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Biomedical subjects

A W Partin

Publications and source records attributed to A W Partin.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ability of the 1992 and 1997 American Joint Committee on Cancer staging systems for prostate cancer to predict progression-free survival after radical prostatectomy for stage T2 disease.

PURPOSE: In a revised 1997 edition the American Joint Committee on Cancer (AJCC) staging for prostate cancer reduced the subdivision of T2 disease from 3 (T2a, T2b and T2c) to 2 substages by combining single lobe disease (T2a and T2b) into a single stage, now termed T2a. We retrospectively reviewed a large series of men with clinically organ confined prostate cancer who underwent surgery by a single surgeon to determine how this change affected the ability of the staging system to predict outcome. MATERIALS AND METHODS: Of 2, 293 cases treated with radical prostatectomy from 1982 to 1998, 1, 314 were clinically staged to have T2 disease. We analyzed the freedom from biochemical prostate specific antigen (PSA) progression after radical prostatectomy according to the 1992 and 1997 AJCC staging criteria. RESULTS: Overall the actuarial 5 and 10-year biochemical progression-free survival rates for the whole group were 82% and 71%, respectively. The actuarial recurrence-free rate was significantly different for patients with 1992 AJCC T2a (T2a92) versus T2b (T2b92) disease (p <0.0001) but similar for those with 1992 T2b versus T2c (T2c92) disease (p = 0.1165). The actuarial recurrence-free rate was significantly different for patients with 1997 AJCC T2a (T2a97) versus T2b (T2b97) disease (p = 0.0001). However, the overall recurrence-free rate was lower in the T2a97 group compared with the T2a92 group. CONCLUSIONS: The 1992 AJCC staging of T2 prostate cancer yielded a significant difference in the outcome of patients with single lobe disease (T2a92 and T2b92), which is obscured by the 1997 staging criteria. Therefore, we believe that the next revision of the AJCC staging system should revert back to the 1992 AJCC system of subdividing a single lobe disease category into T2a and T2b. Alternatively the committee may want to merge T2b92 and T2c92 stages into a new staging entity, since there was no statistical difference in the outcome of these 2 groups.

Adult↗
PubMed2000

Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer.

PURPOSE: The accurate prediction of pathological stage of prostate cancer using preoperative factors is a critical aspect of treatment. In 1997 Partin et al published tables predicting pathological stage using clinical stage, Gleason score and prostate specific antigen (PSA). We tested the validity of the Partin tables. MATERIALS AND METHODS: From 1990 to 1996 inclusively 5,780 patients underwent bilateral pelvic lymphadenectomy and radical prostatectomy for prostate cancer at the Mayo Clinic. However, only 2,475 of these patients met all inclusion criteria of no preoperative treatment, known biopsy Gleason score, available preoperative PSA done either before biopsy or more than 28 days after biopsy and clinical stage T1, T2 or T3a. Among the 2,475 patients 15 had positive lymph nodes and planned prostatectomy was abandoned. The receiver operating characteristics (ROC) curve area, observed and predicted Partin rates of each pathological stage, and positive and negative predictive values were used to compare the Mayo study to the Partin tables. RESULTS: The distribution of pathological stage was organ confined in 67% of Mayo cases versus 48% in the Partin study, extracapsular without seminal vesicle or node involvement in 18% versus 40%, seminal vesicle involvement without nodes in 9% versus 7% and were positive nodes in 6% versus 5%. Using the predicted probabilities of Partin et al the ROC curve area for predicted node positive disease was 0.84 for Mayo cases compared to an estimated 0. 82 in the Partin series. The ROC curve area for predicting organ confined cancer was 0.76 for the Mayo Clinic compared to an estimated 0.73 for the Partin series. The observed rates of node positive disease were similar to those predicted (Partin) based on clinical stage, PSA and Gleason score. For organ confined disease Mayo rates were consistently higher than those predicted from the Partin series using a cut point of 0.50 or greater. Positive and negative predictive values were 0.83 and 0.49 versus 0.63 and 0.70 for the Mayo Clinic and Partin series. CONCLUSIONS: Our study provides strong evidence that sensitivity and specificity of the Partin tables for external clinical sites are similar to what was reported.

Humans↗
PubMed2000

Neural network prediction of prostate tissue composition based on magnetic resonance imaging analysis. A pilot study.

