Alessandro D’Addessi

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.

Bladder Perforation: A Potential Risk of Early Endovesical Chemotherapy with Mitomycin C

The use of chemotherapeutic agents in the treatment of superficial bladder cancer is well known. In particular, mitomycin C (MMC) is globally accepted also in the early treatment after an endoscopic resection. Complications related to MMC are usually scarce as a systemic absorption is quite absent, while its use is effective for the bladder recurrence reduction. In our experience we report a female patient with a bladder perforation after an early instillation of a single dose of MMC. In this case, systemic toxicity occurred requiring subintensive care for a complete repair.

Results of 4 years of experience with bladder replacement using an ileocecal segment with multiple transverse teniamyotomies

Since 1987, 30 patients with bladder cancer underwent cystoprostatectomy with bladder replacement via ileocecourethrostomy. Multiple transverse teniamyotomies were made in the cecum to assure a large capacity reservoir with low pressures. The particular anatomy and physiology of the cecum, short length of the intestinal segment needed and teniamyotomies are the 3 factors that have allowed for good functional and metabolic results. All patients achieved daytime continence. After 3 years of followup 67% of the patients were continent at night if they voided every 3 or 4 hours and 22% if they voided every 2 or 3 hours, while 11% experienced enuresis. Urodynamic data after 1 year showed a mean capacity of 396 ml. for the new bladder, a mean full filling pressure of 28 cm. water and a mean maximum pressure of 55 cm. water. Post-micturition residual urine volume was consistently less than 55 ml. These results indicate that the ileocecal segment can be enlarged with myotomies through the tenia to produce an adequate capacity and a low pressure bladder replacement without the need for formal detubularization.

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.

Social, economic, and health utility considerations in the treatment of overactive bladder.

Overactive bladder (OAB) is a highly prevalent urinary syndrome with a profound impact on quality of life (QoL) of affected patients and their family because of its adverse effects on social, sexual, interpersonal, and professional function. Cost-of-illness analyses showed the huge economic burden related to OAB for patients, public healthcare systems, and society, secondary to both direct and indirect costs; however, intangible costs related to QoL impact are usually omitted from these analyses. Recently many novel treatment modalities have been introduced and the need to apply the modern methodology of health technology assessment to these treatment strategies was immediately clear in order to evaluate objectively their value in term of both improvement in length/quality of life and costs. Health utilities are instruments that allow a measurement of QoL and its integration in the economic evaluation using the quality-adjusted life-years model and cost-utility analysis. The development of suitable instruments for quantifying utility in the specific group of OAB patients is vitally important to extend the application of cost-utility analysis in OAB and to guide healthcare resources allocation for this disorder. Studies are required to define the cost-effectiveness of available pharmacological and nonpharmacological therapy options for this disorder.

[Italian validation of the English PROM-USS-Q questionnaire in patients undergoing anterior urethroplasty].

Background. The aim of this study was to translate and validate in Italian the condition-specific patient-reported outcome measure for urethral stricture surgery (PROM-USS-Q) and evaluate its psychometric properties to determine whether it was suitable for routine use. Methods. We translated the English version; 52 men scheduled for bulbar urethroplasty at our high volume center agreed to self-complete PROM-USS-Q pre-operatively and between four and six months post-operatively We undertook an in-depth psychometric assessment of the questionnaire constructs. Results. There was excellent correlation between change in voiding symptom score and change in Qmax (p=0.746) with parallel improvements in EQ-5D visual analogue and time trade-off scores demonstrating criterion validity. Test-retest reliability and internal consistency statistics were similarly robust: intra-class correlation coefficients ranged from 0.81 to 0.90 for the individual voiding questions. Cronbachs alpha was 0.79 for the overall score and ranged between 0.74 and 0.81. These indices exceeded our predefined reliability thresholds for inclusion. Statistically highly significant improvements in construct scores occurred following urethroplasty, demonstrating responsiveness to change. Conclusions. The PROM-USS-Q is a practical and robust instrument for assessing voiding symptoms and health-related quality of life following urethral stricture surgery.

The Risk of Chronic Kidney Disease Associated with Urolithiasis and its Urological Treatments: A Review

Purpose: Urolithiasis can impair kidney function. This literature review focuses on the risk of kidney impairment in stone formers, the specific conditions associated with this risk and the impact of urological surgery. Materials and Methods: The PubMed® and Embase® databases were searched for publications on urolithiasis, its treatment, and the risk of chronic kidney disease, end stage renal disease and nephrectomy in stone formers. Results: In general, renal stone formers have twice the risk of chronic kidney disease or end stage renal disease, and for female and overweight stone formers the risk is even higher. Patients with frequent urinary tract infections, struvite stones, urinary malformations and diversions, malabsorptive bowel conditions and some monogenic disorders are at high risk for chronic kidney disease/end stage renal disease. Shock wave lithotripsy or minimally invasive urological interventions for stones do not adversely affect renal function. Declines in renal function generally occur in patients with preexisting chronic kidney disease or a large stone burden requiring repeated and/or complex surgery. Conclusions: Although the effect size is modest, urolithiasis may cause chronic kidney disease and, thus, it is mandatory to assess patients with renal stones for the risk of chronic kidney disease/end stage renal disease. We suggest that all guidelines dealing with renal stone disease should include assessment of this risk.

