Laparoscopic donor nephrectomy: an increasingly common cause for testicular pain and swelling.

INTRODUCTION: Laparoscopic donor nephrectomy (LDN) is now a well established method for kidney procurement from living donors. In our centre, LDN is currently offered only to donors suitable for left nephrectomy. The aim of this study was to investigate the incidence of testicular pain and swelling following LDN. METHODS: A total of 25 left-sided LDN male patients were assessed in a prospective structured interview together with a control cohort of 25 male patients who had undergone left-sided open donor nephrectomy (ODN). RESULTS: Data were collected on testicular pain, swelling, numbness, urinary symptoms and sexual dysfunction from all 50 patients (100% response rate). Of the 25 LDN patients, 11 (44%) experienced ipsilateral testicular pain and/or swelling. In most instances, pain was of immediate onset, mild to moderate in severity, lasted for a few days to several weeks and was associated with testicular swelling (10 of 11 cases). However, testicular pain and/or swelling were not apparent in ODN patients, with only 2 of 25 (8%) experiencing mild testicular pain, 1 of whom also had swelling. CONCLUSIONS: Testicular pain and swelling following LDN is a common problem. It is underreported in the literature and LDN should be included in the differential diagnoses of testicular pain and swelling. Further investigation is required to confirm our findings.

Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma.

BACKGROUND: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma. METHODS: In this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data. RESULTS: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. In particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis. CONCLUSION: In this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker.

Metaphase and array comparative genomic hybridization: unique copy number changes and gene amplification of medulloblastomas in South America.

Tumors of the central nervous system are the second most frequent malignancy of childhood, accounting for the majority of cancer-related deaths in this age group. Among these tumors, medulloblastomas (MB) remain in need of further genomic characterization toward understanding of pathogenesis and outcome predictors. Eight pediatric embryonal brain tumors were analyzed: five MB (one being desmoplastic), one PNET, one medulloepithelioma, and one ependymoblastoma. Analyses identified genomic imbalances, including the gain of 16p and the nonsyntenic coamplification of MYCN and TERT loci. More detailed FISH analysis showed that coamplification of MYCN and TERT in one of the MBs manifested as dispersed nuclear speckling, consistent with the presence of double minute chromosomes. There was considerable cell-to-cell copy number heterogeneity present, but it was clear that both genes were amplified concordantly. The amplification of oncogenes seems to play an important role in the pathogenesis of MB, and the association between MYCN and TERT amplifications and poor prognosis has not been well recognized. The uncharacteristic pattern of genomic imbalances detected in MB tumors may be a reflection of the characteristics of these tumors occurring in South America.

Leucemia promielocítica aguda: caracterizacão de alteracões cromossômicas por citogenética tradicional e molecular ( FISH ) / Acute promyelocytic leukemia: characterization of chromosome abnormalities by classical cytogenetics and FISH

A leucemia promielocítica aguda (LPA) corresponde a 10 por cento -15 por cento das leucemias mielóides agudas (LMA). Este tipo de leucemia (LMA-M3 de acordo com a classificacão FAB) está associado, em cerca de 90 por cento dos casos, à translocacão t(15;17)(q22;q21), que resulta na fusão dos genes PML e RARalfa. A análise citogenética tradicional tem sido utilizada para confirmar o diagnóstico morfológico da LPA. Embora a t(15;17) não seja detectada em outros tipos de leucemia, podem ocorrer resultados "falso-negativos", decorrentes da análise de células que não pertencem ao clone neoplásico, da dificuldade de visualizacão da translocacão ou, até mesmo, da existência de rearranjos crípticos que mascaram a translocacão. Por outro lado, foram descritas alteracões cromossômicas alternativas em pacientes com LPA e, nesses casos, o tratamento com ATRA não é eficaz. No período de julho de 1993 a dezembro de 2002 foram encaminhados para análise citogenética 47 casos com suspeita e/ou diagnóstico clínico-morfológico de LPA. Trinta e quatro pacientes (72,3 por cento) apresentaram a t(15;17), detectada pela citogenética tradicional e/ou molecular. Em seis destes pacientes foram observadas alteracões cromossômicas adicionais ou rearranjos envolvendo um terceiro cromossomo. Em cinco (10 por cento) pacientes com características de LPA, a técnica de FISH não revelou a fusão PML/RARalfa, dado importante para a orientacão do diagnóstico e da conduta terapêutica desses pacientes. O presente trabalho foi realizado com o objetivo de avaliar a importância da análise citogenética tradicional e molecular no diagnóstico de pacientes com LPA.

