bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk profiles of three clinical types of carcinoma in situ of the bladder
Authors: Meijer Richard P. , van Onna Ilze E.W. , Kok Esther T. , Bosch Ruud 
Published: December 2010

Study Type – Therapy (individual cohort)Level of Evidence 2bWhat’s known on the subject? and What does the study add?Although it has been reported that patients with primary carcinoma in situ of the bladder (CIS) have a better prognosis than patients with concomitant or secondary CIS, the risk profiles of these three clinical types of CIS have not yet been fully clarified.The current study was performed to give further insight into the risk profiles of these three clinical types of CIS. In clinical practice it would be helpful to be able to discriminate ‘high‐risk’ from ‘low‐risk’ CIS before the start of intravesical therapy and as such to tailor the treatment and follow‐up to this risk‐profile.OBJECTIVE• To further clarify the risk profiles of three clinical types of carcinoma in situ (CIS) of the bladder.MATERIALS AND METHODS• Population‐based data from the Comprehensive Cancer Centre Middle Netherlands, as part of the nationwide Netherlands Cancer Registry, were used for patients presenting with CIS in the period from 1987 to 2009.• Patients with muscle‐invasive bladder cancer on primary diagnosis were excluded. The patients were divided into three groups according to their ‘clinical type’, being primary, concomitant or secondary CIS.RESULTS• Overall, 90 patients with CIS were identified with a mean age of 63.4 years, predominantly men (91.1%). Primary CIS (P‐CIS) was found in 43 patients (47.8%), concomitant CIS (C‐CIS) in 21 patients (23.3%) and secondary CIS (S‐CIS) in 26 patients (28.9%). Mean follow up was 81.3 months (range 8–222 months). Recurrence of disease was observed in 68.9% of patients, with significantly more recurrences in the S‐CIS group (88.5%).• Progression to muscle‐invasive disease was seen in 17 patients (18.9%): eight patients (18.7%) with P‐CIS, four (19.0%) with C‐CIS and five (19.2%) with S‐CIS. Overall, 29 patients underwent a cystectomy, equally distributed over the three groups. The duration of bladder preservation was worse in the C‐CIS group but did not differ significantly between the groups.• Overall survival at 5 years was 79.6% for the total group, with poorer results for the C‐CIS group, although the difference was not significant.CONCLUSIONS• Carcinoma in situ is clearly an entity that requires meticulous treatment and thorough follow up because of its high recurrence rate (68.9%) and high rate of progression to muscle‐invasive bladder cancer (18.9%).• The C‐CIS group appears to have a poorer prognosis with a shorter duration of bladder preservation and a worse overall survival.
Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats
Authors: Zhang Min‐Guang , Shen Zhou‐Jun , Zhang Cun‐Ming , Wu Wei , Gao Ping‐Jin , Chen Shan‐Wen , Zhou Wen‐Long 
Published: December 2010

What’s known on the subject? and What does the study add? Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter, and our previous study found that the mRNA expression of VIP was independent of androgens.The present study further investigated the vivo effect of VIP on erection. We found that not only the expression of VIP was independent of androgens, but also the effect of VIP on erection was independent of androgens. In fact, we found that VIP played a more significant role on erection in castrated rats than in normal rats.OBJECTIVE

To investigate the regulatory role of androgen in VIP‐mediated erectile effect. Androgen is essential for physiological erection. Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter. While previous studies demonstrated that VIP expression in the penis was androgen‐independent, it remains controversial whether androgen has any effect on VIP‐mediated erection.

MATERIALS AND METHODS

Male SD rats were divided into a control group, a castration group, and a castration‐with‐testosterone‐replacement group. Four weeks later, each group was subdivided into low and high‐dose VIP subgroups and subjected to intracavernous injection of 0.5 and 2 µg VIP, respectively.
Erectile function was tested by recording intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) before and after VIP injection.
The expressions of the VIP‐receptor (VPAC2), G‐protein stimulatory and inhibitory alpha subunits (Gs‐α, Gi‐α), and PDE3A in rat corpus cavernosum (CC) was qualified by real‐time PCR and Western blot analysis.

RESULTS

Castration reduced erectile function while testosterone restored it. VIP improved erectile function in a dose‐dependent manner.
High‐dose VIP significantly enhanced erectile function in castrated rats and there was no difference of ICP/MAP among three groups after injection of high‐dose VIP.
Low‐dose VIP also resulted in a higher improvement of erectile function in castrated rats, although the ICP/MAP was lower in these rats than in the other two groups. VPAC2 and Gs‐α were up‐regulated while Gi‐α and PDE3A were down‐regulated in CC of castrated rats.

