We investigated the in vitro effects of baicalein and baicalin on human umbilical vein endothelia... more We investigated the in vitro effects of baicalein and baicalin on human umbilical vein endothelial cells (HUVECs) and on human prostate tumor cells (DU-145 and PC3) as well as the effect of orally administered baicalein on the growth of DU-145 cells after subcutaneous injection into SCID mice. In vitro effects of baicalein and baicalin treatment on human prostate cancer cell lines DU-145 and PC-3 were assessed by employing cell proliferation (MTS) assay, cytotoxicity (LIVE/DEAD) assay, and TUNEL assay. In vitro anti-proliferative and anti-angiogenic properties of baicalein and baicalin were studied on HUVECs by sprout assay. The effect of orally administered baicalein on tumor growth in SCID mice was studied in four groups (n=10) of animals injected subcutaneously with DU-145 cells and treated daily for 28 days. The control group received only vehicle (carboxymethylcellulose), whereas the other three groups received escalating doses of baicalein (10, 20, and 40 mg/kg per day). Baica...
Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metasta... more Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1-3 months postoperatively. Only circulating CD117+ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117+ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expr...
To review our experience with severe penile trauma, mechanism of injury, and their treatment moda... more To review our experience with severe penile trauma, mechanism of injury, and their treatment modalities in 16 children younger than 18 years. Management of penile trauma poses diverse challenges to the reconstructive urologist, as injuries vary from abrasions to total emasculation. Analysis of 16 patients with severe penile injuries referred to us between 2002 and 2011 was undertaken. The median age at surgery was 13 years (range, 5-17). Etiology of penile trauma and choice of treatment were evaluated. The management included a wide variety of surgical techniques that were tailored to the individual patient. Results were analyzed to define etiology, that is, mechanism of penile injury and to estimate modalities of surgical management and postoperative outcomes. Also, postoperative questionnaire was used, which included questions on functioning and esthetical appearance of participating patients and overall satisfaction. The causes of penile injury in these series were traffic accidents (2), iatrogenic trauma (5), self-amputation (1), electrocution (1), burns (3), dog bite (2), zipper injury (1), and mother's hair strangulation (1). The mean follow-up was 46 months (range, 14-122), and examinations were uneventful, except for 2 fistulae formation after neophallic urethral reconstruction. The main goal of reconstructive surgery is to have a penis with normal appearance and functions. Severe penile injuries should be treated on a case-by-case basis using the most propitious techniques.
To assess the outcomes of robotic partial nephrectomy in patients with pre-existing chronic kidne... more To assess the outcomes of robotic partial nephrectomy in patients with pre-existing chronic kidney disease (CKD). Patients who underwent robotic partial nephrectomy for renal tumors between 2007 and 2011 were identified from our prospectively maintained institutional database. Perioperative as well as short-term oncological and functional outcomes were assessed. A comparative analysis was performed between patients with pre-existing CKD (estimated glomerular filtration rate [eGFR] 15-60 mL/min, group 1, n = 52) and patients with eGFR >60 mL/min (group 2, n = 303). Group 1 patients were older (median 68 vs 57 years, P < .001), with higher American Society of Anesthesiology (ASA) score (3 vs 2, P < .001) and a higher Charlson comorbidity index (7 vs 4, P < .001). Warm ischemia time (WIT) was similar in both groups (18 vs 18 minutes, P = .52). Group 1 had a higher postoperative complication rate (40.4% vs 21.1%, P = .003). Pathologic and oncological data were similar. After a median follow-up of 3 months (interquartile: 1-10), deterioration of eGFR was lower in group 1 patients (-5% vs -12%, P = .004). No endstage renal disease was noted in either group. There was significantly less CKD upstaging in group 1 than in group 2 (11.5% vs 33.9%, P = .001). After multivariate analysis, preoperative eGFR and WIT were independent predictors of latest eGFR. Less than 15% of patients with normal baseline renal function developed CKD stage III or higher. Despite a high risk of surgical complications, robotic partial nephrectomy only marginally affects renal function in patients with pre-existing CKD.
