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Siamak Daneshmand

Publications and source records attributed to Siamak Daneshmand.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic significance of neuroendocrine expression in lymph node-positive prostate cancer.

OBJECTIVES: To evaluate the expression of chromogranin A, a marker for neuroendocrine (NE) differentiation, in patients with lymph node-positive prostate cancer to determine its prognostic significance. NE cells are involved in cellular growth and differentiation in both normal and pathologic conditions of the prostate. METHODS: We reviewed the data of 140 patients with lymph node-positive prostate adenocarcinoma treated with radical prostatectomy and pelvic lymphadenectomy. The median follow-up was 10.9 years (range 0.8 to 19.7). Immunohistochemical staining for chromogranin A was evaluated in areas of benign epithelium, primary prostate cancer, and lymph node metastasis. The association between chromogranin A expression and the clinical and pathologic factors (preoperative serum prostate-specific antigen and prostatectomy Gleason score and stage) and clinical outcomes, including overall and recurrence-free survival, was evaluated. RESULTS: Staining was positive in 86% of benign areas, 61% of primary cancer specimens, and 12% of lymph node deposits. The preoperative serum prostate-specific antigen level and pathologic stage and grade of the primary tumor did not show any statistically significant correlation with NE staining in any of the areas. Only NE expression in the primary tumor was associated with clinical recurrence, with a 10-year recurrence-free survival rate for those with less than 5% staining of 67% compared with 35% for those with 5% staining or greater (P = 0.03). Furthermore, after adjusting for age, greater NE expression in the primary tumor (relative risk 2.15, P = 0.02) and lymph node deposit (relative risk 2.03, P = 0.03) was associated with poorer overall survival. CONCLUSIONS: NE expression in the primary tumor and lymph node metastasis of patients with node-positive prostate cancer may provide additional prognostic stratification.

Adenocarcinoma↗
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

Evolving treatment paradigms for locally advanced and metastatic prostate cancer.

While men with early stage prostate cancer typically enjoy long-term survival after definitive management, for those who present with locally advanced or metastatic disease, survival is compromised. Multimodality therapy can prolong survival in these patients, with state-of-the-art options including intensity-modulated radiation or brachytherapy in conjunction with androgen ablation, adjuvant androgen ablation and/or chemotherapy with radical retropubic prostatectomy. In addition, novel biological therapies are being explored to target the unique molecular changes in prostate cancer cells and their interactions with the microenvironment. With these advances the outlook will undoubtedly improve, even for patients presenting with advanced disease. Careful application of these emerging therapies to a select group of prostate cancer patients most likely to obtain benefit from them is the challenge for urologists, medical oncologists and radiation oncologists for the future.

Antineoplastic Agents↗
PubMed2006

Management of difficult germ-cell tumors.

Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.

Adult↗
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

Ethnic differences in neuroendocrine cell expression in normal human prostatic tissue.

OBJECTIVES: To determine whether any differences exist in neuroendocrine (NE) cell differentiation in normal prostates among various ethnic groups because the incidence and mortality from prostate cancer vary across racial groups. METHODS: Archived paraffin-embedded prostate samples not containing any malignancy were obtained from cystoprostatectomy specimens. Prostatic tissue was obtained from 15 African Americans, 13 Hispanics, 15 Asians, and 16 whites. NE cells were identified based on immunoreactivity for chromogranin A. The mean number of NE cells per high power field (HPF) for each patient was determined using a visual quantitative method by two observers who were unaware of the race of the patients. RESULTS: The geometric mean number of NE cells was 6.1/HPF for Asians, 5.6/HPF for whites, 4.0/HPF for Hispanics, and 0.7/HPF for African Americans. A highly significant difference was observed in the distribution of NE cells between African Americans and each of the other races (P < or =0.003). A trend toward greater NE expression was noted in Asians and whites compared with Hispanics; however, this difference did not reach statistical significance. CONCLUSIONS: We found a fivefold to eightfold difference in the distribution of NE cells in the normal prostates of African-American men compared with that of other races. The comparatively low NE cell expression in African-American men may play a role in the greater rate of prostate carcinogenesis seen in this ethnic group.

Black or African American↗
PubMed2005

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience.

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.

Adult↗
PubMed2005

Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy.

PURPOSE: We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI. RESULTS: Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival. CONCLUSIONS: Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.

Adult↗
PubMed2004

Primary renal carcinoid tumor.