CONCLUSION

VIP improves erectile function much more significantly in hypogonadal condition, mainly due to the higher expression of VPAC2, Gs‐α, and lower expression of Gi‐α and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect of VIP.
Cost‐effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder
Authors: Leong Randall K. , de Wachter Stephan G.G. , Joore Manuela A. , van Kerrebroeck Philip E.V. 
Published: December 2010

Study Type – Therapy (economic analysis)Level of Evidence 1bOBJECTIVETo assess and compare the costs and effects value of either starting with sacral neuromodulation (SNM) or botulinum toxin A (BTX) treatment in patients with refractory idiopathic overactive bladder from a societal perspective.MATERIALS AND METHODSAn economic model comparing SNM with BTX was developed. A clinical relevant effect (i.e. success) was defined as 50% or greater reduction in incontinence episodes or urgency frequency symptoms. Information on the clinical effectiveness of the two treatments and on the course of the disease with the two treatments were based primarily on published literature and, when required, on expert opinion. Both treatments were assumed to be performed under general anaesthesia and, for SNM treatment, first‐stage tined lead test was used. All costs were based on national data from the year 2008. Analyses from the societal perspective were conducted for a 5‐year duration. Costs were discounted at 4% and effects at 1.5%. In addition, different modelling scenarios were used to see determine any changes in the results obtained.RESULTSStarting with SNM resulted in a higher quality adjusted life year (QALY) gain (differenceof 0.23) and a higher cost (difference of €6428) compared to starting with BTX. The corresponding incremental cost‐effectiveness ratio was €27 991/QALY. The probability of this ratio being cost effective (e.g. under €40 000/QALY) is 88%. SNM starts to be cost‐effective after 4 years. SNM was not cost‐effective in some other scenarios, such as when BTX was conducted under local anaesthesia or when peripheral nerve evaluation or bilateral testing was used for SNM.CONCLUSIONSStarting with SNM, treatment is cost‐effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost‐effective.
Improved cancer specific‐survival in patients with carcinoma invading bladder muscle expressing cyclo‐oxygenase‐2
Authors: Aziz Anis , Lessard Annie , Moore Katherine , Hovington Hélène , Latulippe Eva , Larue Hélène , Fradet Yves , Lacombe Louis 
Published: December 2010

Study Type – Prognosis (case series)Level of Evidence 4OBJECTIVETo determine whether the expression of cyclo‐oxygenase (COX)‐2 has an influence on survival and on the response to chemotherapy in invasive bladder cancer.PATIENTS AND METHODSA population of 266 patients from a tertiary university centre with carcinoma invading bladder muscle without evidence of metastasis at time of cystectomy was analyzed retrospectively. COX‐2 expression was evaluated immunohistochemically with a monoclonal anti‐COX‐2 antibody. All pertinent clinical and pathological parameters were reviewed and correlated with risk factors influencing outcome, including disease‐specific and overall survival, as well as COX‐2 expression. Immunoreactivity was categorized as positive if COX‐2 staining was present in >5% tumour cells.RESULTSThe expression of COX‐2 was not influenced by tumour stage, grade or nodal status, nor any other parameters. The risk factors that influenced disease‐specific survival in carcinoma invading bladder muscle on multivariate analysis were lymph node status (hazards ratio, HR = 2.46 for N1, P= 0.001, HR = 2.90 for N2, P < 0.001, HR = 5.19 for N3, P= 0.012), use of neoadjuvant chemotherapy (HR = 3.54; P= 0.004) or adjuvant chemotherapy (HR = 0.57, P= 0.014) and COX‐2 expression (HR = 0.64 if >5% cells had positive expression; P= 0.025). Kaplan–Meier analysis showed an increased disease‐specific survival (P= 0.0063), as well as longer recurrence‐free survival (P= 0.003), in patients with muscle‐invasive bladder tumours expressing COX‐2 in >5% of the cells. A tendency was also observed in a subgroup with positive nodes treated with adjuvant chemotherapy (P= 0.093).CONCLUSIONSThe overexpression of COX‐2 is associated with a better recurrence‐free and disease‐specific survival in a large cohort of 266 patients with carcinoma invading bladder muscle treated by cystectomy. A trend for increased disease‐specific survival was also observed for patients with COX‐2 overexpression and positive nodes who received adjuvant chemotherapy. Potential of COX‐2 as a prognostic marker in bladder cancer should be considered.
Higher levels of cell apoptosis and abnormal E‐cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome
Authors: Shie Jia‐Heng , Kuo Hann‐Chorng 
Published: December 2010

