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1.  Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders 
BMC Urology  2006;6:31.
Background
The Bladder cooling reflex (BCR) i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO) and painful bladder syndrome (PBS), but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders.
Methods
The BCR, elicited by ice water test (IWT) was performed in patients with painful bladder syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22), neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as controls, n = 21). The IWT was performed by intravesical instillation of cold saline (0 – 4°C). A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test.
Results
A positive IWT was observed in IDO (6/22, 27.3%) and NDO (4/4, 100%) patients, but was negative in all control and PBS patients. Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002), or equivalent amount of bladder filling (100 mls) with saline at room temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients reported any pain during the IWT.
Conclusion
The BCR in DO may reflect loss of central inhibition, which appears necessary to elicit this reflex; the pain elicited in PBS suggests afferent sensitisation, hence sensory symptoms are evoked but not reflex detrusor contractions. The ice water test may be a useful and simple marker for clinical trials in PBS, particularly for novel selective TRPM8 antagonists.
doi:10.1186/1471-2490-6-31
PMCID: PMC1766360  PMID: 17192176
2.  Prevalence and trends of selected urologic conditions for VA healthcare users 
BMC Urology  2006;6:30.
Background
Conducted as part of the Urologic Diseases in America project whose aim was to quantify the burden of urologic diseases on the American public, this study focuses on Veterans Health Administration (VHA) users as a special population to supplement data on overall prevalence rates and trends in the United States. Veterans comprise 25% of the male population 18 years or older and contribute substantially to the overall burden of urologic conditions. The objective of this study is to describe the prevalence rates and trends of urologic cancers and selected benign conditions from 1999 to 2002 for VHA users.
Methods
VHA administrative files for 1999 – 2002 and Medicare claims files for the same years were used to identify those who had a diagnosis of qualifying urologic conditions.
Results
Among the conditions evaluated, prostate cancer was listed as a primary diagnosis for 5.4% of VHA users in 2002, followed in decreasing prevalence by erectile dysfunction (2.9%), renal mass (1.5%), interstitial cystitis (1.4%), and prostatitis (1.1%). Age-adjusted rates showed significant increases for renal mass (31%), interstitial cystitis (14%), and erectile dysfunction (8%) between 1999 and 2002. Systematic variations in prevalence rates and trends were observed by age, race/ethnicity, and region. Those in the Western region generally had lower age-adjusted prevalence rates and their increases were also slower than other regions. Addition of Medicare data resulted in large increases (21 to 489%) in prevalence among VHA users, suggesting substantial amount of non-VA urological care provided to VHA users.
Conclusion
Prevalence rates for many urologic diseases increased between 1999 and 2002, which were not entirely attributable to the aging of veterans. This changing urologic disease burden has substantial implications for access to urologic care and treatment capacity, especially in light of the level of urologic care delivered to veterans by Medicare providers outside the VA. Further study on the factors associated with these increases and how they affect the patterns, cost, and quality of care in veterans is needed.
doi:10.1186/1471-2490-6-30
PMCID: PMC1654168  PMID: 17083728
3.  Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of haematuria 
BMC Urology  2006;6:29.
Background
Primary malignancies of colorectal origin can metastasise to the bladder. Reports are however extremely rare, particularly from the caecum.
Case report
The report describes the case of a 45-year old male with Duke's B caecal carcinoma treated with a laparoscopically-assisted right hemicolectomy and adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the bladder was demonstrated and successfully excised by partial cystectomy.
Conclusion
In order that optimal therapeutic options can be determined, it is important for clinicians to distinguish between primary disease of the bladder and other causes of haematuria. Various immunohistochemical techniques attempt to differentiate primary adenocarcinoma of the bladder from secondary colorectal adenocarcinoma. Suspicion of metastatic disease must be raised when histologically unusual bladder tumours are identified.
doi:10.1186/1471-2490-6-29
PMCID: PMC1624844  PMID: 17040576
4.  Langerhans cell histiocytosis on the penis: a case report 
BMC Urology  2006;6:28.
Background
Langerhans cell histiocytosis affects mainly young children and features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin, and other organs. A few cases of Langerhans cell histiocytosis on the penis have been reported in the literature. We present a case of Langerhans cell histiocytosis on the penis and review the similar cases in the literature.
Case presentation
The patient was a 13-year-old boy who had a history of lymph node, femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis who noticed a painful nodule on the prepuce of his penis. The histological and immunohistochemical examination fulfilled the criteria of Langerhans cell histiocytosis.
