bluuebunny/crossref_metadata_2025 huggingface dataset:
FMRFamide regulates oscillatory activity of the olfactory center in the slug
Authors: Kobayashi Suguru , Hattori Mariko , Elekes Károly , Ito Etsuro , Matsuo Ryota
Published: August 2010

In the olfactory center of terrestrial animals, changes in the oscillatory frequency of the local field potential (LFP) are thought to be involved in olfaction‐based behavior and olfactory memory. The terrestrial slug Limax has a highly developed olfactory center, the procerebrum, in which the LFP spontaneously oscillates. Although changes in the oscillatory frequency are thought to correspond to the preference for specific odors, our knowledge about the mechanism of this frequency regulation is limited. To clarify the mechanism of the bidirectional frequency changes in the procerebrum, we focused on the neuropeptide Phe‐Met‐Arg‐Phe‐NH2 (FMRFamide), which is known to have neuromodulatory functions in invertebrate nervous systems. Application of FMRFamide decreased the oscillatory frequency via G‐protein‐mediated cascades. Immunohistochemistry showed that FMRFamide‐like‐immunoreactive neuronal cell bodies are located in the cell mass layer of the procerebrum, projecting their neurites to the neuropile layers. The procerebrum was shown to also receive innervation from other regions of the cerebral ganglion. Furthermore, according to their morphological and projection characteristics, FMRFamide‐containing neurons belong to the subpopulations of both bursting and nonbursting neurons in the procerebrum. The mRNA splice variant encoding multiple copies of canonical FMRFamide was specifically expressed in the procerebrum. Taking into account previous results showing that serotonin increases the oscillatory frequency, our results indicate that FMRFamide and serotonin both regulate the LFP frequency but in exactly the opposite direction in the olfactory center of the terrestrial slug.
Oral bioavailability of clonidine in children
Authors: Larsson Peter , Nordlinder Anders , Bergendahl Henrik T.G. , Lönnqvist Per‐Arne , Eksborg Staffan , Almenrader Nicole , Anderson Brian J.
Published: August 2010

Background: Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75–100% but is unknown in children.

Methods: Children (3–10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg−1mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography‐mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed‐effects models. Current data were pooled with published time–concentration profiles from children (n = 49) administered intravenous clonidine to determine oral bioavailability.

Results: There were eight children studied (age 3–10 years, weight 10.5–36 kg). A two‐compartment model with first‐order absorption and elimination was used to describe time–concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70‐kg person, were absorption half‐life (Tabs), 0.45 (85.1; 0.221–0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002–0.316) h, Clearance (CL) 17.9 (30.3; 16–20.3) l·h−1per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1–165) l·h−1per 70 kg, central volume (V1) 81.2 (71.5; 60.7–105) l·70 kg−1, peripheral volume of distribution (V2) 113 (33.9; 91–131) l·70 kg−1. The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654).

Conclusions: Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration (Tmax1.04 h,Cmax0.77 mcg·l−1). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults.
Metacommunity phylogenetics: separating the roles of environmental filters and historical biogeography
Authors: Leibold Mathew A. , Economo Evan P. , Peres‐Neto Pedro
Published: August 2010

Ecology Letters(2010)

Biogeographical, evolutionary and ecological processes interact to regulate patterns in metacommunities. However, as there are few quantitative methods for evaluating their joint effects, resolving this interaction is difficult. We develop a method that aims to evaluate the interaction between phylogenetic structure, historical biogeographic events and environmental filtering in driving species distributions in a large‐scale metacommunity. Using freshwater zooplankton as a case study, we contrast the phylogenetic metacommunity structure of calanoid copepods and an ecologically similar but more vagile group, daphniids, in the northeastern US. We find that legacies of historical biogeographical events have strongly constrained calanoid distributions within this area, but that adaptation to different water chemistry and lake morphology drives the metacommunity structure of daphniids. Our findings show that biogeographic history and metacommunity processes jointly regulate community structure in these lakes and suggest that this also depends on factors that affect the colonization rate of different types of organisms.
Positive diversity–stability relationships in forest herb populations during four decades of community assembly
Authors: Dovčiak Martin , Halpern Charles B.
Published: August 2010

Ecology Letters (2010)

It is suggested that diversity destabilizes individual populations within communities; however, generalizations are problematic because effects of diversity can be confounded by variation attributable to community type, life history or successional stage. We examined these complexities using a 40‐year record of reassembly in forest herb communities in two clearcut watersheds in the Andrews Long‐term Ecological Research Site (Oregon, USA). Population stability was higher among forest than colonizing species and increased with successional stage. Thus, life history and successional stage may explain some of the variability in diversity–stability relationships found previously. However, population stability was positively related to diversity and this relationship held for different forest communities, for species with contrasting life histories, and for different successional stages. Positive relationships between diversity and population stability can arise if diversity has facilitative effects, or if stability is a precursor, rather than a response, to diversity.
Signatures of range expansion and erosion in eastern North American trees
Authors: Murphy Helen T. , VanDerWal Jeremy , Lovett‐Doust Jon
Published: August 2010

