Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis.

A single nucleotide polymorphism in the DAB2IP gene is associated with risk of aggressive prostate cancer (PCa), and loss of DAB2IP expression is frequently detected in metastatic PCa. However, the functional role of DAB2IP in PCa remains unknown. Here, we show that the loss of DAB2IP expression initiates epithelial-to-mesenchymal transition (EMT), which is visualized by repression of E-cadherin and up-regulation of vimentin in both human normal prostate epithelial and prostate carcinoma cells as well as in clinical prostate-cancer specimens. Conversely, restoring DAB2IP in metastatic PCa cells reversed EMT. In DAB2IP knockout mice, prostate epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT. Using a human prostate xenograft-mouse model, we observed that knocking down endogenous DAB2IP in human carcinoma cells led to the development of multiple lymph node and distant organ metastases. Moreover, we showed that DAB2IP functions as a scaffold protein in regulating EMT by modulating nuclear beta-catenin/T-cell factor activity. These results show the mechanism of DAB2IP in EMT and suggest that assessment of DAB2IP may provide a prognostic biomarker and potential therapeutic target for PCa metastasis.

Burkitt Lymphoma Presenting as Obstructive Jaundice: A Case Report and Literature Review.

Burkitt lymphoma (BL) is an aggressive, high-grade B-cell lymphoma common in children and young adults. Despite being frequently discovered in extranodal sites, BL rarely occurs in the pancreas. We present a case of a patient with BL presenting as obstructive jaundice.

Impact of histological variants on clinical outcomes of patients with upper urinary tract urothelial carcinoma.

PURPOSE: We investigated the clinical and prognostic impact of variant histologies on upper tract urothelial carcinoma outcomes after radical nephroureterectomy. MATERIALS AND METHODS: Data on 1,648 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy without preoperative chemotherapy or radiotherapy were reviewed for histological differentiation and variants. We analyzed differences between pure upper tract urothelial carcinoma and upper tract urothelial carcinoma with variant histology, and differences in the histological variants using different stratifications. RESULTS: A total of 398 patients (24.2%) had histological upper tract urothelial carcinoma variants. The most common variants were squamous cell and glandular differentiation in 9.9% and 4.4% of cases, respectively. Histological variants were associated with advanced tumor stage, tumor multifocality, sessile tumor architecture, tumor necrosis, lymphovascular invasion and lymph node metastasis compared to pure upper tract urothelial carcinoma (p ≤0.031). On univariable analysis variant histology was associated with disease recurrence (p = 0.002) and cancer specific mortality (p = 0.003). In 174 patients treated with adjuvant chemotherapy there was no difference in disease recurrence or survival between variant histology and pure upper tract urothelial carcinoma (p = 0.42 and 0.59, respectively). On multivariable analysis adjusted for the effects of standard clinicopathological characteristics variant histology was not associated with either end point. CONCLUSIONS: Almost 25% of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy harbored histological variants. Variant histology was associated with features of biologically aggressive upper tract urothelial carcinoma. While variant histology is associated with worse outcomes on univariable analysis but this effect did not remain significant on multivariable analysis.

Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. OBJECTIVE: To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. METHODS: Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. • A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. RESULTS: The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. • Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients. • Median follow-up was 63.2 months. • Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. CONCLUSION: Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.

Splenic Cysts and the Case of Mistaken Identity.

Endometriosis is a well-described pathology, with anatomic location of endometrial cell implantation extending both intraperitoneal and rarely extraperitoneal. Interestingly, previous reports indicated that the spleen enjoys immunity to endometriosis. Here, we present a patient with unremitting abdominal pain who, upon further workup, revealed multicystic disease of the spleen. The patient underwent an open splenectomy with pathology revealing intraparenchymal endometriosis likely due to seeding from traumatic splenorrhaphy. Two-week follow-up demonstrated resolution of symptoms and a well-healing incision with no postoperative complications.

Evidence of epithelial to mesenchymal transition associated with increased tumorigenic potential in an immortalized normal prostate epithelial cell line.