Conclusion
We herein describe the case reported of Langerhans cell histiocytosis on the penis.
doi:10.1186/1471-2490-6-28
PMCID: PMC1634755  PMID: 17034629
5.  Endovascular control of haemorrhagic urological emergencies: an observational study 
BMC Urology  2006;6:27.
Background
Transarterial embolisation (TAE) is an effective method in control of haemorrhage irrespective of the nature of urological emergency. As the technique and technology have evolved, it is now possible to perform highly selective embolisation. The aim of this study was to critically appraise feasibility and efficacy of therapeutic TAE in control of haemorrhagic urological emergencies using selective and non-selective embolisation. Specifically, we aimed to assess the impact of timing of embolisation on the requirement of blood transfusion and long-term morphological and functional follow-up of embolised organs.
Methods
This is a single institutional observational study carried out between March 1992 and March 2006. Records of all patients who underwent selective and non-selective angioembolisation to control bleeding in urological emergencies were reviewed. Data on success rate, periprocedural complications, timing of embolisation, requirement of blood transfusion and the long-term morphological and functional outcomes of embolised organs was recorded.
Results
Fourteen patients underwent endovascular control of bleeding as a result of trauma, iatrogenic injury and spontaneous perinephric haemorrhage during a period of 14 years. All these patients would have required emergency open surgery without the option of embolisation procedure. The mean time between the first presentation and embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation transfusion requirement was 6.8 units (range 0–22 units). None of the patients with successful embolisation required post-procedural blood transfusion. Permanent haemostasis was achieved in all but one patient, who required emergency nephrectomy. There were no serious procedure related post-embolisation complications.
Conclusion
Endovascular control using transarterial angioembolisation is an effective method for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated, this option should be considered early in the management of these cases.
doi:10.1186/1471-2490-6-27
PMCID: PMC1599744  PMID: 17007647
6.  A rare case of renal oncocytoma associated with erythrocytosis: case report 
BMC Urology  2006;6:26.
Background
Oncocytomas are benign tumors of the kidney that are usually diagnosed postoperatively due to differential diagnostic problems from renal cell carcinoma. Although the latter are neoplasms that have been associated with erythrocytosis in 3.5% of cases, there are no reports in the literature about a similar occurrence in oncocytomas.
Case presentation
In this case report we present a unique case of a right lower pole oncocytoma associated with erythrocytosis. Erythrocytosis subsided after partial nephrectomy.
Conclusion
Erythrocytosis can sometimes occur in association with renal oncocytomas.
doi:10.1186/1471-2490-6-26
PMCID: PMC1590043  PMID: 16995951
7.  Frequency and patterns of early recanalization after vasectomy 
BMC Urology  2006;6:25.
Background
Our understanding of early post-vasectomy recanalization is limited to histopathological studies. The objective of this study was to estimate the frequency and to describe semen analysis patterns of early recanalization after vasectomy.
Methods
Charts displaying serial post-vasectomy semen analyses were created using the semen analysis results from 826 and 389 men participating in a randomized trial of fascial interposition (FI) and an observational study of cautery, respectively. In the FI trial, participants were randomly allocated to vas occlusion by ligation and excision with or without FI. In the cautery study, sites used their usual cautery occlusion technique, two with and two without FI. Presumed early recanalization was based on the assessment of individual semen analysis charts by three independent reviewers. Discrepancies were resolved by consensus.
Results
Presumed early recanalization was characterized by a very low sperm concentration within two weeks after vasectomy followed by return to large numbers of sperm over the next few weeks. The overall proportion of men with presumed early recanalization was 13% (95% CI 12%–15%). The risk was highest with ligation and excision without FI (25%) and lowest for thermal cautery with FI (0%). The highest proportion of presumed early recanalization was observed among men classified as vasectomy failures.
Conclusion
Early recanalization, occurring within the first weeks after vasectomy, is more common than generally recognized. Its frequency depends on the occlusion technique performed.
doi:10.1186/1471-2490-6-25
PMCID: PMC1586021  PMID: 16984640
8.  Substance P induces localization of MIF/α1-inhibitor-3 complexes to umbrella cells via paracellular transit through the urothelium in the rat bladder 
BMC Urology  2006;6:24.
Background
Macrophage migration inhibitory factor (MIF) is released into the intraluminal fluid during bladder inflammation in the rat complexed to α1-inhibitor-3 (A1-I3; a rodent proteinase inhibitor in the α-macroglobulin family). The location of A1-I3 in the bladder had not been investigated. Therefore, we examined the location of A1-I3 and MIF/A1-I3 complexes in the bladder and changes due to experimental inflammation.
