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Biomedical subjects

Paul F Schellhammer

Publications and source records attributed to Paul F Schellhammer.

At least 19 recordsLinked to original sources
PubMed2005

Immunotherapy with autologous antigen presenting cells for the treatment of androgen independent prostate cancer.

Prostate cancer is an excellent target for an active vaccine-based approach based on the fact that prostate cancer cells express unique proteins which serve as highly specific targets. APC8015 (Provenge) is one such investigational therapeutic vaccine that uses autologous antigen presenting cells (APCs) loaded with a recombinant fusion protein of prostatic acid phosphatase linked to a molecule that specifically targets a receptor expressed on the surface of human APCs. Clinical trial outcomes have demonstrated activity in patients with androgen independent prostate cancer.

Acid Phosphatase↗
PubMed2005

Laparoscopic radical prostatectomy: evaluation of specimen pathologic features to critically assess and modify surgical technique.

OBJECTIVES: To evaluate laparoscopic radical prostatectomy (LRP) specimens for pathologic stage and the malignant and benign surgical margin status to determine areas for improvement in surgical technique. LRP is gaining significant attention as a viable alternative to retropubic radical prostatectomy. METHODS: A total of 110 consecutive LRP specimens were retrospectively reviewed. A single experienced genitourinary pathologist examined all slides. In addition, exposure of benign glands at the inked margin was reported. Oncologic data were assessed by standard pathologic examination for stage, grade, and margin status. The pathologic data from year 1 (group 1, 52 patients) were compared with the data from subsequent years (group 2, 58 patients). RESULTS: The overall positive surgical margin rate was 18.2% (13.5% for pT2 disease). Benign parenchymal exposure was identified in 16 patients (14.5%). Six of these patients had concomitant negative surgical margins for cancer. The positive margin rate for patients with Stage pT2 disease was 22.2% in group 1 and 5.9% in group 2. The positive margin rate was 34.8%, 13.6%, and 13.8% for bilateral, unilateral, and non-nerve-sparing procedures, respectively. CONCLUSIONS: LRP offers comparable surgical margins to those of reported open prostatectomy series. Careful pathologic review provides feedback so that technique modifications can be implemented and the positive margin rates improved further. A low, but significant, positive margin or benign parenchymal exposure rate in pT2 disease indicates room for improvement in the surgical technique. The presence of benign glands at the inked margin is not routinely reported but does provide an additional parameter of surgical adequacy.

Adult↗
PubMed2005

Prospective longitudinal comparative study of health-related quality of life in patients undergoing invasive treatments for localized prostate cancer.

BACKGROUND AND PURPOSE: Health-related quality of life (QoL) concerns are important for patients selecting treatment options for clinically localized prostate cancer and are critical in evaluating outcomes. We report pretreatment and post-treatment general and disease-specific QoL for the following invasive interventions: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), and palladium-103 ((103)Pd) brachytherapy. PATIENTS AND METHODS: We performed a prospective longitudinal survey of 452 patients with newly diagnosed prostate cancer treated at a single medical center between 2001 and 2003. An Institutional Review Board-approved questionnaire comprised of validated QoL instruments was sent to patients scheduled to undergo ORP (N = 186), LRP (N = 116), or brachytherapy (N = 150). The same questionnaire was sent out 1, 3, 6, 9, and 12 months after therapy. Comparisons were made between the groups to determine if the choice of therapy resulted in differences in QoL. RESULTS: General QoL scores were minimally affected by the choices; however, the disease-specific domains of bowel, urinary, and sexual function were adversely affected by all modalities. The ORP and LRP groups were similar among disease-specific domains and received lower post-treatment urinary and sexual scores than the (103)Pd patients. At 12 months, 38% of ORP and 46% of LRP patients had returned to baseline urinary function compared with 75% of (103)Pd patients. At 12 months, 63% of (103)Pd patients had returned to baseline sexual function compared with 19% of both the LRP and ORP patients. CONCLUSIONS: Invasive treatments for localized prostate cancer have little impact on general QoL but significantly affect disease-specific domains. Both ORP and LRP have a greater initial negative impact on urinary and sexual function than (103)Pd. The differences among the treatments with regard to QoL provide information to patients faced with choosing a treatment.

