostate gland with multiagent chemotherapy: indicators of response to therapy

Journal of the National Cancer Institute, 1979

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland... more Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.

British journal of cancer, 1979

C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been s... more C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.

Commentary on: “Remote Cerebellar Hemorrhage after Revision Lumbar Spine Surgery”

Global Spine Journal, 2015

Technical Note – Lateral Approach to the Lumbar Spine for the Removal of Interbody Cages

Cureus, 2015

Revision surgery to address the migration or fracture of a lumbar interbody cage can be technical... more Revision surgery to address the migration or fracture of a lumbar interbody cage can be technically challenging. Scar tissue and fibrosis, among other anatomic barriers, can make removal of the cage a complicated procedure, potentially increasing postoperative pain as well as the probability of neurologic deficits. Use of the lateral surgical technique for removal of the cage can avoid these potential complications. In this case report, we describe the removal of interbody cages through a lateral approach in three patients without the necessity of additional posterior hardware revision.

Complications of therapy for testicular cancer

The Journal of Urology, 1989

Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 ... more Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.

Neurosurgery Simulation in Residency Training

Neurosurgery, 2013

The effort required to introduce simulation in neurosurgery academic programs and the benefits pe... more The effort required to introduce simulation in neurosurgery academic programs and the benefits perceived by residents have not been systematically assessed. To create a neurosurgery simulation curriculum encompassing basic and advanced skills, cadaveric dissection, cranial and spine surgery simulation, and endovascular and computerized haptic training. A curriculum with 68 core exercises per academic year was distributed in individualized sets of 30 simulations to 6 neurosurgery residents. The total number of procedures completed during the academic year was set to 180. The curriculum includes 79 simulations with physical models, 57 cadaver dissections, and 44 haptic/computerized sessions. Likert-type evaluations regarding self-perceived performance were completed after each exercise. Subject identification was blinded to junior (postgraduate years 1-3) or senior resident (postgraduate years 4-6). Wilcoxon rank testing was used to detect differences within and between groups. One hundred eighty procedures and surveys were analyzed. Junior residents reported proficiency improvements in 82% of simulations performed (P < .001). Senior residents reported improvement in 42.5% of simulations (P < .001). Cadaver simulations accrued the highest reported benefit (71.5%; P < .001), followed by physical simulators (63.8%; P < .001) and haptic/computerized (59.1; P < .001). Initial cost is 341,978.00,with341,978.00, with 341,978.00,with27,876.36 for annual operational expenses. The systematic implementation of a simulation curriculum in a neurosurgery training program is feasible, is favorably regarded, and has a positive impact on trainees of all levels, particularly in junior years. All simulation forms, cadaver, physical, and haptic/computerized, have a role in different stages of learning and should be considered in the development of an educational simulation program.

Heat shock protein 70 (HSP70) does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-β1

Anticancer Research, 2001

Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta s... more Mitogen-activated protein kinase (MAPK) is one of the transforming growth factor-beta (TGF-beta signaling pathways while heat shock protein 70 (HSP70) prevents apoptosis by affecting MAPK signaling downstream. However, the interrelationship between TGF-beta and HSP70 signaling is still unknown. DU-145 prostate cancer cells were treated with 40 pM and 200 pM TGF-beta1. After 3, 6, 9, 12 and 24 hours, cell proliferation assay and cell cycle analysis were performed. The activities of HSP70 and MAPKs (c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 1 (ERK1), ERK2 and p38) were analyzed by Western blot at each time-point. TGF-beta1 inhibited the cell growth in a dose-dependent manner at 3 hours. Late G1 accumulation in the cell cycle was observed in a dose-dependent manner after 24 hours. HSP70 and JNK1 increased only at 3 hours and decreased for up to 24 hours thereafter. ERK1, ERK2 and p38 decreased from 3 to 24 hours after TGF-beta1 treatment. These data suggest that HSP70 does not prevent the inhibition of cell growth in DU-145 cells treated with TGF-beta1.

Testicular seminoma revisited: Time for a multimodal therapeutic approach

World Journal of Urology, 1984

Urology, 1976

An aggressive approach in this systemic disease appears to be warranted.

A review: prostate monoclonal antibodies � the magic bullet

World Journal of Urology, Nov 30, 1986

Impact of pelvic lymphadenectomy in patients with prostatic adenocarcinoma

Urology, 1981

The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy w... more The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy were compared with that of 29 males receiving radical without lymphadenectomy. The adverse survival impact of positive pelvic nodes and the impact of pelvic lymphadenectomy are discussed.

