E. Montanari

A prospective study of recurrence rate and risk factors for recurrence after a first renal stone.

PURPOSE We investigate further the recurrence rate and risk factors for recurrence in 300 consecutive patients who presented to our stone clinic after a first stone episode 7 to 17 years ago. MATERIALS AND METHODS The medical records of the patients who presented consecutively with a first stone episode from 1980 to 1990 were studied and supplemented by a followup mail questionnaire and telephone interviews. At first visit serum samples were taken from all patients and 24-hour urine samples were collected for metabolic testing. RESULTS A total of 195 patients were followed successfully, of whom 52 (27%) experienced symptomatic stone recurrence after a mean plus or minus standard deviation of 7.5+/-5.9 years. However, ultrasound examination of 36 symptom-free patients showed recurrent stones in 28%. Comparison of patients with or without recurrence confirmed that recurrence was not influenced by sex, family history of stones and urinary risk factors. However, age at onset of the disease was lower for patients who had 2 or more stones during followup than those who had only 1 stone or no recurrence. CONCLUSIONS Stones can recur as long as 10 years after the first episode, although the rate is lower than previously reported. The metabolic evaluation after a first stone episode needs to be reappraised in terms of its cost-effectiveness, since recurrences do not seem to be predictable from standard laboratory tests.

Increase in the Prevalence of Symptomatic Upper Urinary Tract Stones during the Last Ten Years

Purpose: In industrialized countries the prevalence of upper urinary tract stones has continually increased during the 20th century, but there are considerable differences between countries and also within the same country. To study whether there is still an increase in the frequency of renal stones, an investigation was undertaken to determine the prevalence of stone formers in a village near Milan, Italy, during two time periods, with an interval of 12 years.Materials and Methods: Questionnaires were administered in 1986 and 1998 to all adult (age >25 years) occupants of two random samples of households in the village. Participants were asked whether they had experienced a kidney stone during their lifetime.Results: The overall prevalence of stone formers among males was 6.8% in 1986 and 10.1% in 1998; that among females was 4.9% in 1986 and 5.8% in 1998. In all age classes, the respondents in the 1998 survey more frequently reported a history of stones than in 1986, but the prevalence of renal stones was significantly higher in 1998 than in 1986 only among males aged 31–40 and 51–60 years. The yearly incidence was estimated at 0.4%, with 0.6 and 0.18% in men and women, respectively.Conclusions: This marked increase in renal stones could be the result of environmental factors such as dietary habits and lifestyle, in particular the influence of an increased consumption of animal protein should be considered.

In Vivo Evaluation of the Chemical Composition of Urinary Stones Using Dual-Energy CT

OBJECTIVE The purpose of this article is to evaluate in vivo the chemical composition of urinary stones using dual-source and dual-energy CT, with crystallography as the reference standard. MATERIALS AND METHODS Forty patients (mean [± SD] age, 49 ± 17 years) with known or suspected nephrolithiasis underwent unenhanced abdominal CT for urinary tract evaluation using a dual-energy technique (tube voltages, 140 and 80 kVp). For each stone 5 mm or larger in diameter, we evaluated the site, diameter, CT density, surface (smooth vs rough), and stone composition. Patients were treated with extracorporeal shock wave lithotripsy (n = 34), percutaneous nephrolithotomy (n = 4), or therapeutic ureterorenoscopy (n = 2). Collected stones underwent crystallography, and the agreement with the results of dual-energy CT was calculated with the Cohen kappa coefficient. The correlation among stone composition, diameter, and CT density was estimated using the Kruskal-Wallis test. RESULTS Thirty-one patients had a single stone and nine had multiple stones, for a total of 49 stones. Forty-five stones were in the kidneys, and four were in the ureters; 23 had a smooth surface and 26 had a rough surface. The mean stone diameter was 12 ± 6 mm; mean CT density was 783 ± 274 HU. According to crystallography, stone composition was as follows: 33 were calcium oxalate, seven were cystine, four were uric acid, and five were of mixed composition. Dual-energy CT failed to identify four stones with mixed composition, resulting in substantial agreement between dual-energy CT and crystallography (Cohen κ = 0.684). Stone composition was not correlated with either stone diameter (p = 0.920) or stone CT density (p = 0.185). CONCLUSION CT showed excellent accuracy in classifying urinary stone chemical composition, except for uric acid-hydroxyapatite mixed stones.

Renal stone fragments following shock wave lithotripsy

PURPOSE We describe a select group of asymptomatic patients with fragments and dust 3 months after extracorporeal treatment, who were followed to evaluate the long-term outcome and therapeutic implications. MATERIALS AND METHODS A total of 129 patients with dust and residual fragments (less than 4 mm.) at 3 months was re-examined at 12 months, and 95 were also evaluated at 24 months. Followup examinations consisted of radiographic studies, renal ultrasonography and urine culture. Dust and residual fragments were sought, and patients were defined as free or as having persistent lithiasis or stone regrowth. At 24 months recurrences in the patients stone-free at 12 months also were considered. RESULTS At the 12-month followup 60 patients (46.5%) were stone-free and 56 (43.5%) still had dust or residual fragments. The localization of the stones or fragments at 3 months and their sizes did not have a significant influence on the stone-free rate but regrowth was greater in patients with stones larger than 10 mm. (11 of 40 patients, 27.5% versus 2 of 89, 2.2%, p = 0.001). The probability of eliminating residual lithiasis at 12 months was significantly greater in patients with dust than in those with residual fragments (42 of 79 patients, 58% versus 18 of 50, 36%, p = 0.026). Regrowth of residual lithiasis was observed in 13 patients (10%). CONCLUSIONS Based on our results, we do not believe that patients with fragments require systematic re-treatment in the short term but they may be followed long term and re-treated if symptoms persist or stones recur.

