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H Zincke

Publications and source records attributed to H Zincke.

At least 37 records · Page 2Linked to original sources

Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4.

PURPOSE: We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. CONCLUSIONS: In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.

Adenocarcinoma↗

Role of early adjuvant hormonal therapy after radical prostatectomy for prostate cancer.

PURPOSE: Recent prospective randomized studies have shown that adjuvant hormonal therapy combined with local treatment can significantly improve overall survival in patients with locally advanced disease. This finding challenges the previous belief that adjuvant hormonal therapy may not be beneficial for minimal stages TxN + M0 or less prostate cancer, particularly when combined with local treatment. We reviewed the benefits of adjuvant hormonal therapy in patients at risk for disease progression, especially when administered after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the current literature and evaluated clinical information on stage pT3b cancer from a large single institution prostate cancer database to determine the current role of adjuvant hormonal therapy after radical prostatectomy for prostate cancer. RESULTS: Retrospective experimental and clinical studies have proved the impact of adjuvant hormonal therapy for decreasing prostate specific antigen (PSA) and clinical disease progression in patients with regionally limited prostatic cancer. This finding applies to stage pT3b as well as to lymph node positive cancer. Our literature review and current data from the Mayo Clinic database show that adjuvant hormonal therapy after prostatectomy has a significant impact on prostate specific antigen (PSA) progression but it also decreases systemic progression and cause specific death in patients with stage pT3b and lymph node positive disease. After adjusting for preoperative PSA, margins, grade, ploidy and patient age the risk ratio for stage pT3b disease in 707 cases was 0.3 (95% confidence interval 0.2 to 0.7). A recent prospective randomized trial showed a significant decrease in cancer death in N+ cases when adjuvant hormonal therapy was administered after radical prostatectomy, supporting previous Mayo Clinic data on N+ disease that favors combination therapy. In the PSA era, that is 1987 and after, our database data on stage pTxN+ cancer indicates that radical prostatectomy and hormonal therapy for single node positive disease resulted in 94% 10-year cause specific survival, which was not significantly different from the rate in patients with N0 disease after adjusting for local stage, Gleason grade, margins, ploidy, PSA and adjuvant hormonal therapy. CONCLUSIONS: Our literature review, including prospective randomized studies, and more recent results in the PSA era from our database indicate that early adjuvant hormonal therapy has a significant impact on time to progression and cause specific survival in patients with seminal vesicle invasion and limited lymph node disease who undergo radical prostatectomy, although in a retrospective nonrandomized study. Future prospective studies with longer followup are needed to evaluate the potential benefit of adjuvant treatment in regard to survival for stages pT2 and pT3a disease with unfavorable pathological variables.

Aged↗

Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies.

OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.

Aged↗

Predicting the survival of bladder carcinoma patients treated with radical cystectomy.

BACKGROUND: Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder. METHODS: The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival. RESULTS: Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender. CONCLUSIONS: Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (< or = pT2) and small size (< or = 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials.

Adult↗

Squamous papilloma of the urinary tract is unrelated to condyloma acuminata.

BACKGROUND: To the authors' knowledge, there is no previous report of squamous papilloma of the urinary tract. It is uncertain whether there is a correlation between squamous papilloma, condyloma acuminatum, and verrucous carcinoma. METHODS: The authors evaluated the clinical and pathologic features of squamous papilloma (5 of the bladder, 2 of the urethra), condyloma acuminatum (3 cases), and verrucous carcinoma (3 cases) of the urinary bladder and performed human papillomavirus (HPV) DNA in situ hybridization studies to determine whether HPV was a common feature shared by these lesions. In addition, DNA ploidy evaluation by image cytometry and p53 immunohistochemical staining were performed. RESULTS: Squamous papilloma of the urinary tract occurred in elderly women and followed a benign clinical course with infrequent recurrence. All squamous papillomas were HPV DNA negative and DNA diploid with no or minimal p53 nuclear accumulation. Condyloma acuminata of the bladder contained HPV DNA, increased p53 protein expression, and aneuploid DNA content. All three cases of condyloma acuminata were associated with coexistent condylomata of the external genitalia, and two required pelvic exenteration for uncontrolled expansile growth. Verrucous carcinoma of the bladder occurred in elderly patients. All three cases of verrucous carcinoma were negative for HPV DNA and DNA aneuploid, and they exhibited consistent p53 expression. CONCLUSIONS: These data indicate that squamous papilloma is a distinct entity not related to condyloma or verrucous carcinoma. These lesions are benign, HPV DNA negative, DNA diploid, and they lack p53 overaccumulation.

