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Biomedical subjects

L L Pisters

Publications and source records attributed to L L Pisters.

At least 19 recordsLinked to original sources
PubMed2003

Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer.

PURPOSE: The optimal role of radiotherapy (RT) to the prostate bed after radical prostatectomy (RP) is the subject of much debate. In this study, the results of adjuvant RT (ART) and salvage RT (SRT) were compared. METHODS AND MATERIALS: A total of 146 lymph node-negative patients were treated postoperatively after RP with RT to the prostate bed between 1987 and 1998. Of these, 75 patients had an undetectable prostate-specific antigen (PSA) level and were treated with ART for adverse pathologic features only to a median dose of 60 Gy (range 51-70). A positive margin was identified in 96%, and two of the three with negative margins had seminal vesicle involvement (SVI). SRT was administered for either a persistently detectable PSA level after RP (n = 27) or for a delayed rise in PSA (n = 44) to a median dose of 70 Gy (range 60-78). Adjuvant androgen ablation was given to 37 patients; 2 who had received ART and 35 had who received SRT. The median duration of androgen ablation was 24 months. The primary end point was freedom from biochemical failure (bNED), which was considered to be an undetectable PSA level. The median follow-up was 53 months for all patients: 68 months for the ART patients and 35 months for the SRT patients. RESULTS: For the ART group, 8 patients subsequently developed a rising PSA level. The 5-year bNED rate was 88%. SVI was the strongest predictor of outcome, with a 5-year bNED rate of 94% for those without SVI and 65% for those with SVI (p = 0.0002). SVI was the only significant factor in Cox proportional hazards regression analysis in the ART cohort. For the SRT group, 20 patients developed a rising PSA level after RT. The 5-year bNED rate was 66% for all SRT patients, and 43% and 78% in those with a persistently detectable PSA and those with a delayed rise in PSA, respectively. In the Cox proportional hazards regression analysis, this subdivision of SRT was statistically significant. Moreover, when the Cox model included all patients and variables, the timing of RT (ART vs. SRT) was an independent correlate of bNED, as was androgen ablation. CONCLUSION: For RP patients with high-risk pathologic features, the timing of postoperative RT and the PSA status after RP were strong determinants of outcome. Because of the potential confounding factors, direct comparisons of ART and SRT are problematic; however, ART is extremely effective and offers the surest approach for maintaining biochemical control.

Epidemiologic Methods↗
PubMed2001

Differential expression of c-erb B2/neu, epidermal growth factor receptor, cytokeratin 8, and the prostatic steroid-binding protein gene in rat ventral prostate during postnatal development.

BACKGROUND: The development and progression of prostate neoplasia may recapitulate the early developmental pattern of expression of genes in the prostate. The study of prostate development may, therefore, provide insights into the molecular mechanisms important in prostate neoplasia and reveal new markers. METHODS: We compared postnatal expression of four genes: neu and epidermal growth factor receptor genes (EGFR), androgen-upregulated in the ventral prostate of adult rats (C-3), and androgen-repressed (CK8) in Sprague-Dawley rats. In situ hybridization was performed on prostate frozen sections collected on postnatal days 1, 5, 10, 15, 20, 30, and 60 from five rats per day. Staining intensities for antisense probes specific for each gene were determined relative to day 1 intensity. RESULTS: Growth factor receptors including neu and EGFR may be coordinately regulated in the basal-cell population during prostate development. CK8 and C-3 show evidence of similar androgen regulation during development. CONCLUSIONS: CK8 and C-3 have distinct patterns of expression in the postnatal period of development and these genes may be good markers of differentiation. Both neu and EGFR may be involved in androgen-independent growth of basal cell population in prostate. Prostate 47:164-171, 2001.

Androgen-Binding Protein↗
PubMed2001

Adult prostate sarcoma: the M. D. Anderson Cancer Center Experience.

