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Biomedical subjects

H Ragde

Publications and source records attributed to H Ragde.

At least 37 records · Page 2Linked to original sources
PubMed1997

Posttreatment biopsy results following interstitial brachytherapy in early-stage prostate cancer.

PURPOSE: To assess pathologic control rates for prostatic carcinoma as determined by postimplant prostate biopsy in a large series of consecutive patients who have received permanent interstitial brachytherapy using a contemporary transrectal ultrasound-directed, transperineal, computer generated, volume technique. METHODS AND MATERIALS: Four hundred and two patients received permanent 125I or 103Pd interstitial brachytherapy as primary treatment for early stage prostatic carcinoma at the Northwest Tumor Institute between January 1988 and January 1994. Of these, 201 have consented to biopsy 12 or more months postimplant with a median follow-up of 40 months (range: 12-83 months). None had received hormonal manipulation. A total of 361 biopsies was performed on 201 patients with a range of one to six annual biopsies per patient (91 received multiple, serial biopsies). Of the 161 patients more than 12 months postimplant who have not been biopsied, most have been unwilling or unable to submit to biopsy. Only six patients with biochemical progression have not been biopsied. There was no difference in the presenting characteristics or implant parameters between those patients biopsied and those that were not. One hundred and forty-three received 125I (71%) prescribed to a MPD of 160 Gy with a median activity of 35.5 mCi, and 58 (29%) received 103Pd prescribed to a MPD of 115 Gy with a median activity of 123 mCi. Multiple biopsies were performed under transrectal ultrasound guidance, and all specimens were classified as either negative, indeterminate, or positive. RESULTS: At the time of last biopsy, 161 (80%) have achieved negative pathology, 34 (17%) remain indeterminate, and 6 (3%) have been positive. Only 2 of the 186 patients with a PSA < 4.0 ng/ml at the time of biopsy were positive. Among those 33 indeterminate patients with a subsequent biopsy, 28 have converted to negative, 2 to positive, and 3 remain unchanged to date. CONCLUSIONS: These data demonstrate at least an 80% pathologically confirmed local control rate following permanent interstitial brachytherapy for early stage prostate cancer. A higher local control rate is expected with further follow-up as the majority of indeterminate biopsies convert to negative over time. The indeterminate category of postirradiation biopsy described here includes specimens that have probably been interpreted as positive in other series, but correlate clinically and biochemically with negative biopsies. These results support the use of modern interstitial brachytherapy techniques for selected patients with early stage adenocarcinoma of the prostate.

Biopsy↗
PubMed1997

Interstitial implantation techniques in prostate cancer.

Brachytherapy is a radiotherapeutic technique that allows the physician to implant radioactive isotopes into a body cavity or directly into tissue. Different radioisotopes have unique characteristics that the brachytherapist may utilize for a particular situation. The use of brachytherapy is part of standard radiation oncology practice in gynecological and head and neck cancer management. The prostate is approachable for interstitial implantation due to its close proximity to the perineum. Over 20 years ago, primitive methods of brachytherapy were utilized in the treatment of prostate cancer. However, poor results due to inconsistency in achieving adequate coverage of the entire prostate and poor patient selection caused this treatment modality to fall out of favor. Technological advances over the last decade have restored attention to brachytherapy for prostate cancer. Particularly important has been the development of transrectal ultrasound, new radioisotopes such as palladium-103, computer tomography, computerized dosimetry systems, and earlier diagnosis. Modern interstitial implantation utilizing transperineal template and transrectal ultrasound guidance has resulted in improved consistency in radiation dose delivery to the entire prostate. Early results are encouraging in terms of the relatively low morbidity of the procedure, improved local control rates, and biochemical progression free survival. This has resulted in an outpatient treatment that has high patient acceptance.

Aged↗
PubMed1996

Evaluation and comparison of two new prostate carcinoma markers. Free-prostate specific antigen and prostate specific membrane antigen.