OBJECTIVE: To develop a neural network model that estimates prostate histology using magnetic resonance imaging (MRI). STUDY DESIGN: Fifty-three men with lower urinary tract symptoms (average age = 63.8 +/- 8.9 years) underwent a prostate MRI (T2) and sextant biopsy of the prostate. Masson Trichome and immunohistochemical prostate-specific antigen staining of the biopsy material were used to calculate the amount of stroma and epithelium in the inner gland (central plus transition zone). MRIs were normalized to the mean intensity of the obturator internus muscle for comparative analyses. Gray scale and texture features were extracted from the inner gland in the midsection transverse MRI slice. Clinical and image variables were used in two neural networks predicting a high amount of stroma and a high amount of epithelium, respectively. RESULTS: The positive and negative predictive values of the stroma and epithelium neural networks were 95%, 69% and 65%, 92%, respectively. CONCLUSION: These data suggest that the combined use of these neural networks may predict patient response to medical therapy targeting prostatic stroma or epithelium.

Adult↗
PubMed2000

Seminal vesicle invasion by prostate cancer: prognostic significance and therapeutic implications.

When the pathologist's report following radical prostatectomy describes seminal vesicle invasion (SVI), generally the outlook for the patient is poor. But are we all on the same page of the same book when we talk about SVI? Does it mean muscular wall invasion? Does it include the ejaculatory duct? Getting a clear definition can have far-reaching clinical implications for patient prognosis and treatment.

Journal Article↗
PubMed1999

Nuclear morphometry predicts disease-free interval for clinically localized adenocarcinoma of the prostate treated with definitive radiation therapy.

Men treated for prostate cancer often have unexpected outcomes despite predictive models based on stage, grade and prostate-specific antigen (PSA). Previous results have indicated that nuclear morphometry can predict patient outcome in urologic malignancies. Application of this analytical method in prostate cancer treated with radiation therapy is limited. We have evaluated the predictive ability of nuclear morphometry in such patients. Histologic sections from 23 men with clinically localized adenocarcinoma of the prostate treated with radiation therapy were studied. Nuclear morphometric parameters were assessed using a previously described and validated system. Univariate and multivariate logistic regression analyses and a Cox proportional hazards model were used to assess the ability of nuclear morphometric parameters to predict recurrence and disease-free interval. Ten patients had no recurrence with median follow-up of 47. 5 months, while 13 had recurrence. Gleason grade was not predictive of treatment outcome. Pre-treatment PSA data, available for only 11 patients, were predictive of treatment outcome. Several nuclear morphometric parameters predicted recurrence, including upper quartile of suboptimal circle fit and upper quartile of feret-diameter ratio. A prognostic factor score incorporating these 2 parameters was derived, which predicted disease-free interval (p = 0.0014). Int. J. Cancer (Pred. Oncol.) 84:594-597, 1999.

Adenocarcinoma↗
PubMed1999

Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer.

Vaccination with irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting gene-transduced cancer vaccines induces tumoricidal immune responses. In a Phase I human gene therapy trial, eight immunocompetent prostate cancer (PCA) patients were treated with autologous, GM-CSF-secreting, irradiated tumor vaccines prepared from ex vivo retroviral transduction of surgically harvested cells. Expansion of primary cultures of autologous vaccine cells was successful to meet trial specifications in 8 of 11 cases (73%); the yields of the primary culture cell limited the number of courses of vaccination. Side effects were pruritus, erythema, and swelling at vaccination sites. Vaccine site biopsies manifested infiltrates of dendritic cells and macrophages among prostate tumor vaccine cells. Vaccination activated new T-cell and B-cell immune responses against PCA antigens. T-cell responses, evaluated by assessing delayed-type hypersensitivity (DTH) reactions against untransduced autologous tumor cells, were evident in two of eight patients before vaccination and in seven of eight patients after treatment. Reactive DTH site biopsies manifested infiltrates of effector cells consisting of CD45RO+ T-cells, and degranulating eosinophils consistent with activation of both Th1 and Th2 T-cell responses. A distinctive eosinophilic vasculitis was evident near autologous tumor cells at vaccine sites, and at DTH sites. B-cell responses were also induced. Sera from three of eight vaccinated men contained new antibodies recognizing polypeptides of 26, 31, and 150 kDa in protein extracts from prostate cells. The 150-kDa polypeptide was expressed by LNCaP and PC-3 PCA cells, as well as by normal prostate epithelial cells, but not by prostate stromal cells. No antibodies against prostate-specific antigen were detected. These data suggest that both T-cell and B-cell immune responses to human PCA can be generated by treatment with irradiated, GM-CSF gene-transduced PCA vaccines.