Doping and urologic tumors

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.

Intensive Intravesical Mitomycin C Therapy in Non-Muscle-Invasive Bladder Cancer: A Dose Intensity Approach

Objective: The aim of this work was to verify the tolerability and the preliminary clinical results of intensive intravesical instillations of a mitomycin C (MMC) regimen. Patients and Methods: From September 2007 to November 2009, 40 consecutive evaluable patients with pathologically confirmed intermediate-risk non-muscle-invasive bladder cancer (NMIBC) were enrolled after complete transurethral resection of all visible tumors. The mean age of the patients was 64.5 years. 40 mg MMC diluted in 50 ml of saline was instilled in the bladder three times a week for 2 weeks. The median follow-up was 9 months. Results: All patients fulfilled the scheduled treatment. The local adverse events seen were negligible, while no significant deviation from normal values was observed in blood counts for each patient. Twenty-three of 40 patients (57.5%) showed negative at the cystoscopic control which was performed every 3 months with normal spontaneous and washing cytological exams. Conclusion: MMC is a well-known chemotherapeutic agent for the intravesical therapy of NMIBC. With a view to improving its results, we changed the frequency and intensity of the instillations. No significant local or systemic toxicity was reported. Intensive intravesical instilllations of MMC might become a tool in the management of NMIBC.

Ayurvedic medicine and NADPH oxidase: a possible approach to the prevention of ESRD in hyperoxaluria

Saeed Khan’s longstanding commitment to investigating the pathogenesis of renal stones adds to our knowledge ever more with new evidence to support the hypothesis that exposure of the renal tubular cells to high oxalate and calcium oxalate (CaOx) crystals triggers an oxidative stress cascade that has a pivotal role in crystal retention in the kidney. In this Nephrology Dialysis Transplantation issue, Zuo et al. [1] clearly demonstrates in a model of hyperoxaluria that inhibiting reactive oxygen species (ROS) synthesis reduces tubular injury and prevents crystal retention in thekidney.Inaway,theyhavecompleted 30yearsofstudies which began after the serendipitous observation reported by Baggio et al. [2] that idiopathic CaOx stone formers have tubular damage, as shown by their increased urinary excretion of proximal tubule enzymes. Unfortunately, there is no valid model of human idiopathic calcium oxalate nephrolithiasis (ICN), although there are many models of hyperoxaluria. Mild hyperoxaluria, i.e. an oxalate excretion of up to 60 mg/24 h, is frequently observed in ICN patients [3], but the urinary excretion of oxalate is much higher in the rare secondary hyperoxalurias and the even rarer primary hyperoxalurias, generally exceeding 100 mg/24 h. The experimental models used by many groups (including Khan’s laboratory) to investigate CaOx stone pathogenesis reflect, in our opinion, the conditions of primary and secondary hyperoxalurias rather than the more common, mild hyperoxaluria. In these experimental models, crystals are actually observed intraluminally in the upper nephron and downstream, and they are deposited mainly in the interstitium. While neither of these findings have ever been described in ICN patients, they are typically seen in the nephrocalcinosis of primary and secondary hyperoxaluria. For the above reasons, we believe that the results of the investigations performed by Khan et al. in models of severe hyperoxaluria pertain to a different scenario from ICN. The findings reported by Baggio et al. most likely derive from a different pathogenic sequence. We have advanced the hypothesis that ICN has a two-hits pathogenesis: the first hit is a tubular injuring factor which facilitates CaOx crystal formation in the presence of a mild hyperoxaluria (second hit), possibly by delivering cell debris [4]. This corresponds with many findings in ICN and is consistent with the Randall’s plaque theory of lithogenesis—probably the most rational explanation for stone formation in the kidney: according to this theory, stones grow in the renal pelvis on Randall’s plaques, not in the tubular lumen. Of course, the possibility of the tubular injury observed in ICN patients (the first hit) being caused by an oxidative stress (which is easy to envisage in these patients) cannot be ruled out. For instance, there is a known association between metabolic syndrome and hypertension with renal stones, and both conditions are associated with oxidative stress. In this sense, inhibiting ROS synthesis, as in the experi