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Biomedical subjects

Marcus L Quek

Publications and source records attributed to Marcus L Quek.

At least 19 recordsLinked to original sources

Radical cystectomy with extended lymphadenectomy in the presence of a pelvic kidney.

The pelvic kidney represents the most common form of congenital renal ectopia. Because of its location, variable vasculature, and short ureteral length, the presence of a pelvic kidney in a patient undergoing radical cystectomy and pelvic lymphadenectomy creates unique technical challenges for the urologic surgeon. We describe a patient with a right pelvic kidney and invasive bladder cancer for whom radical cystectomy with extended pelvic iliac lymph node dissection and ileal conduit was performed.

Cystectomy↗

Genistein-induced neuroendocrine differentiation of prostate cancer cells.

BACKGROUND: Neuroendocrine (NE) cells are present in normal prostate and their number appears to be increased in advanced prostate cancer (PCA). In this study, we studied the effect of the phytoestrogen, genistein, on NE differentiation of LNCaP cells in vitro. METHODS: Neuroendocrine marker expression of LNCaP cells exposed to genistein was measured by immunohistochemistry, Western blot, and real-time PCR methods. Western blot analysis was used to study cell cycle and signaling pathways induced by genistein treatment. RESULTS: Six days after continuous genistein treatment, the majority of genistein-surviving cancer cells underwent transdifferentiation into a NE-like phenotype overexpressing the NE markers chromogranin A, synaptophysin, serotonin, and beta-III tubulin. This NE differentiation process was associated with upregulation of the cell cycle modulators p21, p27, and p53, and activation of the MAPK and STAT3 pathways. CONCLUSION: Our data indicate that genistein evokes not only apoptosis but also NE transdifferentiation of PCA cells.

Antineoplastic Agents↗

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↗

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↗

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↗

Renal epithelioid angiomyolipoma associated with hyperprolactinemia.

We report a unique case of a 42-year-old woman with a renal epithelioid angiomyolipoma associated with elevated serum prolactin levels and presenting with galactorrhea. Magnetic resonance imaging of the brain showed no pituitary abnormality, and abdominal imaging demonstrated a large right renal mass. Pathologic analysis of the radical nephrectomy specimen revealed an epithelioid angiomyolipoma. She had an uneventful postoperative recovery with complete normalization of her serum prolactin level and resolution of galactorrhea. To our knowledge, the association between epithelioid angiomyolipoma and hyperprolactinemia has never before been reported.

Adult↗

Combined radical prostatectomy and bladder augmentation for concomitant prostate cancer and detrusor instability.

OBJECTIVES: To determine the outcomes of a select cohort of patients with severe voiding dysfunction, refractory to medical management, and a concomitant diagnosis of prostate cancer, who were treated with radical prostatectomy and augmentation enterocystoplasty. METHODS: Four men with biopsy-proven prostatic adenocarcinoma, as well as a diagnosis of severe overactive bladder, underwent combined radical retropubic prostatectomy and augmentation enterocystoplasty. All patients underwent fluorourodynamic testing confirming nonobstructive detrusor instability or hyperreflexia. Three patients underwent nerve-sparing radical retropubic prostatectomy with a clamshell ileocystoplasty, and one with neurogenic hyperreflexia underwent sigmoid cystoplasty with a continent catheterizable stoma at radical retropubic prostatectomy. RESULTS: The mean follow-up was 21.5 months (range 8 to 48). All patients had an undetectable prostate-specific antigen level postoperatively. The average hospitalization was 8 days. Perioperative complications occurred in 2 patients, including a prolonged urine leak managed with catheter drainage and postoperative hematuria requiring cystoscopic clot evacuation. Erectile function was preserved in 2 patients with good preoperative erections. At last follow-up, the 3 patients who voided per urethra had minimal postvoid residual urine volumes and maintained good continence, with only 1 patient describing occasional mild stress incontinence. At last follow-up, the patient with the sigmoid cystoplasty catheterized every 4 hours with volumes of about 300 mL and complete stomal continence. No patient required anticholinergic medications postoperatively. CONCLUSIONS: The concomitant diagnosis of prostate cancer and severe detrusor instability may be difficult to treat. The results of our study have shown that for those desiring surgical management for their prostate cancer, a combined bladder augmentation and radical prostatectomy may be performed with minimal added morbidity and significantly improved voiding function in the properly selected individual.