BACKGROUND: The majority of established human prostate cancer cell lines are derived from metastatic lesions and are already tumorigenic in vivo, therefore immortalized normal prostate cell lines may provide a more relevant model to unveil the mechanisms associated with cancer progression and metastasis. METHODS: PZ-HPV-7, an immortalized human prostate epithelial cell line was used to generate xenograft tumors in mice. A subline designated HPV-PZ-7T was subsequently derived from the subrenal capsule xenograft of a nude mouse. These cells were further characterized using karyotyping, immunofluorescence, qRT-PCR, Western blotting, and three-dimensional cultures in Matrigel. RESULTS: The PZ-HPV-7 cell line possesses a typical epithelial morphology, expresses basal cell markers, and is capable of forming web-like structures with evidence of budding on Matrigel. PZ-HPV-7 is non-tumorigenic in immunocompromised mice by either subcutaneous injection or subrenal grafting. In contrast, the PZ-HPV-7T cells, derived from a xenograft tumor induced by co-inoculation with matrigel using subrenal grafting, possess a mesenchymal phenotype as well as luminal cell markers and are highly tumorigenic and metastatic in nude mice. Functionally and biochemically, the PZ-HPV-7T subline appears to have undergone an epithelial-to-mesenchymal transition (EMT) from the parental PZ-HPV-7 line. CONCLUSION: We have developed a novel EMT model using an immortalized normal prostate epithelial cell line and generated a new prostate cancer cell line, PZ-HPV-7T, which may represent an excellent system to study mechanisms associated with prostate cancer progression and metastasis.

Prognostic value of cyclooxygenase-2 expression in squamous cell carcinoma of the bladder.

PURPOSE: Inflammation is associated with the pathogenesis of carcinoma, including squamous cell carcinoma of the bladder. Cyclooxygenase-2 is an enzyme that is induced at inflammation sites. We assessed the expression pattern of cyclooxygenase-2 in patients with squamous cell carcinoma of the bladder and determined whether cyclooxygenase-2 expression is associated with clinical outcomes after radical cystectomy. MATERIALS AND METHODS: Immunohistochemical staining for cyclooxygenase-2 was done on archival bladder specimens from 152 patients treated with radical cystectomy for squamous cell carcinoma on the Autostainer (DakoCytomation, Carpinteria, California). Bright field microscopy imaging coupled with advanced color detection software was used. Cyclooxygenase-2 was defined as over expressed when greater than 20% cells were positive. We assessed the relationship of cyclooxygenase-2 expression with pathological parameters and clinical outcome. RESULTS: The study included 99 male and 53 female patients with a mean age of 52 years who had squamous cell carcinoma, including 80.9% with bilharziasis. Presenting stage was T2 or greater and presenting grade was GII or less in 93.4% of patients. Median followup was 63.2 months. Cyclooxygenase-2 was over expressed in 74 cystectomy specimens (48.7%) and associated with higher pathological stage (p=0.003) and grade (p=0.049). On multivariate Cox proportional hazards regression analysis cyclooxygenase-2 over expression was associated with disease recurrence (p=0.031) and bladder cancer specific mortality (p=0.046). CONCLUSIONS: Cyclooxygenase-2 over expression is associated with pathological stage, grade and worse outcomes after radical cystectomy, suggesting a role in bladder squamous cell carcinoma progression. Our findings support the need for further evaluation of cyclooxygenase-2 and inflammatory signaling pathways, and cyclooxygenase-2 targeted prevention or therapy in patients with bladder squamous cell carcinoma.

Irreversible electroporation (IRE): a novel method for renal tissue ablation.

OBJECTIVE: • To evaluate the effects of irreversible electroporation (IRE) on renal parenchyma and the renal collecting system in a porcine model. MATERIALS AND METHODS: • Eight female Yorkshire pigs underwent a series of laparoscopic ablations using either monopolar or bipolar IRE (Angiodynamics, Queensbury, NY, USA). • The pigs were killed between 10 min and 14 days after IRE, and the kidneys were harvested for gross and histological analysis, including NADH staining for cellular viability. RESULTS: • In all, 24 ablations were performed and all the pigs survived without complications. • Initial gross lesions were diffusely haemorrhagic, decreasing progressively in size (30-40%) to small white scars over the 14-day period. • Immediately after IRE, ablated tissue was characterized by diffuse tubular desquamation, eosinophilia, and nuclear pyknosis, with absence of cellular viability by NADH. • At 7 days after IRE, there was diffuse cellular necrosis with early peripheral granulation changes, and by 14 days there was marked tissue granulation, chronic inflammation, and dystrophic calcification with early fibrosis and cellular contraction. • Initial patchy urothelial injury and ulceration showed signs of repair and viability by 14 days after IRE. CONCLUSIONS: • Renal IRE in the porcine kidney leads to predictable histological changes characteristic of cellular death within 1 h of ablation, with relative urothelial sparing. • Further animal studies are warranted to determine safety and efficacy of this novel ablation technology.