To examine the ability of surgery as initial management in avoiding androgen deprivation therapy ... more To examine the ability of surgery as initial management in avoiding androgen deprivation therapy (ADT) in patients with high-risk localized prostate cancer. A total of 267 men were identified from a cohort of patients treated by radical prostatectomy (RP) between January 1998 and June 2004. Patients were included if they presented with clinical stage ≥T2b and/or prostate-specific antigen (PSA) ≥15 ng/mL, and/or Gleason score ≥8. Information on biochemical recurrence, distant metastasis, cancer-specific survival, and use of ADT was obtained from a prospectively maintained database. The median follow-up was 6.7 years (range, 1-146 months). Biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were observed in 112 (42%), 28 (10%), and 15 (6%) patients, respectively. Salvage treatment was performed in 95 (85%) of 112 patients with BCR. Only 71 (27%) of 267 men were subjected to ADT. Overall, 8-year probabilities of freedom from BCR, DM, PCSM, and ADT were 46% (95% CI, 38-54), 87% (95% CI, 84-90), 93% (95% CI, 91-95), and 71% (95% CI, 65-77), respectively. RP provides excellent long-term clinical outcomes for patients with high-risk localized prostate cancer and avoids the use of ADT in approximately 70% of these patients.
To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is ... more To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is a rare variant of urothelial carcinoma with aggressive clinical behavior. Radical cystectomy is considered the standard approach for treatment of patients with localized disease; however, the role of perioperative systemic therapy has been poorly defined. A retrospective review identified 38 consecutive patients who had been treated at our institution for MPBC from 2000 to 2010. The patient data were analyzed for the pre- and postoperative clinicopathologic features, treatment course, and cancer-specific survival. The median follow-up of surviving patients after cystectomy was 17 months (range 2-75). At the initial transurethral biopsy, 28 patients (74%) had clinical Stage T2N0 or less. In this group, 26 (93%) of 28 were upstaged to nonorgan-confined and/or lymph node-positive disease. Overall, 32 patients (86%) had evidence of lymph node metastasis on the final pathologic examination. All patients with cTis-T1 who had undergone initial bladder-sparing therapy with bacille Calmette-Guérin had pathologically advanced disease at cystectomy. All 15 patients who had received perioperative cisplatin-based chemotherapy died of metastatic disease. The 5-year overall survival rate was 40% (95% confidence interval 16-64). MPBC is an aggressive disease with a high likelihood of regional lymph node metastasis at the initial presentation. Although radical cystectomy plays a critical role in treatment, systemic neoadjuvant chemotherapy might be a more appropriate strategy than immediate cystectomy. Because of the poor response to current chemotherapy agents, the development of new and effective drugs for this subset of patients could be needed.
To analyze the acceptance rate and durability of surveillance among contemporary men with low-ris... more To analyze the acceptance rate and durability of surveillance among contemporary men with low-risk prostate cancer managed at a large, US academic institution. Patients with low-risk parameters on initial and repeat biopsy were offered surveillance regardless of age. Regular clinical evaluation and repeat prostate biopsy were recommended every 1-2 years, and intervention was recommended based on adverse clinical and pathologic parameters on follow-up. Acceptance rate of active surveillance, freedom from intervention, and freedom from recommended intervention were measured. Of 202 low-risk patients, 86 (43%) chose immediate treatment and 116 (57%) underwent repeat biopsy for consideration of surveillance. Intervention was recommended after initial repeat biopsy in 27 (23%) men because of higher-risk features, leaving a total of 89 men on surveillance. Over a median follow-up of 33 months, 16 men were ultimately treated and 8 were recommended to undergo treatment because of adverse clinical features on subsequent evaluations. Of the men on surveillance, the 3-year freedom from intervention and freedom from recommended intervention was 87% (95% CI, 78-93) and 93% (95% CI, 85-97), respectively. Acceptance of surveillance (57%) in low-risk patients in this series is substantially higher than previous reports, and approximately one-third of these patients are ultimately managed by surveillance using stringent criteria. The risk of reclassification to a more aggressive cancer over short-term follow-up in appropriately selected patients is low.
Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical feat... more Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated. Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5-, CD10- (11 cases); CD5+, CD10- (3 cases), and CD5-, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission. Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.
We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions i... more We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.