Ecology Letters (2010)

Abundance and occupancy of populations at high‐ and low‐latitude geographic range edges will be critically important in determining a species’ response to climate change. Low abundance and occupancy at expanding (high latitude) edges of the range may limit a species capacity to migrate, and at trailing (low latitude) edges, may result in range erosion and regional extinction. We examined abundance–occupancy distributions across the geographic ranges of 102 eastern North American trees and looked for signatures reflecting capacity to respond to climate change. We found that 62% of species display a signature consistent with higher climatic suitability in the northern latitudes of their range. However, our results suggest that the most common response is likely to involve range erosion in the south and limited range expansion in the north, possibly leading to an overall reduction in range size for many species. In particular, species with smaller ranges centred at lower latitudes may not have the capacity to successfully track the current rate of climate change.
Dimethoate, fenvalerate and their mixture affects Hylyphantes graminicola (Araneae: Linyphiidae) adults and their unexposed offspring
Authors: Peng Yu , Shao Xiao‐li , Hose Grant C. , Liu Feng‐xiang , Chen Jian
Published: August 2010

Mixtures of organophosphorus and pyrethroid insecticides are widely used to combat resistance in agricultural pests, although few studies have been conducted on the effects of pesticide mixtures on beneficial nontarget organisms.

In the present study, we exposed adult females (F0) of Hylyphantes graminicola (Araneae: Linyphiidae) to fenvalerate, dimethoate and their commercially available 1 : 1 mixture (by mass). We investigated the acute toxicity of these pesticides to the exposed adults, as well as sublethal effects on reproduction and acetylcholinesterase and carboxylesterase activity. We also studied the effects of parental exposure on the size, development and enzyme activity of unexposed offspring.

All three formulations were acutely toxic to H. graminicola, with synergism between dimethoate and fenvalerate leading to greater toxicity in the 1 : 1 mixture than for the two insecticides alone. The sublethal effects of direct pesticide exposure were a reduction in acetylcholinesterase and carboxylesterase activity and a reduction in the number of egg sacs produced by exposed spiders relative to the control spiders. The unexposed offspring of the fenvalerate and mixture exposed spiders were smaller and took longer to mature than the control spiders. Offspring of all exposed spiders also had significantly reduced carboxylesterase activity relative to control spiders.

We concluded that the effects of parental exposure on the offspring were likely to increase their susceptibility to future pesticide exposures, and reduce the capacity of this spider to serve as a pest control agent.
Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes
Authors: Rose F. J. , Webster J. , Barry J. B. , Phillips L. K. , Richards A. A. , Whitehead J. P.
Published: August 2010

Aim: To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action.

Methods: We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα.

Results: AA supplementation significantly increased secretion of HMW adiponectin (1.7‐fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3‐fold) and secretion of total (1.4‐fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3‐fold) and secretion of total (1.8‐fold) and HMW (5‐fold) adiponectin. Similar results were seen in cells co‐treated with TNFα.

Conclusions: These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.
Beyond ONTARGET: angiotensin‐converting enzyme inhibition and angiotensin II receptor blockade in combination, a lesser evil in some?
Authors: Wong J. , Molyneaux L. , Constantino M. , Twigg S. M. , Yue D. K.
Published: August 2010

Aim: Following the recent Ongoing Telmistartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) finding of adverse renal outcomes, dual renin‐angiotensin blockade has fallen out of favour, despite antihypertensive and antiproteinuric efficacy. However, in high‐risk severe hypertension, not studied in ONTARGET, whether combination treatment should be withheld or withdrawn is not clear. We examine the renal effects of angiotensin‐converting enzyme inhibitor (ACE‐I) and angiotensin II receptor blocker (ARB) monotherapy versus combination therapy in patients with type 2 diabetes and varying degrees of hypertension.

Methods: Subjects attending a hospital diabetes centre were selected as case (combination therapy, n = 120) and control (monotherapy, n = 480). Subjects were matched for age, gender, ethnicity, estimated glomerular filtration rate (eGFR), blood pressure (BP) and study duration. Patients were stratified by BP, hypertension stage 1 (BP < 160/100, n = 506) and stage 2 (≥160/100, n = 94), and by treatment group. Data were analysed for the primary renal outcome of eGFR decline ≥20 ml/min, over a median of 3.7 years.

Results: In keeping with the ONTARGET study, for stage 1 hypertension, combination treatment is significantly worse than monotherapy for the primary outcome of eGFR decline ≥20 ml/min (20 vs. 10.7%, p = 0.01). In contrast, for stage 2 hypertension, this endpoint was reached less often for combination versus monotherapy (12.0 vs. 23.2%, p = 0.2). Combination treatment was also not detrimental in patients with proteinuria or eGFR < 60 ml/min and was associated with fewer macrovascular events.