Adult↗

Paraganglioma of the urinary bladder: can biologic potential be predicted?

BACKGROUND: Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome. METHODS: The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years). RESULTS: Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-to-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The tumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). At the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin. CONCLUSIONS: Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (>/=T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection.

Adolescent↗

Extranodal extension in lymph node-positive prostate cancer.

Evaluation of extranodal tumor extension may provide prognostic information for patients with epithelial malignancies. However, its importance for the patient who has prostate cancer with regional lymph node metastasis requires further investigation and clarification. This study was performed to evaluate the prognostic significance of extranodal extension (ENE) in a large series of node-positive patients. The study group included 212 node-positive patients who were treated by bilateral pelvic lymphadenectomy, radical retropubic prostatectomy, and androgen deprivation between 1987 and 1992 at the Mayo Clinic. ENE was defined as cancer perforating through the lymph node capsule into perinodal tissue. Nodal cancer volume was measured by the grid method. Univariate and multivariate risk ratios (RR) for distant metastasis-free and cancer-specific survival were estimated using the Cox proportional model. The mean follow-up was 6.3 years (median, 6.1 years). Distant metastasis-free and cancer-specific survival at 5 years for all patients was 91% and 95%, respectively. ENE was found in 126 of 212 patients (59%). The presence of ENE was not significantly associated with distant metastasis-free (RR = 1.6; 95% confidence interval [CI], 0.7 to 3.9) or cancer-specific survival (RR = 2.2; 95% CI, 0.7 to 6.8). Among 98 patients with a single positive node, there was no significant difference in distant metastasis or cancer-specific survival according to the presence of ENE (P = .88 and P = .36, respectively). After adjusting for Gleason score, DNA ploidy, and ENE, only nodal cancer volume was significantly associated with adverse distant metastasis-free (RR = 1.9; 95% CI, 1.5 to 2.8) and cancer-specific survival (RR = 1.4; 95% CI, 1.1 to 1.9). Our data indicate that the presence of ENE is not associated with unfavorable survival in patients with node-positive prostate cancer treated by radical retropubic prostatectomy, bilateral pelvic lymphadenectomy, and androgen deprivation therapy. In contrast, nodal cancer volume was predictive of distant metastasis-free survival and cancer-specific survival.

Adenocarcinoma↗

Preoperative prediction of surgical margin status in patients with prostate cancer treated by radical prostatectomy.

PURPOSE: We sought to determine the preoperative factors associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. PATIENTS AND METHODS: The study group consisted of 339 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at the time of surgery was 66 years (range, 45 to 79 years). All specimens were totally embedded and whole-mounted. Positive surgical margin was defined as the presence of cancer cells at the inked margins. Numerous pathologic characteristics in needle biopsies and preoperative clinical findings were analyzed. RESULTS: The overall margin positivity rate was 24%. In univariate analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason score, perineural invasion, percentage of cancer in the biopsy specimens, and number and percentage of biopsy cores involved by cancer were all associated with positive surgical margins. In multivariate analysis, preoperative serum PSA level (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to 2.4; P <.001) and percentage of cancer in the biopsy specimens (odds ratio for a 10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P <.001) were predictive of margin status in radical prostatectomy. With use of preoperative serum PSA level and percentage of cancer in the biopsy as predictors of surgical margins, the overall accuracy as measured by the area under the receiver operating characteristic curve was 0.74. CONCLUSION: Preoperative serum PSA level and percentage of cancer in the biopsy specimens were independently associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides a high level of predictive accuracy for margin status.

Aged↗

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Adult↗

Management and extended outcome of patients with synchronous bilateral solid renal neoplasms in the absence of von Hippel-Lindau disease.