Adult↗
PubMed2004

Laparoscopic radical prostatectomy: is intact organ removal attainable? Study of margin status.

PURPOSE: To determine the initial oncologic results (pathology) of specimens removed by laparoscopic radical prostatectomy (LRP) by examining the surgical margins. PATIENTS AND METHODS: The 70 consecutive LRP procedures performed for clinically localized prostate cancer at Eastern Virginia Medical School from April 2001 to November 2002 were reviewed for preoperative and important intraoperative variables. The initial histopathology report and a prospective review by a single genitourinary pathologist for margin status as well parenchymal exposure of benign glands were assessed. Postoperative prostate specific antigen (PSA) levels were noted. RESULTS: The clinical stage distribution was as follows: T1c = 59, T2a = 10, and T2b = 1. The preoperative median PSA value was 6.96 ng/mL. The mean operative time was 307 minutes. The mean estimated blood loss was 298 mL. The prospective pathologic review results were as follows: 1 pT0 (1.4%), 60 pT2 (85.7%), and 9 pT3 (12.8%). The overall positive surgical-margin rate was 15.7%. Of those patients with pT2 disease; 8 specimens (13.3%) had a positive margin, whereas 33% of patients with pT3 disease had a positive surgical margin. Parenchymal exposure of benign glands on the inked surface was recognized in 8 patients (13.3%). Data from PSA assays 1 month postoperatively were available in 69 patients. Serum PSA was undetectable (< or =0.1 ng/mL) in 67 men (97%). CONCLUSION: An LRP can offer surgical margins comparable to those of open procedures series reported in the literature. Long-term progression and survival outcome data are necessary before this procedure should be offered as a replacement for open prostatectomy.

Aged↗
PubMed2004

Periprostatic lidocaine infiltration and/or synthetic opioid (meperidine or tramadol) administration have no analgesic benefit during prostate biopsy. A prospective randomized double-blind placebo-controlled study comparing different methods.

OBJECTIVES: To examine in a prospective, randomized, double-blind, placebo-controlled study the analgesic effect of periprostatic nerve block and/or intravenous synthetic opioid administration during a 12-core prostate biopsy. PATIENTS AND METHODS: Patients were prospectively randomized to receive unilateral periprostatic lidocaine administration and/or intravenous synthetic opioid (meperidine or tramadol) administration. Placebo groups received sterile normal saline. Unilateral infiltration was performed and biopsy was begun on this side. The degree of pain was recorded using the visual analog scale/numeric analog scale (VAS/NAS) score before the procedure, during probe introduction into the rectum, during unilateral periprostatic nerve blockade, during the first 6-core biopsy and during the second 6-core biopsy, and 30 min after biopsy completion. RESULTS: Most of the patients had mild or moderate pain (VAS/NAS <6) during the actual biopsy procedure. However, no significant differences existed between the groups with regard to the pain scores at any time (p > 0.05). Compared with pain scores, no significant differences existed between the first 6-core (blocked side) and second 6-core biopsies (p > 0.05). CONCLUSION: Periprostatic lidocaine infiltration and/or intravenous synthetic opioid analgesics are not beneficial in significantly reducing pain during biopsy. We think that most of the patients do have pain during biopsy, however the intensity of pain is tolerable and does not require analgesics.

Analgesics, Opioid↗
PubMed2004

An evaluation of bicalutamide in the treatment of prostate cancer.

Although prostate cancer is traditionally considered a disease of old age, improved diagnostic techniques have resulted in early diagnosis, and many men are now treated while still physically and sexually active. Current therapies for prostate cancer often include medical or surgical castration, which cause adverse effects on physical and sexual function; therefore, greater attention has been focused on quality of life. The nonsteroidal antiandrogen bicalutamide is an effective agent with a favorable tolerability profile and, in some settings, represents an alternative to castration. Mature survival data reveal that bicalutamide monotherapy provides survival benefits for untreated locally advanced disease that do not differ significantly from those of castration and maintains better physical capacity and sexual interest. Recent data from a prospective randomized trial demonstrate that bicalutamide given as immediate therapy, either alone or as adjuvant to therapy of curative intent, significantly reduces the risk of objective disease progression in patients with localized or locally advanced prostate cancer. Antiandrogens are also used in combination with castration, a treatment known as combined androgen blockade (CAB), for advanced disease. A randomized trial demonstrated that CAB with bicalutamide is associated with similar survival outcome to CAB with flutamide and is better tolerated. Current evidence demonstrates that bicalutamide currently has a favorable risk-benefit ratio in several stages of prostate cancer and that the role of bicalutamide will be further defined by ongoing studies.