Conclusion: Given that hypertension control is paramount and in the spirit of primum non nocere, these data are reassuring should clinicians choose to use ACE‐I and ARB combination therapy in the very hypertensive diabetic patient.
Late relapse (>2 years) on surveillance in stage I non‐seminomatous germ cell tumours; predominant seminoma only histology
Authors: Nolan Luke , Wheater Matthew , Kirby Julie , Simmonds Peter , Mead Graham
Published: August 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVES

Surveillance is a standard management approach following orchidectomy for stage I non‐seminomatous and mixed germ cell tumours. Patients who relapse following this approach are treated with cisplatin‐based chemotherapy, with retroperitoneal lymph node dissection considered for patients with post‐chemotherapy residual masses.

PATIENTS AND METHODS

We reviewed the clinicopathological data for all patients who relapse greater than 24 months after commencing our surveillance programme.

RESULTS

Between 1989 and 2008, 453 patients with a median age of 30 years were entered into our surveillance program for stage I non‐seminomatous germ cell tumours (NSGCTs) after orchidectomy alone. All primary tumour specimens contained NSGCT, with seminomatous elements identified in 168 cases (37%). One‐hundred patients (22%) relapsed and the majority of relapses occurred within the first 2 years (76 ≤ 12 months, 15 ≥ 12 months ≤ 2 years). Nine patients relapsed after more than 2 years of surveillance. We found a high incidence of pure seminoma (56%) at sites of metastatic disease in this group. All late‐relapsing patients were alive and disease free at a median follow up of 45 months from relapse.

CONCLUSIONS

We recommend that late‐relapsing patients with normal serum alpha fetoprotein levels undergo biopsy to define histologically the nature of recurrent disease. In those with pure seminoma retroperitoneal lymph node dissection for post chemotherapy residual masses can be avoided.
Epstein–Barr virus DNA load in tumour tissues correlates with poor differentiation status in non‐muscle invasive urothelial carcinomas
Authors: Chuang Kun‐Lung , Pang See‐Tong , Liao Shuen‐Kuei , Wu Chun Te , Chang Ying Hsu , Chuang Heng‐Chang , Chuang Cheng‐Keng
Published: August 2010

What’s known on the subject? and What does the study add?

Epstein‐Barr virus (EBV) could be detected in bladder cancer. In our paper, we showed that DNA of EBV could be detected more in the high grade urothelial carcinoma. In superficial bladder cancer, although high grade tumour associated with higher EBV titers, the recurrence free survival was not compromised by high EBV DNA load.

OBJECTIVE

To detect the correlation between the clinical staging, grading and genomic Epstein–Barr virus (EBV) viral numbers in tumour tissues of urothelial carcinoma patients.

PATIENTS AND METHODS

From June 2004 to May 2008, 60 urothelial carcinoma patients (50 cases of bladder carcinoma and 10 of upper tract urothelial carcinoma (UTUC) were enrolled in the study. Eight patients who underwent transurethral resection of prostate for prostate hyperplasia and two patients receiving nephrectomy for non‐function kidney were used as normal controls. The EBV viral copy numbers in genomic DNA were evaluated using a real‐time PCR‐based study. The BamHI W region of the Namalwa cell line was constructed to the plasmid clone and was used as standard curve for absolute quantitative PCR (Q‐PCR).

RESULTS

Epstein–Barr virus DNA was detected in 56% (28/50) and 60% (6/10) of the bladder and UTUC patients, respectively. The EBV DNA could not be detected in the normal control group. By pooling the UTUC and bladder patients in stage Ta,T1, the high copy number in fixed genomic DNA amount (100 ng/20 µL) was correlated with the high grading in stage Ta,T1 urothelial carcinoma (P= 0.014). The overall grading was not statistically associated with EBV copy number (P= 0.25). Although the copy numbers between paired tumour and normal tissues were not statistically different (P= 0.169), there were more copies of EBV in the normal tissues adjacent to the tumours than in those free from urothelial carcinoma. There was no significant difference between recurrence of non‐muscle invasive bladder cancer and the presence of EBV (P > 0.05).

CONCLUSIONS

Epstein–Barr virus DNA could be detected in the genome of the urothelial carcinoma specimens. The poor differentiation status was correlated with the high load of the EBV genome in non‐muscle invasive urothelial carcinoma. However, recurrence‐free survival was not greater in EBV‐positive patients than in EBV‐negative patients.
Novel ZEB1 expression in bladder tumorigenesis
Authors: Kenney Patrick A. , Wszolek Matthew F. , Rieger‐Christ Kimberly M. , Neto Brasil Silva , Gould Justin J. , Harty Niall J. , Mosquera Juan Miguel , Zeheb Ron , Loda Massimo , Darling Douglas S. , Libertino John A. , Summerhayes Ian C.
Published: August 2010

What’s known on the subject? and What does the study add?

Epithelial‐mesenchymal transition (EMT) is involved in tumor progression where the underlying cellular changes associated with EMT have been identified in in vitro models and confirmed in a limited number of in vivo studies. ZEB1, which targets E‐cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers. Regulation of ZEB1 expression has been shown to involve different microRNAs (miRNAs), identifying a potential role for miRNA in EMT.