The impact of the Dornier Compact Delta lithotriptor on the management of primary ureteric calculi.

OBJECTIVE: To assess the effectiveness of the Dornier Compact Delta lithotriptor on the management of in situ primary ureteric stones. PATIENTS AND METHODS: 137 patients with primary ureteric stones were treated at a tertiary urological center using the latest Dornier Compact Delta lithotriptor between January 1999 and January 2002. Effectiveness of lithotripsy, retreatment rate, reasons for failure and complications were assessed. RESULTS: 102 males and 35 females with primary ureteric stones underwent ESWL treatment at our center. 74 patients had upper, 37 middle and 26 lower ureteric locations respectively. Mean stone size was 10 mm (range 8-25 mm). Mean numbers of sessions required were 1.8 (range 1-3). The retreatment rate was 33% in upper ureteric, 29% in mid ureteric and 26% in lower ureteric locations respectively. Complete clearance rate at 3 months was 86% for upper ureteric, 79% for mid ureteric and 79% for lower ureteric. 29 patients had auxiliary treatment in the form of double J ureteric stenting or percutaneous nephrostomies. 26 patients failed treatment and underwent ureteroscopic or ante grade percutaneous removal. Stone size was the only significant factor correlating with failure. The mean size of stones in the successful group was 12 mm as compared to 17 mm in failure group. The likelihood of success following a failed second session (no disintegration or disintegration with fragments more than 6 mm) of treatment was 13.4%. Complications including, steinstrasse, colic, UTI and petechial haemorrhage were seen in 35 patients. One patient developed pyonephrosis and subsequently required nephrectomy. CONCLUSION: An electromagnetic shock wave lithotriptor using the EMSE-150 shock wave emitter is an effective in situ treatment of primary ureteric stones. Patients with large stone size are likely to have a higher retreatment rate, more auxiliary procedures and complications. Having a failed second treatment session, the likelihood of a successful outcome after third session of ESWL is poor.

The efficacy of a range of contact media as coupling agents in extracorporeal shockwave lithotripsy.

OBJECTIVE: To determine if the nature of the coupling agent normally used between the lithotripter and the patient affects the stone fragmentation rate during extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: A jig designed to hold 'phantom' 10-mm stones at the focal point was fixed against the shock wave delivery point of an electromagnetic lithotripter (Dornier Compact, Germany). A layer of either petroleum jelly (Vaseline, Cheeseborough-Ponds Ltd, London, UK) ultrasonography jelly, a eutectic mixture of local anaesthetic (EMLA) cream, Instillagel (Farco-Pharma, Cologne, Germany) or a commercial water-soluble lubricating jelly was placed between the jig and shockwave head, and the number of shock waves required to fragment the stones was recorded. RESULTS: Significantly more shock waves were required to fragment stones when petroleum jelly was used as the coupling agent than with all the other agents under test, whereas significantly fewer shock waves were required when using Instillagel or lubricating jelly than for all other agents. CONCLUSION: The coupling agent used in water-free lithotripsy can affect the stone fragmentation rate and should not be considered inert. Ultrasonography jelly is probably the optimum agent available for use as a lithotripsy coupling agent.

The interaction of nitric oxide and prostaglandins in the control of corporal smooth muscle tone: evidence for production of a cyclooxygenase-derived endothelium-contracting factor.

