Search PubMed⌕ Search

Biomedical subjects

P T Scardino

Publications and source records attributed to P T Scardino.

At least 19 recordsLinked to original sources
PubMed2004

Apolipoprotein-D: a novel cellular marker for HGPIN and prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN) is a putative pre-malignant lesion of the prostate. While apolipoprotein-D (Apo-D), an androgen-regulated hydrophobic transporter protein, is expressed in prostate tumors, its expression in HGPIN is unknown. METHODS: Immunoreactivity for Apo-D and another androgen-regulated protein, prostate specific antigen (PSA), was investigated in 64 radical prostatectomy tissues by video image analysis. RESULTS: Eighty two percent of prostatectomy specimens demonstrated moderate to strong Apo-D immunoreactivity in areas of HGPIN. In comparison, weak Apo-D immunoreactivity was observed in non-malignant areas in only 24% of specimens. The median (range) percentage cellular area of HGPIN immunopositive for Apo-D (9.7%, 0-42.9), and the cellular concentration of Apo-D (MIOD 3.1, 0-13.3), were intermediate between that of normal (area 0%, 0-53.5%, MIOD 0, 0-12.6) and early stage prostate cancer tissues (area 29.2%, 0-90.8%, MIOD 6.7, 0-28.1). This increase in Apo-D expression from non-malignant, through HGPIN to prostate cancer was statistically significant (P < 0.001), and contrasted with the decrease observed in PSA staining between adjacent areas of normal glands, HGPIN, and cancer (P = 0.026). CONCLUSIONS: The presence of high levels of immunoreactive Apo-D in HGPIN and prostate cancer, but not in non-malignant epithelial cells, is consistent with HGPIN being an intermediate lesion in the transition to prostate cancer, and suggests that cellular Apo-D expression is a marker of malignant transformation of the prostate.

Apolipoproteins↗
PubMed2003

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy].

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.

Biomarkers, Tumor↗
PubMed2001

Reduced expression of hMSH2 and hMLH1 and risk of prostate cancer: a case-control study.

BACKGROUND: Although prostate cancer is the most common incident cancer in men, not much is known about its etiology. We tested the hypothesis that expression levels of hMSH2 and hMLH1 in unaffected (normal) tissue play a role in the etiology of prostate cancer. METHODS: Total RNA was extracted from peripheral blood lymphocytes of subjects ascertained by a case-control study (70 patients and 97 age- and ethnicity-matched controls). A multiplex reverse transcription-polymerase chain reaction assay was used to simultaneously evaluate the relative expression of hMSH2 and hMLH1, using beta-actin as the internal control. RESULTS: The relative gene expression levels of hMSH2 and hMLH1 were significantly lower in cases than in controls (P < 0.05 for both genes). When compared with the highest tertile of the controls, low expression levels (the middle and lowest tertiles) of hMLH1 were associated with significantly increased risk of prostate cancer in a dose-response relationship (ORs = 2.68, and 4.31; 95% confidence interval = 1.00-7.23 and 1.64-11.30, respectively) after adjustment for age, ethnicity, smoking status, and family history of prostate cancer. CONCLUSIONS: These results suggest that reduced expression of hMLH1 in peripheral lymphocytes may be a risk factor for prostate cancer. However, it cannot be ruled out that the reduced expression we observed may be caused by the disease status. Our findings and the factors that may affect the expression of hMLH1 need further confirmation in larger prospective studies.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer.