In the present study we have identified novel expression of ZEB1 in bladder tumours and shown a role for ZEB1 in enhanced migration and invasion potential in in vitro assays. Confirmation of ZEB1 expression in bladder tumours was shown in tissue microarrays (TMAs).

OBJECTIVE

To evaluate ZEB1 expression in bladder tumorigenesis and define a possible role for this transcription factor in urothelial carcinomas of the bladder (UCBs).

MATERIALS and METHODS

Five hundred and fifty‐eight samples were assembled in 10 tissue microarrays (TMAs; 263 non‐muscle‐invasive Ta/T1/Tis, 295 muscle‐invasive T2–T4). All tumours were transitional cell carcinomas (TCCs) and processed for immunohistochemistry to assess nuclear ZEB1 expression. Expression levels of ZEB1 were modulated in bladder carcinoma cell lines CUBIII or UM‐UC‐3 after forced expression or shRNA knockdown, respectively. Protein expression levels were determined using western blot analysis and transfectants were assessed for migration and invasion potential in standard in vitro assays.

RESULTS

Nuclear ZEB1 expression was recorded in 22.8% of non‐muscle‐invasive UCBs and 21.7% of muscle‐invasive UCBs, including 24.1% grade I/II and 21.1% grade III tumours, and absent in normal bladder mucosa. No significant correlation was observed for tumour stage and grade, nodal involvement, vascular invasion, metastasis and overall or cancer‐specific survival. The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively. Changes in ZEB1 expression were accompanied by altered microRNA (miRNA) expression underlying events linked to epithelial–mesenchymal transition (EMT).

CONCLUSION

The results in the present study showed novel expression of ZEB1 in bladder cancer in the absence of a link to clinical variables of change, including metastasis and survival. However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines. Modulation in expression of ZEB1 was closely linked to changes in the miR‐200 family along with alternative known prognostic indicators of bladder tumour progression.
Update on the management of T1 renal cortical tumours
Authors: Cutress Mark L. , Ratan Hari L. , Williams Simon T. , O’Brien M. Frank
Published: August 2010

There are a range of treatment strategies for the management of patients with small incidental renal cortical tumours including active surveillance, radiofrequency ablation, cryotherapy, radical nephrectomy and partial nephrectomy. A large number of such tumours are benign and might therefore be over‐treated with radical nephrectomy. There are emergent short‐term oncological and clinical outcomes for cryotherapy and radiofrequency ablation, and recent studies have illustrated the benefits of partial nephrectomy for minimizing the risk of progression to chronic kidney disease. The outcomes of these different treatment methods are discussed.
Clinical significance of runt‐related transcription factor 1 polymorphism in prostate cancer
Authors: Huang Shu‐Pin , Lan Yu‐Hsuan , Lu Te‐Ling , Pao Jiunn‐Bey , Chang Ta‐Yuan , Lee Hong‐Zin , Yang Wen‐Hui , Hsieh Chi‐Jeng , Chen Lu‐Min , Huang Li‐Chia , Ting Wen‐Chien , Bao Bo‐Ying
Published: August 2010

What’s known on the subject? and What does the study add?

Although most clinically localized prostate cancer patients who underwent radical prostatectomy have a favorable outcome, molecular markers capable of providing prognostic information are still urgently needed to identify high‐risk patients who might benefit from aggressive treatment. In this study, we found that RUNX1 rs2253319 polymorphism was significantly associated with higher risks of advanced pathological stage, lymph node metastasis, and time to disease recurrence. Our results suggest that a simple and pretreatment analysis of genetic variants might add prognostic value to the currently used indicators for outcome prediction in patients receiving radical prostatectomy.

OBJECTIVE

To investigate the association of RUNX1 rs2253319 with clinicopathological characteristics of prostate cancer (PCa) and disease recurrence after radical prostatectomy (RP).

PATIENTS AND METHODS

Taking advantage of the systematic stage and grade for each tumor in a cohort of 314 patients with localized PCa receiving RP, we evaluated the associations of RUNX1 rs2253319 with age at diagnosis, preoperative prostate‐specific antigen (PSA) level, Gleason score, surgical margin, pathologic stage, status of lymph node metastasis, and PSA recurrence after RP.

RESULTS

The minor allele, T, and the minor homozygote TT genotype of RUNX1 rs2253319 were significantly associated with a 1.49‐ to 2.76‐fold higher risk for advanced pathologic stage and a 3.35‐ to 9.52‐fold higher risk for lymph node metastasis. RUNX1 rs2253319 TT genotype was also associated with poorer PSA‐free survival compared with the major homozygote CC genotype in Kaplan–Meier analysis (log‐rank test, P= 0.038) and multivariate Cox proportional hazards model adjusting for age and PSA concentration (P= 0.045).

CONCLUSION

RUNX1 rs2253319 is associated with adverse clinicopathological features and might be a prognostic factor for the recurrence of PSA in patients with PCa receiving RP.
Findings of fat‐suppressed T2‐weighted and diffusion‐weighted magnetic resonance imaging in the diagnosis of non‐palpable testes
Authors: Kato Toshiki , Kojima Yoshiyuki , Kamisawa Hideyuki , Takeuchi Mitsuru , Mizuno Kentaro , Sasaki Shigeru , Kohri Kenjiro , Hayashi Yutaro
Published: August 2010

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b

What’s known on the subject? and What does the study add?