Anilides↗
PubMed2004

Contemporary management of prostate cancer with lethal potential.

Screening for prostate cancer by determining serum prostate-specific antigen (PSA) levels has resulted in a stage migration such that patients with high-risk disease are more likely to be candidates for curative local therapy. By combining serum PSA, clinical stage, and biopsy information--both Gleason score and volume of tumor in the biopsy cores--specimen pathologic stage and patient biochemical disease-free survival can be estimated. This information can help patients and clinicians understand the severity of disease and the need for multimodal therapy, often in the context of a clinical trial. While the mainstays of treatment for local disease control are radical prostatectomy and radiation therapy, systemic therapy must be considered as well. A randomized trial has shown a survival benefit for radical prostatectomy in patients with positive lymph nodes who undergo immediate adjuvant androgen deprivation. Clinical trials are needed to clarify whether adjuvant radiation therapy after surgery confers a survival benefit. PSA is a sensitive marker for follow-up after local treatment and has proven that conventional external-beam irradiation alone is inadequate treatment for high-risk disease. Fortunately, the technology of radiation delivery has been dramatically improved with tools such as three-dimensional conformal radiation, intensity-modulated radiation therapy, and high-dose-rate brachytherapy. The further contributions of pelvic irradiation and neoadjuvant, concurrent, and adjuvant androgen deprivation therapy have been defined in clinical trials. Future management of high-risk prostate cancer may be expanded by clinical trials evaluating neoadjuvant and/or adjuvant chemotherapy in combination with androgen deprivation.

Androgen Antagonists↗
PubMed2003

Orthotopic treatment model of prostate cancer and metastasis in the immunocompetent mouse: efficacy of flt3 ligand immunotherapy.

We established an orthotopic treatment model of prostate cancer to generate reproducible primary and metastatic carcinoma in immunocompetent C57BL/6 mice. Using an in vivo selection scheme of intraprostatic implantation of TRAMP-C1 cells, primary prostate tumors were cultured and recycled three times by intraprostatic injection resulting in the selection and establishment of the recycled cell line TRAMP-C1P3. Prostate tumors were detected approximately 30 days post-implantation with periaortic lymph node metastasis in 19/20 (95%) of mice. Tissue culture amplification, DNA ploidy and PCR amplification of the SV40 transgene were used to detect metastatic TRAMP-C1P3 in lymph node specimens. Tissue culture amplification and DNA ploidy were as sensitive as SV40 transgene amplification by PCR in detection of early metastatic disease in draining lymph nodes. To establish the use of the orthotopic model of prostate cancer for immunotherapy, mice were injected orthotopically with TRAMP-C1P3 cells and 7 days post-implantation treated daily for 28 days with either flt3L or carrier control. Carrier-treated mice had clinically detectable prostate tumors, lymph node metastasis and were moribund at 29-35 days, whereas flt3L therapy markedly suppressed primary TRAMP-C1P3 growth and lymph node metastasis, and prolonged survival. In summary, we have established a reproducible and clinically relevant orthotopic treatment model of prostate cancer in immunocompetent mice with application to a variety of therapeutic strategies. We demonstrate that flt3L treatment suppressed orthotopic prostate tumor growth and lymph node metastasis reinforcing a role for flt3L as an immunotherapeutic strategy for prostate cancer.

Adjuvants, Immunologic↗
PubMed2003

Impact of the tumor microenvironment on host infiltrating cells and the efficacy of flt3-ligand combination immunotherapy evaluated in a treatment model of mouse prostate cancer.