Bilharzial vs non-bilharzial related bladder cancer: pathological characteristics and value of cyclooxygenase-2 expression.

OBJECTIVE: • To assess the expression pattern of cyclooxygenase-2 (COX-2) in bilharzial and non-bilharzial related bladder cancer (BBC and NBBC) and its association with clinical outcome after radical cystectomy (RC). We also determined the clinico-pathological differences between BBC and NBBC. PATIENTS AND METHODS: • Immunohistochemical (IHC) staining for COX-2 was performed on archival bladder specimens from 315 patients treated with RC between 1997 and 2003. • Patients were divided into 2 groups: Group 1 comprised 205 patients (65%) with BBC and group 2 comprised 110 patients (35%) with NBBC. • Clinico-pathological differences were compared and altered IHC expression of COX-2 was correlated with clinical outcome in both groups. RESULTS: • The study included 315 patients (239 males and 76 females) with median age 54 y (range 31-79) and median follow up of 63.2 months after RC. • There was significant difference in histological types, tumor stage, grade, and architecture and COX-2 alterations between both groups (P < 0.05). • BBC presented with lower grade, higher stage, and non-papillary non-urothelial carcinoma. COX-2 overexpression was associated with pathological T stage (P= 0.01), grade (P < 0.001) and lymphovascular invasion (LVI) (P= 0.041). • COX-2 expression was an independent predictor of disease recurrence (HR 1.9, CI 0.99-3.626 and P= 0.05) and cancer specific mortality (HR 2.8, CI 1.155-6.73 and P= 0.023) only in BBC but not in NBBC (HR 1.6, CI 0.598-4.364, P= 0.344 and HR 0.349, CI 0.076-1.595, P= 0.175, respectively). CONCLUSIONS: • BBC differs pathologically and biologically from NBBC. BBCs present more frequently as low-grade, high stage non-papillary and non-urothelial cancers. BBCs with COX-2 alterations are associated with worse outcome after RC. • Our findings support the need for further evaluation of COX-2 and inflammatory signaling pathways as well as COX-2-targeted prevention and therapies in BC.

Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration.

OBJECTIVE: • To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases. PATIENTS AND METHODS: • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC. RESULTS: • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively). CONCLUSIONS: • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.

Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy.

PURPOSE: beta-Lapachone (ARQ 501, a formulation of beta-lapachone complexed with hydroxypropyl-beta-cyclodextrin) is a novel anticancer agent with selectivity against prostate cancer cells overexpressing the NAD(P)H:quinone oxidoreductase-1 enzyme. Lack of solubility and an efficient drug delivery strategy limits this compound in clinical applications. In this study, we aimed to develop beta-lapachone-containing polymer implants (millirods) for direct implantation into prostate tumors to test the hypothesis that the combination of a tumor-specific anticancer agent with site-specific release of the agent will lead to significant antitumor efficacy. EXPERIMENTAL DESIGN: Survival assays in vitro were used to test the killing effect of beta-lapachone in different prostate cancer cells. beta-Lapachone release kinetics from millirods was determined in vitro and in vivo. PC-3 prostate tumor xenografts in athymic nude mice were used for antitumor efficacy studies in vivo. RESULTS: beta-Lapachone killed three different prostate cancer cell lines in an NAD(P)H:quinone oxidoreductase-1-dependent manner. Upon incorporation of solid-state inclusion complexes of beta-lapachone with hydroxypropyl-beta-cyclodextrin into poly(D,L-lactide-co-glycolide) millirods, beta-lapachone release kinetics in vivo showed a burst release of approximately 0.5 mg within 12 hours and a subsequently sustained release of the drug ( approximately 0.4 mg/kg/d) comparable with that observed in vitro. Antitumor efficacy studies showed significant tumor growth inhibition by beta-lapachone millirods compared with controls (P < 0.0001; n = 10 per group). Kaplan-Meier survival curves showed that tumor-bearing mice treated with beta-lapachone millirods survived nearly 2-fold longer than controls, without observable systemic toxicity. CONCLUSIONS: Intratumoral delivery of beta-lapachone using polymer millirods showed the promising therapeutic potential for human prostate tumors.