Both conventional magnetic resonance imaging (MRI) and ultrasonography (US) have been used for children with non‐palpable testes to facilitate a preoperative diagnosis, but the accuracy of these examinations was not satisfactory. In the present study, to improve the diagnostic accuracy of non‐palpable testes by MRI examination, we employed fat‐suppressed T2‐weighted imaging and DWI, as well as conventional MRI. Additional MRI assessments are useful methods to improve the accuracy of diagnosing non‐palpable testes.

OBJECTIVE

To evaluate the magnetic resonance imaging (MRI) findings, diagnostic accuracy and clinical usefulness of fat‐suppressed T2‐weighted and diffusion‐weighted imaging (DWI) in the management of non‐palpable testes.

PATIENTS AND METHODS

In all, 56 children (63 non‐palpable testes) aged 8 months–11 years (mean 24.7 months) with non‐palpable testes were enrolled.

T1‐ and T2‐weighted imaging, as well as fat‐suppressed T2‐weighted imaging and DWI were performed during MRI examination, and the imaging results were compared with surgical findings.

RESULTS

In the 63 non‐palpable testes, MRI identified 22% (14/63) as intra‐abdominal, 20% (13/63) as intra‐canalicular, 29% (18/63) as testicular nubbins, and 29% (18/63) as unidentifiable. Although it was difficult to confirm their presence in the abdominal cavity using T1‐ and T2‐weighted imaging alone, additional assessment, including fat‐suppressed T2‐weighted imaging and DWI facilitated the detection of intra‐abdominal testes more easily because they were imaged at a markedly higher signal intensity. The sensitivity, specificity and positive and negative predictive values for the MRI vs the operative findings were 100, 97.3, 96.3, and 100%, respectively. The overall prediction accuracy was 98.4%.

CONCLUSION

Additional MRI assessments, fat‐suppressed T2‐weighted imaging and DWI are useful examinations to improve the preoperative diagnostic accuracy of non‐palpable testes.
Trends in the treatment of localized prostate cancer using supplemented cancer registry data
Authors: Hamilton Ann S. , Albertsen Peter C. , Johnson Terri Kang , Hoffman Richard , Morrell Donna , Deapen Dennis , Penson David F.
Published: August 2010

Study Type – Therapy (cohort) Level of Evidence 2b

What’s known on the subject? and What does the study add?

Variation in treatment of localized prostate cancer has been shown to exist according to demographic and clinical factors, patient and provider preference, and region of residence since there is no consensus concerning appropriate treatment.

Between 1998 and 2002 the proportion of men choosing watchful waiting declined from 12.6% to 9.0% while those receiving brachytherapy (with or without external beam radiation therapy) increased from 14.9% to 17.7%. Based on Gleason score, PSA, and age at diagnosis, younger African‐American men may be receiving less aggressive therapy than indicated, while older men with low risk tumours may be receiving more aggressive therapy than necessary.

OBJECTIVE

To conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002.

PATIENTS AND METHODS

Results from the National Cancer Institute’s Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods.

RESULTS

Patients with localized prostate cancer in 2002 were younger, had lower prostate‐specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age‐adjusted percentages of men who were treated with a radical prostatectomy (45–46%) or by external beam radiation (EBRT) alone (19–20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African‐American men with intermediate/high‐risk disease were less likely to receive any type of aggressive therapy in comparison with Non‐Hispanic White men. Over 70% of men who were ≥75 years of age, with low‐risk disease, were treated with EBRT or BT.

CONCLUSIONS

Older men with low‐risk disease might be overtreated with aggressive therapy, while younger intermediate/high‐risk African‐American men appear less likely to receive indicated aggressive therapy.
Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high‐risk men: effect of TMPRSS2 Met160Val
Authors: Giri Veda N. , Ruth Karen , Hughes Lucinda , Uzzo Robert G. , Chen David Y.T. , Boorjian Stephen A. , Viterbo Rosalia , Rebbeck Timothy R.
Published: August 2010

What’s known on the subject? and What does the study add?

The TMPRSS2‐ERG fusion is a common gene fusion event in prostate tumours. Germline genetic variants that predict fusion in the tumour are under study.

This study evaluates one germline genetic variant regarding predicting time to prostate cancer diagnosis among high‐risk men undergoing screening for prostate cancer. A specific genotype is associated with earlier time to prostate cancer diagnosis among Caucasian men with a family history of prostate cancer. The results suggest that such variants may be useful after further study in stratifying high‐risk men for individualized early detection approaches.

INTRODUCTION

To evaluate the TMPRSS2‐ERG gene polymorphism with respect to self‐identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high‐risk men.

PATIENTS AND METHODS

A total of 631 men aged between 35 and 69 years were studied. ‘High‐risk’ was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations.