OBJECTIVE: To investigate the interaction of endothelium-derived nitric oxide (NO) and prostaglandins (PGs) in regulating corporal smooth muscle tone in vitro. Materials and methods Strips of rabbit corpus cavernosum were mounted in organ chambers for the measurement of isometric tension. Strips were submaximally contracted with noradrenaline and concentration-response curves (CRCs) to acetylcholine (ACh) were constructed before and after treatment with 5 micromol/L atropine, 20 micromol of the cyclooxygenase inhibitor indomethacin and 10 micromol of the PGH2/thromboxane A2 receptor antagonist SQ29548. The NO synthase (NOS) inhibitors L-NG-monomethyl arginine (L-NMMA) and L-NG-nitroarginine (L-NOARG) were added to strips at tonic tension in the presence and absence of indomethacin, and after this CRCs to ACh were constructed. RESULTS: The addition of ACh to strips produced a concentration-dependent relaxation which was inhibited by atropine. Indomethacin, but not SQ29548, significantly increased relaxation to ACh. Relaxation to ACh was impaired by L-NMMA, but adding ACh to strips treated with L-NOARG resulted in contractile responses, whilst both effects were reversed by indomethacin. L-NMMA and L-NOARG led to increases in tonic tone which were unaffected by indomethacin. CONCLUSIONS: In rabbit corpus cavernosum there is a tonic release of NO which does not appear to be inhibited by a vasoconstrictor prostanoid. Endothelium-dependent relaxation to ACh results in the dual production of NO and a cyclooxygenase-derived endothelium contracting factor which acts in opposition to NO; this factor is unlikely to act on PGH2/TXA2 receptors.

Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation.

OBJECTIVE: To develop a new protocol for conserving fertile potential in men undergoing sterilizing chemotherapy by low temperature banking of germ cells which can be returned to the patient's testes after thawing. DESIGN: Isolation of human and murine germ cells for comparing cellular viability after cooling to liquid nitrogen temperatures by the use of different cryoprotective agents and for infusion into the testis. SETTING: Laboratory research environment. PATIENT(S): Men undergoing routine surgery in a urology department. INTERVENTION(S): Testicular biopsy. MAIN OUTCOME MEASURE(S): Cellular viability and infusion of seminiferous tubules. RESULT(S): After isolation using a two-step enzymatic disaggregation protocol, 66% to 87% of germ cells from human and murine specimens, respectively, were still viable. Cell survival was similar in four commonly used cryoprotective agents after cooling to liquid nitrogen temperatures. Seminiferous tubules infused by back flow with dye solution via the rete testis were filled with an efficiency of 55%. CONCLUSION(S): Judging from the high viability of unfractionated germ cells, it is feasible to isolate germ cells from testicular biopsies for low temperature banking with the aim of attempting to restore fertility after iatrogenic sterilization.

The effect of cyclic GMP on rabbit corporal smooth muscle tone and its modulation by cyclo-oxygenase products.

Corporal smooth muscle (CSM) tone is maintained by a finite balance between relaxant and contractile neurotransmitters. The aim of these experiments was to ascertain the degree to which cyclic GMP is involved in these interactions. We also sought to elucidate the pharmacological mechanism of action of MB in rabbit corpus cavernosum (RCC), an important tool in nitric oxide research. Using an organ chamber technique, strips of RCC were treated with the guanylate cyclase inhibitors Methylene Blue (MB) and LY83583; 100 microM MB led to increases in resting tension which were antagonized by indomethacin, nifedipine, phentolamine, but not superoxide dismutase (SOD). Contractile responses to noradrenaline (NA) were increased and relaxation to ACh was impaired by both MB and LY83583 and reversed with indomethacin, but not SOD. Pyrogallol had no effect on agonist-induced responses. The pharmacological action of MB in RCC does not depend on the generation of superoxide anions. Endothelium-dependent relaxation in RCC results in activation of soluble guanylate cyclase and release of a stable endothelium derived contracting factor(s), which is likely to be a constrictor prostanoid(s). Tonic production of cGMP in RCC inhibits the presynaptic release and contractile effects of NA and can be modulated by cyclo-oxygenase inhibition, demonstrating the important interaction and functional antagonism between cGMP and prostaglandins in the control of CSM tone.