OBJECTIVES: To develop a prognostic nomogram to predict the freedom from recurrence for patients treated with permanent prostate brachytherapy for localized prostate cancer. METHODS: We performed a retrospective analysis of 920 patients treated with permanent prostate brachytherapy between 1992 and 2000. The clinical parameters included clinical stage, biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) value, and administration of external beam radiation. Patients who received neoadjuvant androgen deprivation therapy were excluded. Failure was defined as any post-treatment administration of androgen deprivation, clinical relapse, or biochemical failure, defined as three PSA rises. Patients with fewer than three PSA rises were censored at the time of the first PSA rise. Data from two outside institutions served as validation. RESULTS: A nomogram that predicts the probability of remaining free from biochemical recurrence for 5 years after brachytherapy without adjuvant hormonal therapy was developed using Cox proportional hazards regression analysis. External validation revealed a concordance index of 0.61 to 0.64, and calibration of the nomogram suggested confidence limits of +5% to -30%. CONCLUSIONS: The pretreatment nomogram we developed may be useful to physicians and patients in estimating the probability of successful treatment 5 years after brachytherapy for clinically localized prostate cancer.

Adenocarcinoma↗
PubMed2001

Bilateral nerve grafting during radical retropubic prostatectomy: extended follow-up.

OBJECTIVES: To confirm the benefit of using an interposition sural nerve graft at the time of radical retropubic prostatectomy in an extended series of men with at least 1 year of follow-up. We previously reported the return of erectile function after resection of both cavernous nerves. METHODS: Twenty-eight potent men with clinically localized prostate cancer underwent radical retropubic prostatectomy with deliberate wide bilateral neurovascular bundle resection and the placement of bilateral nerve grafts. Erectile dysfunction questionnaires and patient interviews were completed at 6-month intervals. A minimum of 12 months of follow-up (mean 23 +/- 10 months) was obtained for 23 men (mean age 58 +/- 6 years). A control group of 12 men who underwent bilateral nerve resections, but declined nerve graft placement, was also followed up. RESULTS: Of the 23 men, 6 (26%) had spontaneous, medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 6 men (26%) described "40% to 60%" spontaneous erections (fullness, no rigidity, not able to penetrate). Ten men (43%) had intercourse with sildenafil. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function thus far was observed at 18 months after surgery. CONCLUSIONS: This surgical technique continues to show promise as an advance in prostate cancer surgery. The results of this study demonstrated recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Case-Control Studies↗
PubMed2001

Prognostic significance of the diameter of perineural invasion in radical prostatectomy specimens.

We assessed whether the quantification of cancer invasion into the perineural space influences the prognosis of patients treated with radical prostatectomy. We conducted a retrospective study of clinical and pathologic features in 640 consecutive patients with clinical stage Tla-T3bNXM0 prostate cancer who were treated with radical retropubic prostatectomy by the same surgeon between 1989 and 1995. None had received preoperative hormonal therapy or radiotherapy. Detailed pathologic analysis, including the presence and maximum diameter of perineural invasion (PNI), was performed by 2 pathologists. Treatment failure was defined as either a serum prostate-specific antigen (PSA) level > 0.4 ng/mL and rising or initiation of adjuvant therapy. The median follow-up time was 48 months (range, 1 to 111 months). Overall, PNI was detected in 477 patients (75%). The progression-free 5-year probability rate after prostatectomy for patients with PNI was 70% +/- 3% compared with 94% +/- 2% for patients without PNI (P <.001). The mere presence of PNI was not an independent predictor of progression in a Cox proportional hazards analysis when the other established prognostic factors (serum PSA level, pathologic stage, surgical margin, and tumor volume) were considered. However, the increasing diameter of the largest focus of PNI was strongly associated with other established prognostic factors and the probability of progression after radical prostatectomy. Although little adverse effect in patients with PNI < 0.25 mm was seen 5 years after surgery, those with a PNI diameter of 0.25 to 0.5 mm were significantly (P <.001) less likely to remain free of progression; only 36% of those with PNI of 0.5 to 0.75 mm (P <.001) and 14% of those with PNI > or =0.75 mm (P =.002) were free of progression. In a Cox proportional hazard analysis, the PNI diameter was an independent predictor of prognosis. These results support that the measurement of the PNI diameter, easily recorded from prostatectomy specimens, could add important information to the prognosis of prostate cancer patients. Controversy regarding the significance of PNI may result from the lack of quantitative assessment of PNI in previous studies.

