Urologic surgery in gynecologic oncology: a large single-institution experience.

OBJECTIVE: The increasing tendency to a tailored treatment in gynecologic oncology has required the extension of the intervention to other non-gynecological structures, as the urinary district. Moreover the role of the urological surgery in gynecologic oncology is still not completely explored. The objective of the study is to evaluate the occurrence of urological procedures in gynecologic oncology surgery. METHODS: Patients admitted to the Division of Gynecologic Oncology, Catholic University of Sacred Hearth, Rome, Italy, between January 2009 and December 2012, were retrospectively analyzed. Clinical charts identified the occurrence of urological procedures in major gynecological surgery. RESULTS: A total of 728 patients were analyzed for the study. A total of 204 urologic procedures were carried out in 83 patients. In all patients, preoperative hydronephrosis appears to be the only statistically significant predisposing factor to urological procedures. At multivariate analysis, stratifying data for different neoplasm, recurrence was the only adjunctive significant variable for ovarian cancer, as well as neo-adjuvant treatment and recurrence for cervical cancer. CONCLUSIONS: This study has identified preoperative factors influencing the needing of urological procedures in different gynecologic neoplasms, allowing a proper planning of surgical treatment, tailored on each patient.

Size of bladder cancers: correlation among different types of measurement.

OBJECTIVE: It was the aim of this study to evaluate the accuracy of the measurement of tumor size comparing the objective size with that measured by preoperative cystoscopy, by preoperative ultrasound (US) and with the diameter described by the operator before the transurethral resection. PATIENTS AND METHODS: This study included 100 patients with bladder papillary endoscopic features of single or multiple neoplasms who were candidates for transurethral resection. The sizes of the same neoplasms measured during preoperative cystoscopy, preoperative US and described by the operator before the transurethral resection were evaluated. A statistical analysis of the errors of measurement was performed if compared with an objective measurement done with an ureteral catheter. RESULTS: The statistical analysis of the data shows that there are no substantial differences between the objective and subjective measurement, and therefore, the measurements reported by individual operators are reliable. On the contrary, the diameters given by preoperative cystoscopy and US differ significantly from the objective measurement. CONCLUSIONS: This study shows that the most reliable measurement is the subjective measurement made directly by the urologist in the operating room.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Thermochemotherapy for non-muscle-invasive bladder cancer: is there a chance to avoid early cystectomy?.

OBJECTIVES: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. PATIENTS AND METHODS: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. RESULTS: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. CONCLUSIONS: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Value of current chemotherapy and surgery in advanced and metastatic bladder cancer.

The aim of the present paper was to review findings from the most relevant studies and to evaluate the value of current chemotherapy and surgery in advanced unresectable and metastatic bladder cancer. Studies were identified by searching the MEDLINE® and PubMed® databases up to 2011 using both medical subject heading (Mesh) and a free text strategy with the name of the known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'chemotherapeutics agents', and 'surgery in advanced bladder cancer'. At the end of our literature research we selected 141 articles complying with the aim of the review. The results showed that it has been many years since the MVAC (methotrexate, vinblastine, adriamycin, cisplatin) regimen was first developed. The use of cisplatin-based combination chemotherapy is associated with significant toxicity and produces long-term survival in only approximately 15-20% of patients. Gemcitabine + cisplatin represents the gold standard in the treatment of metastatic bladder cancer. In conclusion, the optimal approach in the management of advanced urothelial cancer continues to evolve. Further progress relies on the expansion of research into tumor biology and an understanding of the underlying molecular 'fingerprints' that can be used to enhance diagnostic and therapeutic strategies. Cisplatin-based therapy has had the best track record thus far.

[Sports and genitourinary traumas]. / Sport e traumi genitourinari.

INTRODUCTION: Statistical data referring to sports-related traumas of the urinary tract are quite scarce; nevertheless, it is possible to draw general data on the relationship between sports and urological traumas. METHODS: Literature review of peer-reviewed articles published by May 2009. RESULTS: Urological traumas account for about 10% of all traumas, and about 13% of them is sports-related. Genitourinary traumas are among the most common cause of abdominal injuries in sports. Blunt injuries are more common than penetrating ones and renal injuries are by far the most common, followed by testicular injuries; ureters, bladder and penis injuries are much more infrequent. Considering chronic microtraumas, injuries of bulbar urethra are also common in sports that involve riding. Overall, the incidence of genitourinary trauma due to sports is low. Renal traumas in sports injuries usually consist of grade I-II lesions and usually do not require surgical treatment. Cycling is the sporting activity most commonly associated with genitourinary injuries, followed by winter sports, horse riding and contact/collision sports. Literature data suggest that significant injuries are rare also in athletes with only one testicle or kidney. General preventive measures against sport-related injuries, along with the use of protective cups for male external genitalia, are generally sufficient to reduce the incidence of urogenital trauma. CONCLUSIONS: Overall, studies show that urogenital injuries are uncommon in team and individual sports, and that most of them are low-grade injuries. Participation in sports that involve the potential for contact or collision needs to be carefully assessed in the athletes with only one testicle or kidney, even though urogenital injuries should not preclude sports participation to an appropriately informed and counseled patient. Further research is needed to acquire more knowledge on genitourinary injuries according to age, sports type and technical skill.