Methods
Anesthetized male rats had bladders removed with no treatment (intact) or were injected with Substance P (SP; s.c.; saline vehicle). After one hour intraluminal fluid was removed, bladder was excised and MIF and A1-I3 levels were determined using ELISA and/or western-blotting. MIF co-immunoprecipitation determined MIF/A1-I3 complexes in the bladder. Bladder sections were immunostained for A1-I3 and MIF/A1-I3.
Results
A1-I3 immunostaining was observed in interstitial spaces throughout the bladder (including submucosa) but not urothelium in intact and saline-treated rats. RT-PCR showed that the bladder does not synthesize A1-I3, therefore, A1-I3 in the interstitial space of the bladder must be plasma derived. In SP-treated rats, A1-I3 in the bladder increased and A1-I3 was observed traversing through the urothelium. Umbrella cells that do not show MIF and/or A1-I3 immunostaining in intact or saline-treated rats, showed co-localization of MIF and A1-I3 after SP-treatment. Western blotting demonstrated that in the bladder MIF formed non-covalent interactions and also binds covalently to A1-I3 to form high molecular weight MIF/A1-I3 complexes (170, 130 and 75-kDa, respectively, verified by co-immunoprecipitation). SP-induced inflammation selectively reduced 170-kDa MIF/A1-I3 in the bladder while increasing 170 and 130-kDa MIF/A1-I3 in the intraluminal fluid.
Conclusion
A1-I3 and MIF/A1-I3 complexes are resident in bladder interstitium. During SP-induced inflammation, MIF/A1-I3 complexes are released from the bladder into the lumen. Binding of MIF/A1-I3 complexes to urothelial cells during inflammation suggests these complexes participate in the inflammatory reaction through activation of receptors for MIF and/or for A1-I3.
doi:10.1186/1471-2490-6-24
PMCID: PMC1599743  PMID: 16981995
9.  Clipless management of the renal vein during hand-assist laparoscopic donor nephrectomy 
BMC Urology  2006;6:23.
Background
Laparoscopic live donor nephrectomy has become the preferred method of donor nephrectomy at many transplant centers. The laparoscopic stapling device is commonly used for division of the renal vessels. Malfunction of the stapling device can occur, and is often due to interference from previously placed clips. We report our experience with a clipless technique in which no vascular clips are placed on tributaries of the renal vein at or near the renal hilum in order to avoid laparoscopic stapling device misfires.
Methods
From December 20, 2002 to April 12, 2005, 50 patients underwent hand-assisted laparoscopic left donor nephrectomy (LDN) at our institution. Clipless management of the renal vein tributaries was used in all patients, and these vessels were divided using either a laparoscopic stapling device or the LigaSureTM device (Valleylab, Boulder, CO). The medical and operative records of the donors and recipients were reviewed to evaluate patient outcomes.
Results
The mean follow-up time was 14 months. Of the 50 LDN procedures, there were no laparoscopic stapling device malfunctions and no vascular complications. All renal allografts were functioning at the time of follow-up.
Conclusion
Laparoscopic stapling device failure due to deployment across previously placed surgical clips during laparoscopic live donor nephrectomy can be prevented by not placing clips on the tributaries of the renal vein. In our series, there were no vascular complications and no device misfires. We believe this clipless technique improves the safety of laparoscopic donor nephrectomy.
doi:10.1186/1471-2490-6-23
PMCID: PMC1584247  PMID: 16978416
10.  Ruptured renal artery aneurysm during pregnancy, a clinical dilemma 
BMC Urology  2006;6:22.
Background
Rupture of a renal artery aneurysm (RAA) during pregnancy is a rare event, with a high mortality rate for both mother and fetus. Increased blood flow and intra-abdominal pressure, and vascular changes secondary to increased steroid production are postulated as contributory to the increased risk of rupture during pregnancy.
Case presentation
We present here a case report of total avulsion of solitary kidney secondary to rupture of RAA in a pregnant patient with congenital absence of the contralateral kidney. The main indication for nephrectomy was severely damaged kidney. Diagnosis was made during operation and both mother and fetus were saved. There are no previous reports of an intact renal artery aneurysm diagnosed either antepartum or postpartum.
Conclusion
The possibility of a ruptured RAA should be considered in pregnant women with evidence of retroperitoneal hemorrhage. This case was unusual because it occurred in a solitary kidney, during the third trimester of pregnancy.
doi:10.1186/1471-2490-6-22
PMCID: PMC1569431  PMID: 16945133
11.  Epidemiology of complications of male circumcision in Ibadan, Nigeria 
BMC Urology  2006;6:21.