Adenocarcinoma↗
PubMed2001

Primary Gleason pattern as a predictor of disease progression in gleason score 7 prostate cancer: a multivariate analysis of 823 men treated with radical prostatectomy.

Gleason score (GS) is a powerful predictor of disease progression in men with prostate cancer (PCa). The majority of clinically localized prostate cancers, however, are moderately (GS5/6) or moderate to poorly (GS7) differentiated tumors with indeterminate prognosis. Differences in disease progression between patients with GS5/6 and GS7 tumors suggest the presence of any component of high-grade tumor (Gleason pattern [GP] 4/5) worsens prognosis markedly. Indeed, McNeal et al. have shown that quantification of GP4/5 provides prognostic information beyond the standard GS. Few investigators have analyzed whether primary and secondary GPs are important prognostically within GS7 PCa. All 823 whole-mount radical prostatectomy specimens with GS7 from a single surgeon (P.T.S.) were analyzed. Tumors were either 3+4 or 4+3, and primary GP was assigned by the same pathologist (T.M.W.). A total of 643 patients with 3+4 tumors and 180 patients with 4+3 tumors were studied. Statistical analysis using the log-rank test showed a significant difference in recurrence-free survival between patients with primary GP4 and those with GP3 (p <0.0001). However, in multivariate analysis with preoperative prostate-specific antigen, total tumor volume, surgical margin status, and the presence or absence of seminal vesicle involvement, extraprostatic extension, and lymph node metastasis, the primary GP did not retain independent significance (p = 0.0557). GS7 PCa is a heterogeneous group of tumors. In this cohort of men with GS7 tumors treated by radical retropubic prostatectomy, primary GP showed a significant correlation with other histologic and clinical predictors of disease progression; however, it was not independently predictive of disease progression in multivariate analysis (p = 0.76).

Adenocarcinoma↗
PubMed2001

Incidence, location, and significance of periprostatic and periseminal vesicle lymph nodes in prostate cancer.

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.

Adenocarcinoma↗
PubMed2001

Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup.

PURPOSE: With the interposition of a sural nerve graft to replace resected cavernous nerves at radical retropubic prostatectomy, we have previously reported the return of effective erectile function. We determine the efficacy of this procedure in a series of men with at least 1-year followup. MATERIALS AND METHODS: A total of 12 potent men (mean age plus or minus standard deviation 57 +/- 6 years) with clinically localized prostate cancer underwent radical retropubic prostatectomy, with deliberate wide bilateral neurovascular bundle resection and placement of bilateral nerve grafts. A series of patient and partner erectile dysfunction questionnaires, and patient interviews were performed at 3, 6, 12 and 18 months postoperatively. Only results for those men with a followup of 12 months or greater (mean 16 +/- 4) are presented. A control group of 12 men who had undergone bilateral nerve resection but declined nerve graft placement, was also followed. RESULTS: Of the 12 men 4 (33%) had spontaneous medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 5 (42%) men describe "40 to 60%" spontaneous erections, with fullness, no rigidity and not able to penetrate. Overall, 9 (75%) men had return of erectile activity. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function was observed at 14 to 18 months after surgery. CONCLUSIONS: This surgical technique has minimal morbidity and represents a significant advance in prostate cancer surgery in men requiring bilateral nerve resection. Our study clearly demonstrates recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Aged↗
PubMed2001

A catalog of prostate cancer nomograms.

PURPOSE: Prediction is central to the management of prostate cancer. Nomograms are devices that make predictions. We organized many nomograms for prostate cancer. MATERIALS AND METHODS: Using MEDLINE a literature search was performed on prostate cancer nomograms from January 1966 to February 2000. We recorded input variables, prediction form, the number of patients used to develop the nomogram and the outcome being predicted. We also recorded the accuracy measures reported by the original authors and whether the nomograms have withstood validation. In addition, we noted whether the nomograms were proprietary or in the public domain. Each nomogram was classified into patient clinical disease state and the outcome being predicted. RESULTS: The literature search generated 42 published nomograms that may be applied to patients in various clinical stages of disease. Of the 42 nomograms only 18 had undergone validation, of which 2 partially failed. Few nomograms have been compared for predictive superiority and none appears to have been compared with clinical judgment alone. CONCLUSIONS: Patients with prostate cancer need accurate predictions. Prognostic nomograms are available for many clinical states and outcomes, and may provide the most accurate predictions currently available. Selection among them and progress in this field are hampered by the lack of comparisons for predictive accuracy.