PURPOSE: Sarcoma of prostate origin is rare. Historically, long-term survival rates for adult patients with prostate sarcoma are poor. We analyzed the experience of 1 institution with prostate sarcoma during the last 3 decades. MATERIALS AND METHODS: The records of 21 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, presence and development of metastases, staging evaluation, histological subtype, grade and size of the primary tumor, and treatment sequence, including surgery, and preoperative and postoperative therapies. Several clinicopathological variables were assessed for prognostic importance. RESULTS: Most patients presented with urinary obstruction. The diagnosis of prostate sarcoma was usually established with ultrasound guided biopsy or transurethral resection. Histological subtypes were leiomyosarcoma in 12, rhabdomyosarcoma in 4, malignant fibrous histiocytoma in 1 and unclassified sarcoma in 4 patients. At last followup, 8 patients had no evidence of disease after a median of 81.5 months (range 10 to 197). The remaining 13 patients died of sarcoma (median survival 18 months, range 3 to 94). The 1, 3 and 5-year actuarial survival rates for all 21 patients were 81%, 43% and 38%, respectively. Factors predictive of long-term survival were negative surgical margins (p = 0.0005) and absence of metastatic disease at presentation (p = 0.0004). Tumor size and grade, and the histological subtype of prostate sarcoma had no significant influence on actuarial survival. CONCLUSIONS: The long-term disease specific survival rate for adults with prostate sarcoma is poor. Early diagnosis and complete surgical resection offer patients the best chance for cure.

Humans↗
PubMed2001

Local tumor control with salvage cryotherapy for locally recurrent prostate cancer after external beam radiotherapy.

PURPOSE: We identified variables associated with a positive prostate biopsy after salvage cryotherapy in patients in whom initial external beam radiotherapy for prostate cancer failed to improve our cryotherapy technique, optimize local control and improve our patient selection criteria for salvage cryotherapy. MATERIALS AND METHODS: Between July 1992 and January 1995, 145 patients underwent salvage cryotherapy. Post-cryotherapy sextant prostate biopsies were performed in 107 cases. We evaluated certain variables on univariate and multivariate analysis as predictors of a positive biopsy after cryotherapy, including the type of previous therapy, tumor stage and grade at initial diagnosis, prostate volume, pre-cryotherapy prostate specific antigen (PSA), number of positive biopsy cores before cryotherapy, PSA nadir after cryotherapy, stage and grade of local recurrence, number of cryoprobes, number of freeze-thaw cycles and use of a urethral warming catheter during cryotherapy. RESULTS: Biopsies were positive in 23 cases (21%) after salvage cryotherapy. Variables associated with a positive biopsy on univariate analysis were initial stage, precryotherapy PSA, PSA nadir after cryotherapy, number of cryoprobes, number of freeze-thaw cycles and a history of chemotherapy (p = 0.005, 0.027, 0.001, 0.009, 0.018 and 0.008, respectively). Variables that remained associated with a positive biopsy on multivariate analysis were the number of probes used and post-cryotherapy PSA nadir (p = 0.013 and 0.019, respectively). CONCLUSIONS: Patients with initial clinical stage T1-2N0M0 disease and PSA no more than 10 ng./ml. have a higher rate of negative biopsies after salvage cryotherapy. Therefore, they are better candidates for salvage cryotherapy for locally recurrent prostate adenocarcinoma after external beam radiotherapy. To optimize the potential for local control the technique of salvage cryotherapy should include 2 freeze-thaw cycles and a minimum of 5 cryoprobes. Detectable PSA after salvage cryotherapy is a strong predictor of local failure.

Biopsy↗
PubMed2000

Ad5CMVp53 gene therapy for locally advanced prostate cancer--where do we stand?

Despite the introduction of screening procedures and an increased public awareness of prostate cancer, a substantial number of patients present with locally advanced prostate cancer. Traditional therapies (such as radiation therapy or radical prostatectomy) applied either alone or in combination fail to control local disease in a large number of cases and have no effect on disseminated disease. Recent advances in molecular oncology and genetics have led to such novel therapies as p53 gene therapy, which we are currently evaluating in a clinical protocol in patients with locally advanced (nonmetastatic) prostatic cancer. Ad5CMVp53 (RPR/INGN 201) has previously shown promise in both patients with lung cancer and those with head and neck cancer. The traditional end points used to appraise prostate cancer preclude rapid evaluation of the patient's disease and prevent modification of the therapeutic strategy, and we suggest that the pathologic stage after therapy be evaluated as an intermediate end point.

Adenoviridae↗
PubMed2000

Salvage prostatectomy with continent catheterizable urinary reconstruction: a novel approach to recurrent prostate cancer after radiation therapy.