BACKGROUND: Two new prostate cancer markers, free-prostate specific antigen (f-PSA) and prostate specific membrane antigen (PSMA) were recently introduced. This report summarizes a prospective two-year multicenter test of their diagnostic or prognostic capabilities. Total PSA was also measured. METHODS: There were four clinical groups studied: (1) 226 individuals from a screening project undergoing ultrasound and biopsy evaluation had markers obtained: (2) 68 patients suspected of having prostate cancer and undergoing 2 or more biopsies had the markers obtained on multiple occasions: (3) 100 patients undergoing radical prostatectomy had markers obtained pre- and post-operatively: and (4) 31 patients with metastatic prostate cancer each had multiple samples for marker assay obtained over a 2-year period. In all, 465 patients had one or more samples obtained and studied. RESULTS: Free-PSA affords little additional diagnostic advantage compared with total PSA in the screening population. The receiver operating characteristic curves for diagnostic accuracy were ranked: (1) PSA density; (2) total PSA; (3) f-PSA; and (4) PSMA, PSMA showed the best correlation with stage of the primary tumor in the screened group. In the multiple negative biopsy group, f-PSA varied from 12 to 21%. PSMA values were evaluated in all histologic categories. PSA density was > or = 0.15 in all categories. In the prostatectomy cases PSA values postoperatively were quite low in Stage II; f-PSA was of no value. Later, f-PSA was increased in association with elevated total PSA values. Mean PSMA values were above normal in all postoperative time periods except in Stage III patients at 6 months to 1 year postoperatively. PSA densities were all > or = 0.15. In patients with metastatic carcinoma, elevated PSMA values correlated best with a poor prognosis (clinical progression), as has been described. CONCLUSIONS: These data suggest that f-PSA values do not provide additional diagnostic benefit compared with total PSA in screening populations, in the presence of suspected cancer, postprostatectomy, or in metastatic disease. PSMA is of prognostic significance, especially in the presence of metastatic disease, and correlates well with the stage of disease in cancers detected in a screened population.

Antigens, Neoplasm↗
PubMed1996

Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity.

Dendritic cells (DCs) are "professional" antigen-presenting cells capable of stimulating T-cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T-cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA-restricted fashion in order to stimulate T-cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.

Amino Acid Sequence↗
PubMed1996

Measurement of prostate-specific membrane antigen in the serum with a new antibody.

Work to date has identified prostate-specific membrane antigen (PSMA) as a membrane-bound glycoprotein with high specificity for prostatic epithelial cells. PSMA reacts with the monoclonal antibody 7E11.C5, which is present in serum, seminal fluid, and prostatic epithelial cells, and is increased in its expression in the presence of a hormone refractory state associated with prostatic cancer. This report confirms these results and further documents the presence of the monoclonal antibody 3F5.4G6, which reacts with the extracellular domain of PSMA. This region of PSMA is also an element present in a truncated version of the protein, so-called PSM'. Immune precipitation with either 7E11.C5 or 3F5.4G6 yields an isolated protein species that are reactive with the reciprocal antibody in Western blot analysis. Thus, 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5, but at different epitopes on essentially opposite ends of the molecule. These two antibodies are well suited for use in a sandwich immunoassay, either one as a capture or detection antibody. Current work on this is underway. This report also confirms that 7E11.C5 Western blots for PSMA are negative with normal human brain tissue. The monoclonal antibody 9H10 does not react with 3F5.4G6 or with 7E11.C5 in studies conducted herein. Moreover, 3F5.4G6 reacts with PSMA found in the LNCaP cell line, but not DU-145 or PC3, which lack PSMA.

Amino Acid Sequence↗
PubMed1996

Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.

BACKGROUND: Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer. METHODS: A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively). RESULTS: No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. CONCLUSIONS: Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.

Dendritic Cells↗
PubMed1996

Should brachytherapy be considered a therapeutic option in localized prostate cancer?

Contemporary prostate brachytherapy incorporates advances in computer analysis, imaging technology, and delivery apparatus, allowing exacting and reproducible results compared with historical approaches. The advances permit brachytherapy to be performed on a cost-effective, outpatient basis with low morbidity in the appropriately selected patient. Although unsettled questions remain regarding dosimetric issues, long-term outcomes, and morbidity, the weight of evidence to date appears to support the use of brachytherapy in selected patients. Brachytherapy may be considered a therapeutic option: as monotherapy for early-stage disease and also a boost following moderate doses of external beam irradiation for locally advanced disease.

Brachytherapy↗
PubMed1996

Does brachytherapy have a role in the treatment of prostate cancer?