Biopsy↗
PubMed2000

Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer.

PURPOSE: Several studies have defined risk groups for predicting the outcome after external-beam radiotherapy of localized prostate cancer. However, most models formed patient risk groups, and none of these models considers radiation dose as a predictor variable. The purpose of this study was to develop a nomogram to improve the accuracy of predicting outcome after three-dimensional conformal radiotherapy. MATERIALS AND METHODS: This study was a retrospective, nonrandomized analysis of patients treated at the Memorial Sloan-Kettering Cancer Center between 1988 and 1998. Clinical parameters of the 1,042 patients included stage, biopsy Gleason score, pretreatment serum prostate-specific antigen (PSA) level, whether neoadjuvant androgen deprivation therapy was administered, and the radiation dose delivered. Biochemical (PSA) treatment failure was scored when three consecutive rises of serum PSA occurred. A nomogram, which predicts the probability of remaining free from biochemical recurrence for 5 years, was validated internally on this data set using a bootstrapping method and externally using a cohort of patients treated at the Cleveland Clinic, Cleveland, OH. RESULTS: When predicting outcomes for patients in the validation data set from the Cleveland Clinic, the nomogram had a Somers' D rank correlation between predicted and observed failure times of 0.52. Predictions from this nomogram were more accurate (P<.0001) than the best of seven published risk stratification systems, which achieved a Somers' D coefficient of 0.47. CONCLUSION: The development process illustrated here produced a nomogram that seems to predict more accurately than other available systems and may be useful for treatment selection by both physicians and patients.

Aged↗
PubMed2000

Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging.

OBJECTIVES: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. METHODS: Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays were used. RESULTS: %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. CONCLUSIONS: The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.

Age Factors↗
PubMed2000

Epidemiologic determinants of clinically relevant prostate cancer.

While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a university-based hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were </=0.5 ml. The comparison group was comprised of 225 men with larger-volume disease or with histologic evidence of extracapsular extension but without lymph node involvement. The matching criteria were ethnicity, age at diagnosis (+/-5 years), and date of diagnosis (+/-1 year). Epidemiologic data, current weight, and height were obtained. The comparison group was significantly more likely than cases to be current smokers (7.6% vs. 3.9%) and to report more pack-years smoked (30.1 vs. 23.0 years, p = 0.06). Cases tended to weigh less (85.2 vs. 87.1 kg, p = 0.1) and have lower body mass indices (26.8 vs. 27.6, p = 0.07). A similar trend was evident for weight at age 40 (79 vs. 81 kg). Cases reported a mean weight gain of 4.9 kg compared with 6. 6 kg in the comparison subjects (p = 0.05) between the ages of 25 and 40. There was no significant difference in weight gain from age 40 to current age. Cases were more likely to report having prostate cancer screening (90% vs. 80%, p = 0.02). Cases with Gleason scores </=7 (3 + 4, with 3 being the dominant grade) were younger at diagnosis than those with scores of 7 (4 + 3, with 4 being the dominant grade), were more likely (93%) to have had prostate screening, were less likely to be current smokers (4%), reported the fewest pack-years smoked (21.5 vs. 28.6 years for high-score cases and 30.1 for comparison subjects), and had the lowest average weight gain from ages 25 to 40 (4.62 vs. 6.31 kg for high-score cases). Weight gain in early adulthood and smoking thus appear to be important predictors of virulent prostate cancer. Our data also suggest that prior screening is associated with diagnosis of lower-volume and lower-score disease.

Age Factors↗