OBJECTIVE: To gain information regarding long-term follow-up in patients with synchronous bilateral solid renal neoplasms in whom renal-preserving surgery is imperative. PATIENTS AND METHODS: We examined our surgical experience and the survival outcome, as evaluated by Kaplan-Meier and log-rank analysis, of 94 patients (64 men and 30 women) who presented to the Mayo Clinic in Rochester, Minn, from 1973 to 1998 with bilateral synchronous solid renal neoplasms in the absence of von Hippel-Lindau disease. Follow-up of these patients ranged from 1 to 25 years, with a mean of 5.86 years and a median of 4.18 years. Tumors were staged according to the TNM classification. Pathologic staging and grading were usually performed on the kidney with the most extensive cancer. The Cox proportional hazards model was used to assess the relationship of grade (1-4), tumor size, and enucleation as opposed to extended (1 cm) partial nephrectomy on overall, cancer-specific, local recurrence-free, and metastasis-free survival. RESULTS: Seventy-one patients (76%) had bilateral synchronous renal cell carcinoma, and 14 patients (15%) had a unilateral renal cell carcinoma with a contralateral benign solid neoplasm. Nine patients (10%) had bilateral benign solid lesions. Sixty-six patients (70%) underwent a single procedure, whereas 28 (30%) underwent staged surgical procedures. Fifty-one patients (54%) are alive, and 43 (46%) have died. Twenty patients (21%) died of metastatic disease, and 5 (5%) had a local recurrence. Cancer-specific survival of the 85 patients with at least 1 renal cell carcinoma still under observation was 81% (+/- 4.9% SE) and 59% (+/- 8.1% SE) at 5 and 10 years, respectively, and survival to local recurrence was 96% (+/- 2.6% SE) at 5 years and 93% (+/- 3.7% SE) at 10 years with 14 patients still under observation. Grade 3 was a statistically significant factor for metastasis (P < .001). A significant difference in metastasis-free survival and cancer-specific survival was noted dependent on pathologic T stage (P < .001 and P = .02, respectively), with patients with local pT3 disease having a higher rate of metastasis and cancer-specific death. Multivariate analysis revealed that tumor grade was associated with metastasis-free survival (P = .002) and tumor size with cancer-specific survival (P = .04). There was no statistical significance on survival outcome end points according to procedure performed, i.e., enucleation vs extended partial nephrectomy. CONCLUSION: Long-term results of renal-preserving procedures for a series of patients with bilateral solid renal neoplasms indicate that grade, stage, and tumor size are significant predictors of outcome. Mean follow-up of over 5 years supports nephron-sparing techniques in selected patients because local recurrence was infrequent compared with distant metastasis.

Adult↗

Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney.

OBJECTIVE: To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney. PATIENTS AND METHODS: Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (< or = 30 days) complications and proteinuria at last follow-up. RESULTS: At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52-1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30-5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively (P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2-11.2; P = .01). CONCLUSIONS: This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS.

Carcinoma, Renal Cell↗

Renal cell carcinoma metastatic to the pancreas: clinical and radiological features.

OBJECTIVE: To review the clinical features, computed tomographic (CT) appearance, and treatment outcomes in a case series of patients with renal cell carcinoma (RCC) metastatic to the pancreas. PATIENTS AND METHODS: We retrospectively reviewed the records of 23 patients (15 men and 8 women) with RCC metastatic to the pancreas, detected by CT examination between 1986 and 1996. All patients had undergone a previous nephrectomy for RCC. RESULTS: Isolated mild elevation in liver function test results (in 5 patients) or in serum amylase level (in 8 patients) was observed. New-onset diabetes was detected in 3 patients. The CT characteristics of the pancreatic metastases generally resembled those of primary RCC with well-defined margins and greater enhancement than normal pancreas with a central area of low attenuation. The mean interval between resection of the primary RCC and detection of the pancreatic metastases was 116 months (range, 1-295 months). In 18 patients (78%), the pancreatic metastases were diagnosed more than 5 years after nephrectomy. The pancreas was the initial metastatic site in 12 patients (52%). Survival was shortened with higher tumor grade (mean survival time of 41 months and 10 months in patients with grade 2 and 3, respectively). Surgical resection was carried out in 11 patients (7 distal and 3 total pancreatectomies and 1 distal pancreatectomy followed 4 years later by total pancreatectomy), with 8 patients alive at a mean follow-up of 4 years, 6 of whom remained free of recurrence. Overall, 12 patients (52%) were alive at a mean of 42 months after diagnosis of metastatic disease. CONCLUSIONS: The appearance of metastatic RCC lesions in the pancreas closely resembles the appearance of primary RCC on CT images. Pancreatic metastases from RCC are frequently detected many years after nephrectomy. Patient survival correlates with tumor grade. Histologic analysis of pancreatic masses in patients with a history of resected primary RCC is important since the prognosis for RCC metastatic to the pancreas is much better than that for primary pancreatic adenocarcinoma.