[Doping and urologic tumors]. / Doping e neoplasie urologiche.

Several substances such as growth hormone (GH), erythropoietin (Epo), and anabolic steroids (AS) are improperly utilized to increase the performance of athletes. Evaluating the potential cancer risk associated with doping agents is difficult since these drugs are often used at very high doses and in combination with other licit or illicit drugs. The GH, via its mediator, the insulin-like growth factor 1 (IGF-1), is involved in the development and progression of cancer. Animal studies suggested that high levels of GH/IGF-1 increase progression of androgen-independent prostate cancer. Clinical data regarding prostate cancer are mostly based on epidemiological studies or indirect data such as IGF-1 high levels in patients with prostate cancer. Even if experimental studies showed a correlation between Epo and cancer, no clinical data are currently available on cancer development related to Epo as a doping agent. Androgens are involved in prostate carcinogenesis modulating genes that regulate cell proliferation, apoptosis and angiogenesis. Most information on AS is anecdotal (case reports on prostate, kidney and testicular cancers). Prospective epidemiologic studies failed to support the hypothesis that circulating androgens are positively associated with prostate cancer risk. Currently, clinical and epidemiological studies supporting association between doping and urological neoplasias are not available. Nowadays, exposure to doping agents starts more prematurely with a consequent longer exposition period; drugs are often used at very high doses and in combination with other licit or illicit drugs. Due to all these elements it is impossible to predict all the side effects, including cancer; more detailed studies are therefore necessary.

[Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives]. / La deprivazione androgenica nel carcinoma prostatico: evidenze cliniche e prospettive future.

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

Peyronie's disease: lights and shadows.

Peyronie's disease (PD) is characterized by the onset of fibrous plaque inside the tunica albuginea of the penile corpora cavernosa that can cause pain and bending during the erection, making intercourse difficult or impossible. Evidence of the literature supports the autoimmune etiology of PD and suggests genetic and familiar conditions, penile traumatisms, and a history of genital tract diseases as risk factors, but no definitive conclusions arise about the pathogenesis of the disease. Few randomized trials demonstrated that medical therapies, such as vitamin E, colchicine, potassium aminobenzoate, tamoxifen, and injection therapy with verapamil, can stabilize the acute phase of the disease. Extracorporeal shock wave therapy and iontophoresis cannot be considered first-line or gold standard therapies. Satisfactory results have been published with the Nesbit operation in large series with low-stage disease, whereas plication procedures have shown significant relapse rates. A high incidence of long-term penile retractions has been reported in high-stage disease treated with plaque incision and simple graft insertion. Malleable, soft, or inflatable prostheses combined with graft implantation have given the best results in terms of penile straightening and lengthening and patient satisfaction. In conclusion, the etiopathogenesis of PD is not yet clearly understood, no medical therapy is fully effective, and surgery remains the gold standard in patients with severe deformity and/or erectile dysfunction.

[Regenerative medicine: applications and development in urology].

PURPOSE. Congenital abnormalities and acquired disorders can lead to organ damage and loss. Nowadays, transplantation represents the only effective treatment option. However, there is a marked decrease in the number of organ donors, which is even yearly worsening due to the population aging. The regenerative medicine represents a realistic option that allows to restore and maintain the normal functions of tissues and organs. This article reviews the principles of regenerative medicine and the recent advances with regard to its application to the genitourinary tract. RECENT FINDINGS. The field of regenerative medicine involves different areas of technology, such as tissue engineering, stem cells and cloning. Tissue engineering involves the field of cell transplantation, materials science and engineering in order to create functional replacement tissues. Stem cells and cloning permit the extraction of pluripotent, embryonic stem cells offering a potentially limitless source of cells for tissue engineering applications. Most current strategies for tissue engineering depend upon a sample of autologous cells from the patient's diseased organ. Biopsies from patients with extensive end-stage organ failure, however, may not yield enough normal cells. In these situations, stem cells are envisaged as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. Regenerative medicine and tissue engineering scientists have increasingly applied the principles of cell transplantation, materials science and bioengineering to construct biological substitutes that will restore and maintain normal function in urological diseased and injured tissues such as kidney, ureter, bladder, urethra and penis. CONCLUSIONS. Regenerative medicine offers several applications in acquired and congenital genito-urinary diseases. Tissue engineering, stem cells and, mostly, cloning have been applied in experimental studies with excellent results. Few preliminary human applications have been developed with promising results.