Background
The number of infants managed for neonatal circumcision injuries in our unit has been on the increase over the past 16 years. In our search for the sources and reasons for these injuries, we were unable to identify any previous studies of circumcision injuries from our environment. We therefore decided to carry out this study in order to shed some light on this growing problem.
Methods
The patients were made up of 370 consecutive consented children attending our infant welfare clinic for immunization over a period of 3 months. Information on their demographic data, their age at circumcision, where, why and who circumcised them was obtained from their mothers. They were clinically examined for the presence and type of complications of circumcision.
Results
Our circumcision rate was 87%. Neonatal circumcision had been performed in 270 (83.9%) of the children. Two hundred and fifty nine (80.7%) were performed in hospitals. The operation was done by nurses in 180 (55.9%), doctors in 113 (35.1%) and by the traditional circumcisionist in 29 (9%) of the children. Complications of circumcision occurred in 65 [20.2%] of the children. Of those who sustained these complications, 35 (53.8%) had redundant foreskin, 16 (24.6%) sustained excessive loss of foreskin, 11 (16.9%) had skin bridges, 2 (3.1%) sustained amputation of the glans penis and 1 (1.5%) had a buried penis. One of the two children who had amputation of the glans also had severe hemorrhage and was transfused. Even though the complications tended to be more likely with nurses than with doctors or traditional circumcisionists, this did not reach statistical significance (p = 0.051).
Conclusion
We have a very high rate of complications of circumcision of 20.2%. We suggest that training workshops should be organized to adequately retrain all practitioners of circumcision on the safe methods available.
doi:10.1186/1471-2490-6-21
PMCID: PMC1560152  PMID: 16934157
12.  Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report 
BMC Urology  2006;6:20.
Background
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers.
Case presentation
A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-α immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery.
Conclusion
This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.
doi:10.1186/1471-2490-6-20
PMCID: PMC1564030  PMID: 16925812
13.  Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder 
BMC Urology  2006;6:19.
Background
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumour invasion and metastasis in several malignant tumour entities. The goal of this study is to evaluate the diagnostic value of various circulating MMPs and TIMPs in blood plasma for a non-invasive detection of transitional cell carcinoma of the bladder (TCC).
Methods
In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of the bladder and from 79 healthy controls. The mROC program was used to calculate the best two- and three- marker combinations. The diagnostic values for all single markers and the marker combinations were estimated both by the overall diagnostic performance index area under the ROC curve (AUC) and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 90% and 95% limits of sensitivity and specificity, respectively.
Results
The median MMP2 concentration was elevated in blood plasma in all patient groups with TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1, TIMP2, and MTC1 in plasma probes were significantly lower from patients with non-metastasized TCC compared to the controls. MMP2 tested alone reached the highest sensitivity and specificity at 75%, respectively. The sensitivity and specificity increased when tested in combination with MMP9 and TIMP1 (97%, 94%, respectively). The combination of MMP9 and TIMP1 also showed an improved sensitivity (80%) and specificity (99%) than tested alone.
Conclusion
MMP2 is a statistically significant marker in blood plasma for bladder cancer detection with an increased diagnostic value in combination with MMP9 and TIMP1. This study showed that the highest sensitivities and specificities are not obtained by testing each marker alone. As shown by the best two-marker combination, which includes MMP9 and TIMP1, the optimized combination does not always include the best single markers.
doi:10.1186/1471-2490-6-19
PMCID: PMC1560390  PMID: 16901349
14.  Ectopic thyroid in an adrenal mass: a case report 
BMC Urology  2006;6:18.
Background
It is difficult to explain ectopic thyroid beneath the diaphragm because during the development the thyroid descends from the tongue to the anterior of the trachea. A few cases of ectopic lesions have been reported in the literature for abdominal organs including the adrenal glands, but the mechanism by which the thyroid components migrate into the abdomen has been poorly understood.
Case presentation
A 54-year-old woman was diagnosed as having an adrenal mass. Laparoscopic adrenalectomy was carried out. Microscopically, the mass was composed of normal adrenal and ectopic thyroid tissues.
Conclusion
We herein describe the fourth case reported of ectopic thyroid in the adrenal gland.
doi:10.1186/1471-2490-6-18
PMCID: PMC1555601  PMID: 16899136
15.  Testicular infarction secondary to protein S deficiency: a case report 
BMC Urology  2006;6:17.
