Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two ...families of isoforms, pro- and anti-angiogenic, only the former of which is upregulated in prostate cancer (PCa). In renal epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is controlled by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed a significant increase in SRPK1 expression both in prostate intra-epithelial neoplasia lesions as well as malignant adenocarcinoma compared with benign prostate tissue. We therefore tested the hypothesis that the selective upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 activity. A switch in the expression of VEGF165 towards the anti-angiogenic splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with decreased microvessel density. No effect was seen as a result of SRPK1-KD on growth, proliferation, migration and invasion capabilities of PC-3 cells in vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when administered intraperitoneally in an orthotopic mouse model of PCa. Our study suggests that modulation of SRPK1 and subsequent inhibition of tumour angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and supports further studies for the use of SRPK1 inhibition as a potential anti-angiogenic therapy in PCa.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim Ketamine is a short-acting dissociative anaesthetic whose hallucinogenic side effects have led to an increase in its illicit use amongst club and party goers. There is a general misconception ...amongst users that it is a safe drug with few long term side effects, however ketamine abuse is associated with severe urinary tract dysfunction. Presenting symptoms include urinary frequency, nocturia, dysuria, haematuria and incontinence. Materials and methods We describe the radiological findings found in a series of 23 patients, all with a history of ketamine abuse, who presented with severe lower urinary tract symptoms (LUTS). Imaging techniques used included ultrasonography (US), intravenous urography (IVU), and computed tomography (CT). These examinations were reviewed to identify common imaging findings. All patients with positive imaging findings had also undergone cystoscopy and bladder wall biopsies, which confirmed the diagnosis. The patients in this series have consented to the use of their data in the ongoing research into ketamine-induced bladder pathology. Results Ultrasound demonstrated small bladder volume and wall thickening. CT revealed marked, generalized bladder wall thickening, mucosal enhancement, and perivesical inflammation. Ureteric wall thickening and enhancement were also observed. In advanced cases ureteric narrowing and strictures were identified using both CT and IVU. Correlation of clinical history, radiological and pathological findings was performed to confirm the diagnosis. Conclusion This case series illustrates the harmful effects of ketamine on the urinary tract and the associated radiological findings. Delayed diagnosis can result in irreversible renal tract damage requiring surgical intervention. It is important that radiologists are aware of this emerging clinical entity as early diagnosis and treatment are essential for successful management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
OBJECTIVE
To report on the first use of a quality‐of‐life (QoL) measure specific for erectile dysfunction (ED), the ‘ED effect on QoL’ (ED‐EQoL), to assess the effect of ED on QoL after radical ...prostatectomy (RP).
PATIENTS AND METHODS
We retrospectively identified 89 patients who had undergone RP at one institution. Each was sent the ED‐EQoL and a second questionnaire asking whether they had been counselled before RP about possible ED afterward.
RESULTS
The response rate was 91% and the median time since RP 92 months; 76% of those who were potent before RP were impotent afterward. The overall results showed that the QoL of 72% of patients was moderately or severely affected. For each question, on average a third of the patients reported that their QoL was affected either ‘quite a lot’ or ‘a great deal’.
CONCLUSIONS
This study shows that ED after RP has a profound effect on QoL; it is therefore important when assessing ED to use an ED‐specific QoL questionnaire such as the ED‐EQoL to measure the psychosocial effect of ED, in addition to using an instrument such as the International Index of Erectile Function to measure the functional aspects of ED.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer were assigned to active monitoring, prostatectomy, or radiotherapy. Although more patients assigned to active ...monitoring had disease progression, overall survival was similar in the three groups.
The management of clinically localized prostate cancer that is detected on the basis of prostate-specific antigen (PSA) levels remains controversial. In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease.
1
The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have . . .
3-D Printed Metal-Pipe Rectangular Waveguides D'Auria, Mario; Otter, William J.; Hazell, Jonathan ...
IEEE transactions on components, packaging, and manufacturing technology (2011),
09/2015, Volume:
5, Issue:
9
Journal Article
Peer reviewed
Open access
This paper first reviews manufacturing technologies for realizing air-filled metal-pipe rectangular waveguides (MPRWGs) and 3-D printing for microwave and millimeter-wave applications. Then, 3-D ...printed MPRWGs are investigated in detail. Two very different 3-D printing technologies have been considered: low-cost lower-resolution fused deposition modeling for microwave applications and higher-cost high-resolution stereolithography for millimeter-wave applications. Measurements against traceable standards in MPRWGs were performed by the U.K.'s National Physical Laboratory. It was found that the performance of the 3-D printed MPRWGs were comparable with those of standard waveguides. For example, across X-band (8-12 GHz), the dissipative attenuation ranges between 0.2 and 0.6 dB/m, with a worst case return loss of 32 dB; at W-band (75-110 GHz), the dissipative attenuation was 11 dB/m at the band edges, with a worst case return loss of 19 dB. Finally, a high-performance W-band sixth-order inductive iris bandpass filter, having a center frequency of 107.2 GHz and a 6.8-GHz bandwidth, was demonstrated. The measured insertion loss of the complete structure (filter, feed sections, and flanges) was only 0.95 dB at center frequency, giving an unloaded quality factor of 152 - clearly demonstrating the potential of this low-cost manufacturing technology, offering the advantages of lightweight rapid prototyping/manufacturing and relatively very low cost when compared with traditional (micro)machining.