Antigens, Neoplasm↗
PubMed1999

Monoclonal antibody to prostate cancer nuclear matrix protein (PRO:4-216) recognizes nucleophosmin/B23.

BACKGROUND: The nuclear protein B23, nucleophosmin, is an RNA-associated nucleolar phosphoprotein reported to be more abundant in malignant and growing cells than in normal nondividing cells. We examined the levels of B23 in fresh human prostate tissue and in five human prostate cancer cell lines with monoclonal antibodies (mAb) to nucleophosmin (alpha-B23) and to human prostate cancer nuclear matrix proteins (PRO:4-216). METHODS: mAb PRO:4-216 and mAb alpha-B23 were used for protein level detection. Nuclear matrix proteins (NMPs) were prepared from prostate tumor and five human prostate cancer cell lines: LNCaP, TSU, DU145, PC-3, and PPC-1. The NMPs were run on one-dimensional and two-dimensional (2D) electrophoresis gels for Western blot analysis with the two mAbs. Histologic sections from paraffin-embedded normal and cancerous prostate tissue were stained immunohistochemically with both mAbs. RESULTS: PRO:4-216 and B23 mAbs identified a 40-kD protein (pI approximately 5.0) by Western blot analysis in the human prostate cancer cell lines and on two-dimensional blots of human prostate cancer NMPs. Immunohistochemical staining demonstrated large punctate nuclear dots in most cancer nuclei, while staining of normal tissue was less intense or absent. Predominant reactivity was of epithelial nuclei, with some minor reactivity of stromal nuclei. Red blood cells (RBCs) and white blood cells (WBCs) were routinely negative. CONCLUSIONS: PRO:4-216, previously characterized as recognizing prostate cancer nuclear matrix proteins, recognized B23/nucleophosmin. PRO:4-216 and alpha-B23 showed intense immunohistochemical staining of B23/nucleophosmin in cancer nuclei compared to adjacent normal cells in paraffin-embedded prostate tissue. This preliminary study showed the potential of B23 as a tumor marker for human prostate cancer.

Antibodies, Monoclonal↗
PubMed1999

Bioimpedance: novel use of a minimally invasive technique for cancer localization in the intact prostate.

BACKGROUND: Prostate cancer is presently diagnosed by transrectal ultrasound (TRUS)-guided sextant needle biopsy. While echo texture of the tissue can prompt localization of tumor, it is presently imprecise. From 50-75% of men biopsied, based on an abnormal digital rectal examination (DRE) or elevated prostate-specific antigen (PSA) level, have negative biopsy results. Improvements in tumor localization during TRUS-guided prostate biopsy are greatly needed. Bioimpedance is an electrical property of biologic tissue. Electric current is limited in living tissue by highly insulating cell membranes; however, different tissue architecture such as cancer may impede current differently and allow detection of differences between normal and abnormal or malignant prostate tissue. Our goal was to assess the utility of bioimpedance measurements in differentiating tumor from normal prostatic tissue in an ex vivo model. METHODS: Bioimpedance was measured in six ex vivo prostates, which were removed for clinically localized prostate cancer. Two bioimpedance needles, 1 mm apart, were inserted 3 mm into the posterior surface of the prostate an average of 16 times per gland. Frequencies ranging from 100 kHz-4 MHz were used to obtain 594 bioimpedance measurements from the six glands. These measurements were then correlated with histology to determine the presence or absence of prostate cancer. RESULTS: Prostate cancer was found to have a higher impedance, of 932+/-170 ohms, compared to areas of no cancer within the same prostate, 751+/-151 ohms, P < 0.0001, at 2 MHz. This phenomenon was observed across all frequencies tested. CONCLUSIONS: This study demonstrates for the first time application of bioimpedance to distinguish areas of prostate cancer from areas of normal prostate. This technology may improve identification and localization of cancer within the prostate. Moreover, bioimpedance can potentially guide needle placement during prostate biopsy and thus improve sampling of tumors. Currently, our ex vivo model is limited by variables such as temperature and lack of blood flow. Further studies in an in vivo model will be needed to assess their effect.

Diagnostic Techniques and Procedures↗
PubMed1999

Natural history of progression after PSA elevation following radical prostatectomy.