Aged↗

The percent of cores positive for cancer in prostate needle biopsy specimens is strongly predictive of tumor stage and volume at radical prostatectomy.

PURPOSE: Pretreatment clinical staging of prostatic adenocarcinoma is important due to the increasing use of nonsurgical treatment options. Using multivariate analysis we assessed the predictive value of biopsy cores positive for cancer as a percent of all cores obtained as well as the percent surface area of needle cores involved with tumor for determining tumor volume and pathological stage at radical prostatectomy. Candidate variables for the multivariate model included patient age, clinical disease stage, serum prostate specific antigen (PSA) and Gleason score of cancer in the needle biopsy. MATERIALS AND METHODS: We reviewed prostate needle biopsy findings in 207 consecutive patients who subsequently underwent radical retropubic prostatectomy. Each biopsy specimen was assessed for tumor involvement by calculating the percent of cores positive for cancer, percent surface area involved in all cores and Gleason score. Initial serum PSA and preoperative clinical disease stage were incorporated with biopsy results into a multivariate model to determine the parameters most predictive of pathological stage and tumor volume at radical retropubic prostatectomy. RESULTS: Of the 207 patients 152 (73.4%) had organ confined cancer and 55 (26.6%) had extraprostatic extension (pathological stages T2 and T3 or greater, respectively). Preoperative clinical staging information was available in 195 cases, in which disease was clinically confined and not confined in 184 (94.4%) and 11 (5.6%), respectively. Needle biopsy revealed a surface area of cancer ranging from less than 5% in 69 patients (33.3%) to 90% (mean 16, median 10). Univariate analysis demonstrated that the risk of extraprostatic extension was predicted by preoperative serum PSA (p = 0.027), the percent of cores and percent of surface area positive for cancer (p <0.0001), and Gleason score (p = 0.0009). Clinical stage approached significance (p = 0.071). Multivariate analysis showed that the percent of positive cores (p = 0.0003), initial serum PSA (p = 0.005) and Gleason score of cancer in the needle biopsy (p = 0.03) were the only parameters that jointly predicted pathological stage (T2 versus T3). Percent of tumor surface area involvement in the needle biopsies did not add any more information after the percent of positive cores was known. Univariate analysis revealed that the percent of cores positive for cancer (Spearman r = 0.52, p <0.0001), Gleason score (Spearman r = 0.34, p <0.0001) and initial serum PSA (Spearman r = 0.24, p = 0.003) were predictive of log tumor volume at radical prostatectomy, while clinical stage was not (rank sum test p = 0.14). On multivariate analysis the percent of positive cores (p <0.0001), Gleason score (p <0.0001) and initial serum PSA (0.0033) were the only variables that jointly were predictive of tumor volume. CONCLUSIONS: The percent of needle biopsy cores and surface area positive for cancer are the strongest predictors of pathological stage and tumor volume on multivariate analysis incorporating preoperative serum PSA and Gleason score.

Adenocarcinoma↗

Technique for nerve dissection.