Intravesical bacille Calmette-Guérin (BCG) has been used by urologists for several years after its first reported use as a cancer therapy in the 1930s. Morales in 1976 described the usage of BCG as a ...once weekly intravesical instillation for six weeks; this is a treatment regimen that still exists today. Its success as a treatment depends on it being used appropriately. It is employed: (1) to treat carcinoma in situ or occasionally residual papillary tumours; (2) to reduce the number and frequency of recurrent high grade superficial tumours; and (3) to prevent disease progression (although this remains a controversial point, on which there is no consensus view). Unfortunately, the more widespread use of BCG is often limited due its high side effect profile. Present research is directed towards reducing its side effect profile, improving its efficacy, and understanding its exact mechanism of action, which is not fully understood.
To assess the lymph node content of anterior prostatic fat (APF) sent routinely at robot-assisted laparoscopic radical prostatectomy (RALP) and the incidence of positive nodes in the extended pelvic ...lymph node dissection.
Between September 2008 and April 2012, APF excised from 282 patients who underwent RALP was sent for pathological analysis. This tissue was completely embedded and lymph nodes counted.
In total, 49/282 (17%) patients had lymph nodes in the APF, median lymph node yield in this tissue was 1 (range 1–5). In four patients, the lymph nodes contained metastatic deposits. These patients did not have positive nodes elsewhere in the extended lymph node dissection.
APF contains lymph nodes in 1 in 6 patients and infrequently these may be malignant. APF should always be removed at radical prostatectomy. APF should be routinely sent for pathological analysis.
Renal oncocytomas are classified as benign renal neoplasms in the 2004 World Health Organization classification of renal tumours. 1 Cases of metastatic tumours have been documented, 2- 4 but ...subsequent reports have identified subtypes of renal tumours having similar histological morphology but having malignant potential. Professor Susani performed immunohistochemical analysis for the novel marker kidney-specific cadherin (Ksp cadherin), and both the renal tumour and the metastasis showed <10% marking, which is consistent with a renal oncocytoma. 5 Electron microscopy on the renal tumour showed cells containing large numbers of mitochondria (fig 2), a finding characteristic of oncocytomas. Another marker studied is c-kit, which encodes the membrane-bound tyrosine kinase KIT, and in a recent study was found to be expressed by both chromophobe and oncytomas, but was not detected in most other subtypes. 7 Pan et al 8 studied a variety of markers and found EMA to be expressed similarly by oncocytomas and chromophobe carcinomas, and BerEP4 to be negative in all but one renal oncocytoma while positive in all but two chromophobe carcinomas.
Background
Osseointegration, an approach for direct skeletal attachment of a prosthesis to an amputated limb, may address many of the problems associated with socket prostheses. The safety of ...osseointegration remains uncertain. The aim of this study was to summarize evidence on functional and clinical outcomes, as well as adverse effects of osseointegration for patients with a limb amputation.
Methods
MEDLINE, Embase, Web of Science and the Cochrane Library were searched to April 2018. Eligible studies were observational, case and qualitative studies, and RCTs conducted in patients with a limb amputation, who were managed with osseointegrated prostheses and had follow‐up data.
Results
Twenty‐two eligible articles comprising 13 unique studies were included. No RCT was identified. Apart from three case reports that comprised one to five patients, the sample size of studies ranged from 11 to 100 participants. All relevant studies reported improvement in functional outcomes (walking ability, prosthetic use and mobility), satisfaction and quality of life following osseointegration, compared with their preoperative status or when using a conventional socket prosthesis. Infection rates ranged from 1 (95 per cent c.i. 0 to 5) to 77 (59 to 88) per cent. The majority of infections were described as low‐grade soft tissue or superficial infections related to the skin–implant interface, and were treated effectively with antibiotics. None of the studies reported additional amputation or death as a result of osseointegration.
Conclusion
Osseointegration after limb amputation improves prosthetic use, comfort when sitting, walking ability, mobility, gait and quality of life. However, it is associated with an increased risk of soft tissue infection.
Technology with potential
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select ...patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse.
A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors.
Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were blc-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively).
Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.
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