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Biomedical subjects

John P Stein

Publications and source records attributed to John P Stein.

At least 19 recordsLinked to original sources
PubMed2006

Detection of occult lymph node metastases in locally advanced node-negative prostate cancer.

PURPOSE: The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation. METHODS: Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN-), and with the 94 N+ patients. RESULTS: A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN- patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease. CONCLUSION: The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.

Aged↗
PubMed2006

Radical cystectomy for invasive bladder cancer: long-term results of a standard procedure.

Radical cystectomy with an appropriate lymphadenectomy remains the standard of therapy for high-grade invasive bladder cancer. This surgical approach provides the best survival rates with the lowest local recurrence rates and orthotopic diversion can be performed safely in most patients with an acceptable outcome and quality of life. Pathologic analysis of the bladder tumor and regional lymph nodes will help direct the need for adjuvant therapy in high-risk individuals. Equivalent long-term local control and survival are not seen with other forms of treatment including radiation therapy, chemotherapy, or a combination of the two. The rationale and clinical results of large, contemporary cystectomy series are presented, which provide a benchmark of outcomes with this form of surgical treatment.

Aged↗
PubMed2006

Improving outcomes with radical cystectomy for high-grade invasive bladder cancer.

It is clear that the optimal clinical outcomes in bladder cancer patients requiring radical cystectomy are related to standard histopathologic variables of tumor grade, stage and lymph node status. However, other less well defined variables are also critical to the successful outcomes of these patients. Patients with muscle invasive bladder cancer and treating physicians should avoid unnecessary and significant treatment delays. In addition, hospital and surgeon-volume/experience are thought to be factors that may too be important components that relate to the clinical outcomes of patients following surgery. Lastly, there is a growing body of literature to support the concept of an appropriate lymphadenectomy at the time of surgery, for both node-positive and node-negative bladder cancer patients. It is becoming more obvious that there are multiple variables involved in the clinical success and outcomes of patients with bladder cancer following radical cystectomy. As treating physicians and surgeons we must be aware of these components to ensure the best outcomes for our patients.

Cystectomy↗
PubMed2006

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy.

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.

Adult↗
PubMed2006

Salvage radical prostatectomy: quality of life outcomes and long-term oncological control of radiorecurrent prostate cancer.

PURPOSE: We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer. Using a standardized questionnaire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy. MATERIALS AND METHODS: Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy. Clinical information was obtained from a prospective database. Quality of life data were collected using the UCLA Prostate Cancer Index, a validated, patient administered instrument. RESULTS: At 5 years 47% of patients were progression-free without androgen deprivation therapy. Among patients with pT2 disease 100% were progression-free at 5 years, compared with 35% of patients with pT3N0 disease or higher and 0% of patients with node positive (pTxN+) disease (p < 0.001). Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease, and strongly associated with prolonged progression-free and overall survival (p < 0.001 and 0.01, respectively). Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after standard, nonsalvage prostatectomy. Sexual dysfunction was nearly uniform in patients undergoing standard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinically significant improvement in sexual function. CONCLUSIONS: When initiated early in the course of recurrent disease, salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for androgen ablation. Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters.

Aged↗
PubMed2006

A critical analysis of perioperative mortality from radical cystectomy.

PURPOSE: Operative mortality from radical cystectomy has decreased as a result of improvements in surgical and anesthetic care. We reviewed the perioperative deaths from a large group of patients treated with radical cystectomy for primary bladder cancer. MATERIALS AND METHODS: All perioperative mortalities from radical cystectomy were identified from a single high volume institution. The medical records were reviewed to assess the cause of death as well as possible contributing factors. RESULTS: From August 1971 to December 2001, 1,359 patients with primary bladder cancer were treated with radical cystectomy and pelvic iliac lymphadenectomy at our institution. Of these patients, 27 (2%) died within 30 days of surgery or before discharge from hospital. Median patient age at surgery was 67 years (range 47 to 78) and males accounted for 81% of the patients. The median time to death was 28 days from cystectomy (range 0 to 80). Most deaths were cardiovascular related (including acute myocardial infarction, cerebrovascular accident, arterial thrombosis) or due to septic complications with resulting multi-organ system failure, followed by pulmonary embolism, hepatic failure and hemorrhage. Septic related mortality was most often associated with postoperative urine or bowel leak. While most deaths occurred before hospital discharge, 2 patients died at home due to a late pulmonary embolus. No association was seen between pathological stage or type of urinary diversion and mortality. CONCLUSIONS: Perioperative mortality from radical cystectomy is low in this group of patients. Most deaths are due to cardiovascular or septic complications. Careful patient selection and meticulous surgical technique may help decrease the incidence of perioperative mortality.

Aged↗
PubMed2006

Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer.