Adenocarcinoma↗

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↗

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↗

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↗

Adenomatoid tumor of the tunica albuginea.

Adenomatoid tumors are benign mesothelial tumors most commonly found in the paratesticular structures, especially the epididymis. Herein, we report a case of adenomatoid tumor originating in the tunica albuginea and mimicking an intratesticular neoplasm. We review the ultrasonographic presentation and literature regarding adenomatoid tumors originating in the tunica albuginea and testicular parenchyma.

Adenomatoid Tumor↗

Postchemotherapy residual masses in advanced seminoma: current management and outcomes.

Although pure testicular seminoma is most often confined to the testis, it can present with advanced-stage bulky retroperitoneal metastases in nearly a quarter of cases. While highly treatable with cisplatin-based chemotherapy, up to 80% of patients with advanced disease are found to have a radiographically detectable residual mass after chemotherapy. The management of these postchemotherapy residual masses remains controversial. Surgical resection is technically challenging due to a desmoplastic reaction resulting from seminoma treatment and regression. In addition, these residual masses often demonstrate a protracted period of regression that can span several months to years. Surveillance protocols, therefore, may be appropriate for most patients. Several retrospective studies have supported surgical resection only for discrete, well-delineated masses over 3 cm in size. Despite the highly radiosensitive nature of seminoma, radiation therapy in this setting has not been shown to provide significant benefit, and may limit the tolerability of subsequent salvage chemotherapy. The incorporation of noninvasive imaging modalities, such as positron emission tomography, into the management algorithm may better delineate the presence of viable residual tumor and thus allow better risk stratification.

Algorithms↗

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↗

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↗

The orthotopic T pouch ileal neobladder: experience with 209 patients.

PURPOSE: A serous lined extramural ileal flap valve technique called the T limb was developed to prevent reflux of urine in an orthotopic bladder substitute called the T pouch. We evaluate our intermediate clinical and functional experience with the orthotopic T pouch ileal neobladder. MATERIALS AND METHODS: From November 1996 through May 2000, 209 patients (169 men [80%], 40 women), with a mean age of 69 years (range 33 to 93) underwent construction of an orthotopic T pouch ileal neobladder after cystectomy. The indication for cystectomy included bladder cancer in 198 patients (95%). Median followup for the entire cohort was 33 months (range 0 to 69). Data were analyzed according to perioperative mortality, early (within 3 months) and late diversion related and diversion unrelated complications, radiographic evaluation of the upper urinary tract and urinary reservoir, and determination of renal function. RESULTS: Three patients (1.4%) died perioperatively. A total of 63 (30%) early complications occurred, 53 (25%) diversion unrelated and 10 (5%) diversion related. The most common early diversion unrelated complication was dehydration (10 patients). The most common early diversion related complication was urine leak in 6 patients. There were no early complications directly related to the antirefluxing T limb. Late complications occurred in 68 (32%) patients including 30 (14%) diversion unrelated and 38 (18%) diversion related. The most common late diversion unrelated complication was incisional hernia in 16 patients. Of the 38 late diversion related complications the most common were pouch calculi in 17 and ureteroileal obstruction in 9 patients. The only late complication directly related to the T limb was stenosis in 4 patients, 3 of whom received adjuvant pelvic radiation. A total of 181 patients had radiographic evaluation of the upper urinary tract including 162 (90%) with a normal radiographic study or evidence of postoperative decompression. An abnormal upper tract study was seen in 18 patients (10%) including 9 with ureteroileal obstruction and 4 with afferent T limb stenosis. Gravity cystography of the neobladder was normal in 143 of 158 (90%) evaluable patients. Reflux was seen in 15 patients (10%). Renal function as determined by serum creatinine was stable or improved in 96% of patients. Good daytime and nighttime continence was reported in 87% and 72% of evaluable patients, respectively. Overall 75% of patients complete void while 25% required some form of intermittent catheterization to empty the neobladder completely including 20% of men and 43% of women. CONCLUSIONS: With intermediate followup the functional results of the T pouch ileal neobladder are acceptable. The antirefluxing T limb provides unobstructed urinary flow in 95% and reflux prevention in 90% of patients. Although these results are encouraging, further followup is required to assess the long-term results of the T pouch ileal neobladder.

Adult↗