Background
Protein S deficiency is an inherited cause of thrombophilia. We present the second reported case in the literature of a man developing testicular infarction secondary to protein S deficiency.
Case presentation
A 63 year old man presented with sudden onset of pain in his left hemi-scrotum. Despite oral warfarin therapy the plasma INR was only 1.4 at presentation. Doppler ultrasound scan of the scrotum confirmed absent blood flow to the left testis with increased echogenicity. Orchidectomy was performed to remove the necrotic testis. Post-operatively the patient did well and was referred to the Regional Haemophilia and Thrombosis Centre for further management.
Conclusion
The case highlights a rare but potential complication of protein S deficiency and demonstrates the importance of adequate anticoagulation in these patients.
doi:10.1186/1471-2490-6-17
PMCID: PMC1543644  PMID: 16827935
16.  Factors affecting calcium oxalate dihydrate fragmented calculi regrowth 
BMC Urology  2006;6:16.
Background
The use of extracorporeal shock wave lithotripsy (ESWL) to treat calcium oxalate dihydrate (COD) renal calculi gives excellent fragmentation results. However, the retention of post-ESWL fragments within the kidney remains an important health problem. This study examined the effect of various urinary conditions and crystallization inhibitors on the regrowth of spontaneously-passed post-ESWL COD calculi fragments.
Methods
Post-ESWL COD calculi fragments were incubated in chambers containing synthetic urine varying in pH and calcium concentration: pH = 5.5 normocalciuria (3.75 mM), pH = 5.5 hypercalciuria (6.25 mM), pH = 6.5 normocalciuria (3.75 mM) or pH = 6.5 hypercalciuria (6.25 mM). Fragment growth was evaluated by measuring increases in weight. Fragment growth was standardized by calculating the relative mass increase.
Results
Calcium oxalate monohydrate (COM) crystals formed on COD renal calculi fragments under all conditions. Under pH = 5.5 normocalciuria conditions, only COM crystals formed (growth rate = 0.22 ± 0.04 μg/mg·h). Under pH = 5.5 hypercalciuria and under pH = 6.5 normocalciuria conditions, COM crystals and a small number of new COD crystals formed (growth rate = 0.32 ± 0.03 μg/mg·h and 0.35 ± 0.05 μg/mg·h, respectively). Under pH = 6.5 hypercalciuria conditions, large amounts of COD, COM, hydroxyapatite and brushite crystals formed (growth rate = 3.87 ± 0. 34 μg/mg·h). A study of three crystallization inhibitors demonstrated that phytate completely inhibited fragment growth (2.27 μM at pH = 5.5 and 4.55 μM at pH = 6.5, both under hypercalciuria conditions), while 69.0 μM pyrophosphate caused an 87% reduction in mass under pH = 6.5 hypercalciuria conditions. In contrast, 5.29 mM citrate did not inhibit fragment mass increase under pH = 6.5 hypercalciuria conditions.
Conclusion
The growth rate of COD calculi fragments under pH = 6.5 hypercalciuria conditions was approximately ten times that observed under the other three conditions. This observation suggests COD calculi residual fragments in the kidneys together with hypercalciuria and high urinary pH values may be a risk factor for stone growth. The study also showed the effectiveness of specific crystallization inhibitors in slowing calculi fragment growth.
doi:10.1186/1471-2490-6-16
PMCID: PMC1526447  PMID: 16822299
17.  Impact of hormonal therapy on the detection of promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1) in prostate cancer 
BMC Urology  2006;6:15.
Background
In spite of excellent cure rates for prostate cancer patients with favorable tumor characteristics, patients with unfavorable characteristics after radical prostatectomy are still at a significantly increased risk of tumor progression. Early adjuvant hormonal therapy (AHT) has been shown to be of prognostic benefit in these patients. Unfortunately initiation and duration of early AHT in the individual patient is based on statistic data. PSA, as the standard prostate marker is neither able to reliably indicate minimal residual tumor disease in the early postoperative phase, nor can it be used for therapy monitoring due to the suppressive effect of hormonal therapy on PSA production. Promoter hypermethylation of the detoxifying glutathione-S-transferase P1 gene (GSTP1-HM) has been shown to be the most common DNA alteration of primary prostatic carcinoma which, when used as a marker, is supposed to be able to overcome some of the disadvantages of PSA. However until now information on the impact of hormonal therapy on the detection of GSTP1-HM is lacking. The purpose of our study was to assess the impact of endocrine therapy on the detection of GSTP1-HM by methylation-specific PCR (MSP) in prostate cancer.