PURPOSE: Salvage prostatectomy after full dose radiation therapy is associated with a high risk of urinary incontinence. We evaluated the complications of salvage prostatectomy with continent catheterizable reconstruction and its impact on urinary incontinence. MATERIALS AND METHODS: Between August 1995 and February 1999, 13 patients with biopsy proved, locally recurrent prostate cancer after radiation therapy underwent salvage prostatectomy with complete bladder neck closure and reconstruction with an appendicovesicostomy to the native bladder in 9 and ileovesicostomy in 4. RESULTS: There were no intraoperative complications. Four patients had serious complications necessitating reoperation, including a vesicourethral fistula requiring delayed cystectomy, wound dehiscence with disruption of the appendicovesical anastomosis, leakage from the small bowel anastomosis that resulted in sepsis and death, and stomal stenosis requiring delayed stomal revision in 1 each. Of 12 patients 2 (17%) used pads for incontinence, while 10 were dry during the day and night with a catheterization interval of 2 to 6 hours. CONCLUSIONS: Salvage prostatectomy with continent catheterizable reconstruction is a technically challenging operation with the potential for serious complications. The postoperative continence rate is excellent and appears superior to those in the literature for salvage prostatectomy and vesicourethral anastomosis.

Humans↗
PubMed2000

Magnetic resonance imaging and magnetic resonance angiography before postchemotherapy retroperitoneal lymph node dissection.

OBJECTIVES: Retroperitoneal lymph node dissection (RPLND) after primary chemotherapy is an accepted therapeutic approach for metastatic nonseminomatous germ cell testicular cancer. Because of the intense desmoplastic reaction and adherence to venous and arterial walls, accurate imaging of the retroperitoneal vasculature and its relation to residual tumor is essential. We report our experience with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), including the recently developed technique of bolus-contrast MRA, in patients undergoing postchemotherapy RPLND. METHODS: Eighteen patients underwent MRI of the retroperitoneal region before RPLND. In addition to routine sequences, MRA was performed in 10 patients, including 8 with a three-dimensional technique using bolus intravenous MR contrast. Results were compared with intraoperative and pathologic findings. RESULTS: MRI and MRA provided detailed information on retroperitoneal vasculature and its relation to tumor, including multiple renal vessels (n = 5), duplex inferior vena cava (n = 1), left retroaortic renal vein (n = 2), and common iliac vein thrombus (n = 1). In all cases, bolus-contrast MRA provided unique information on the location and number of renal and lumbar arteries, in addition to information on the aorta and the mesenteric and iliac vessels. The origin and number of renal arteries were accurately identified in all patients by bolus-contrast MRA; 2 patients had supernumerary renal arteries discovered at RPLND that had not been identified on non-bolus-contrast MRI. CONCLUSIONS: Bolus-contrast three-dimensional MRA provides unique information on renal and lumbar vessels. The potential benefit of avoiding vascular injury during dissection should be prospectively evaluated.

Adult↗
PubMed2000

Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results.

PURPOSE: We assessed the feasibility and efficacy of integrating chemotherapy and androgen ablation with radical prostatectomy in patients with locally advanced prostate cancer. The neoadjuvant approach was adopted because it allows an in situ assessment of antitumoral activity. PATIENTS AND METHODS: Thirty-three patients were enrolled who met the clinical criteria of stage T1-2, Gleason score of >/= 8 or T2b-T2c, Gleason score of 7 and prostate-specific antigen (PSA) level greater than 10 ng/mL (n = 15), or clinical stage T3 (n = 18). Therapy consisted of 12 weeks of ketoconazole and doxorubicin alternating with vinblastine, estramustine, and androgen ablation followed by prostatectomy. The ability of neoadjuvant chemotherapy and hormonal therapy to induce a 20% rate of pT0 in the prostatectomy specimen as well as surgical feasibility were assessed. RESULTS: Chemotherapy complications were comparable to those reported with this regimen previously. No major intraoperative complications occurred. Postoperative complications occurred in 10 (33%) of 30 patients. One patient died at home after discharge (postoperative day 17; no autopsy was performed). Ten (33%) of the 30 patients had organ-confined disease, and 20 (70%) of 30 had extraprostatic extension; 11 (37%) of the 30 had positive lymph nodes. Only five (17%) of 30 exhibited positive surgical margins. All patients achieved an undetectable PSA level postoperatively, and 20 of the surviving 29 patients remain without disease recurrence with a median follow-up of 13 months (range, 9 to 18 months). CONCLUSION: Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.