Primary carcinoid tumors originating in a normal kidney are exceptionally rare. We describe a case of a 52-year-old woman who presented with vague back pain and was found to have a 4-cm mass in the medial aspect of the left kidney. Radical nephrectomy and retroperitoneal lymphadenectomy were performed. Histopathology revealed a typical carcinoid tumor with 1 out of 17 lymph nodes involved. She has no evidence of recurrence or metastasis on 7-month follow-up.

Carcinoid Tumor↗
PubMed2004

Continent right colon reservoir using a cutaneous appendicostomy.

INTRODUCTION: Although orthotopic reconstruction has become the preferred form of lower urinary tract reconstruction after cystectomy there remains a select group of patients who are not appropriate for an orthotopic neobladder substitute. A continent cutaneous reservoir provides an alternative means to store urine and protect the upper urinary tract without the need for a urostomy appliance. We report our surgical technique of a continent cutaneous right colon reservoir using a catheterizable submucosally embedded appendicostomy. TECHNICAL CONSIDERATIONS: The continent cutaneous right colon reservoir with bilateral ureteroileal coloappendicostomy incorporates the ascending and proximal transverse colon, which are detubularized and folded to form the reservoir component of the urinary diversion. The terminal ileum acts as the afferent limb, with the intact native ileocecal valve providing the antireflux mechanism. The continence catheterizable mechanism incorporates the submucosally tunneled appendix with preservation of the mesentery in a flap-valve technique. CONCLUSIONS: The continent cutaneous right colon reservoir with bilateral ureteroileal coloappendicostomy is a reasonable alternative for cutaneous urinary diversion when an intact appendix is present, with good functional results and excellent continence.

Appendix↗
PubMed2004

New molecular markers for bladder cancer detection.

PURPOSE OF REVIEW: Bladder cancer continues to be one of the most common genitourinary malignancies. The mainstay of diagnosis remains cystoscopic visualization with transurethral biopsy or resection. As over two-thirds of bladder tumors recur, vigilant surveillance is required. Due to the invasiveness and expense of frequent cystoscopies and the lack of sensitivity of urinary cytology, especially for low-grade superficial lesions, novel molecular markers have been investigated as a means to detect bladder cancer noninvasively. RECENT FINDINGS: As our understanding of the pathogenesis of urothelial neoplasia improves, coupled with recent advances in molecular biological techniques, an array of new approaches to the diagnosis of bladder cancer has emerged. Several urine-based markers have been tested against the standard of urinary cytology with promising results. However, lack of standardization of technique and heterogeneity of bladder cancer itself may hinder the widespread dissemination of these diagnostic aids. SUMMARY: A host of new molecular markers based on the pathogenesis of bladder cancer have been investigated, such as telomerase, survivin, and multitarget fluorescence in situ hybridization, which may eventually improve detection and management of urothelial malignancies. By improving the sensitivity of urinary cytology for low-grade superficial lesions and detecting recurrent disease noninvasively early in its course, these new molecular markers might someday allow changes in the way bladder cancer is diagnosed and followed. At the present time, however, no single molecular marker provides 100% accuracy. Perhaps panels utilizing the most promising of these markers may alter bladder cancer detection and management policy.

Biomarkers, Tumor↗
PubMed2004

Angiomyolipoma of the kidney: expanding disease spectrum demonstrated by 3 cases.

We report 3 recent cases of angiomyolipoma of the kidney. Although generally regarded as a benign neoplasm, angiomyolipoma rarely behaves in an aggressive manner, producing complicated clinical courses leading to metastasis and death. The presence of epithelioid elements within the tumor can result in difficulty differentiating benign from malignant angiomyolipoma and differentiating this tumor from renal adenocarcinoma. The presence of lymph node involvement can cause difficulty in differentiating multicentric disease in lymph nodes from metastasis to lymph nodes. The presence of cytologic abnormalities in the primary tumor can result in difficulty in differentiating atypia in benign angiomyolipoma from malignant sarcomatous transformation of a benign lesion. The 3 cases reported show many of these problems. Criteria for predicting malignancy in epithelioid tumors and sarcomatous transformation are not well recognized because of the rarity of this entity. The typical immunophenotype of all types of angiomyolipoma (cytokeratin-negative and melanomarkers-positive) is very useful in diagnosis but does not help in the differentiation from renal adenocarcinoma at frozen section. We report the empiric use of Ki67 and p53 in these cases as adjuncts to clinical and histologic assessment in predicting behavior. High Ki67 expression was a feature of malignant epithelioid angiomyolipoma. Low levels of p53 expression were seen in the angiomyolipoma with sarcomatous transformation. Benign angiomyolipomas were consistently negative for both Ki67 and p53.