PURPOSE: Vascular endothelial growth factor has a critical role in maintaining tumor microvasculature and, as such, is an attractive target for anti-angiogenic therapy. Aberrant expression of VEGF receptors, especially VEGFR2, on epithelial tumor cells allows VEGF to stimulate growth and migration of tumor cells in an autocrine and/or paracrine manner. Therefore, we studied the expression of VEGF and VEGFR2 in bladder cancer, and the relationship to disease characteristics. MATERIALS AND METHODS: Expression of VEGF and VEGFR2 was studied in a cohort of 72 patients with transitional cell cancer of the bladder. Tumor tissues from all patients were analyzed by immunohistochemistry and examined by a pathologist blinded to patient outcome. Patient demographics and disease outcome were correlated with expression of these markers. Bladder cancer cell lines that express VEGFR2 were studied in vitro and in vivo to establish the significance of VEGF/VEGFR2 signaling. RESULTS: Expression of VEGF and VEGFR2 was observed in 58% and 50% of urothelial tumor cells, respectively. VEGF expression failed to correlate with clinical variables. However, VEGFR2 expression correlated with disease stage (coefficient 0.23, p = 0.05). In addition, VEGFR2 expression increased with tumor invasion into the muscle (p <0.01). Experiments with VEGFR2 positive bladder cancer cell lines in vitro demonstrated increased invasion in response to VEGF. In addition, VEGF inhibition augmented the effect of docetaxel in a murine xenograft model of bladder cancer with a significant inhibition in proliferative index and microvascular density, and induction of apoptosis. CONCLUSIONS: Increased VEGFR2 expression correlates with several features that predict progression of urothelial cancer, including disease stage and invasive phenotype. VEGF targeted therapy may enhance the efficacy of standard therapy for bladder cancer.

Adult↗
PubMed2006

The prognostic and staging value of lymph node dissection in the treatment of invasive bladder cancer.

Regional lymph node dissection (LND) at the time of radical cystectomy is an essential component of the surgical management of invasive bladder cancer and might provide diagnostic and therapeutic benefits for both node-negative and node-positive patients. The benefits obtained in pathologically node-negative patients might result from more complete resection of undetected micrometastases or from a more meticulous surgical technique. Advanced nodal disease also seems to be amenable to thorough surgical resection in a subpopulation of patients with bladder cancer. Despite the growing body of evidence to support the role of a more extended LND, no guidelines regarding the optimal boundaries of LND have been established. An increased number of resected nodes and wider LND boundaries have been associated with improved local disease control and prolonged survival. Additionally, mapping series indicate that the common iliac and presacral nodal regions are more frequently involved with tumor metastases than previously recognized. Efforts to limit any unnecessary dissection in patients at low risk for metastases--a tailored approach--has been proposed, but remains unproven. From the available evidence, the most reliable diagnostic and therapeutic approach to LND includes the routine extended LND in all patients undergoing cystectomy with curative intent.

Cystectomy↗
PubMed2006

Superficial bladder cancer: part 1. Update on etiology, classification and natural history.

Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.

Carcinogens, Environmental↗
PubMed2006

Pathologic guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature.

Orthotopic lower urinary tract reconstruction to the native intact urethra following radical cystectomy for bladder cancer was slower to gain clinical acceptance for women than for men. Until the 1990s, little was known about the natural history of urethral involvement by urothelial carcinoma in women with primary bladder cancer. The increasing availability of pathologic data to define the incidence of and risks for urethral involvement in women sparked an increasing interest in orthotopic diversion in female patients. Pathologic guidelines have been suggested to identify women suitable for orthotopic diversion. Preoperative involvement of the bladder neck is a significant risk factor for secondary tumor of the urethra, but is not an absolute contraindication, as long as full-thickness, intraoperative frozen-section analysis demonstrates no tumor involvement of the proximal urethra. Although less common, anterior vaginal wall tumor involvement may be a significant risk factor for urethral tumor involvement. Other pathologic parameters, including tumor multifocality, carcinoma in situ of the bladder, and tumor grade and stage, do not seem to be absolute contraindications. Long-term follow-up is critical for all patients. Women undergoing orthotopic reconstruction, if appropriately selected, should be assured of an oncologically sound operation and good function with their neobladder.

Journal Article↗
PubMed2005

Radical cystectomy in the elderly: comparison of clincal outcomes between younger and older patients.

BACKGROUND: The authors report their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder comparing clinical outcomes, including complication rates, among older patients versus younger patients in a high-volume center specializing in the treatment of patients with advanced carcinoma of the urinary bladder. METHODS: A retrospective review was undertaken of 1054 patients who underwent radical cystectomy for bladder TCC from 1971 through 1997. Four age groups were compared; < 60 years at the time of cystectomy (n = 309 patients), age 60-69 years (n = 381 patients), age 70-79 years (n = 314 patients), and age > or = 80 years (n = 50 patients). RESULTS: The median length of hospital stay in patients ages < 60 years, 60-69 years, 70-79 years, and > or = 80 years was 10 days, 10 days, 11 days, and 11 days, respectively (P < 0.001). The corresponding rates of overall early complications were 24%, 25%, 37%, and 30%, respectively (P = 0.002); whereas the corresponding late complication rates were 36%, 30%, 22%, and 14%, respectively (P < 0.001). The rate of early diversion-related complications did not differ significantly (11%, 8%, 12%, and 6%, respectively; P = 0.14). The operative mortality rates were 1%, 3%, 4%, and 0%, respectively (P = 0.14). There was no difference with respect to early complications, early diversion-related complications, late complications, or operative mortality comparing patients age > 70 years who underwent ileal conduit versus orthotopic urinary diversion (P = 0.20, P = 0.61, P = 0.53, and P = 0.78, respectively). CONCLUSIONS: Elderly patients who underwent cystectomy for TCC had similar mortality and early diversion-related complication rates. Carefully selected elderly patients safely can be offered an orthotopic urinary diversion. Chronological age, per se, is not a contraindication for radical cystectomy in the setting of invasive bladder carcinoma.