We have previously reported that Fms-like tyrosine kinase-3 ligand (flt3-L) induced tumor stabilization and regression of palpable ectopic prostate tumors (TRAMP-C1). Although some mice remained "tumor free" for several months following termination of therapy, tumors invariably reappeared and grew progressively in all animals. The lack of a curative response suggests that TRAMP-C1 tumors may inhibit the development of a flt3-L-induced anti-tumor immune response. Consistent with this view, we demonstrate herein that TRAMP-C1 tumors isolated from flt3-L treated animals contained a marked dendritic cell (DC) infiltrate that was temporally correlated with tumor regression. However, tumor-associated DCs, especially in a flt3-L setting, progressively lost MHC class II antigen expression during tumor growth. Treatment with the DC maturation factor trimeric CD40 ligand (CD40-L) either alone or in combination with fl3-L neither prevented loss of DC class II antigens nor disease relapse. Because loss of class II antigens would prevent CD4+ helper T (Th) cell development, we treated tumor-bearing mice with agonistic anti-4-1BB antibody (Ab), which can promote cytotoxic T lymphocyte (CTL) development independent of Th cell function. However, anti-4-1BB Ab alone did not alter TRAMP-C1 growth kinetics, and, when used in combination, was no more effective than flt3-L alone. The inability of the 4-1BB co-stimulatory signal to promote tumor regression may have been related to two additional features of TRAMP-C1 tumors. First, tumor-associated T cells, but not splenic T cells from tumor-bearing animals, were profoundly deficient in expression of CD3-epsilon (CD3epsilon) and T cell receptor-beta chain (TCRbeta). Second, CTLs required 24 h to efficiently kill TRAMP-C1 target cells even after up-regulation of MHC class I antigens by interferon-gamma. This rate of tumor cell destruction by CTLs may not be sufficient to prevent tumor progression. Taken together, these data reveal several important immunosuppressive characteristics of the prostate tumor microenvironment (TME) that immunotherapeutic interventions must first overcome to achieve longterm cures. These data also highlight the importance of utilizing treatment versus vaccination models in the evaluation of immunotherapeutic modalities.

Animals↗
PubMed2003

Voiding impairment after prostate biopsy: does tamsulosin treatment before biopsy decrease this morbidity?

OBJECTIVES: To evaluate the association of transrectal ultrasound (TRUS)-guided prostate biopsy with voiding impairment and to investigate whether tamsulosin treatment given before prostate biopsy could improve voiding impairment after the procedure. METHODS: The study included 66 consecutive patients who underwent TRUS-guided 12-core prostate biopsy and were prospectively randomized. Of the patients, 33 were treated with tamsulosin (0.4 mg daily) beginning the day before the biopsy procedure for 30 days. The remaining 33 patients underwent TRUS-guided prostate biopsy only with no tamsulosin treatment and served as the control group. The International Prostate Symptom Score (IPSS) and maximal flow rate (Qmax) were recorded in all patients before the procedure and on postbiopsy days 7 and 30. All patients were followed up and questioned about difficulty voiding and acute urinary retention after the procedure. RESULTS: No difference was found in the mean IPSS and Qmax before biopsy between the two groups (P >0.05). Acute urinary retention after the biopsy procedure developed in 1 patient in the tamsulosin group and 3 patients in the control group. The rate of voiding difficulty on postprocedure day 7 was significantly lower in the tamsulosin group (9.09%) than in the control group (42.42%), a statistically significant difference (P <0.001). In the tamsulosin group, the IPSS was significantly decreased on postbiopsy days 7 and 30 compared with the baseline value (P <0.05 and P <0.001, respectively), and Qmax was significantly elevated on postbiopsy day 30 (P <0.01). In the control group, the IPSS was significantly greater (P <0.05) and the Qmax was significantly lower (P <0.001) on postbiopsy day 7 compared with the baseline value. CONCLUSIONS: The results of our study show that TRUS-guided prostate biopsy leads to transient voiding impairment, and therefore, the alpha(1)-blocker tamsulosin before biopsy and for a brief interval afterward may decrease this morbidity.