Apoptosis-related gene expression in benign prostatic hyperplasia and prostate carcinoma.

BACKGROUND: The aim of this study was to examine the expressions of the bcl-2, bax, fas and c-myc apoptosis-related genes in benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) to determine whether significant differences exist within each disease and between the two groups of patients. The correlation between gene expression and tumour diameter, stage, Gleason score and serum PSA was also investigated. PATIENTS AND METHODS: Tissue specimens from 51 cases of BPH and 27 cases of CaP were examined for bcl-2, bax, fas and c-myc expression by reverse transcriptase-PCR (RT-PCR). RESULTS: In BPH, bcl-2 and bax gave the weakest signals (p < 0.001). In CaP, bcl-2 was the least expressed gene (p < 0.001). In both patient groups, fas and c-myc were the most highly expressed genes (p < 0.05). Both bcl-2 and bax were expressed at higher levels in CaP than in BPH (p < 0.02). The bcl-2/bax ratio was lower in CaP than in BPH (p < 0.001). Bcl-2 was more highly expressed in high Gleason grade (> 7) tumours (p < 0.05). In the BPH group, bax showed a positive relationship with fas (p < 0.01), while the bcl-2 level inversely correlated with that of c-myc (p < 0.05). CONCLUSION: Our data showed that all the apoptosis-related genes were expressed in both BPH and CaP. The stronger expression of bax and the lower bcl-2/bax ratio observed in CaP may suggest a pro-apoptotic stimulus, while the higher bcl-2 levels appear to counterbalance the tendency to cell death.

Benign prostatic hyperplasia: correlations between receptor density and binding affinity of alpha(1)-adrenoceptors and several clinical parameters.

The aim of the study was to determine whether relations do exist between the concentration and activity of alpha(1)-adrenoceptors, both inside the prostatic adenoma and the periurethral zone corresponding to the bladder neck, and clinical and biological parameters such as symptoms, evaluated by the American Urological Association (AUA) score, age, weight of the prostate, PSA, and the flow rate. Twenty patients with symptomatic benign prostatic hyperplasia were selected for an open prostatectomy. One gram of tissue was dissected from inside the adenoma and 1 g from the periurethral zone corresponding to the bladder neck. The alpha(1)-adrenoceptors were evaluated for the apparent dissociation constant (K(d)) and the maximal number of binding sites (B(max)). A correlation seems to exist between receptor density inside the adenoma and the bladder neck and an inverse correlation between receptor density and the AUA total symptoms score. Finally, a highly significant difference was found in patients with an AUA score of <15 or >15. No relationship was found between receptor binding affinity and the considered clinical parameters.

Diagnosis of T1 bladder transitional cell carcinoma by denaturing gradient gel electrophoresis urinalysis.

OBJECTIVE: The diagnosis and follow-up of patients with T1 bladder cancer relies invasive procedures. We developed a non-invasive method for detection of T1 bladder cancer based on a feasible non-radioactive molecular approach. MATERIALS AND METHODS: Urine DNA samples were collected from 24 patients with T1 transitional cell carcinoma (TCC) of the bladder and were processed by denaturing gradient gel electrophoresis (DGGE) analysis. Urine samples obtained from 10 individuals with no clinical evidence of genitourinary malignancy were used as controls. RESULTS: Ten patients out of 24 (41%) had p53 mutations in their tumor samples. Seven of these presented the same mutation in matched urine samples. The p53 mutation pattern found in urine was always identical to that identified in the primary tumor. Decision diagnostic criteria showed that molecular screening by DGGE of amplified DNA from urine sediment had 69.2 % sensitivity, 100% specificity, 95.8 % accuracy, 100% prediction of positive result and 95.4 % prediction of negative result, respectively. No p53 mutation was found in the urine from control subjects. CONCLUSION: DGGE analysis of urine samples could be a useful tool for the early detection of T1 bladder cancer or its recurrence, potentially leading to a reduction in the frequency of invasive procedures used for the management of this disease.

Long-term behavior of secretory immunity in ileocecal and ileal orthotopic neobladders.

OBJECTIVE: To compare secretory immunity in cecal and ileal orthotopic neobladders, and to detect its permanence over time. PATIENTS AND METHODS: IgA was studied in the urine of 33 patients with ileocecourethrostomy (ICUS) and 13 patients with ileal reservoir (IR). The mean follow-up was 55 months. Results were compared in terms of the type of operation, a healthy control group, and the time since surgery. RESULTS: Urinary IgA levels were significantly higher in ICUS and IR patients than in normal controls. No significant differences in IgA concentrations were detected in patients with different reservoirs and with regard to time. CONCLUSION: Both the reservoirs maintain the function of producing IgA. In particular no differences were detected over time and urine could be a permanent antigenic stimulus. IgA could be considered an adjunctive factor for upper urinary tract protection. For this reason we prefer to use a simple, indirect antireflux mechanism, thus avoiding direct manipulation of the uretero-intestinal anastomosis.

