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Abstract Introduction Testicular neoplasms metastasizing to the retroperitoneum rarely involve the upper gastrointestinal tract. Gastrointestinal tract metastases usually present with complications including intestinal obstruction, gastrointestinal hemorrhage, and rarely ulceration of the bowel mucosa. Case presentation We describe an unusual case of duodenal perforation as the presenting manifestation of metastatic classic type seminoma in a 45-year-old man. Conclusion Germ cell tumor diagnosis should be considered when an ulcerating small bowel mass is identified in a young man.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

We present a rare finding of concurrent right testis non-seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57-year-old homeless man. The socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy. The patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin-based chemotherapy.

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 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.

Objective: To compare the outcomes of active surveillance (AS) series between African American men (AAM) and non-AAM diagnosed with low-risk prostate cancer at 3 medical centers., Methods: Between 2005 and 2012, 214 men accepted AS on the basis of favorable clinical features and parameters after initial and repeat biopsy. Failure was defined as increase in Gleason score >6, total positive cores >33%, maximum cancer volume in any core >50%, or a prostate-specific antigen >10 ng/mL. Disease progression and overall AS failure were compared between the 2 groups., Results: Of 214 men, 75 were excluded, leaving 67 AAM and 72 non-AAM on AS. Median age at diagnosis was 64 and 67 years for AAM and non-AAM, respectively, and median follow-up was 34 and 46 months, respectively. During this time, 44 AAM (66%) remained on AS, and 23 (34%) underwent treatment, of whom 6 (26%) were treated by patient choice and 17 (74%) because of disease progression. In the non-AAM group, 59 (82%) men remained on AS, and 13 (18%) underwent treatment, 8 (62%) were treated by patient choice and 5 (38%) because of disease progression. The 3-year freedom from overall treatment was 74% and did not differ by race (P = .06). The 3-year freedom from disease progression was 85%, where AAM were at significantly higher risk of disease progression (hazard ratio = 3.8; 95% confidence interval: 1.4-10.4; P = .01)., Conclusion: Our study suggests a higher disease progression rate in AAM who choose AS for low-risk prostate cancer compared with non-AAM, signifying a potential need for closer follow-up and more stringent enrollment criteria in AAM., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Adrenocortical carcinoma (ACC) is a rare and clinically aggressive cancer. Previous studies reported increased recurrence rates associated with laparoscopic adrenalectomy (LA). We evaluated a single-center experience of LA versus open adrenalectomy (OA) for the management of ACC., Methods: Between 1993 and 2011, 44 consecutive patients with primary ACC were treated at our institution. Baseline patient characteristics and surgical and pathological outcomes were compared between OA and LA groups. Multivariable Cox proportional hazards analysis was used to estimate the association between OA versus LA with recurrence-free and overall survival., Results: Eighteen and 26 patients underwent LA and OA, respectively. Patients who underwent OA had larger tumors and more advanced clinical stage compared with LA group. During a median follow-up of 22 months, 22 recurrences and 26 deaths were observed. The 2-year, recurrence-free and overall survivals for OA and LA were 60 vs. 39 % (P = 0.7) and 54 vs. 58 % (P = 0.6), respectively. After adjusting for clinical stage, OA was associated with lower risk of recurrence (hazard ratio (HR) 0.4; 95 % confidence interval (CI) 0.2-1.2; P = 0.099) and improved overall survival (HR 0.5; 95 % CI 0.2-1.2; P = 0.122) compared with LA, although differences were not statistically significant., Conclusions: A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.