We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochl... more We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochloride) (Frontier Scientific, Logan, Utah) and photodynamic therapy for the removal of small intestinal mucosa in augmented bladders in a rat model. Enterocystoplasty was performed in 70 female rats using a patch of terminal ileum. A total of 28 were used to determine the pharmacokinetics (0.3, 0.6 and 0.9 M) and dwell time (30, 60 and 90 minutes) of intravesically administered aminolevulinic acid to optimize intestinal mucosal absorption and minimize bladder mucosal absorption. The remaining augmented rats were treated with intravesical photodynamic therapy at light doses of 75, 100 and 125 J. Ileal and bladder tissues were evaluated by light microscopy. Cystometric studies to evaluate bladder volume were measured before and after photodynamic therapy. The concentration of 0.3 M aminolevulinic acid with a dwell time of 30 minutes resulted in an average +/- SE bowel-to-bladder concentration of 2,156 +/- 269/749 +/- 62 ng/gm (ratio 2.9:1). After photodynamic therapy histology revealed uniform ablation and replacement of the intestinal mucosa with urothelium and minimal damage to the bladder wall at all light doses. Bladder cystometry revealed no significant change in bladder capacity after photodynamic therapy. In the rat model intravesical aminolevulinic acid and photodynamic therapy resulted in the replacement of intestinal mucosa with urothelium, leaving the underlying muscular layer intact. This could potentially be a viable option for patients with a preexisting bladder augment.
We investigated the in vitro effects of baicalein and baicalin on human umbilical vein endothelia... more We investigated the in vitro effects of baicalein and baicalin on human umbilical vein endothelial cells (HUVECs) and on human prostate tumor cells (DU-145 and PC3) as well as the effect of orally administered baicalein on the growth of DU-145 cells after subcutaneous injection into SCID mice. In vitro effects of baicalein and baicalin treatment on human prostate cancer cell lines DU-145 and PC-3 were assessed by employing cell proliferation (MTS) assay, cytotoxicity (LIVE/DEAD) assay, and TUNEL assay. In vitro anti-proliferative and anti-angiogenic properties of baicalein and baicalin were studied on HUVECs by sprout assay. The effect of orally administered baicalein on tumor growth in SCID mice was studied in four groups (n=10) of animals injected subcutaneously with DU-145 cells and treated daily for 28 days. The control group received only vehicle (carboxymethylcellulose), whereas the other three groups received escalating doses of baicalein (10, 20, and 40 mg/kg per day). Baica...
Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metasta... more Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1-3 months postoperatively. Only circulating CD117+ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117+ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expr...
To review our experience with severe penile trauma, mechanism of injury, and their treatment moda... more To review our experience with severe penile trauma, mechanism of injury, and their treatment modalities in 16 children younger than 18 years. Management of penile trauma poses diverse challenges to the reconstructive urologist, as injuries vary from abrasions to total emasculation. Analysis of 16 patients with severe penile injuries referred to us between 2002 and 2011 was undertaken. The median age at surgery was 13 years (range, 5-17). Etiology of penile trauma and choice of treatment were evaluated. The management included a wide variety of surgical techniques that were tailored to the individual patient. Results were analyzed to define etiology, that is, mechanism of penile injury and to estimate modalities of surgical management and postoperative outcomes. Also, postoperative questionnaire was used, which included questions on functioning and esthetical appearance of participating patients and overall satisfaction. The causes of penile injury in these series were traffic accidents (2), iatrogenic trauma (5), self-amputation (1), electrocution (1), burns (3), dog bite (2), zipper injury (1), and mother's hair strangulation (1). The mean follow-up was 46 months (range, 14-122), and examinations were uneventful, except for 2 fistulae formation after neophallic urethral reconstruction. The main goal of reconstructive surgery is to have a penis with normal appearance and functions. Severe penile injuries should be treated on a case-by-case basis using the most propitious techniques.