The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland either as permanent or temporary seeds. Permanent seed implantation is capable of delivering two times the radiobiologically equivalent dose of external beam irradiation to the prostate and tumor. In the past, the results of prostate brachytherapy were likely poor owing to the technical difficulty in accurately placing the radioactive seeds uniformly throughout the prostate. The use of low-dose-rate I-125 to treat high-grade cancers probably also contributed to the poorer results as compared with external beam irradiation. Over the last 10 years, however, technologic advances in transrectal ultrasonography, computer dosimetry, and template-based transperineal techniques have dramatically improved the accuracy and consistency of the brachytherapist to place radioactive sources directly into the prostate gland. Transperineal ultrasound or CT directed seed implantation has replaced the older retropubic method. Brachytherapists are now able to accurately map out the gland prior to the implant and carefully evaluate preoperatively seed placement. The availability of such radioactive sources as iodine-125, palladium-103, and iridium-192 has also given the brachytherapist isotopes that can be more carefully matched to the biology and stage of the tumor. More sensitive definitions of failure have prompted radiation oncologists and urologists to carefully evaluate the efficacy of external beam irradiation and surgery. Accurate comparison of the efficacy of brachytherapy to surgery and to external beam radiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Imbalances in stage, grade, initial PSA extraprostatic disease, and nodal status of patient groups make comparisons difficult. Most of the long-term data for permanent seed implantation are the result of work at a single institution. These results will need to be repeated at other institutions treating patients in a similar manner. Because techniques vary from institution to institution, permanent implant results will need to be carefully evaluated for technique as well as stratified for pretreatment variables. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after radiation. As more patients are diagnosed with very early and nonpalpable disease, future studies will need to stratify patients based on these pretreatment factors. Patients with early-stage disease but identified as high risk for extraprostatic disease will require more intensive regimens. The treatment outcomes based on biopsy results are inconclusive. A lack of consensus on the definition of a truly positive biopsy remains forthcoming. The value of a positive prostate biopsy as an outcome predictor for clinical failure is still unclear. The use of prostate nuclear cell antigen staining may help clarify the issue. Comparison of treatment outcome based on absolute PSA is also difficult. The Seattle series suggest that brachytherapy by permanent seed implantation is as efficacious as external beam irradiation for early-stage disease in patients with a low PSA (< 10 ng/mL). As the PSA value rises above 10 ng/mL, the probability of failure after external beam rises substantially. Results from the Seattle series suggest an advantage to seed implant alone or the judicious application of seed implant boost to external beam radiation for these patients with more advanced cancer. The most sensitive measurement of therapeutic outcome is progression-free survival. Few studies to date have evaluated progression-free survival.

Biopsy↗
PubMed1995

In vitro propagated dendritic cells from prostate cancer patients as a component of prostate cancer immunotherapy.

T cell-mediated cancer immunotherapy requires efficient antigen-presenting cells. Dendritic cells (DCs) are arguably the most efficient antigen-presenting cells studied to date. Individuals with prostate cancer often undergo various therapies which may compromise their immune system, including the state of their DC precursors. We report the in vitro propagation of DCs from peripheral blood of patients with prostate cancer, most of whom are in clinical stages D1 or D2 and have undergone radiation therapy. After 7 days in culture, the number of DCs recovered were 20-50-fold higher than those isolated directly from peripheral blood. This number is comparable to findings of previous studies with healthy individuals. Cultured patients' DCs were capable of presenting tetanus toxoid to autologous T cells in vitro. Furthermore, T cells from 2 of 4 patients proliferated when cultured with their DCs and the lysate of a human prostate cancer cell line (LNCaP), demonstrating the potential role of autologous DCs in prostate cancer immunotherapy studies.

Aged↗
PubMed1995

Prostate specific antigen based disease control following ultrasound guided 125iodine implantation for stage T1/T2 prostatic carcinoma.

PURPOSE: We report the prostate specific antigen (PSA) based recurrence-free survival rate after 125iodine (125I) implantation for early stage prostatic carcinoma. MATERIALS AND METHODS: A total of 197 patients with clinical stage T1 and T2 prostatic carcinoma underwent outpatient 125I seed implantation. Followup was 1 to 7 years (median 3). Pretreatment serum PSA levels were elevated (greater than 4.0 ng./ml.) in 138 patients (70%). There were 105 well differentiated (Gleason score 2 to 4), 87 moderately differentiated (Gleason score 5 to 6) and 5 indeterminate tumors. The prescribed minimum prostatic dose was 160 Gy. The total dosage of 125I implanted ranged from 15 to 62 mCi. (median 37). Staging lymph node dissection and seminal vesicle biopsies were not routinely performed. RESULTS: Among 138 patients with an elevated PSA level before implantation and no prior hormonal treatment, the PSA value returned to normal in 98% and decreased to less than 1.0 ng./ml. in 82% within 24 months of treatment. In 97% of those 138 patients the PSA level decreased to less than 1.0 ng./ml. at 48 months after implantation. Of 8 patients with an increasing PSA value 5 also had clinically evident failure. The actuarial rate of chemical (increasing PSA) or clinical failure at 5 years following implantation was 7%, with 15 patients still at risk at 5 years. There was a trend for higher failure rates among patients with higher pretreatment PSA levels (p = 0.57), Gleason scores 5 and 6 versus 2 to 4 (p = 0.51) or higher stage of disease (p = 0.17). CONCLUSIONS: There is a high rate of clinical and chemical freedom from progression following 125I implantation for select patients with early stage prostatic carcinoma.