Background and Purpose: Intraoperative frozen section (FS) analysis has been regarded as a paramount tool for immediate evaluation of tumor margin status during partial nephrectomy procedures. The aim of this study was to assess the utility of FS during robot-assisted partial nephrectomy (RAPN)., Patients and Methods: A retrospective review of our Institutional Review Board-approved prospectively maintained minimally invasive partial nephrectomy database yielded 342 consecutive RAPN procedures from June 2007 to September 2011. Of these, the initial 128 cases underwent FS evaluation, whereas the following 214 cases did not. Patient demographics, perioperative outcomes, and final pathology results were analyzed and compared between the two groups., Results: Body mass index, Charleson Comorbidity Index, tumor size, renal score, preoperative creatinine level, and estimated glomerular filtration rate (eGFR) were similar between both groups. Operative time was significantly longer in the no-FS group (193 vs 180 min; P=0.04). Warm ischemia time (median 19 vs 19 min), estimated blood loss (150 vs 200 mL), postoperative creatinine level (1.0 vs 1.1 mg/dL), and postoperative eGFR (75.6 vs 75.9) were similar between the no-FS group and FS group, respectively. Complications occurred in 32 (15.0%) and 31 (24.2%) cases in no-FS and FS, respectively (P=0.06). Final pathology results demonstrated seven cases of positive margins, 1 (1%), in the FS group and 6 (3%) in the no-FS group (P=0.19). Of the cases with positive margins at final pathology analysis, a R.E.N.A.L. score of 3/3 was found on closeness to renal sinus. Overall, three intraoperative positive margins were noted in the FS group (2.3%): One patient underwent radical nephrectomy and one reresection; one case was managed with observation only., Conclusion: Routine application of FS analysis during RAPN seems to provide a limited benefit. FS might be advisable for tumors with sinus invasion because they seem to carry a higher likelihood of positive surgical margin at final pathology determination.

Purpose: In 2010 the AJCC (American Joint Committee on Cancer) excluded urothelial carcinoma with subepithelial prostatic stromal invasion from the pT4a bladder cancer staging class, which is otherwise defined by direct prostatic invasion transmurally from the bladder. We determined if the new guidelines were reflective of differences in survival between subepithelial prostatic stromal invasion and transmural pT4a disease., Materials and Methods: A retrospective, multi-institutional cohort of cystectomy cases with subepithelial prostatic stromal invasion from the University of Chicago and Cleveland Clinic were compared to a cohort with transmural pT4a disease. All pathological specimens were rereviewed at the respective institutions. Patients were excluded from the final cohort if variant bladder cancer histology, pT3 bladder disease or extraprostatic extension of urothelial carcinoma were identified. The primary end points were cancer specific and overall survival., Results: Our study sample consisted of 48 patients with subepithelial prostatic stromal invasion and 49 patients with transmural pT4a disease. Median followup was 12.8 months (IQR 4.9 to 31.4). Patients with subepithelial prostatic stromal invasion had lower rates of lymph node involvement than those with transmural pT4a disease (14.6% vs 61.2%, p <0.001) and lower rates of positive surgical margins (18.7% vs 61.2%, p <0.001). Rates of perioperative chemotherapy were similar in both groups. When comparing subepithelial prostatic stromal invasion and transmural pT4a groups, overall survival was 64.0 vs 9.8 months and median cancer specific survival was not achieved vs 16.5 months, respectively (p <0.001)., Conclusions: Subepithelial prostatic stromal invasion from urothelial carcinoma has more favorable outcomes compared to transmural pT4a disease. Our results support the exclusion of subepithelial prostatic stromal invasion from the pT4a bladder urothelial carcinoma staging class., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Urethral stents were initially developed for the management of urethral strictures and obstructive voiding disorders in select patients. Urethral stent complications are common and may require stent explantation, which is often quite challenging. We present our experience with endoscopic removal of an encrusted UroLume proximal urethral stent in a 72-year-old male using a holmium laser. The literature on various management options and outcomes for urethral stent removal is reviewed. Endoscopic removal of proximal urethral stents is feasible and safe and should be considered as the primary treatment option in patients requiring stent extraction.

High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.