Off-label high-risk HPV DNA testing of vaginal ASC-US and LSIL cytologic abnormalities at Parkland hospital.

OBJECTIVE: To investigate the frequency and outcome of high-risk human papillomavirus (HPV) DNA testing of atypical squamous cell of unknown significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) vaginal ThinPrep Pap tests (TPPTs). METHODS: Atypical squamous cell of unknown significance and LSIL vaginal TPPTs (from women without a cervix) from 2005 to 2008 were identified retrospectively. The frequency of HPV testing in response to these cytologic abnormalities and results of testing were determined and compared with cervical TPPTs. The frequency and results of subsequent vaginal biopsies were reviewed. RESULTS: Of the ASC-US vaginal TPPTs, 76.5% (270/353) underwent HPV testing, with 31.9% (86/270) positive. Atypical squamous cell of unknown significance cervical TPPTs underwent HPV testing less often (69.5%, 7,155/10,297) but were more commonly HPV-positive (49.7%, 3,558/7,155). Similarly, the majority of LSIL vaginal TPPTs (59.2%, 202/341) underwent HPV testing, with 66% (133/202) testing positive. This compares with only 11.0% (1,092/9,947) of cervical LSIL TPPTs undergoing HPV testing, with 73.2% (799/1,092) positive. The increased rates of HPV test performance and lower rates of HPV positivity in vaginal ASC-US and LSIL TPPTs compared with similarly abnormal cervical TPPTs were statistically significant (p <.05) by χ analysis. Histologic evaluation was more common after HPV-positive ASC-US or LSIL vaginal TPPTs compared with HPV-negative results. Most high-grade vaginal neoplasias were diagnosed subsequent to a positive HPV result. CONCLUSIONS: Human papillomavirus testing of ASC-US and LSIL vaginal TPPTs is common; lower rates of HPV positivity were found in vaginal versus cervical ASC-US and LSIL TPPTs. The majority of high-grade vaginal neoplasias were diagnosed subsequent to positive HPV testing. Evidence-based guidelines for the use of HPV testing for the management of vaginal cytologic abnormalities are needed.

Impact of lymph node dissection on cancer specific survival in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy. MATERIALS AND METHODS: Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival. RESULTS: Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only. CONCLUSIONS: Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients.

OBJECTIVE: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive. PATIENTS AND METHODS: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary. RESULTS: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001). CONCLUSION: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.

A comparison of kidney oxygenation profiles between partial and complete renal artery clamping during nephron sparing surgery in a porcine model.

OBJECTIVE: To compare kidney oxygenation profiles between partial and complete renal artery clamping during nephron sparing surgery (NSS) in a porcine model. MATERIALS AND METHODS: Twelve female farm pigs underwent a laparoscopic nephrectomy. Subsequently, an open partial nephrectomy was performed on the remaining kidney using either total (n = 6, TC) or partial (n = 6, PC) clamping of the renal artery. Real time renal partial oxygen pressure (rPO2) was monitored using a Licox probe (Integra, San Diego, CA). Creatinine levels were measured prior to open partial nephrectomy and on POD #3 and #7. The remaining kidney was harvested for pathologic evaluation. RESULTS: Compared to TC, the PC group demonstrated a more favorable renal oxygenation profile during the NSS. Specifically, rPO2 decreased less from baseline (58% versus 84%, p = 0.03), took a longer interval to nadir (23.1 min versus 8.7 min, p = 0.04), and experienced a more rapid recovery to maximal or baseline values (4.8 min versus 10.4 min, p = 0.03) in the PC group. Furthermore animals undergoing TC had significantly higher creatinine levels at POD #3 (2.2 mg/dl versus 1.6 mg/dl, p = 0.03) and POD #7 (2.5 mg/dl versus 1.7 mg/dl, p = 0.009). Histological analysis demonstrated varying levels of acute inflammation in the two groups. Finally, the intraoperative blood loss was greater in the PC versus TC group (40 cc versus 10 cc, p = 0.04). CONCLUSIONS: In this porcine model, partial clamping of the renal artery during NSS was feasible and demonstrated a favorable renal oxygenation profile. Theoretically, intraoperative rPO2 monitoring may provide a novel means to allow real time assessment and titration of kidney perfusion during partial nephrectomy.