Vincristine, bleomycin, methotrexate, 5-fluorouracil, and prednisone in metastatic, hormonally unresponsive prostatic adenocarcinoma☆

Urology, 1981

Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chem... more Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chemotherapy program using bleomycin, 5-fluorouracil, methotrexate, vincristine, and prednisone. Analysis of survival curves indicated that deletion of an alkylating agent from this five-drug program reduced survival when patients with equal risk factors were compared. Bleomycin was poorly tolerated by this aged population.

Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement

Prostate Cancer and Prostatic Diseases, 2007

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radic... more The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Radical Surgery Versus Radiation Therapy in Early Prostatic Carcinoma

Patients with organ-confined prostatic cancer, as determined by digital examination, bone scans a... more Patients with organ-confined prostatic cancer, as determined by digital examination, bone scans and serum acid phosphatase determination, were randomized to radical prostatectomy or external-beam radiation therapy. With respect to first evidence of treatment failure, there was a significant difference in favor of the patients who had surgical treatment. In the patients given radiotherapy there was no essential difference in time to failure as compared with comparable patients in two recent observation-only trials on record.

Immediate Adjuvant Chemotherapy versus Observation with Treatment at Relapse in Pathological Stage II Testicular Cancer

New England Journal of Medicine, 1987

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study ... more Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Cancer Immunol Immunother, 1984

The a-Pro 13-secreting hybridoma was produced by immunizing mice with an equal mixture of PC-3, D... more The a-Pro 13-secreting hybridoma was produced by immunizing mice with an equal mixture of PC-3, DU145, and LNCaP established prostatic carcinoma cell lines. The specificity of a-Pro 13 monocIonal antibody was evaluated by the criteria of differential binding to cultured cells; differential binding to extracts of malignant prostate, nonmalignant prostate, and malignant and nonmalignant tissues of various histiotypes in solid phase radioimmun6assay; and by immunoperoxidase staining of primary surgical tissues of varied histiotypes. The data generated by multiple assay investigation indicate that a-Pro 13 exhibits preferential binding to the ductal epithelium of prostate tissue; immunoperoxidase evaluation indicates a considerable heterogeneity of staining of ductal epithelial cells. The most prevalent cross-reactivity of a-Pro 13 monoclonal antibody with non-prostate tissue occurs with blood vessel endothelium of restricted tissues. Electrophoretic analysis of immunoprecipitates from radioiodinated prostatic tumor extracts indicates that the molecule recogn&ed by a-Pro 13 is of 120,000 dalton apparent nonreduced molecular weight. Under reducing conditions, the antigen (p40) consists of a major component of 40,000 dalton apparent MW and a minor component of 17,000 dalton MW. p40 has an isoelectric point of 3.5-4.5. The antigen is intrinsically st¢.ble on the PC-3 cell surface; its release into spent culture medium is negligible, p40 is also stable upon complexation with a-Pro 13 antibody in that it is not shed from the cell surface as an immune complex nor is it endocytosed to any extent as an immune complex.

p53 Immunohistochemical and Genetic Alterations are Associated at High Incidence with Post-Irradiated Locally Persistent Prostate Carcinoma

The Journal of Urology, 1996

Several reports have shown that cells with p53 mutations display increased resistance to ionizing... more Several reports have shown that cells with p53 mutations display increased resistance to ionizing radiation, a treatment often used clinically for localized prostate carcinoma. Totals of 18 post-irradiated locally recurrent prostatic carcinoma specimens and 25 (no radiation) stage D1 node-positive (TxN+MO) primary prostatic carcinoma specimens were tested for p53 immunoreactivity by immunohistochemistry. Of the 18 post-radiation locally recurrent prostatic carcinomas 10 were further analyzed by single strand conformational polymorphism to assess the validity of using this immunohistochemistry approach in irradiated tissue for detecting p53 alterations. Specimens showing p53 alterations by single strand conformational polymorphism were subjected to nucleotide sequence analysis or tested for loss of heterozygosity at a locus within the p53 gene. Of the 25 stage TxN+MO prostatic carcinomas without radiation 5 (20%) were immunoreactive (consistent with the reported incidence of positive immunoreactivity in clinical/surgical stage TxN+MO primary prostatic carcinomas). In contrast, 13 of 18 post-radiation locally recurrent prostatic carcinoma specimens (72%) were immunoreactive. Multivariate logistic regression analysis showed no dependence of p53 immunoreactivity to grade, stage or androgen status in the post-radiation locally recurrent prostatic carcinoma group, while 8 of 10 hormone naive prostatic carcinoma specimens (80%) were immunoreactive. The temporal relationship between p53 alterations and radiotherapy was assessed. Pre-irradiation prostatic carcinomas available from 5 patients with immunoreactive post-radiation locally recurrent disease were analyzed and all were immunoreactive. p53 Alteration in localized prostatic carcinoma is uncommon. Our study confirms others in that even aggressive locally advanced nonirradiated primaries (stage TxN+MO) contain only 20% incidence of p53 alterations. However, our study demonstrates that p53 alterations are found in the preponderant majority of post-radiation locally recurrent prostatic carcinoma specimens. Limited evaluation of pretreatment prostatic carcinoma biopsies uniformly documented the presence of p53 alterations before ionizing radiation, thereby demonstrating that p53 alteration was already present and was not radiation-induced or only correlated with late stage disease. This finding suggests a potential for p53 immunoreactivity to be used as a pretreatment marker that might predict local treatment failure with ionizing radiation. Large scale prospective trials would appear warranted to evaluate conclusively the potential prognostic applicability of p53 pre-screening before enrollment in definitive radiotherapy.