Adult↗
PubMed2000

Major surgery to manage definitively severe complications of salvage cryotherapy for prostate cancer.

PURPOSE: Severe complications of salvage cryotherapy may be debilitating and chronic but these complications may be managed by definitive extirpative surgical procedures. We evaluated the effectiveness of the major surgical procedures performed to manage these complications, and assessed patient survival and complications after extirpative surgery. MATERIALS AND METHODS: Between 1992 and 1995 salvage cryotherapy was performed in 150 men with biopsy proved, locally recurrent prostate cancer after radiotherapy and/or systemic therapy. We retrospectively reviewed patient charts to assess the complications managed by extirpative surgery. RESULTS: Extirpative surgery was performed in 6 of the 150 patients for serious complications, including uncontrollable hematuria, osteitis pubis, rectourethral fistula, refractory perineal pain, bladder outlet obstruction and complete urinary incontinence. Cystoprostatectomy was done in 4 patients, of whom 3 also underwent en bloc pubic symphysectomy. In the remaining 2 men salvage prostatectomy was performed with bladder neck closure and continent catheterizable stomal creation. Surgery successfully managed severe cryotherapy complications in all 6 cases. The complications of extirpative surgery included superficial wound infection in 1 patient and 3 incisional hernias in another. Prostate specific antigen was undetectable in 4 of the 6 men at 36, 38, 39 and 42 months, and detectable in 2 at 31 and 41 months, respectively. CONCLUSIONS: Extirpative surgery may successfully alleviate severe salvage cryotherapy complications without major additive morbidity. Long survival duration justifies extirpative surgery in select patients with severe complications of salvage cryotherapy.

Adenocarcinoma↗
PubMed1999

Transrectal ultrasound-guided intraprostatic injection of absolute ethanol with and without carmustine: a feasibility study in the canine model.

OBJECTIVES: To develop a reliable intraprostatic injection technique and to define the local and systemic toxicity of intraprostatic injection of dehydrated ethanol with and without carmustine. METHODS: Twenty-three random-source male canines were divided into a control group (n = 3), a dehydrated ethanol-alone group (group 1, n = 10), and a dehydrated ethanol-plus-carmustine group (group 2, n = 10). A reliable intraprostatic injection technique was developed with the control animals. The optimal volume of dehydrated ethanol for intraprostatic injection and the local tissue effects of dehydrated ethanol injection were defined with group 1. The local tissue effects of escalating doses of carmustine were defined with group 2. All animals were injected under general anesthesia using transrectal ultrasound (TRUS) guidance. Fourteen days after injection, a repeated TRUS of the prostate was done, the animals were killed, and the bladder, prostate, and periprostatic tissues were excised for pathologic examination. RESULTS: Sonographic changes in the prostate 2 weeks after injection were present in all group 1 and 2 animals. All prostates had varying amounts of hemorrhagic and coagulative necrosis, which correlated with the TRUS findings. There were no differentiating pathologic features between group 1 and group 2 specimens. The relative amount of necrosis varied with the doses of dehydrated ethanol and carmustine injected, but was not predictable on the basis of the doses administered. Subclinical prostatic microabscesses were identified in 6 of 10 group 1 animals and 4 of 10 group 2 animals. Only group 2 animals had alterations in their blood chemistry results, all of which were self-limited. Two had white blood cell nadirs of less than 2000 5 days after injection. No animals developed incontinence, and there were no rectal injuries. CONCLUSIONS: Intraprostatic dehydrated ethanol and carmustine injections were readily controllable under TRUS guidance and resulted in hemorrhagic and coagulative necrosis of prostatic tissue with minimal associated morbidity and no incontinence in the dog model. Hematologic changes observed in the animals that received carmustine were self-limiting.

Animals↗
PubMed1999

Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy.