Selective prostate cancer thermal ablation with laser activated gold nanoshells.

PURPOSE: Laser activated gold nanoshell thermal ablation represents a new, minimally invasive technology that offers benign tissue sparing thermal ablation of malignant tumors. We evaluated the efficacy of this technology for eradicating prostate cancer in a subcutaneous tumor model. MATERIALS AND METHODS: The 110 nm gold nanoshells with a 10 nm gold shell are designed to act as intense near infrared absorbers. PC-3 cells were injected on the dorsum of nude mice in 3 groups, including 1-gold nanoshell plus near infrared laser, 2-saline alone and 3-near infrared laser alone. Animals received 7.0 ml/gm body weight (low dose) or 8.5 ml/gm body weight (high dose) nanoshells via tail vein injection. Control animals received saline. A 810 nm near infrared laser with a 200 mu laser fiber and an energy setting of 4 W/cm(2) was aimed at the tumor bed for 3 minutes. Tumors were measured at days 0, 7, 14 and 21. Tissue temperature was monitored during laser activation. Tumors were harvested at day 21 and stained with hematoxylin and eosin, and for nicotinamide adenine dinucleotide diaphorase activity. RESULTS: We observed 93% tumor necrosis and regression in the high dose treated group. Nicotinamide adenine dinucleotide staining corroborated this finding. The ablation zone was sharply limited to the laser spot size. There was no difference in the size or tumor histology in control groups, indicating a benign course for near infrared laser treatment alone. Temperatures up to 65.4C were attained in the treated group. CONCLUSIONS: Laser activated gold nanoshell ablation is an effective and selective technique for prostate cancer ablation in an ectopic murine tumor model.

Absence of viable renal carcinoma in biopsies performed more than 1 year following radio frequency ablation confirms reliability of axial imaging.

PURPOSE: Radio frequency ablation is an emerging nephron sparing treatment option in select patients with small renal tumors. Some have questioned the completeness of cell death and the reliability of axial imaging for radio frequency ablation followup. We present results in patients with no evidence of radiographic active disease who underwent biopsy more than 1 year following ablation. MATERIALS AND METHODS: Patients who had no clinical evidence of disease, defined as absent lesion growth and contrast enhancement on computerized tomography, 1 year or more following radio frequency ablation underwent percutaneous renal biopsy to evaluate cell viability in the ablative zone. A total of 19 patients (20 lesions) were included in the study. Histological comparison of pre-ablation and post-ablation specimens was performed using hematoxylin and eosin staining. RESULTS: Pre-ablation biopsies confirmed that 17 of 20 tumors were renal cell carcinoma, while the remaining 3 were oncocytoma. Following ablation at a mean followup of 26.9 months (range 13.1 to 58.0) all 20 lesions were stable in size without evidence of contrast enhancement on computerized tomography. At repeat biopsy all histology specimens showed unequivocal tumor eradication with no evidence of cellular viability. Histological changes beyond 1 year demonstrated coagulative necrosis, hyalinization, inflammatory cell infiltration and residual ghost cells. CONCLUSIONS: Pathological examination of radiographically negative lesions biopsied more than 1 year following radio frequency ablation confirmed no evidence of disease in all specimens. Therefore, axial imaging can reliably monitor treatment efficacy in the long term. Chronic changes after radio frequency ablation demonstrate coagulative necrosis and nonviable cells. This suggests an evolution of pathological changes that renders early post-ablative biopsy unreliable.

Does topical haemostatic agent have an adverse effect on the function of the prostatic neurovascular bundle?