Adrenergic alpha-Antagonists↗
PubMed2003

Laparoscopic radical prostatectomy: decreasing the learning curve using a mentor initiated approach.

PURPOSE: Laparoscopic radical prostatectomy is being evaluated at several centers in the United States as a treatment option for localized prostate cancer. It is a technically difficult operation to perform with a steep learning curve. It has been stated that 50 procedures are necessary to satisfy the learning curve. To expedite performance and evaluation of laparoscopic radical prostatectomy a surgeon (mentor) who had performed 200 cases was invited to instruct a fellowship trained laparoscopist (trainee). MATERIALS AND METHODS: From March 2001 through September 2001 we performed 30 laparoscopic radical prostatectomies. The mentor performed the first 12 procedures with the trainee acting as assistant (group 1). The subsequent 18 procedures were performed by the trainee with the mentor acting as assistant (group 2). A final set of 20 procedures was performed by the trainee alone using 1 of 3 urological residents as the assistant (group 3). The transperitoneal approach was used and all suturing was intracorporeal. Preoperative data included prostate specific antigen, clinical stage, Gleason grade and median patient age. Intraoperative data included operative time, the blood loss/transfusion rate and intraoperative complications. Postoperative data included pathological stage, prostate specific antigen, the positive margin rate, catheter dwell time and hospital stay. When applicable, statistical significance was determined using the standard paired t test. RESULTS: There was no statistical difference in median operative time in groups 1 and 2 (248 and 258 minutes, respectively, p = 0.15). Similarly there was no difference in groups 2 (trainee and mentor assistant) and 3 (trainee alone) (p = 0.26). There was a difference in operative time in groups 1 and 3 (p = 0.04). Mean estimated blood loss was comparable in groups 1 to 3 and not statistically different (150, 250 and 250 cc, respectively, p = 0.15). Mean organ weight was also comparable (64, 59 and 55 gm., respectively). Hospital stay was 3 days in all groups. Catheter time decreased as confidence was gained with the procedure (range 6 to 33 days). Final pathological stage was compared among the 3 groups. There was an overall increase in positive margins in groups 1 to 3 (16%, 22% and 30%, respectively, p not significant). However, the positive margin rate for stage pT2 disease was similar at 15.5% for groups 1 and 2, and 14% for group 3. CONCLUSIONS: Laparoscopic radical prostatectomy is a technically challenging operation that is in the early stages of evolution and evaluation. We present an intensive, mentor initiated approach to decrease the learning curve and maintain outcomes.

Education, Medical, Continuing↗
PubMed2003

Prostate cancer grade assignment: the effect of chronological, interpretive and translation bias.

PURPOSE: Surveillance, Epidemiology and End Results (SEER) data reveal an increasing incidence in the detection of moderately differentiated prostate cancer and a stable or decreasing incidence in well and poorly differentiated cancer. Plausible reasons for this phenomenon include the decrease in transurethral resections performed and an increase in the number of prostate specific antigen triggered ultrasound guided needle biopsies. We examined additional explanations for the grade shift with time and addresses the impact of this grade shift on clinical end points. MATERIALS AND METHODS: Archived slides from 100 patients (82 needle biopsy specimens and 18 transurethral resection specimens) treated for prostate cancer between 1975 and 1985 were reexamined. Current grades were assigned using the WHO and the Gleason grading systems, and they were compared with the original grade assignments. Current Gleason score was translated to WHO grade by operational SEER criteria (2 to 4-well, 5 to 7-moderately and 8 to 10-poorly differentiated). Analysis of the 100 specimens by life table methodology calculated cancer specific survival according to the era of grade assignment. RESULTS: There was significant upward grade migration from the historic to the current WHO grade and from the translation by SEER methodology of the current Gleason score to WHO grade (p <0.0001). Interpretive and chronological bias caused expansion of the moderately differentiated category at the expense of well differentiated cancer and significant deviation in cancer specific survival curves (p <0.013). SEER translation bias resulted in expansion of the moderately differentiated grade category at the expense of poorly differentiated cancer and eliminated the significant difference in cancer specific survival between Gleason 5/6 and 7 (p <0.006). CONCLUSIONS: Contemporary understanding of Gleason grading has lowered the threshold for assignment to higher grade. While a change in tumor biology may be partially responsible for the trend toward higher grade assignment, grade migration as described is also a significant contributing factor in reported histological trends for newly diagnosed prostate cancer and it significantly compromises efforts at historical comparisons.