PURPOSE: Our objective was to identify clinical pretreatment factors associated with early treatment failure after salvage cryotherapy. PATIENTS AND METHODS: Between 1992 and 1995, 145 patients underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Treatment failure was defined as an increasing postcryotherapy serial prostate-specific antigen (PSA) level of more than or equal to 2 ng/mL above the postcryotherapy nadir or as a positive posttreatment biopsy. We evaluated the following factors as predictors of treatment failure: tumor stage and grade at initial diagnosis, type of prior therapy, stage and grade of locally recurrent tumor, number of positive biopsy cores at recurrence, and precryotherapy PSA level. RESULTS: Among patients with a prior history of radiation therapy only, the 2-year actuarial disease-free survival (DFS) rates were 74% for patients with a precryotherapy PSA less than 10 ng/mL and 28% for patients with a precryotherapy PSA more than 10 ng/mL, P <.00001. The DFS rates were 58% for patients with a Gleason score of less than or equal to 8 recurrence and 29% for patients with a Gleason score greater than or equal to 9 recurrence, P <.004. Among patients with a precryotherapy PSA less than 10 ng/mL, DFS rates were 74% for patients with a prior history of radiation therapy only and 19% for patients with a history of prior hormonal therapy plus radiation therapy, P <.002. CONCLUSION: Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged. Patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only.

Adenocarcinoma↗
PubMed1999

p53 mutations in prostate cancer bone metastases suggest that selected p53 mutants in the primary site define foci with metastatic potential.

PURPOSE: This study was undertaken to establish the pattern of specific p53 gene mutations in prostate cancer within primary tumors and distant metastases. MATERIALS AND METHODS: We performed polymerase chain reaction-single-strand conformation polymorphism and sequencing analyses of p53 exons 5-8 in DNA extracted from 22 formalin-fixed, paraffin-embedded tissues from 17 patients. Samples from three patients included specimens from primary and metastatic sites (paired specimens). RESULTS: G:C-to-A:T transitions were the most common point mutations (64%). Six (55%) of 11 G:C-to-A:T transitions occurred at CpG dinucleotides in five hot-spot codons (175, 245, 248, 273, and 282). Sequencing analysis of the paired samples revealed that two of the three pairs had the same mutation in both. Sequencing analysis of DNA from a different area of one of the primary tumors revealed a different mutation in the p53 gene. CONCLUSIONS: Our results suggest that specific p53 mutations participate in the progression of human prostate cancer. These findings support those of others that indicate that the primary cancer is heterogeneous and clonal expansion occurs during the progression of clinically detectable prostate cancer. Our data also imply that p53 mutations at the primary site may be predictive of metastases.

Aged↗
PubMed1999

Quality of life after salvage cryotherapy: the impact of treatment parameters.

PURPOSE: Cryotherapy has emerged as a promising salvage therapy option for treatment of locally recurrent prostate cancer after initial therapy. In this retrospective study we evaluate patient quality of life after salvage cryotherapy and correlate complications impairing quality of life with specific cryotherapy treatment parameters. MATERIALS AND METHODS: A modified UCLA Prostate Cancer Index measuring health related quality of life was sent to 150 patients who underwent salvage cryotherapy between July 1992 and April 1995. We evaluated the relationships among incontinence, pain, impotence, sloughing of tissue and problematic voiding symptoms, and cryotherapy treatment parameters, including use of a urethral warming catheter, number of cryotherapy probes and number of freeze-thaw cycles. We also evaluated patient overall degree of satisfaction with the procedure. RESULTS: Of 150 surveys 112 (74%) were returned. Mean followup was 16.7 months (range 0.5 to 31.5). Treatment without an effective urethral warming catheter was highly associated with urinary incontinence (p<0.003), perineal pain (p<0.001), tissue sloughing (p<0.003) and American Urological Association symptom score greater than 20 (p<0.004). Impotence was higher in the double freeze-thaw cycle group (p<0.05). Overall satisfaction with cryotherapy was 33%. CONCLUSIONS: Quality of life may be compromised by urinary incontinence, impotence, tissue sloughing, problematic voiding symptoms and/or perineal pain in a substantial number of patients following salvage cryotherapy. Effective urethral warming is essential in reducing complications and maximizing quality of life. Salvage cryotherapy does not appear to offer any quality of life advantages compared to salvage prostatectomy.

Adenocarcinoma↗