OBJECTIVE: To assess the functional and histological effects of a bovine thrombin topical haemostatic agent used clinically to aid in surgical haemostasis (FloSeal(TM), Baxter International Inc., Deerfield, IL, USA) on the cavernous nerves in a canine model of survival, as there are concerns that the fibrotic/inflammatory response to this product could affect neural function. MATERIALS AND METHODS: In phase I, nine adult male dogs had the bilateral neurovascular bundles (NVBs) dissected. A small intravenous catheter placed directly into the erectile bodies of the penis was used to record the intracorporal pressure (ICP). Erection was induced by electrical stimulation of the NVB on each side. After intraoperative randomization to treatment or control, 5 mL of FloSeal was unilaterally applied along the NVB on the treatment side. In phase II, after 2 weeks of survival, both control and treatment NVB were again dissected and re-stimulated to produce an erectile response. The mean arterial pressure and ICP were recorded. The prostate and the NVBs were then removed for histological analysis. RESULTS: All dogs achieved erections after electrical stimulation on both the control and treatment side. There was no statistically significant difference in absolute ICP, pressure increase from baseline or systemic pressure after stimulating the NVB on the treatment side between phases I and II. Histological analysis showed a giant-cell reaction around the FloSeal granules and mild focal perineural oedema, but the cavernous nerves were otherwise normal in appearance. CONCLUSION: In this short-term functional study, FloSeal did not adversely affect cavernous nerve function, measured as the erectile response to electrical stimulation. We found no evidence contraindicating its use during radical prostatectomy.

Conservative management in selected patients with upper tract urothelial carcinoma compares favourably with early radical surgery.

OBJECTIVE: To compare the outcomes of patients treated for upper tract urothelial carcinoma with either immediate nephroureterectomy (NU) or initial endoscopic management. PATIENTS AND METHODS: The treatments of 108 patients (120 renal units) at the authors' institution were retrospectively reviewed and divided into two groups, i.e. those who received immediate NU and those who had conservative initial therapy, which included renal units solely treated with endoscopy with or without delayed NU. Overall and disease-specific survival (DSS) were compared between the treatment groups. RESULTS: There were 48 low-grade tumours, of which 27 (56%) were managed conservatively and 21 (44%) by immediate NU. Seven patients treated conservatively had stage or grade progression and had delayed NU. The mean (sd) DSS at 5 years in patients with low-grade disease was equally good for conservative treatment and immediate NU, at 86.2 (9.1)% vs 87.4 (8.4)% (P = 0.909). There were 68 high-grade tumours, of which 12 (18%) patients had conservative management and 56 (82%) had immediate NU. Among the former, seven of 12 had a solitary kidney and three had bilateral disease. In patients managed endoscopically, four of 30 (13%) required delayed NU. The DSS for the conservative and immediate NU groups were 68.6 (18.6)% vs 75.0 (8.1)% (P = 0.528). CONCLUSION: Management with a conservative approach in selected patients provides comparable outcomes to immediate NU in patients with low-grade disease.

Prognostic value of syndecan-1 expression in patients treated with radical prostatectomy.

OBJECTIVE: To investigate the association of syndecan-1 expression with pathological features and disease progression in patients treated with radical prostatectomy (RP) as syndecan-1 plays a role in the regulation of cell proliferation, migration, and differentiation and its expression is altered in various malignancies. PATIENTS AND METHODS: Syndecan-1 immunostaining was performed on a tissue microarray containing cores from 232 consecutive patients treated with RP and bilateral lymphadenectomy for clinically localized prostatic adenocarcinoma. Patients were categorized as having features of aggressive progression if they had evidence of metastases, an after progression prostate-specific antigen (PSA) doubling time of < 10 months, and/or failure to respond to local salvage radiation therapy. Expression was defined as > or = 10% cells staining for syndecan-1. RESULTS: Syndecan-1 was expressed in 86 patients (37.1%). Expression of syndecan-1 was associated with higher PSA levels (P = 0.004), higher pathological Gleason sum (P = 0.027) and lymph nodes metastases (P = 0.027). Patients with syndecan-1 expression were at significantly greater risk of PSA-progression after surgery (P = 0.034) in univariate but not in multivariate analysis. Patients with features of aggressive progression (n = 22) were more likely to express syndecan-1 than those with features of nonaggressive progression (63.6% vs 36.4%, P = 0.010). Patients with syndecan-1 expression were at significantly greater risk of aggressive progression after surgery (P = 0.005) in univariate but not in multivariate analysis. CONCLUSIONS: Expression of syndecan-1 was associated with established features of biologically aggressive prostate cancer and PSA-progression in univariate analysis. These findings suggest a role for syndecan-1 in prostate carcinogenesis and progression.