What’s known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) is considered to result from long‐standing inflammation of the bladder. Urothelial dysfunction and increased urothelial permeability are known to result in clinical symptoms such as pain and urgency, however the actual pathophysiology remains unclear.This study demonstrated increased cell apoptosis, decreased cell proliferation, increased mast cell activation, and impaired expression of E‐cadherin were significant in IC/PBS bladders. There was a significant correlation between mast cell activation and urothelial cell apoptosis and the reduced E‐cadherin expression was significantly correlated with clinical pain VAS scale, suggesting the barrier defect of the bladder wall may lead to increasing bladder sensitivity and pain.OBJECTIVE• To investigate the relationships between suburothelial inflammation and urothelial dysfunction in interstitial cystitis/painful bladder syndrome (IC/PBlS).MATERIALS AND METHODS• Immunofluorescence staining of ki‐67 (to assess cell proliferation), junction protein E‐cadherin, tryptase (to assess mast cell activation) and TUNEL (to assess urothelial apoptosis) were performed in bladder tissues from 20 patients with IC/PBlS and from 6 control patients.• The fluorescence intensity of E‐cadherin was measured using the ImageJ method.• The percentage of apoptotic cells, proliferated cells and activated mast cells were measured and quantified as positive cells (±SD) per area unit (4 µm2).RESULTS• The ratio of ki‐67‐positive cells in the bladder tissue of the patients with IC/PBlS was significantly down‐regulated compared with that of the control patients (0.559 ± 0.658 vs. 1.23 ± 1.28, P= 0.001).• TUNEL staining revealed a significantly higher number of apoptotic cells in the IC/PBlS bladder tissue compared with control bladder tissue (2.26 ± 2.04 v 0.051 ± 0.124, P= 0.000).• The tryptase signal was significantly stronger in the IC/PBlS bladder tissue compared with that of control patients (6.16 ± 4.35 v 1.15 ± 0.436, P= 0.000).• The apoptotic cell number in IC/PBlS bladder tissue correlated significantly with mast cell activation (P= 0.021).• Immunofluorescence also showed a significantly lower distribution of E‐cadherin in IC/PBlS bladder tissue compared with that of control patients (8.50 ± 6.83 v 17.2 ± 11.9, P= 0.000).• Lower expression of E‐cadherin in IC/PBlS bladder tissue was significantly correlated with higher visual analogue pain scores in patients with IC/PBlS (P= 0.008).CONCLUSIONS• The results of the present study suggest that urothelial homeostasis in IC/PBlS bladders was impaired, and abnormal urothelial function was significantly associated with chronic inflammation.• The junctions between urothelial cells in IC/PBlS bladders were abnormal, which was associated with the patient’s self‐report pain scales.
Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience
Authors: Yafi Faysal A. , Aprikian Armen G. , Chin Joseph L. , Fradet Yves , Izawa Jonathan , Estey Eric , Fairey Adrian , Rendon Ricardo , Cagiannos Ilias , Lacombe Louis , Lattouf Jean‐Baptiste , Bell David , Drachenberg Darrel , Kassouf Wassim 
Published: December 2010

Study Type – Therapy (case series)Level of Evidence 4OBJECTIVETo evaluate data obtained from a large, multi‐institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables.MATERIALS AND METHODSData were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan‐Meier method and Cox regression analysis.RESULTSThe median age of patients was 68 years with a mean (median) follow‐up time of 35 (29) months. The 30, 60 and 90‐day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5‐year overall, recurrence‐free and cancer‐specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was <pT2N0, n= 498 (23%); pT2N0, n= 365 (17%); pT3N0, n= 463 (21%); pT4N0, n= 170 (8%); and pTxN+, n= 507 (23%). Only 3.1% of patients received neoadjuvant chemotherapy and 19.4% received adjuvant chemotherapy. On multivariate analysis, lower pathological stage, negative surgical margins, receipt of adjuvant chemotherapy, performance of pelvic lymphadenectomy and an absence of smoking were associated with prolonged disease‐specific and overall survival.CONCLUSIONSRC performed at academic centres provides excellent local control of disease and an acceptable clinical outcome with low perioperative mortality in patients who are treated within a universal healthcare system. Smoking, pelvic lymphadenectomy and receipt of adjuvant chemotherapy are independent prognostic factors for survival. Neoadjuvant chemotherapy continues to be under‐utilized in Canada.
Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer
Authors: Ahallal Youness , Shariat Shahrokh F. , Chade Daher C. , Mazzola Clarisse , Reuter Victor E. , Sandhu Jaspreet S. , Laudone Vincent P. , Touijer Karim A. , Guillonneau Bertrand D. 
Published: December 2010