To assess the outcomes of robotic partial nephrectomy in patients with pre-existing chronic kidne... more To assess the outcomes of robotic partial nephrectomy in patients with pre-existing chronic kidney disease (CKD). Patients who underwent robotic partial nephrectomy for renal tumors between 2007 and 2011 were identified from our prospectively maintained institutional database. Perioperative as well as short-term oncological and functional outcomes were assessed. A comparative analysis was performed between patients with pre-existing CKD (estimated glomerular filtration rate [eGFR] 15-60 mL/min, group 1, n = 52) and patients with eGFR >60 mL/min (group 2, n = 303). Group 1 patients were older (median 68 vs 57 years, P < .001), with higher American Society of Anesthesiology (ASA) score (3 vs 2, P < .001) and a higher Charlson comorbidity index (7 vs 4, P < .001). Warm ischemia time (WIT) was similar in both groups (18 vs 18 minutes, P = .52). Group 1 had a higher postoperative complication rate (40.4% vs 21.1%, P = .003). Pathologic and oncological data were similar. After a median follow-up of 3 months (interquartile: 1-10), deterioration of eGFR was lower in group 1 patients (-5% vs -12%, P = .004). No endstage renal disease was noted in either group. There was significantly less CKD upstaging in group 1 than in group 2 (11.5% vs 33.9%, P = .001). After multivariate analysis, preoperative eGFR and WIT were independent predictors of latest eGFR. Less than 15% of patients with normal baseline renal function developed CKD stage III or higher. Despite a high risk of surgical complications, robotic partial nephrectomy only marginally affects renal function in patients with pre-existing CKD.
To examine the ability of surgery as initial management in avoiding androgen deprivation therapy ... more To examine the ability of surgery as initial management in avoiding androgen deprivation therapy (ADT) in patients with high-risk localized prostate cancer. A total of 267 men were identified from a cohort of patients treated by radical prostatectomy (RP) between January 1998 and June 2004. Patients were included if they presented with clinical stage ≥T2b and/or prostate-specific antigen (PSA) ≥15 ng/mL, and/or Gleason score ≥8. Information on biochemical recurrence, distant metastasis, cancer-specific survival, and use of ADT was obtained from a prospectively maintained database. The median follow-up was 6.7 years (range, 1-146 months). Biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM) were observed in 112 (42%), 28 (10%), and 15 (6%) patients, respectively. Salvage treatment was performed in 95 (85%) of 112 patients with BCR. Only 71 (27%) of 267 men were subjected to ADT. Overall, 8-year probabilities of freedom from BCR, DM, PCSM, and ADT were 46% (95% CI, 38-54), 87% (95% CI, 84-90), 93% (95% CI, 91-95), and 71% (95% CI, 65-77), respectively. RP provides excellent long-term clinical outcomes for patients with high-risk localized prostate cancer and avoids the use of ADT in approximately 70% of these patients.
To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is ... more To analyze the treatment outcomes of patients with micropapillary bladder cancer (MPBC). MPBC is a rare variant of urothelial carcinoma with aggressive clinical behavior. Radical cystectomy is considered the standard approach for treatment of patients with localized disease; however, the role of perioperative systemic therapy has been poorly defined. A retrospective review identified 38 consecutive patients who had been treated at our institution for MPBC from 2000 to 2010. The patient data were analyzed for the pre- and postoperative clinicopathologic features, treatment course, and cancer-specific survival. The median follow-up of surviving patients after cystectomy was 17 months (range 2-75). At the initial transurethral biopsy, 28 patients (74%) had clinical Stage T2N0 or less. In this group, 26 (93%) of 28 were upstaged to nonorgan-confined and/or lymph node-positive disease. Overall, 32 patients (86%) had evidence of lymph node metastasis on the final pathologic examination. All patients with cTis-T1 who had undergone initial bladder-sparing therapy with bacille Calmette-Guérin had pathologically advanced disease at cystectomy. All 15 patients who had received perioperative cisplatin-based chemotherapy died of metastatic disease. The 5-year overall survival rate was 40% (95% confidence interval 16-64). MPBC is an aggressive disease with a high likelihood of regional lymph node metastasis at the initial presentation. Although radical cystectomy plays a critical role in treatment, systemic neoadjuvant chemotherapy might be a more appropriate strategy than immediate cystectomy. Because of the poor response to current chemotherapy agents, the development of new and effective drugs for this subset of patients could be needed.