Men with elevated prostate‐specific antigen (PSA) concentrations or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis.

Cox models were used to evaluate time to PCA diagnosis by genotype.

RESULTS

Genotype distribution differed significantly by SIRE (CT/TT vs CC, P < 0.0001). Among 183 Caucasian men with at least one follow‐up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (hazard ratio = 2.55, 95% CI = 1.14–5.70) after controlling for age and PSA.

No association was seen among AA men by TMPRSS2 genotype.

CONCLUSIONS

The T‐allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2–ERG fusion, may be informative of time to PCA diagnosis for a subset of high‐risk Caucasian men who are undergoing regular PCA screening.

This variant, along with other genetic markers, warrant further study for personalizing PCA screening.
Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate‐induced changes in rat urinary bladder
Authors: Çetinel Şule , Çanıllıoğlu Yasemin Ersoy , Çikler Esra , Şener Göksel , Ercan Feriha
Published: August 2010

What's known on the subject? and What does the study add?

The mastocytosis in detrusor muscle and the leaky epithelium in interstitial cystitis were the most studied features. In this study the leaky epithelium was shown using the ruthenium red staining in electron microscopy and uroplakin distribution in light microscopy besides the mast cell concentration in detrusor muscle using tryptase immunohistochemistry.

OBJECTIVE

To study the effects of montelukast (ML), a leukotriene receptor antagonist which has been shown to be effective in inhibiting the action of cysteinyl‐containing leukotrienes, on protamine sulphate (PS)‐induced changes in rat urinary bladder.

MATERIALS AND METHODS

Wistar female rats were catheterized and intravesically infused with PBS (control group) or PS (PS group) dissolved in PBS twice in 24 h.

In the PS‐applied and ML‐treated group (PS + ML group) after the 10 mg/kg PS instillation, ML was injected i.p. twice daily for 3 days.

The urinary bladder was investigated for general morphology under a light microscope.

Tryptase immunohistochemistry was used to observe mast cell distribution and activation. Uroplakin distribution was also identified with immunohistochemistry.

RESULTS

Alterations of glycosaminoglycan (GAG) and urothelial permeability were seen with ruthenium red (RR) staining techniques under a transmission electron microscope, and topographical changes of luminal urothelial structure were seen with a scanning electron microscope.

Biochemically malondialdehyde (MDA) and gluthatione (GSH) concentrations were analysed. In the PS group, there was degenerated urothelium with irregular uroplakin distribution, increased inflammatory cell infiltration, increased number of both granulated and activated mast cells, irregularity of GAG and penetration of RR into the intercellular spaces and dilated tight junctions.

In PS + ML group, there was relatively regular uroplakin distribution, a decrease in inflammatory cell infiltration, a decreased number of both activated and granulated mast cells in the mucosa, regular GAG and no penetration of RR into the intercellular areas, and regular tight junctions in most regions.

The significant decrease in MDA and the increased GSH concentrations in the PS + ML group was in accordance with the histological findings.

CONCLUSION

Montelukast appears to have a protective function in the bladder injury model via the anti‐inflammatory effects of this leukotriene receptor antagonist.
Expression of integrin proteins in non‐muscle‐invasive bladder cancer: significance of intravesical recurrence after transurethral resection
Authors: Behnsawy Hosny M. , Miyake Hideaki , Abdalla Medhat A. , Sayed Mohamed A. , Ahmed Abd El‐Fattah I. , Fujisawa Masato
Published: August 2010

Study Type – Aetiology (case control) Level of Evidence 3b

What’s known on the subject? and What does the study add?

A number of studies have reported several clinicopathological factors closely associated with intravesical recurrence of non‐muscle invasive bladder cancer (NMIBC). In addition, various types of molecular markers have been shown to be useful for predicting intravesical recurrence of NMIBC following transurethral resection (TUR).

Of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, the expression level of the β4 subunit in NMIBC, in addition to pathological T stage and concomitant carcinoma in situ appeared to be independently related to intravesical recurrence. Therefore, consideration of the expression levels of integrins, particularly that of the β4 subunit, in TUR specimens would contribute to further accurate prediction of intravesical recurrence of NMIBC.

OBJECTIVES

To evaluate the expression of integrin proteins, a family of transmembrane heterodimers, in non‐muscle‐invasive bladder cancer (NMIBC).

To assess the significance of these proteins as prognostic indicators in patients undergoing transurethral resection (TUR).

PATIENTS AND METHODS

The present study comprised 161 patients diagnosed as having NMIBC after TUR.

Expression levels of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, were measured in TUR specimens by immunohistochemical staining.

RESULTS

Of the six proteins, expression levels of α2‐, α3‐, α6‐ and β4‐subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of α3‐, α6‐ and β4‐subunits as important predictors of intravesical recurrence, while tumour size, pathological T stage and concomitant carcinoma in situ (CIS) were also important.

Multivariate analysis showed that the expression level of the β4 subunit, pathological T stage and concomitant CIS are independently related to intravesical recurrence.