A Longitudinal Assessment of Bowel Related Symptoms and Fecal Incontinence Following Radical Perineal Prostatectomy

The Journal of Urology, 2003

Recent studies have suggested an increased incidence of fecal incontinence following radical peri... more Recent studies have suggested an increased incidence of fecal incontinence following radical perineal prostatectomy. We provide a prospective and longitudinal assessment of bowel related symptoms of patients undergoing radical perineal prostatectomy. A total of 78 patients who underwent radical perineal prostatectomy between January 1 and December 31, 2001 and had a minimal followup of 6 months were included in the analysis. Patient information was obtained from the chart and the bowel domain specific questions of a validated quality of life questionnaire, the Expanded Prostate Cancer Index Composite. The questionnaire was administered to the candidates preoperatively, at 4 weeks following surgery and subsequently at 3-months intervals. A mean bowel function, bother and summary health related quality of life score was calculated at each interval. The duration of new or worsened symptoms with respect to baseline was evaluated using Kaplan-Meier analysis. Symptoms of involuntary stool leakage and rectal urgency were reported by 11.5% (9 of 78) and 19.2% (15) of patients preoperatively. While all bowel related symptoms transiently increased following surgery, rectal urgency was the most persistent symptom, yet normalized in more than 90% of patients within 9 1/2 months. Compared to individual baseline 15.4%, 7.7%, 5.1% and 3.9% of patients reported worsened symptoms of fecal incontinence after 3, 6, 9 and 12 months, respectively. In the subset of 69 patients who denied preoperative fecal incontinence the incidence of involuntary stool leakage was 2.9% by 12 months following radical perineal prostatectomy. Of 10 patients 9 recovered individual health related quality of life score by 6 months after prostatectomy. Longitudinal assessment of self-reported questionnaire data suggests that fecal incontinence and bowel related symptoms are more prevalent following radical perineal prostatectomy compared to baseline, yet resolve in the majority of patients with time in the early postoperative period.

An in vitro assay was developed to measure the Chemother apeutic drug susceptibility of cells fro... more An in vitro assay was developed to measure the Chemother apeutic drug susceptibility of cells from human tumors. The assay utilized live cells, freshly isolated from tumor tissue, which were incubated for a short period in vitro. The drug- induced inhibition of incorporation of radiolabeled precursor into DNA, RNA, and protein was measured. The assay is sensitive to concentrations of

Ultrasound Determination of Prostate Volume: Comparison of Transrectal (Ellipsoid v Planimetry) and Suprapubic Methods

Journal of Endourology, 1991

Page 1. JOURNAL OF ENDOUROLOGY Volume 5, Number 3, 1991 Mary Ann Liebert, Inc., Publishers Ultras... more Page 1. JOURNAL OF ENDOUROLOGY Volume 5, Number 3, 1991 Mary Ann Liebert, Inc., Publishers Ultrasound Determination of Prostate Volume: Comparison of Transrectal (Ellipsoid Planimetry) and Suprapubic Methods ...

Treatment of metastatic endocrine-unresponsive carcinoma of the prostate gland with multiagent chemotherapy: indicators of response to therapy

Journal of the National Cancer Institute, 1979

Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland... more Eighty-eight patients with metastatic and hormonally unresponsive carcinoma of the prostate gland were treated with a multiagent chemotherapy protocol. Because of the difficulty in evaluating the response of patients to therapy, data were collected in a prospective fashion and analyzed for clinical or laboratory changes that correlated with improved survivorship. Decrease of initially abnormal values of either acid or alkaline phosphotase into the normal range was associated with prolonged survival; weight gain of more than 10% was also associated with improved survival. Thirty-three patients demonstrated a fall of acid or alkaline phosphatase into the normal range or they increased their weight by at least 10%. The median survival time for this group of patients was 76.1 weeks as compared to 28.2 weeks for patients who failed to exhibit these changes. In future studies of the treatment of metastatic prostate cancer, these changes might be used as criteria of response to therapy.

British journal of cancer, 1979

C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been s... more C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.