Methods
Paraffin embedded tumor samples from the radical prostatectomy (RP) specimens from 15 patients after hormonal therapy (HT) (mean 8 months) were assessed by MSP. In 8 of the patients the GSTP-1 status of the tumors before HT was assessed on the corresponding initial diagnostic biopsies.
Results
Following HT MSP showed GSTP1-HM in 13/15 of the RP specimens. In two patients analysis of the RP specimens failed to show GSTP1-HM. All initial tumor samples (8/8 biopsy specimens) showed GSTP1-HM, including both patients negative for GSTP1 HM in the corresponding RP specimen.
Conclusion
In most cases hormonal therapy appears to not alter GSTP1 HM detection. However the change from a positive to a negative GSTP1 HM status in a subset of the patients may point to an, at least partial androgen dependency. Further studies on a larger cohort of patients are necessary to assess its frequency and the exact hormonal interactions.
doi:10.1186/1471-2490-6-15
PMCID: PMC1540432  PMID: 16803634
18.  Systematic review and meta-analysis of Transurethral Needle Ablation in symptomatic Benign Prostatic Hyperplasia 
BMC Urology  2006;6:14.
Background
Benign prostatic hyperplasia (BPH) constitutes a major clinical problem. Minimally invasive therapies for the treatment of symptomatic BPH include Transurethral Needle Ablation (TUNA), but it is unclear what impact this technique has on the disease and its role among other currently available therapeutic options. The objective of this study is to ascertain the efficacy and safety of TUNA in the treatment of BPH.
Methods
Systematic review of the literature until January 2005 and meta-analysis of clinical studies assessing TUNA in symptomatic BPH. Studies were critically appraised. Estimates of effect were calculated according to the random-effects model.
Results
35 studies (9 comparative, 26 non-comparative) were included. Although evidence was limited by methodological issues, the analysis of relevant outcomes indicates that while TUNA significantly improves BPH parameters with respect to baseline, it does not reach the same level of efficacy as TURP in respect to all subjective and objective variables. Further, its efficacy declines in the long-term with a rate of secondary-treatment significantly higher than of TURP [OR: 7.44 (2.47, 22.43)]. Conversely, TUNA seems to be a relatively safe technique and shows a lower rate of complications than TURP [OR:0.14 (0.05, 0.14)] with differences being particularly noteworthy in terms of postoperative bleeding and sexual disorders. Likewise, TUNA has fewer anesthetic requirements and generates a shorter hospital stay than TURP [WMD: -1.9 days (-2.75, -1.05)]. Scarce data and lack of replication of comparisons hinder the assessment of TUNA vs. other local therapies. No comparisons with medical treatment were found.
Conclusion
The body of evidence on which TUNA has been introduced into clinical practice is of only moderate-low quality. Available evidence suggest that TUNA is a relatively effective and safe technique that may eventually prove to have a role in selected patients with symptomatic BPH. TUNA significantly improves BPH parameters with respect to baseline values, but it does not reach the same level of efficacy and long-lasting success as TURP. On the other hand, TUNA seems to be superior to TURP in terms of associated morbidity, anesthetic requirements and length of hospital stay. With respect to the role of TUNA vis-à-vis other minimally invasive therapies, the results of this review indicate that there are insufficient data to define this with any degree of accuracy. Overall cost-effectiveness and the role of TUNA versus medical treatment need further evaluation.
doi:10.1186/1471-2490-6-14
PMCID: PMC1538609  PMID: 16790044
19.  The hypoactive corpora cavernosa with degenerative erectile dysfunction: a new syndrome 
BMC Urology  2006;6:13.
Background
In a group of 22 patients with erectile dysfunction, vasculogenic, neurogenic, endocrinologic or psychogenic investigations failed to find a cause for their erectile dysfunction. The electro-cavernosograms of these patients recorded a diminished activity. We investigated the hypothesis that diminished corpus cavernosum electromyography activity was the cause of erectile dysfunction in these patients.
Methods
The study comprised the above mentioned 22 patients (study group, 43.8 ± 5.9 SD years) and 15 healthy volunteers (control group, 41.8 ± 5.1 SD years). The electro-cavernosograms were recorded in the flaccid, erectile and detumescent phases by 2 electrodes inserted into the corpus cavernosum.