Acid-base and electrolyte balance in urinary intestinal orthotopic reservoir: ileocecal neobladder compared with ileal neobladder.

OBJECTIVES: To compare acid-base and electrolyte balance in ileocecal and ileal neobladders. METHODS: Acid-base and electrolyte balance were studied in 45 patients with an ileocecourethrostomy and 18 patients with an ileal reservoir. The mean follow-up was 51 months. Results were compared with regard to both the type of operation and the time since surgery. RESULTS: No significant differences were found with regard to either the type of operation or the length of follow-up. A preserved renal function is important in maintaining a healthy status. CONCLUSIONS: The use of 35 to 40 cm of ileum or 10 cm of cecum with the ileocecal junction seems to be safe even after a long follow-up. The length rather than the kind of bowel used for bladder replacement appears to be important in safeguarding hydroelectrolyte and acid-base homeostasis. This is particularly true in the presence of preserved renal function.

Haemodynamic changes detected during open prostatectomy and transurethral resection for benign prostatic hyperplasia.

To detect possible intraoperative haemodynamic differences, 60 patients undergoing transurethral (n = 18) or open prostatectomy (n = 42) for benign prostatic hyperplasia were evaluated. The same type of general anaesthesia was used in the two groups. Data, including temperature and cardiac output, were collected at five standard times during the procedures. No significant differences were found between the two groups. However, in all patients, irrespective of the operation, significant decreases in cardiac output and increases in systemic resistance occurred during surgery. Body temperature showed a mild, insignificant decrease, which may play a role in determining the mild haemodynamic derangement observed in all patients. Our patients subjected to open prostatectomy and transurethral resection presented the same kind of haemodynamic derangement, with no significant differences. Therefore it seems unlikely that the kind of surgery could play a relevant role in the late mortality rate of these patients.

Xylose absorption and metabolic status in urinary intestinal orthotopic reservoir: ileocecal compared with ileal neobladder.

PURPOSE: We compare the absorption of D-xylose and vitamin B12, and the metabolic status in ileocecal and ileal orthotopic neobladders. MATERIALS AND METHODS: D-xylose plasma levels after an oral load, body composition, plasma vitamin B12, acid base and electrolyte balance were studied in 33 patients with an ileocecal reservoir and 13 patients with an ileal reservoir. Mean followup was 55 months. Results of both types of operation and a healthy control group were compared. RESULTS: Plasmic levels of D-xylose and vitamin B12 were significantly lower in the ileal reservoir than in ileocecal reservoir group and normal controls. CONCLUSIONS: Despite an acceptable body composition, intestinal malabsorption could be present in patients with an ileal reservoir but the ileocecal tract appears to be safe.

Adenocarcinoma of the urachus: radical or conservative surgery? A report of a case and a review of the literature.

AIMS: To identify the most appropriate surgical strategy for carcinoma of the urachus. METHODS: Analysis of a case of adenocarcinoma of the urachus and an examination of the current literature were carried out. CONCLUSIONS: Partial cystectomy is considered the most appropriate surgical strategy but the need for close follow-up is underlined.

Clinical review of 100 consecutive surgically treated patients with upper urinary tract transitional tumours.

OBJECTIVE: To determine the outcome of conservative or radical treatment in a retrospective study of 100 consecutive patients with upper urinary tract tumours. PATIENTS AND METHODS: From 1965 to 1995, 100 patients (78 men and 22 women, mean age 65 years, range 27-82) with upper urinary tract tumours were treated surgically, using nephroureterectomy with excision of a cuff of bladder in 53 and organ-sparing treatment in 47. The outcome was assessed as survival and recurrence during a follow-up of up to 15 years. RESULTS: After radical and organ-sparing treatment, the 15-year cancer-specific survival was 69% and 25%, respectively; metastases developed in 17% and 19% and global recurrence in 40% and 70%, respectively. While locoregional and bladder recurrences were similar in the two groups (9% vs 8% and 30% vs 38%, respectively), ureteric-stump recurrence in the conservative group was 23%. There were no significant differences in survival rates between patients with single or multiple presentation, or for localization, while the grading of the lesions proved to be an accurate prognostic indicator. CONCLUSION: This experience of urothelial neoplasia of the upper tract highlights the difficulty in diagnosing this pathology and in entrusting screening to a non-invasive technique such as urinary cytology. The percentage recurrence observed after organ-sparing therapy indicates that this treatment should be used cautiously.