Background: Open partial nephrectomy (OPN) remains the gold standard for treatment of small renal masses (SRMs). Laparoscopic cryoablation (LCA) has provided encouraging outcomes. Robotic partial nephrectomy (RPN) represents a new promising option but is still under evaluation., Objective: Compare the outcomes of RPN and LCA in the treatment of patients with SRMs., Design, Setting, and Participants: We retrospectively analyzed the medical charts of patients with SRMs (≤4cm) who underwent minimally invasive nephron-sparing surgery (RPN or LCA) in our institution from January 1998 to December 2010., Intervention: RPN and LCA., Measurements: Perioperative complications and functional and oncologic outcomes were analyzed., Results and Limitations: A total of 446 SRMs were identified in 436 patients (RPN, n=210; LCA, n=226). Patients undergoing RPN were younger (p<0.0001), had a lower American Society of Anesthesiologists score (p<0.001), and higher baseline preoperative estimated glomerular filtration rate (eGFR) (p<0.0001). Mean tumor size was smaller in the LCA group (2.2 vs 2.4cm; p=0.004). RPN was associated with longer operative time (180 vs 165min; p=0.01), increased estimated blood loss (200 vs 75ml; p<0.0001), longer hospital stay (72 vs 48h; p<0.0001), and higher morbidity rate (20% vs 12%, p=0.015). Mean follow-ups for RPN and LCA were 4.8 mo and 44.5 mo, respectively (p<0.0001). Local recurrence rates for RPN and LCA were 0% and 11%, respectively (p<0.0001). Mean eGFR decrease after RPN and LCA was insignificant at 1 mo, at 6 mo after surgery, and during last follow-up. Limitations include retrospective study design, length of follow-up, and selection bias., Conclusions: Both techniques remain viable treatment options in the management of SRMs. A higher incidence of perioperative complications was found in patients undergoing RPN. However, the technique was not predictive of the occurrence of postoperative complications. Early oncologic outcomes are promising for RPN, which also seems to be associated with better preservation of renal function. Long-term follow-up and well-designed prospective comparative studies are awaited to corroborate these findings., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: 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., Materials and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: 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., Material and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To examine the ability of surgery as initial management in avoiding androgen deprivation therapy (ADT) in patients with high-risk localized prostate cancer., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To analyze the acceptance rate and durability of surveillance among contemporary men with low-risk prostate cancer managed at a large, US academic institution., Methods: 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., Results and Limitations: 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., Conclusions: 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., (Copyright © 2011. Published by Elsevier Inc.)

To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is unclear if these factors are tumor-derived or actually represent the host defense. To analyze the concentrations of tumor- and microenvironment-derived factors associated with neoplastic growth, we used ELISA-based arrays specific for murine or human proteins to establish a profile of tumor- or host-derived factors circulating in the plasma or within the platelets upon human tumor implantation into mice. Many factors characterized as tumor-derived were actually secreted by host tissues. This study uncovered the origin of various cytokines and revealed their circulation methods. We found that tumor-produced cytokines are predominantly sequestered in platelets. Sequestered proteins are protected from degradation and, thus, may be functional at metastatic sites. These findings identify tumor-specific targets for the detection and prevention of tumor growth and metastasis. As predicted by our model, monocyte chemotactic protein 1 and tumor necrosis factor alpha may be biomarkers for human cancers. Thus, our study identified several potential biomarkers that might be predictive of prostate cancer.

Purpose: Tumor spillage from bladder perforation during transurethral bladder tumor resection or cystectomy risks seeding the peritoneum with transitional cell carcinoma. We determined the lowest effective mitomycin C dose to prevent tumor implantation and the potential efficacy of delayed therapy. Additionally, we investigated the effect of tumor debulking combined with intraperitoneal mitomycin C., Materials and Methods: Using our established murine model of intraperitoneal transitional cell carcinoma implantation mitomycin C was instilled at decreasing concentrations to find the lowest effective dose. To evaluate the effectiveness of delayed therapy mitomycin C was administered on day 3 or 7 after tumor implantation. Finally, surgical debulking of established tumors with or without mitomycin C was performed., Results: All control animals had disseminated carcinomatosis. The lowest effective intraperitoneal mitomycin C dose to prevent implantation was 0.3125 mg/m(2). Administration of mitomycin C on day 3 after instillation resulted in tumor-free status in 50% of the animals, although no rats were tumor-free when treated on day 7. Tumor debulking only for established disease cured 40% of the animals, whereas debulking combined with mitomycin C had a 100% cure rate., Conclusions: Intraperitoneal mitomycin C prevents tumor growth after transitional cell carcinoma implantation. Delayed therapy is not as effective as immediate treatment but cure is still possible, particularly when combined with surgical debulking, in a rat model.

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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 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). Baicalein and baicalin exhibit dose-dependent growth inhibitory effects on human prostate cancer cells and umbilical vein endothelial cells in vitro. Also, treatment by these two flavonoid compounds significantly decreased the average number and length of sprouts formed by the endothelial cell aggregates in a dose-dependent manner. In vivo, treatment of mice with baicalein demonstrated a statistically significant tumor volume reduction (p<0.01) when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered baicalein on human prostate tumors in mice.

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.