Bias↗
PubMed2003

Data reduction using a discrete wavelet transform in discriminant analysis of very high dimensionality data.

We present a method of data reduction using a wavelet transform in discriminant analysis when the number of variables is much greater than the number of observations. The method is illustrated with a prostate cancer study, where the sample size is 248, and the number of variables is 48,538 (generated using the ProteinChip technology). Using a discrete wavelet transform, the 48,538 data points are represented by 1271 wavelet coefficients. Information criteria identified 11 of the 1271 wavelet coefficients with the highest discriminatory power. The linear classifier with the 11 wavelet coefficients detected prostate cancer in a separate test set with a sensitivity of 97% and specificity of 100%.

Data Compression↗
PubMed2002

Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men.

The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better biomarkers for early detection of PCA using protein profiling technologies that can simultaneously resolve and analyze multiple proteins. Evaluating multiple proteins will be essential to establishing signature proteomic patterns that distinguish cancer from noncancer as well as identify all genetic subtypes of the cancer and their biological activity. In this study, we used a protein biochip surface enhanced laser desorption/ionization mass spectrometry approach coupled with an artificial intelligence learning algorithm to differentiate PCA from noncancer cohorts. Surface enhanced laser desorption/ionization mass spectrometry protein profiles of serum from 167 PCA patients, 77 patients with benign prostate hyperplasia, and 82 age-matched unaffected healthy men were used to train and develop a decision tree classification algorithm that used a nine-protein mass pattern that correctly classified 96% of the samples. A blinded test set, separated from the training set by a stratified random sampling before the analysis, was used to determine the sensitivity and specificity of the classification system. A sensitivity of 83%, a specificity of 97%, and a positive predictive value of 96% for the study population and 91% for the general population were obtained when comparing the PCA versus noncancer (benign prostate hyperplasia/healthy men) groups. This high-throughput proteomic classification system will provide a highly accurate and innovative approach for the early detection/diagnosis of PCA.

Aged↗
PubMed2002

Superficial bladder carcinoma treated with bacillus Calmette-Guerin: progression-free and disease specific survival with minimum 10-year followup.

PURPOSE: Intravesical bacillus Calmette-Guerin (BCG) treatment of high risk superficial bladder cancer has reduced recurrence and progression, and lengthened disease specific survival. However, documentation of treatment durability is limited. MATERIALS AND METHODS: Between 1981 and 1989, 98 patients with high risk or recurrent transitional cell carcinoma were treated with complete transurethral resection followed by 1 or more 6-week induction courses of BCG, and were followed through 2000. No maintenance regimen was used. A total of 44 cases were carcinoma in situ plus or minus papillary and 35 were stage T1, which was assigned only if muscularis propria free of tumor was present on the biopsy specimen. RESULTS: Of 98 patients with minimum followup greater than 10 years disease progressed to stage T2 or greater in 27 at a median of 30.7 months (range 1.2 to 143.7), of whom cystectomy was performed in 16, cystectomy for recurrent high risk Ta/T1 disease was required in 10, death from transitional cell carcinoma occurred in 13 at a median of 69.7 months (range 11 to 135), upper tract tumor developed in 13 at a median of 49 months (range 9 to 146) and there was evidence of prostatic urethral involvement in 21. The 10-year progression-free survival was 67%, and progression-free survival with a retained bladder 59%. The total cystectomy rate was 26%, permitting a number of patients to be rendered disease-free. The 10-year disease specific survival was 85%. CONCLUSIONS: After complete tumor resection and careful pathological staging intravesical BCG for high risk and/or recurrent superficial bladder carcinoma resulted in overall progression-free and disease specific survival rates that support this bladder sparing strategy. Patients must be followed closely and cystectomy recommended for those with an initial incomplete response after initial therapy or recurrent high risk disease.

Aged↗