Adult↗
PubMed2004

Microscopic and gross extravesical extension in pathological staging of bladder cancer.

PURPOSE: We evaluated clinical outcomes in patients with pathological microscopic (pT3a) and gross (pT3b) extravesical tumor extension with transitional cell carcinoma (TCC) of the bladder following radical cystectomy. MATERIALS AND METHODS: A total of 236 patients, including 173 males (73%) and 63 females, underwent radical cystectomy for pathological primary bladder TCC with extravesical extension (pT3), of whom 69 (29%) had pT3a and 167 (71%) had pT3b disease. At a median followup of 8.9 years (range 0 to 19.4) lymph node involvement, local and distant recurrences, and clinical outcomes were determined. RESULTS: Of the 236 patients with pT3 tumors 106 (45%) had lymph node positive disease, including 34 of 69 (49%) with pT3a and 72 of 167 (43%) with pT3b disease. The 10-year recurrence-free survival rate for patients with pT3a tumors was 48% compared with 47% for those with pT3b disease (p = 0.89). Recurrence-free survival was significantly better in patients with lymph node negative disease than in those with positive lymph nodes irrespective of the extent of extravesical involvement (pT3a vs pT3b). Local pelvic recurrence developed in 13 of the 236 patients (6%), while 84 (36%) had distant metastatic disease. Of the patients with recurrence, the type of recurrence (local or distant) was not associated with tumor stage (pT3a vs pT3b, p = 0.71). Lymph node involvement was a significant risk factor for distant tumor recurrence (p <0.001). CONCLUSIONS: Differentiating between microscopic (pT3a) and gross (pT3b) extravesical tumor involvement of TCC as outlined in the revised 1997 TNM staging system does not appear to have prognostic significance.

Adult↗
PubMed2004

Prognosis of seminal vesicle involvement by transitional cell carcinoma of the bladder.

PURPOSE: Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy. MATERIALS AND METHODS: From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots. RESULTS: There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p <0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status. CONCLUSIONS: Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

Adult↗
PubMed2004

Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results.

PURPOSE: We determined the prognostic factors that affect recurrence and survival in patients with lymph node positive prostate cancer. MATERIALS AND METHODS: Between 1972 and 1999, 1,936 patients underwent radical retropubic prostatectomy and pelvic lymph node dissection for clinically organ confined prostate cancer. A total of 235 patients (12.1%) were found to have disease metastatic to the lymph nodes (stage D1). Of the patients 69% received no adjuvant treatment. We reviewed the tumor stage (TNM), Gleason score, number and percent of involved lymph nodes (lymph node density), preoperative prostate specific antigen when available and adjuvant treatment. Overall survival and recurrence-free survival were estimated using Kaplan-Meier plots. RESULTS: Followup was 1 to 24 years (median 11.4). Overall median survival was 15 years. Overall clinical recurrence-free survival at 5, 10 and 15 years was 80%, 65% and 58%, respectively. Patients who had 1 or 2 positive lymph nodes had a clinical recurrence-free survival of 70% and 73% at 10 years, respectively, vs 49% in those who had 5 or more involved lymph nodes (p = 0.0031). When stratified by lymph node density, patients with a lymph node density of 20% or greater were at higher risk for clinical recurrence compared to those with a density of less than 20% (relative risk = 2.32, p <0.0001). On stratified log rank test only prostate cancer T stage, and the number and percent of positive lymph nodes correlated with recurrence-free and overall survival. CONCLUSIONS: Local tumor bulk and the number/percent of involved lymph nodes significantly affect disease progression and the survival rate. Radical prostatectomy may offer long-term survival in patients who have limited tumor bulk and nodal involvement.

Aged↗
PubMed2004

The importance of an extended lymphadenectomy in the management of high-grade invasive bladder cancer.

The role of a regional lymphadenectomy in the surgical management of high-grade invasive bladder cancer has evolved over the last several decades. A growing body of evidence suggests that an extended lymph node dissection may provide, not only improved prognostic information, but also a clinically significant therapeutic benefit for both lymph node-positive and -negative patients undergoing radical cystectomy. The extent of the primary bladder tumor, number of lymph nodes removed and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy. In addition, the concept of lymph node density may further improve stratification of lymph node-positive patients. The historical development and contemporary rationale for an extended pelvic lymphadenectomy in patients undergoing radical cystectomy are reviewed.

Cystectomy↗