There were significant differences in intravesical recurrence‐free survival for patients who were positive for the three independent risk factors; intravesical recurrence occurred in 10 of 49 (20.4%) patients who were negative for all risk factors, 31 of 68 who were positive for one risk factor (45.6%), and 30 of 44 who were positive for two or three risk factors (68.2%).

CONCLUSIONS

Consideration of the expression levels of integrins, particularly those of the β4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients.
Frequency of regulatory T cells in peripheral blood and in tumour‐infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma
Authors: Liotta Francesco , Gacci Mauro , Frosali Francesca , Querci Valentina , Vittori Gianni , Lapini Alberto , Santarlasci Veronica , Serni Sergio , Cosmi Lorenzo , Maggi Laura , Angeli Roberta , Mazzinghi Benedetta , Romagnani Paola , Maggi Enrico , Carini Marco , Romagnani Sergio , Annunziato Francesco
Published: August 2010

What’s known on the subject? and What does the study add?

Treg overexpression has been demonstrated in several neoplasms, including liver, breast, pancreas and melanoma, while it has not been well evaluated in renal cancer.

In renal cancer patients versus controls we found an increased expression of these cells, especially in tumour‐infiltrating lymphocytes. Moreover, Treg frequency significantly correlated with pathological stage, nuclear grade and prognostic models.

OBJECTIVE

To compare the frequency of T regulatory cells (Tregs) in peripheral blood of patients (pPB) affected by renal cell carcinoma (RCC) both with the frequency of Tregs found in PB of healthy donors (hPB) and that of Tregs present in tumour infiltrating lymphocytes (TILs). To verify in vitro the inhibitory activity of tumour isolated Tregs on the effector T cells and, finally, to assess the prognostic role of Treg frequency determination.

PATIENTS AND METHODS

Treg frequency in hPB, pPB and TILs was evaluated in 30 patients and 20 healthy controls by measuring both membrane‐CD25 and intracytoplasmic‐Foxp3 expression by flow cytometry.

Treg inhibitory activity was evaluated by an in vitro proliferation assay performed on total, CD25‐depleted mononuclear cells (MNC) and CD25‐depleted MNC cultured in the presence of purified CD25+ Tregs.

Finally, Treg frequency in pPB and TIL were correlated with conventional prognostic factors and scores of University of California Los Angeles and Kattan predictive models.

RESULTS

Treg frequency was higher in TILs than in pPB (P= 0.002), whereas there were no important differences between hPB and pPB. CD25+ cells isolated either from PB and tumours showed the ability to significantly suppress in vitro both proliferation and interferon‐γ production by CD25‐depleted MNC, thus demonstrating that they are active Tregs.

Treg frequency was found to significantly correlate both with pathological stage (pPB, P= 0.03; TIL, P= 0.04) and nuclear grade (TIL, P= 0.005), both for UCLA and Kattan models (all: P < 0.05 for both pPB and TIL).

CONCLUSION

Treg frequency is significantly higher in TIL than in pPB of patients with RCC. Tregs showed in vitro an inhibitory activity on effector T cells isolated from kidney tumours. The increase in both peripheral and intratumoral Tregs in subjects affected with RCC were associated with worse prognosis.
Detection of circulating tumour cells in peripheral blood of patients with advanced non‐metastatic bladder cancer
Authors: Rink Michael , Chun Felix K.H. , Minner Sarah , Friedrich Martin , Mauermann Oliver , Heinzer Hans , Huland Hartwig , Fisch Margit , Pantel Klaus , Riethdorf Sabine
Published: August 2010

What’s known on the subject? and What does the study add?

Circulating tumour cells (CTC) have prognostic relevance for patients with different metastatic carcinomas. Detection of CTC using the CellSearch system has also been reported in bladder cancer, but mainly in patients with metastatic disease.

This is the largest report demonstrating that detection of CTC in non‐metastatic bladder cancer patients is feasible using the CellSearch system. Presence of CTC may be predictive for early systemic disease.

OBJECTIVE

To prospectively detect and evaluate the biological significance of circulating tumour cells (CTC) in patients with bladder cancer, especially in those patients with non‐metastatic, advanced bladder cancer (NMABC).

PATIENTS AND METHODS

Between July 2007 and January 2009, blood samples of 50 consecutive patients with localized bladder cancer and five patients with metastatic disease scheduled for cystectomy were prospectively investigated for CTC. Peripheral blood (7.5 ml) was drawn before cystectomy.

Detection of CTC was performed using the USA Food and Drug Administration‐approved CellSearchTM system. Data were compared with the clinical and histopathological findings.

RESULTS

CTC were detected in 15 of 50 patients (30%) with non‐metastatic disease and five of five patients with metastatic disease. The overall mean number of CTC was 33.7 (range: 1–372; median: 2). In non‐metastatic patients, the mean number of CTC was 3.1 (range: 1–11; median: 1). Except for a univariate association between CTC with vessel infiltration (P= 0.047), all other common clinical and histopathological parameters did not reveal a significant correlation with CTC detection.

A median 1‐year follow up was available for 53 patients (96.4%). Ten out of 19 preoperatively CTC‐positive patients died as a result of cancer progression.