Nerve-sparing radical retropubic prostatectomy is a reasonable treatment option in localized prostate cancer with minimal morbidity. Recent techniques in neurovascular bundle preservation could lead to an overall improvement in postoperative quality of life without compromising cancer control in the appropriately selected patient. Different techniques for neurovascular bundle preservation have been described by most major centers. This brief article describes the updated technique of nerve-sparing radical retropubic prostatectomy for clinically localized prostate cancer. Our technique of nerve dissection starts at the lateral aspect of the prostate with secondary urethral dissection. We believe this technique is easy to learn and decreases dissection around the striated sphincter.

Humans↗

Benefit of adjuvant radiation therapy for localized prostate cancer with a positive surgical margin.

PURPOSE: Positive surgical margins are common after radical prostatectomy, and the role of adjuvant therapy in such cases is controversial. We determined the benefit of postoperative external beam radiation therapy in patients with margin positive prostate cancer with respect to biochemical progression or cancer recurrence. To decrease confounding factors that may affect the likelihood of biochemical progression our study was limited to men with organ confined cancer and a single positive margin. MATERIALS AND METHODS: We retrospectively evaluated the records of a nested matched cohort of 76 patients with pathological stage T2N0 prostate cancer and a single positive margin who underwent adjuvant radiation therapy within 3 months of radical prostatectomy. There was a positive margin at the prostatic apex in 35 cases, prostatic base in 18, posterior prostate in 11, urethra in 7, and prostatic apex and urethra in 5. These patients were matched 1:1 with 76 controls who did not receive adjuvant radiation therapy. Neither group received androgen deprivation therapy. Patients and controls were matched exactly for the margin positive site, age at surgery, preoperative serum prostate specific antigen, Gleason score and DNA ploidy. Biochemical relapse was defined as posttreatment PSA greater than 0.2 ng./ml. RESULTS: Overall there was significant estimated improvement plus or minus standard error in 5-year clinical and biochemical progression-free survival in 88%+/-5% versus 59%+/-11% of patients treated with adjuvant radiation therapy versus no radiation therapy (p = 0.005). No patient who received radiation therapy had local or distant recurrence, while 16% of controls had recurrence (p = 0.015). When stratified by site of margin positivity, the 5-year estimated clinical and biochemical progression-free rate in 18 cases and controls with a positive base margin was 95%+/-15% and 65%+/-13%, respectively (p = 0.02). The rate in 35 cases and cases with a positive apex margin was 95%+/-5% and 64%+/-15%, respectively (p = 0.07). Limited sample size precluded analysis of the other sites. CONCLUSIONS: Patients with localized prostate cancer and a singe positive surgical margin appear to have a lower rate of biochemical relapse at 5 years when adjuvant radiation therapy is administered. Definitive evidence of the beneficial effect of adjuvant radiation therapy for patients with involved surgical margins awaits conclusion of randomized clinical trials.

Adult↗

The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.

We evaluated p27KIP1 and p21WAF1 expression in 52 patients treated by salvage radical prostatectomy and bilateral pelvic lymphadenectomy for biopsy-proven locally persistent or recurrent prostate cancer after external beam radiation therapy. We defined low and high expression based on the median value observed in our sample. Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p21 (< or =5%), compared with 94 and 100%, respectively, for those with high expression of p21 (>5%; P = 0.02 and 0.01, respectively). Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p27 (<50%), compared with 88 and 96%, respectively, for those with high expression of p27 (> or =50%; P = 0.06 and 0.01, respectively). These findings indicate that p21 and p27 expression levels are significant predictors of survival for patients selected for salvage prostatectomy for recurrent prostate cancer.

Aged↗

Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years.