Results
The electro-cavernosogram of the healthy volunteers registered in the flaccid phase regular slow waves and random action potentials. The wave variables declined significantly in the erectile phase (p < 0.01). In the study group, the slow wave variables in the flaccid phase exhibited a significant decrease (p < 0.05) compared to the healthy volunteers, and the rhythm was irregular. Erection did not occur with sildenafil administration or intracavernosal papaverine injection, and penile implant was performed. Biopsy examination showed degenerated muscle fibers, and fragmented collagen and elastic fibers with areas of fibrosis.
Conclusion
A novel concept of the cause of erectile dysfunction was presented. Corpora cavernosa showed degenerative changes on histopathologic examination and exhibited diminished electromyography activity. They did not respond to sildenafil administration or intracavernosal papaverine injection. Penile implants were the only treatment. The condition is given the name 'hypoactive corpus cavernosum'. The cause of corpus cavernosum degenerative changes needs further study.
doi:10.1186/1471-2490-6-13
PMCID: PMC1523357  PMID: 16723018
20.  Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs 
BMC Urology  2006;6:12.
Background
With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH).
Methods
Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A.
Results
In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%.
Conclusion
Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH.
doi:10.1186/1471-2490-6-12
PMCID: PMC1481565  PMID: 16620393
21.  Adult clear cell sarcoma of the kidney: A case report 
BMC Urology  2006;6:11.
Background
Clear cell sarcoma of the kidney (CCSK) in adults is extremely rare. Optimal treatment of adult patients with CCSK remains unclear.
Case presentation
A 22-year-old man presented with a 2-month history of left flank pain. A color duplex sonography revealed a hypervascular, heterogeneous renal mass. Abdominal and pelvic computerized tomography showed a heterogeneous mass originating from the lower pole of the left kidney and infiltrating to the psoas muscle. Further evaluation including bone scan did not demonstrate any evidence of metastases. A left radical nephrectomy with hilar lymphadenectomy through an intraperitoneal approach with an anterior subcostal incision was performed. The histopathological diagnosis of the mass was a clear cell sarcoma of the kidney. No lymph node metastases were found. Concomitant chemo-radiotherapy was performed. Therapy-related serious side effects were not observed. There was no evidence of local recurrence or metastases during the following twenty-four months after therapy.
Conclusion
We believe that the combination therapy is efficacious for preventing the local recurrence and distant metastases. Accurate diagnosis is very important and therapy must also include doxorubicin regardless of the disease stage in adult patients with CCSK.
doi:10.1186/1471-2490-6-11
PMCID: PMC1513593  PMID: 16584570
22.  Long term effects of micro-surgical testicular sperm extraction on androgen status in patients with non obstructive azoospermia 
BMC Urology  2006;6:9.
Background
The aim of our study was to review the results of microsurgically performed testicular sperm extraction (TESE) and to evaluate its possible long term effects on serum testosterone (T).
Methods
We operated on 48 men (35 +/- 8 years) with non-obstructive azoospermia (NOA). If no spermatozoa were found following a micro epididymal sperm extraction (Silber et al., 1994) and testicular biopsy, testicular microdissection was performed or multiple microsurgical testicular biopsies were taken. The mean follow-up of the serum T was 2.4 +/- 1.1 years.
Results
Sperm was retrieved in 17/48 (35%) of the men. The per couple take home baby rate if sperm was retrieved was 4/17 (24%). Serum T decreased significantly at follow-up (p < 0.05) and 5/31 (16%) de novo androgen deficiencies developed
Conclusion
In patients with non-obstructive azoospermia in whom no spermatozoa were found following a micro epididymal sperm aspiration and a simple testicular biopsy, we were able to retrieve spermatozoa in 35% of the men. The take home baby rate was 24% among couples with spermatozoa present upon TESE. De novo androgen deficiency occurred in 16% of the male patients following TESE indicating that, in men with NOA, long term hormonal follow up is recommended after TESE.
doi:10.1186/1471-2490-6-9
PMCID: PMC1444919  PMID: 16549019
23.  Coexistence between renal cell cancer and Hodgkin's lymphoma: A rare coincidence 
BMC Urology  2006;6:10.
Background
Renal cell carcinoma is the most common kidney tumor in adults and accounts for approximately 3% of adult malignancies. An increased incidence of second malignancies has been well documented in a number of different disorders, such as head and neck tumors, and hairy cell leukemia. In addition, treatment associated second malignancies (usually leukemias and lymphomas but also solid tumors) have been described in long term survivors of Hodgkin's lymphoma (HL), Non Hodgkin's lymphoma and in various pediatric tumors.