CTC‐positive patients showed significantly worse overall (P= 0.001), progression‐free (P < 0.001) and cancer specific survival (P < 0.001) compared to preoperatively CTC‐negative patients.

CONCLUSION

This is the largest study demonstrating that detection of CTC in NMABC patients is feasible using the CellSearchTM system. Our findings suggest that the presence of CTC may be predictive for early systemic disease.
Long‐term functional and morphological outcome after pyeloplasty for huge renal pelvis
Authors: Sarhan Osama , Helmy Tamer , Abou‐El Ghar Mohamed , Baky Mohamed A. , El‐Assmy Ahmed , Dawaba Mohamed
Published: August 2010

Study Type – Therapy (case series)

Level of Evidence 4

OBJECTIVE

• To evaluate the functional and morphological outcome after open pyeloplasty for ureteropelvic junction obstruction (UPJO) with huge renal pelvis.

PATIENTS AND METHODS

• A retrospective review of all cases who underwent pyeloplasty for huge renal pelvis was conducted.

• Records were evaluated with respect to age at presentation, preoperative imaging, surgical details and postoperative course. Patients were followed up regularly for both functional and morphological outcome.

• Success was defined as both symptomatic relief and radiographic resolution of obstruction at last follow‐up.

RESULTS

• Between 1998 and 2008, 526 cases of primary UPJO underwent open dismembered pyeloplasty at our centre.

• Of these patients, 41 (8%) had UPJO with huge renal pelvis.

• No perioperative complications were encountered in the study group. Mean (range) follow‐up was 34 (18–84) months and nine patients were lost to follow‐up. The overall success rate was 91%.

• Two patients underwent redo pyeloplasty, whereas secondary nephrectomy was necessary in one.

• Improvement of hydronephrosis was evident in all patients, except in three patients who underwent secondary procedures.

• However, persistent obstruction on diuretic renography was seen in most cases (65%).

CONCLUSIONS

• Open pyeloplasty for huge pelvis UPJO is feasible with a high success rate.

• Varying degrees of hydronephrosis and radiological obstruction after pyeloplasty are not uncommon.

• Nephrectomy is rarely indicated in cases with severely deteriorated renal function.
Predictors of health‐related quality of life recovery following laparoscopic simple, radical and donor nephrectomy
Authors: Wiesenthal Joshua D. , Schuler Trevor D. , Honey R. John D’A. , Pace Kenneth T.
Published: August 2010

Study Type – Therapy (case series) Level of Evidence 4

What’s known on the subject? and What does the study add?

Despite laparoscopy becoming the favoured approach for nephrectomy, there is very little research into the predictors of recovery following surgery and return of health‐related quality of life following laparoscopic nephrectomy. The current study demonstrates that patients who are younger, have lower BMI, have more active lifestyles and those who are not donating a kidney recover more quickly following surgery. Older, more obese, less active patients, and those donating a kidney take longer to recover from surgery.

OBJECTIVES

To objectively quantify the recovery of health‐related quality of life (HRQL) in patients undergoing laparoscopic nephrectomy.

To determine which factors are predictive of a more expedited recovery.

MATERIALS AND METHODS

Patient recovery was prospectively measured among patients undergoing laparoscopic simple (n= 12), radical (n= 42) and donor (n= 95) nephrectomy.

All procedures were performed using a 3‐ or 4‐trocar, transperitoneal fully‐laparoscopic technique with intact specimen extraction using impermeable sacs for simple and radical nephrectomy, and hand extraction for donor nephrectomy.

Postoperative recovery and quality of life were measured using the Postoperative Recovery Scale (PRS) administered preoperatively, immediately postoperatively and as an outpatient at 4, 8, 12, and 16 weeks postoperatively.

ANOVA and Pearson’s χ2 tests were performed on demographic data. Multivariate logistic regression analysis was used to calculate odds ratios for factors predictive of recovery.

RESULTS

Statistically significant differences were found at baseline for age (P= 0.02), gender (P < 0.01), body mass index (BMI; P= 0.03), surgical side (P < 0.01) and activity‐based lifestyle (P= 0.04) across the three groups.

Minimal adverse events were seen.

Factors predictive of expedited recovery include age < 50 years (OR: 2.1, P < 0.01), body‐mass index (BMI) < 30 kg/m2 (OR: 1.7, P < 0.01), active lifestyles (OR: 1.3, P < 0.01) and those patients undergoing nephrectomy for benign or malignant indications rather than for organ donation (OR: 1.4, P < 0.01).

There was a significant delay in the donor group vs the non‐donor group with respect to the median number of days both groups took to recover 75% and 90% of their baseline PRS scores (11 days, P= 0.02; 20 days, P= 0.02, respectively).

CONCLUSIONS

Predictive factors of recovery from laparoscopic nephrectomy include age, BMI, lifestyle and surgical indication.

Differences between HRQL recovery following donor vs non‐donor laparoscopic nephrectomy are significant, and suggest the possible interplay of underlying psychological factors.