Extra-anatomic stents in ureteric obstruction: experience and complications.

OBJECTIVE: To assess the role of extra-anatomic stents (EAS) as a means of urinary diversion in patients with ureteric obstruction secondary to malignancy. PATIENTS AND METHODS: The technique for inserting EAS in patients with ureteric obstruction was described previously; to date, 13 patients (seven women and six men, mean age 45.3 years, range 22-78) have been treated. All patients had ultrasonographic evidence of hydronephrosis and/or significant biochemical evidence of renal impairment. Patients had advanced malignancy and one patient an abdominal aortic aneurysm. RESULTS: Urinary diversion was successful in all patients; two survived for more than 1 year, with stent changes at 6-monthly intervals. In three patients the stents were replaced by percutaneous nephrostomies because of problems with leakage or infection. The remaining patients died with functioning EAS in situ. CONCLUSIONS: In patients with ureteric obstruction secondary to malignancy or medical conditions excluding them from more invasive surgery, EAS provide a further therapeutic option instead of a permanent nephrostomy, which has associated inherent problems. This technique is not without potential problems and careful selection of patients remains vital in this difficult area.

Minimally invasive treatment of urinary tract calculi in children.

OBJECTIVE: To report experience of a broad multimodality approach to the treatment of calculi in children using extracorporeal shock wave lithotripsy (ESWL), ureteroscopy/laser lithotripsy, lithoclast and percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: The treatment and outcome were reviewed in 43 children managed by a range of minimally invasive modalities, either singly or in combination, between 1990 and 1997. These patients represent a selected group deemed suitable for minimally invasive management during a period of developing experience with these techniques. Of this cohort, six children had previously undergone open stone surgery and contributory metabolic abnormalities were identified in seven. ESWL was the sole treatment modality in 24 children (56%). In five children (12%) ureteroscopy/laser lithotripsy was combined with ESWL, eight (18%) underwent ureteroscopy/laser lithotripsy alone, whilst three with bladder stones were treated with the lithoclast. Combined therapy including PCNL was required in three patients. RESULTS: Of the 43 children treated, 38 (88%) were rendered stone-free. Metabolic disorders accounted for three of the five cases of residual calculi. Complications requiring intervention occurred in two children (7%) and three subsequently underwent open pyelolithotomy or ureterolithotomy after unsuccessful minimally invasive treatment. CONCLUSIONS: Used selectively, the range of minimally invasive procedures available for adults, including ureteroscopy and PCNL, can be safely and effectively extended to the treatment of urinary tract calculi in children. The role of open surgery will diminish further with the availability of specialized instruments for paediatric PCNL.

Molecular cytogenetics as a tools for predicting cancer prognosis with special reference to neuroblastoma tumors

Consistent cytogenetic abnormalities have been identified in a variety of human cancer cells and some of them are related to patiente prognosis. Fluorescence "in situ" hybridization (FISH) is a new methodology which can be used to detect cytogenetic anomalies within interphase cells. We present several aspects of FISH methodology and its application in several examples, including trisomy 8 detection with higt specificity and sensitivy in patients with myeloid leukemias; trisomy 12 detection with highter efficiency than conventional cytogenetics in patients with chronic lymphocytic leukemia; assessment of engraftment success; chimerism, and relapse in opposite sex bone marrow transplantation; and correlation of trisomy 7 with survival time in patients with prostate tumors. We discuss also some aspects of neuroblastoma tumors, one of the most frequent malignant solid tumor in childhood. At diagnosis the patient's age and tumor stage are the major prognostic factors. Favorable prognosis is associated with triploid karyotype, lack of 1 p abnormalities and absence of N-myc amplification, whereas unfavorable prognosis is associated with pseudodiploid or tetraploid karyotype, 1 p deletion and N-myc amplification. These abnormalities can be investigated quickly and effecctively in interphase cells using FISH.

The evaluation of sexual function in men presenting with symptomatic benign prostatic hyperplasia.