PURPOSE: Cure from malignancy is commonly defined as a disease-free state lasting 5 years after treatment. We analyzed clinical and biochemical progression rates after radical prostatectomy for men with clinically localized prostate cancer with particular attention to recurrence beyond 5 years. Annual hazard rates of progression were calculated to determine the probability of recurrence at specific intervals following surgery. MATERIALS AND METHODS: The records of 2,782 men with clinically localized prostate cancer (cT1-T2) undergoing radical prostatectomy between 1987 and 1993 were reviewed. All patients were treated in the prostate specific antigen (PSA) era so that serial followup PSA values were available from the time of surgery. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Disease progression was defined as documented local recurrence, systemic progression and/or PSA 0.4 ng./ml. or greater. Lymph node positive cases were eliminated from analysis since almost all received adjuvant hormonal therapy. Annual hazard rates for progression were calculated using the formula: [No. events / No. patients at risk] x 100. Progression-free survival probabilities were determined using the Kaplan-Meier method. RESULTS: Pathological stage was pT2a-b, N0 (68%), pT3a, N0 (21%) and pT3b, N0 (11%). Biochemical progression-free survival at 5 and 10 years was 76% and 59%, respectively, for the entire study population while those with pathologically organ confined (pT2, N0) cancers had progression-free survival rates of 82% and 68% at 5 and 10 years, respectively. A total of 819 patients (29%) eventually had disease progression, including 160 (6%) with progression after 5 years. Annual hazard rates were highest during the first 2 years after radical prostatectomy for the entire population. Patients with adverse prognostic features (pT3b, PSA 10 ng./ml. or greater, Gleason score 8-10 and nondiploid cancers) had high initial hazard rates that decreased with time to lower levels. Those with pathologically organ confined cancer had low but constant hazard rates throughout followup. CONCLUSIONS: Although progression after radical prostatectomy usually occurs early, reflecting the impact of clinical under staging, a significant number of men, including those with organ confined cancers, will continue to have disease progression after 5 years. Patients undergoing radical prostatectomy should be subjected to long-term followup to allow the option of early intervention should progression occur.

Adult↗

Outcome of isolated renal cell carcinoma fossa recurrence after nephrectomy.

PURPOSE: Local recurrence of renal cell carcinoma in the renal fossa after complete radical nephrectomy is uncommon. We characterize and determine outcome in a small subset of patients. MATERIALS AND METHODS: From 1970 to 1998 the incidence of isolated renal bed recurrence among 1,737 T1-3N0M0 unilateral nephrectomy cases was 1. 8% (standard error [SE] 0.4) at 5 years. There were 30 patients in whom isolated local fossa carcinoma recurred after complete radical nephrectomy without evidence of metastatic disease. Patients with any nodal involvement at radical nephrectomy were excluded from study as were those who had undergone any form of partial nephrectomy. Patient charts were reviewed for clinical presentation, stage, treatment, development of metastatic disease and survival. Pathological stage was assigned according to the 1997 TNM staging system. Recurrence was identified in 12 (40%) patients during routine followup and the remaining 18 (60%) presented with symptoms related to the recurrent tumor. Patients were divided into 3 treatment groups of observation (9), therapy excluding surgical extirpation (11) and complete surgical resection alone or in conjunction with additional therapy (10). Mean time from local recurrence to development of metastatic disease was calculated. Survival from local recurrence to overall death and disease specific death was estimated using the Kaplan-Meier method. Survival curves for the different treatment groups were then compared. RESULTS: There were 30 patients identified with an ipsilateral renal fossa recurrence of renal cell carcinoma after complete nephrectomy in the absence of disseminated disease. Mean followup was 3.3 years (range 0.006 to 14.8) and no patient was lost to followup. The T stage of the primary tumor was T1/T2 in 13 cases, T3a in 4, T3b in 12, and T3c in 1, and all were node negative. Mean time to metastasis was 1. 6 years (range 0.006 to 7.3) in the 19 patients who had documented interval metastatic disease after local recurrence. There were 26 deaths, of which 25 were disease specific. Estimated overall crude and cause specific survival at 1 and 5 years was 66% and 28%, respectively. Calculating survival among symptomatic and asymptomatic patients revealed no discernible difference in outcome (p = 0.94). The 5-year survival rate with surgical resection was 51% (SE 18) compared to 18% (12) treated with adjuvant medical therapy and only 13% (12) with observation alone. The differences in cause specific survival were significant (p </=0.02). CONCLUSIONS: Isolated local recurrence is rare with less than a 2% incidence at 5-year followup. Presently long-term survival with locally recurrent renal cell carcinoma is poor with a 28% survival rate at 5 years. However, patients who underwent surgical resection had an improved 5-year cause specific survival rate of 51% compared to 18% treated with adjuvant medical therapy and 13% with observation alone. This finding suggests that select patients may benefit from an aggressive surgical approach.

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