Age Factors↗
PubMed2005

EphB4 expression and biological significance in prostate cancer.

Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study was to examine the expression and biological role of EphB4 in prostate cancer. EphB4 mRNA is expressed in 64 of 72 (89%) prostate tumor tissues assessed. EphB4 protein expression is found in the majority (41 of 62, 66%) of tumors, and 3 of 20 (15%) normal prostate tissues. Little or no expression was observed in benign prostate epithelial cell line, but EphB4 was expressed in all prostate cancer cell lines to varying degrees. EphB4 protein levels are high in the PC3 prostate cancer cell line and several folds higher in a metastatic clone of PC3 (PC3M) where overexpression was accompanied by EphB4 gene amplification. EphB4 expression is induced by loss of PTEN, p53, and induced by epidermal growth factor/epidermal growth factor receptor and insulin-like growth factor-I/insulin-like growth factor-IR. Knockdown of the EphB4 protein using EphB4 short interfering RNA or antisense oligodeoxynucleotide significantly inhibits cell growth/viability, migration, and invasion, and induces apoptosis in prostate cancer cell lines. Antisense oligodeoxynucleotide targeting EphB4 in vivo showed antitumor activity in murine human tumor xenograft model. These data show a role for EphB4 in prostate cancer and provide a rationale to study EphB4 for diagnostic, prognostic, and therapeutic applications.

Animals↗
PubMed2005

Radical cystectomy in the elderly: Comparison of survival between younger and older patients.

BACKGROUND: The authors reported their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder. They compared pathologic features and survival rates between older and younger patients. METHODS: The authors retrospectively reviewed the records of 1054 patients who underwent radical cystectomy for bladder TCC between 1971 and 1997. Four age groups were compared: < 60 years old at the time of cystectomy (n = 310), 60-69 years old (n = 381), 70-79 years old (n = 313), and >/= 80 years old (n = 50). RESULTS: There were no significant differences in pathologic features among the groups regarding frequency of carcinoma in situ, high-grade disease, p53 status, and lymph node positivity. However, in the age groups < 60, 60-69, 70-79, and >/= 80, 45%, 49%, 51%, and 72% of patients, respectively, had extravesical TCC (P=0.004). Significant differences also were seen in the proportion of patients who received adjuvant chemotherapy (26%, 26%, 15%, and 6%, respectively; P < 0.001). The 5-year overall survival rates for patients < 60, 60-69, 70-79, and >/= 80 years old were 72%, 58%, 54%, and 33%, respectively (P < 0.001). The 5-year disease recurrence-free survival rates were 75%, 65%, 68%, and 45%, respectively (P = 0.003). The elderly had a lower probability of receiving adjuvant chemotherapy. CONCLUSIONS: Elderly patients undergoing cystectomy for TCC had similar pathologic features (except for disease stage) as younger patients. In the current series, elderly patients undergoing cystectomy had a higher pathologic stage and were less likely to receive adjuvant chemotherapy. The elderly had worse disease recurrence-free survival rates. Further work is needed to identify the causes for this and to develop strategies to improve cancer control in elderly patients.

Age Factors↗
PubMed2005

The role of lymphadenectomy in high-grade invasive bladder cancer.

Radical cystectomy with bilateral pelvic iliac lymphadenectomy is a standard treatment for high-grade, invasive bladder cancer. Cystectomy arguably provides the best survival outcomes and the lowest local recurrence rates. Although the extent or absolute limits of the lymph node dissection are unknown and remain to be better defined, an ever-growing body of data supports a more extended lymphadenectomy at the time of cystectomy in all patients who are appropriate surgical candidates. An extended lymph node dissection should include the distal para-aortic and paracaval lymph nodes as well as the pre-sacral nodes, known anatomic sites of lymph node drainage from the bladder and potential sites of lymph node metastases in patients with bladder cancer. An extended dissection may provide a survival advantage in patients with node-positive and node-negative tumors without significantly increasing the morbidity or mortality of the surgery. The extent of the primary bladder tumor (p stage), the number of lymph nodes removed, and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastases. Lymph node density may become an even more useful prognostic variable in these high-risk, node-positive patients with bladder cancer. This concept simultaneously incorporates the lymph node tumor burden (number of lymph nodes involved) and the number of lymph nodes removed (extent of the lymphadenectomy), improving the stratification of lymph node-positive patients following radical cystectomy. This notion may also be useful in future staging systems. Adjuvant therapies and clinical trials should consider applying these concepts, because they may help reduce bias and incorporate the extent of the lymphadenectomy, which currently is not standardized.

Carcinoma, Transitional Cell↗