Study Type – Therapy (case series)Level of Evidence 4What’s known on the subject? and What does the study add?After primary radiation therapy or cryotherapy for prostate cancer, a biochemical‐only recurrence poses a diagnostic and therapeutic dilemma for clinicians and patients alike. Open radical prostatectomy (ORP) represents the most effective curative treatment option for these patients.Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy.OBJECTIVE• To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology‐proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer.MATERIALS AND METHODS• This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1).• Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic‐assisted) with bilateral pelvic dissection.RESULTS• Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization.• Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8‐month median follow‐up, 11 patients were disease‐free and three had persistent postoperative prostate‐specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months.• Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6‐month mean follow‐up continued to need one or two pads per day.• Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery.CONCLUSION• Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer‐term data are required.
A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin
Authors: Matsumoto Kazumasa , Noguchi Masanori , Satoh Takefumi , Tabata Ken‐Ichi , Fujita Tetsuo , Iwamura Masatsugu , Yamada Akira , Komatsu Nobukazu , Baba Shiro , Itoh Kyogo 
Published: December 2010

Study Type – Therapy (case series)Level of Evidence 4What’s known on the subject? and What does the study add?This phase I study showed the safety and boosted immune responses of personalized peptide vaccination for advanced urotherial carcinoma.This study showed feasibility of personalized peptide vaccination as a new therapeutic modality for advanced urotherial carcinoma patients who failed cisplatin‐based chemotherapy.OBJECTIVE• To investigate the safety and immune responses of 12 consecutive weeks of once‐weekly personalized peptide vaccine (PPV) administration in patients with advanced urothelial carcinoma (UC) for whom therapy with methotrexate, vinblastine, adriamycin and cisplatin (MVAC) has failed.PATIENTS AND METHODS• A phase I trial was designed. Ten patients with MVAC‐refractory advanced or metastatic UC were treated with weekly personalized peptide vaccine 12 times using positive peptides chosen from 14 and 16 peptides in patients with human leucocyte antigens A24 and A2, respectively.• Peptide‐specific cytotoxic T lymphocyte precursor analysis by interferon‐γ production and peptide‐reactive immunoglobulin G (IgG) using an enzyme‐linked immunosorbent assay was monitored during the treatment.RESULTS• The peptide vaccination was safe and well tolerated with no major adverse effects. Increased cytotoxic T lymphocyte response and the anti‐peptide IgG titre were revealed by the post‐vaccination sera in eight patients.• Clinical responses were as follows: one complete response, one partial response, two stable disease and six progressive disease.• Median progression‐free survival and overall survival were 3.0 and 8.9 months, respectively. In the four responders, median progression‐free survival and overall survival were 21 and 24 months, respectively.CONCLUSIONS• This phase I study showed the safety of and boosted immune responses in response to PPV for advanced UC.• The potential efficacy of 12 consecutive weekly vaccinations with PPV in patients with advanced UC merits further investigation based on these findings.
Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?
Authors: Kirkman Matthew A. , van Dellen David , Mehra Sanjay , Campbell Babatunde A. , Tavakoli Afshin , Pararajasingam Ravi , Parrott Neil R. , Riad Hany N. , McWilliam Lorna , Augustine Titus 
Published: December 2010

Study Type – Therapy (case series)Level of Evidence 4 What’s known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation.Post‐transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre‐transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre‐transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy.OBJECTIVETo analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation.PATIENTS AND METHODSA retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken.RESULTSThere were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43–65).Twenty patients were in the pre‐transplant nephrectomy group, 12 in the post‐transplant group, and three underwent the sandwich technique.Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety).Seven individuals in the pre‐transplant group and three in the post‐transplant group required critical care admission after nephrectomy.Transient renal graft dysfunction occurred in two post‐transplant bilateral nephrectomy patients.Two patients in the bilateral nephrectomy pre‐transplant group and one in the bilateral nephrectomy post‐transplant group died in the immediate post‐operative period.No complications were noted in the sandwich technique group.CONCLUSIONNative nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre‐transplant group.Post‐transplant unilateral nephrectomy appears to be the safest approach with fewest complications.