Aged↗
PubMed1993

Brachytherapy and Organ Preservation in the Management of Carcinoma of the Prostate.

The treatment of organ-confined carcinoma of the prostate with permanent radioisotopes by the retropubic method has generated variable and controversial results. In this article, the technical flaws of the retropubic approach are discussed. Issues of radiobiological factors, dose inhomogeneity, and case selection are addressed relative to the reported results. Recent advances in radioisotope development, computer based dosimetry, and transrectal ultrasound and computed tomographic imaging have fostered techniques of closed transperineal implantation that produce a more homogeneous, reproducible, and larger volume implant with a higher peripheral dose rate than was possible in the past. With a median follow-up of 37 months (range 12 to 78 months), 93% of 291 early stage A-B patients treated with (125)I or (130)Pd alone showed a normal posttreatment prostate-specific antigen (PSA) (median value 0.4). In 160 more advanced stage A-C patients treated with external beam irradiation and implant boost, 85% showed a normal PSA (median value 0.3). The elimination of surgery with these techniques permits outpatient treatment resulting in high patient acceptance. If longer follow-up substantiates the favorable early results, these methods may potentially offer the least morbid and least expensive method of treatment for early stage carcinoma of the prostate.

Journal Article↗
PubMed1991

Transperineal ultrasound-guided implantation of the prostate: morbidity and complications.

Two hundred and seventy four patients with early carcinoma of the prostate were treated by ultrasound-guided transperineal I-125 implantation. One hundred and ninety six received implant alone, and 78 were treated with combined external beam and I-125 implantation. Operative, early and late complications were reviewed with a median follow-up time of 40 months (minimum 13, maximum 64 months). Operative complications were negligible. Early morbidity (less than 12 months post implant) was noted in 10-15% of patients and consisted of self-limited irritative uropathy or obstruction. Late complications (more than 12 months post implant) were noted in 13%. Seven percent of patients had some combination of permanent sequelae of treatment: 14 patients had some degree of incontinence, 17 had irritative uropathy symptoms, and 7 had proctitis, 5 of whom resolved spontaneously. Most complications were mild to moderate with a notable absence of severe problems. Urinary morbidity was strongly related to prior or post-implant transurethral resection of the prostate (TURP) (24% with TURP, 3% without). Transperineal implantation in our experience is associated with an acceptable acute and chronic complication rate.

Brachytherapy↗
PubMed1988

Ultrasound-guided prostate biopsy. Biopty gun superior to aspiration.

We used a 7 MHz transrectal ultrasound scanner to perform guided core biopsy and aspiration cytologies on 292 patients with findings suspicious for prostate cancer. One hundred two cancers were identified, 35 of which were not palpable and were detected only by ultrasound. Aspiration needles were guided by ultrasound through the center of the suspicious lesion. Core biopsies were performed using an 18-gauge Tru-Cut type of needle with an automatic, spring-powered needle biopsy device (Biopty). All patients received only local anesthetic and biopsies were done as an outpatient office procedure. The core biopsies gave excellent specimens which detected 89 percent of the cancers, whereas the aspiration method detected 51 percent (P less than 0.001). Aspiration cytology was significantly less sensitive among well-differentiated compared with moderately differentiated cancers. High-resolution transrectal ultrasound and the Biopty device are detecting and documenting prostate cancer with much greater sensitivity than preceding techniques have achieved.

Biopsy, Needle↗
PubMed1978

Simplified correction of female stress incontinence.

A simplified operation for female stress incontinence, using a pair of double-prong needles, is described. A 90.4 per cent cure was achieved in 62 patients followed for a mean of 11.2 months. Merits of this procedure include operative simplicity and brevity, short hospitalization and a high rate of cure.

Adult↗