Case presentation
We present the case of a 66 year-old woman with abdominal pain and dyspnea. We performed a thorax CT scan that showed lymph nodes enlargement and subsequently by presence of abdominal pain was performed an abdominal and pelvis CT scan that showed a right kidney tumor of 4 × 5 cms besides of abdominal lymph nodes enlargement. A radical right nephrectomy was designed and Hodgkin's lymphoma was diagnosed in the abdominal lymph nodes while renal cell tumor exhibited a renal cell cancer. Patient received EVA protocol achieving complete response.
Conclusion
We described the first case reported in the medical literature of the coexistence between Hodgkin's lymphoma and renal cell cancer. Previous reports have shown the relationship of lymphoid neoplasms with solid tumors, but they have usually described secondary forms of cancer related to chemotherapy.
doi:10.1186/1471-2490-6-10
PMCID: PMC1435921  PMID: 16549035
24.  Quantitative real-time RT-PCR of CD24 mRNA in the detection of prostate cancer 
BMC Urology  2006;6:7.
Background
Gene expression profiling has recently shown that the mRNA for CD24 is overexpressed in prostate carcinomas (Pca) compared to benign or normal prostate epithelial tissues. Immunohistochemical studies have reported the usefulness of anti-CD24 for detecting prostate cancer over the full range of prostate specimens encountered in surgical pathology, e.g. needle biopsies, transurethral resection of prostate chips, or prostatectomies. It is a small mucin-like cell surface protein and thus promises to become at least a standard adjunctive stain for atypical prostate biopsies. We tested the usefulness of real-time RT-PCR for specific and sensitive detection of CD24 transcripts as a supplementary measure for discriminating between malignant and benign lesions in prostatic tissues.
Methods
Total RNA was isolated from snap-frozen chips in 55 cases of benign prostatic hyperplasia (BPH) and from frozen sections in 59 prostatectomy cases. The latter contain at least 50% malignant epithelia. Relative quantification of CD24 transcripts was performed on the LightCycler instrument using hybridization probes for detection and porphobilinogen deaminase transcripts (PBGD) for normalization.
Results
Normalized CD24 transcript levels showed an average 2.69-fold increase in 59 Pca-cases (mean 0.21) when compared to 55 cases of BPH (mean 0.08). This difference was highly significant (p < 0.0001). The method has a moderate specificity (47.3%) but a high sensitivity (86.4%) if the cutoff is set at 0.0498. CD24 expression levels among Pca cases were not statistically associated with the tumor and lymph-node stage, the grading (WHO), the surgical margins, or the Gleason score.
Conclusion
The present study demonstrates the feasibility of quantitative CD24 RNA transcript detection in prostatic tissues even without previous laser microdissection.
doi:10.1186/1471-2490-6-7
PMCID: PMC1435920  PMID: 16539730
25.  Surveillance of testicular microlithiasis?: Results of an UK based national questionnaire survey 
BMC Urology  2006;6:8.
Background
The association of testicular microlithiasis with testicular tumour and the need for follow-up remain largely unclear.
Methods
We conducted a national questionnaire survey involving consultant BAUS members (BAUS is the official national organisation (like the AUA in USA) of the practising urologists in the UK and Ireland), to provide a snapshot of current attitudes towards investigation and surveillance of patients with testicular microlithiasis.
Results
Of the 464 questionnaires sent to the BAUS membership, 263(57%) were returned. 251 returns (12 were incomplete) were analysed, of whom 173(69%) do and 78(31%) do not follow-up testicular microlithiasis. Of the 173 who do follow-up, 119(69%) follow-up all patients while 54(31%) follow-up only a selected group of patients. 172 of 173 use ultra sound scan while 27(16%) check tumour makers. 10(6%) arrange ultrasound scan every six months, 151(88%) annually while 10(6%) at longer intervals. 66(38%) intend to follow-up these patients for life while, 80(47%) until 55 years of age and 26(15%) for up to 5 years. 173(68.9%) believe testicular microlithiasis is associated with CIS in < 1%, 53(21%) think it is between 1&10% while 7(3%) believe it is > 10%. 109(43%) believe those patients who develop a tumour, will have survival benefit with follow-up while 142(57%) do not. Interestingly, 66(38%) who follow-up these patients do not think there is a survival benefit.
Conclusion
There is significant variability in how patients with testicular microlithiasis are followed-up. However a majority of consultant urologists nationally, believe surveillance of this patient group confers no survival benefit. There is a clear need to clarify this issue in order to recommend a coherent surveillance policy.
doi:10.1186/1471-2490-6-8
PMCID: PMC1458345  PMID: 16539727

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