OBJECTIVE: To evaluate quantitatively and qualitatively the degree of sexual dysfunction in an unselected population of men attending a prostate-assessment clinic using a sexual-function inventory, and to ascertain the degree of correlation between sexual dysfunction, urinary symptoms and age. PATIENTS AND METHODS: In all, 168 men with symptomatic BPH attending a prostate assessment clinic were investigated prospectively using the International Prostate Symptom Score (IPSS), BPH Impact Index (BPHII), a measurement of urinary flow rate and residual urine volume, and a sexual function questionnaire. The results were assessed using Spearman's rank order correlation to discern any correlations between the measured variables. RESULTS: The data from 140 patients were available for analysis; of these, low scores were obtained in 59% for sexual drive, in 56% for erections (with 46% of men satisfying the National Institute of Health criterion for impotence) and in 38% for ejaculation. There was a statistically significant rank order correlation between age and the sexual symptom scores for each of the three categories (sexual drive, erection and ejaculation), but no correlation between age and the problem assessment scores for these domains, suggesting that the older patients are just as bothered by their sexual dysfunction as the younger men. Furthermore, the BPHII scores correlated weakly but significantly with all aspects of sexual function, including overall sexual satisfaction, in contrast to the poor correlation seen with the total IPSS and sexual function scores. CONCLUSION: There is a significant number of patients with symptomatic BPH who have sexual dysfunction, with the proportion increasing with advancing age and with the older men still showing a high degree of bother from their symptoms. Sexual function scores were better correlated with BPHII scores than with the total IPSS, although some of the individual IPSS questions correlated well.

Cytokeratin 20 as an objective marker of urothelial dysplasia.

OBJECTIVE: To investigate the dysregulation of cytokeratin 20 (CK20) expression in urothelial dysplasia and its potential as a diagnostic aid. PATIENTS AND METHODS: Twenty-two patients were selected on the basis that they had undergone one or more biopsies showing dysplasia before the development of a transitional cell carcinoma (TCC): 15 of these patients also had a prior history of TCC. The dysplasia was classified as mild in 12, moderate in 14 or severe dysplasia/carcinoma in situ in 10 patients, ensuring that a spectrum of morphological appearances was represented. Control biopsies were obtained from seven children undergoing bladder reconstructions and 23 patients with recurrent urinary tract infections, haematuria or functional bladder symptoms, but no history of TCC. RESULTS: The expression of CK20 was restricted to superficial 'umbrella' cells and occasional intermediate cells in the control biopsies, even in the presence of severe inflammation. In 31 of the 36 cases of dysplasia complete loss of restriction was seen at least focally with positive expression in all layers of the urothelium. CONCLUSION: The abnormal expression of CK20 is a reliable, positive marker of urothelial dysplasia in the urinary bladder. Immunostaining for CK20 is therefore a useful adjunct to morphology in the diagnosis of dysplasia, of particular value in the distinction from reactive states where diagnostic difficulties are greatest.

Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease.

Although approximately 50% of patients with non-invasive (Ta) papillary transitional cell carcinoma show no recurrence of their disease, current histopathological approaches cannot distinguish this sub-group from those patients in whom the disease will recur. In this 5 year retrospective study, we have shown that cytokeratin 20 (CK20) was expressed in 19 of 29 (65.5%) of non-invasive papillary tumours of grades 1 or 2. CK20 expression patterns were predictive of disease non-recurrence in a sub-group of eight patients, representing 51.7% of patients with non-recurrent disease. In normal bladder mucosa, CK20 expression was restricted to the terminally-differentiated superficial cell. In eight CK20-positive tumours which showed no recurrence at 5 years, CK20 expression was either restricted to, or most intense in, the luminal cells of the papillae. This pattern of expression was not seen in any of the 15 tumours from the recurrent group. Disruption of normal CK20 expression was highly significantly correlated with recurrent tumours. These results suggest that changes in the expression of differentiation-associated antigens, such as CK20, may be useful in predicting benign versus malignant behaviour and may, therefore, be useful in defining treatment strategies.