To analyze the acceptance rate and durability of surveillance among contemporary men with low-ris... more To analyze the acceptance rate and durability of surveillance among contemporary men with low-risk prostate cancer managed at a large, US academic institution. Patients with low-risk parameters on initial and repeat biopsy were offered surveillance regardless of age. Regular clinical evaluation and repeat prostate biopsy were recommended every 1-2 years, and intervention was recommended based on adverse clinical and pathologic parameters on follow-up. Acceptance rate of active surveillance, freedom from intervention, and freedom from recommended intervention were measured. Of 202 low-risk patients, 86 (43%) chose immediate treatment and 116 (57%) underwent repeat biopsy for consideration of surveillance. Intervention was recommended after initial repeat biopsy in 27 (23%) men because of higher-risk features, leaving a total of 89 men on surveillance. Over a median follow-up of 33 months, 16 men were ultimately treated and 8 were recommended to undergo treatment because of adverse clinical features on subsequent evaluations. Of the men on surveillance, the 3-year freedom from intervention and freedom from recommended intervention was 87% (95% CI, 78-93) and 93% (95% CI, 85-97), respectively. Acceptance of surveillance (57%) in low-risk patients in this series is substantially higher than previous reports, and approximately one-third of these patients are ultimately managed by surveillance using stringent criteria. The risk of reclassification to a more aggressive cancer over short-term follow-up in appropriately selected patients is low.
Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical feat... more Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated. Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5-, CD10- (11 cases); CD5+, CD10- (3 cases), and CD5-, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission. Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.
We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions i... more We evaluated the incidence of positive lymph nodes in the presacral and retroperitoneal regions in patients who underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer. As part of a prospective mapping study, 143 patients underwent radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 2006 and 2010. Lymph nodes from 6 separate regions were labeled, including bilateral pelvic and common iliac, presacral and retroperitoneal. We evaluated pathological features, treatment outcomes and cancer specific survival in patients with or without lymph node positive disease in the presacral and retroperitoneal regions. A median of 37 lymph nodes (IQR 27-49) were removed. Overall 52 (36%) patients had positive lymph nodes, of whom 24 (46%) had metastatic disease in the presacral or retroperitoneal region. Four patients (3%) had an isolated solitary positive lymph node in these 2 templates. Two-year overall survival in patients without vs with presacral/retroperitoneal lymph node positive disease was 44% (95% CI 24-64) vs 25% (95% CI 5-45) (p = 0.11). In contrast, 2-year cancer specific survival in the 2 groups was 55% (95% CI 33-77) and 29% (95% CI 7-51), respectively (p = 0.02). A substantial proportion of patients have lymph node positive disease in the presacral and retroperitoneal regions, including some with isolated and/or solitary lymph node involvement. While the limited positive lymph node burden in these templates suggests a potential therapeutic role for extending the anatomical boundaries of lymph node dissection, patient survival was poor. Extended lymph node dissection provides important staging information but to our knowledge the therapeutic benefit has yet to be definitively proved.
We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochl... more We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochloride) (Frontier Scientific, Logan, Utah) and photodynamic therapy for the removal of small intestinal mucosa in augmented bladders in a rat model. Enterocystoplasty was performed in 70 female rats using a patch of terminal ileum. A total of 28 were used to determine the pharmacokinetics (0.3, 0.6 and 0.9 M) and dwell time (30, 60 and 90 minutes) of intravesically administered aminolevulinic acid to optimize intestinal mucosal absorption and minimize bladder mucosal absorption. The remaining augmented rats were treated with intravesical photodynamic therapy at light doses of 75, 100 and 125 J. Ileal and bladder tissues were evaluated by light microscopy. Cystometric studies to evaluate bladder volume were measured before and after photodynamic therapy. The concentration of 0.3 M aminolevulinic acid with a dwell time of 30 minutes resulted in an average +/- SE bowel-to-bladder concentration of 2,156 +/- 269/749 +/- 62 ng/gm (ratio 2.9:1). After photodynamic therapy histology revealed uniform ablation and replacement of the intestinal mucosa with urothelium and minimal damage to the bladder wall at all light doses. Bladder cystometry revealed no significant change in bladder capacity after photodynamic therapy. In the rat model intravesical aminolevulinic acid and photodynamic therapy resulted in the replacement of intestinal mucosa with urothelium, leaving the underlying muscular layer intact. This could potentially be a viable option for patients with a preexisting bladder augment.
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