CONTEXT: In men who develop an elevated serum prostate-specific antigen level (PSA) after having undergone a radical prostatectomy, the natural history of progression to distant metastases and death due to prostate cancer is unknown. OBJECTIVE: To characterize the time course of disease progression in men with biochemical recurrence after radical prostatectomy. DESIGN: A retrospective review of a large surgical series with median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between April 1982 and April 1997. SETTING: An urban academic tertiary referral institution. PATIENTS: A total of 1997 men undergoing radical prostatectomy, by a single surgeon, for clinically localized prostate cancer. None received neoadjuvant therapy, and none had received adjuvant hormonal therapy prior to documented distant metastases. MAIN OUTCOME MEASURES: After surgery, men were followed up with PSA assays and digital rectal examinations every 3 months for the first year, semiannually for the second year, and annually thereafter. A detectable serum PSA level of at least 0.2 ng/mL was evidence of biochemical recurrence. Distant metastases were diagnosed by radionuclide bone scan, chest radiograph, or other body imaging, which was performed at the time of biochemical recurrence and annually thereafter. RESULTS: The actuarial metastasis-free survival for all 1997 men was 82% (95% confidence interval, 76%-88%) at 15 years after surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level elevation. Eleven of these underwent early hormone therapy after the recurrence and are not included in the study. Of the remaining 304 men, 103 (34%) developed metastatic disease within the study period. The median actuarial time to metastases was 8 years from the time of PSA level elevation. In survival analysis, time to biochemical progression (P<.001), Gleason score (P<.001), and PSA doubling time (P<.001) were predictive of the probability and time to the development of metastatic disease. An algorithm combining these parameters was constructed to stratify men into risk groups. Once men developed metastatic disease, the median actuarial time to death was 5 years. The time interval from surgery to the appearance of metastatic disease was predictive of time until death (P<.02). CONCLUSIONS: Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in the design of clinical trials, the identification of men for enrollment into experimental protocols, and counseling men regarding the timing of administration of adjuvant therapies.

Disease Progression↗
PubMed1999

Comparison of clinical staging algorithms and 111indium-capromab pendetide immunoscintigraphy in the prediction of lymph node involvement in high risk prostate carcinoma patients.

BACKGROUND: The pretherapy prediction of occult lymph node involvement and the avoidance of otherwise futile and potentially morbid definitive local therapy is paramount in men with newly diagnosed prostate carcinoma. To identify patients with prostate carcinoma who likely have lymph node involvement and would benefit from staging lymphadenectomy prior to definitive local therapy, the authors compared the ability of several predictive staging algorithms and a radiolabeled monoclonal antibody scan to predict lymphatic metastases prior to treatment. METHODS: Between August 1991 and June 1994, 198 men with clinical T2 or T3 classified (TNM) prostate carcinoma (bone scan negative) who were at high risk of lymph node involvement underwent a 111In-capromab pendetide scan prior to staging lymphadenectomy. Several predictive models based on preoperative prostate specific antigen level, biopsy Gleason score, and clinical stage were selected to predict those men having a > or =20% probability of lymph node involvement. The ability to predict pathologic stage using several clinical algorithms and the monoclonal antibody scan was compared with pathologic examination of the lymph nodes. RESULTS: Overall, 39% of the pelvic lymph node specimens were positive for metastatic disease by pathologic analysis. Published algorithms predicting lymph node metastases had a positive predictive value (PPV) ranging from 40.5% to 46.6% and an area under the receiver operating characteristic curve (AUC) ranging from 0.52 to 0.61. The monoclonal antibody scan had a PPV of 66.7% and an AUC of 0.71. The differences between the PPV and the AUC for the individual clinical algorithms when compared with immunoscintigraphy were statistically significant. Combining the radiolabeled monoclonal antibody scan with clinical predictive models, a PPV of up to 72.1% could be obtained. CONCLUSIONS: These data suggest that the PPVs for the clinical predictive algorithms are similar and that the PPV of the radiolabeled monoclonal antibody scan alone or in combination with the algorithms has additional value in predicting lymph node involvement in prostate carcinoma patients at high risk of regional disease spread. These algorithms and the 111In-capromab pendetide scan may be used for the appropriate selection of candidates for definitive local therapy in men with clinically localized prostate carcinoma and significant risk of lymph node involvement.

Aged↗
PubMed1999

Exploratory data analysis groupware for qualitative and quantitative electrophoretic gel analysis over the Internet-WebGel.

Many scientists use quantitative measurements to compare the presence and amount, of various proteins and nucleotides among series of one- and two-dimensional (1-D and 2-D) electrophoretic gels. These gels are often scanned into digital image files. Gel spots are then quantified using stand-alone analysis software. However, as more research collaborations take place over the Internet, it has become useful to share intermediate quantitative data between researchers. This allows research group members to investigate their data and share their work in progress. We developed a World Wide Web group-accessible software system, WebGel, for interactively exploring qualitative and quantitative differences between electrophoretic gels. Such Internet databases are useful for publishing quantitative data and allow other researchers to explore the data with respect to their own research. Because intermediate results of one user may be shared with their collaborators using WebGel, this form of active data-sharing constitutes a groupware method for enhancing collaborative research. Quantitative and image gel data from a stand-alone gel image processing system are copied to a database accessible on the WebGel Web server. These data are then available for analysis by the WebGel database program residing on that server. Visualization is critical for better understanding of the data. WebGel helps organize labeled gel images into montages of corresponding spots as seen in these different gels. Various views of multiple gel images, including sets of spots, normalization spots, labeled spots, segmented gels, etc. may also be displayed. These displays are active and may be used for performing database operations directly on individual protein spots by simply clicking on them. Corresponding regions between sets of gels may be visually analyzed using Flicker-comparison (Electrophoresis 1997, 18, 122-140) as one of the WebGel methods for qualitative analysis. Quantitative exploratory data analysis can be performed by comparing protein concentration values between corresponding spots for multiple samples run in separate gels. These data are then used to generate reports on statistical differences between sets of gels (e.g., between different disease states such as benign or metastatic cancers, etc.). Using combined visual and quantitative methods, WebGel can help bridge the analysis of dissimilar gels which are difficult to analyze with stand-alone systems and can serve as a collaborative Internet tool in a groupware setting.

Electrophoresis↗
PubMed1999

Measurement of urinary N-acetyl-beta-D-glucosaminidase to assess renal ischemia during laparoscopic operations.

BACKGROUND: Oliguria during laparoscopy is a well-documented phenomenon of unknown etiology. Experimental evidence suggests that renal perfusion is reduced during pneumoperitoneum. N-acetyl-beta-D-glucosaminidase (NAG), which is present in renal tubular cells, is released into the urine in response to tubular insults. In this study, urinary NAG was measured before and after procedures to assess for ischemic renal injury. METHODS: A total of 31 patients underwent laparoscopic procedures while 28 patients had conventional surgery. Urine was obtained first at the time of preoperative Foley catheter placement and later during the recovery room stay. NAG levels were measured and indexed to urinary creatinine. RESULTS: Operative time for the laparoscopy group was 105 min (range, 15-255); for the conventional group, it was 179 min (range, 75-385) (P < 0.05). No differences were noted between pre- and postoperative NAG levels or between the groups. There was no correlation between urinary NAG levels and operative time. CONCLUSION: Pneumoperitoneum is not associated with a change in the urinary concentration of NAG. This finding suggests that there is no significant renal tubular injury associated with laparoscopic surgery.

Acetylglucosaminidase↗
PubMed1999

Prostate specific antigen: a decade of discovery--what we have learned and where we are going.

PURPOSE: Many advances have occurred during the last decade in the clinical use of prostate specific antigen (PSA) for detecting, staging and monitoring prostate cancer. We review the clinical usefulness and limitations of serum PSA as a tumor marker of prostate cancer. MATERIALS AND METHODS: The English language literature was reviewed with respect to the major contributions and limitations of PSA in present clinical practice. RESULTS: Although controversial, age specific PSA reference ranges can improve the sensitivity for prostate cancer detection in young men and the specificity in older men. Percent free PSA improves the specificity for prostate cancer detection in men with PSA values between 4 and 10 ng./ml., and a PSA density of greater than 0.15 may better distinguish benign prostatic hyperplasia from prostate cancer. PSA velocity can improve the ability to detect prostate cancer when 3 serial PSA values are measured during a 2-year period. For prostate cancer staging PSA is most useful combined with clinical stage and Gleason score in multivariate analysis. Percent free PSA may prove useful for staging prostate cancer but further clinical trials are needed to determine its clinical usefulness. PSA is the most clinically useful means to monitor disease recurrence after treatment of prostate cancer. With ultrasensitive PSA assays it is now possible to increase the lead time for detection of disease recurrence by several months. CONCLUSIONS: During the last decade much of the focus has been on improving the ability of this tumor marker to detect prostate cancer. PSA remains the best and most widely used tumor marker in urology today.

Forecasting↗