Evaluation of Urinary Level of NMP22 as a Diagnostic Marker for Stage pTa-pT1 Bladder Cancer: Comparison with Urinary Cytology and BTA Test

Background: In the present study we compared the clinical value of two new specific tests for transitional cell carcinoma, urinary nuclear matrix protein (NMP22) levels and bladder tumor antigen (BTA) test, with that of urinary cytology in the follow-up of patients with superficial bladder cancer. Materials and Methods: Hundred and five bladder cancer patients were recruited: 30 stage pTa and 45 stage pT1 (group A), and 30 with a history of bladder cancer but no recurrence at the time of the study (group B). Urine samples were collected before any instrumental manipulation of the genitourinary tract. All patients were negative for urinary tract infections at conventional urine analysis. Results: NMP22 at a cutoff value of 6 U/ml showed a sensitivity of 83.3% in pTa cases and 97.7% in pT1 cases, with a false-positive rate of 23.3%. The BTA test was positive in 26.6% of patients with cancer stage pTa and in 66.6% of pT1 stage, with 30% false-positives in the non-neoplastic group. Urinary cytology, performed on three consecutive samples, was positive in 20% of patients with cancer stage pTa and in 64.4% of pT1 stage and did not show any false-positive cases. Stratifying the neoplastic patients according to lesion grade, NMP22 (at a cutoff value of 6 U/ml) was positive in 86.2% of G1, 97.2% of G2 and 90% of G3. BTA was positive in 37.9, 52.7 and 70% of G1, G2 and G3, respectively, while urinary cytology was positive in 37.9, 44.4 and 80%.

Management of Symptomatic BPH in Italy: Who Is Treated and How?

Objective: To investigate the management of symptomatic benign prostatic hyperplasia (BPH) in Italy. Methods: Information on diagnosis, medical and surgical treatment was obtained from two different questionnaires independently mailed to urological centers in Italy. Data on drug treatments were obtained from a national database. General practitioner (GP) clinical practice patterns were obtained from a panel discussion between general practitioners and urologists. Results: First line medical treatment is currently undertaken by GPs more often and to a smaller extent by urologists to whom patients can self-refer. Primary care diagnostic algorithm consists of patient’s interview, physical rectal examination and urinalysis. The main reason for referral of a BPH patient to the urologist by GPs appears to be an unsatisfactory outcome of first line medical therapy. Examination of the suprapubic area plus rectal examination is always performed by urologists during physical examination while evaluation of motor and sensory function is carried out in 28% of patients only. Voiding diary and I-PSS score are currently used by 17 and 65% of urologists, respectively. Urinalysis, plasma creatinine and prostate specific antigen (PSA) are used in 100, 94 and 89% of cases, respectively. Ninety-four percent of urologists use uroflowmetry with evaluation of post voiding residual by ultrasound. Pressure-flow studies are used in selected cases by 89% of urologists. Ultrasound imaging of the kidney, bladder and prostate transrectal ultrasound (TRUS) is reported as current practice in 79, 71 and 53% of questionnaires, respectively. Over six million medical consultations with prescriptions for BPH were carried out in 1998 accounting for 190,600,000 drug treatment days. Prescriptions for 5α-reductase inhibitors accounted for 71,400,000 days of treatment, α-blockers for 104,000,000 and plant extracts for 15,300,000 days. In 24 to 28% of cases more than one drug was prescribed. Indications for invasive treatment rely on symptoms (98%), presence of BPH complications (90%), flowmetry (65%), residual urine (50%), prostate volume (40%) and urodynamics (20%). About 10% of patients consulting the outpatient clinics were allocated to watchful waiting, 50% received pharmacological treatment and 40% invasive treatment. Analysis of invasive treatment options resulted in 62% of patients receiving transurethral resection of the prostate (TURP), 29% open prostatectomy and the remaining 9% received various forms of minimally invasive treatments. Patients were most commonly followed up for 3 months with 62% of patients followed up at one year post-operatively and then yearly. Conclusions: Our survey suggests that the current clinical practice of primary and secondary care physicians is in line with the recommendations of the IVth International Consultation on BPH. However, Italian urologists seem to use less frequently symptom scores and voiding diaries than recommended. It seems that open surgery is more frequently used in Italy than in other European countries. Minimally invasive treatments remain a very small portion of interventions for the management of BPH in Italy. Fifty-five percent of patient days of treatment are α-blockers, 37% is finasteride. The share of α-blockers has dramatically grown with the introduction of the first prostate-selective agent, tamsulosin.

Percutaneous nephrolithotomy in children in different age groups: data from the Clinical Research Office of the Endourological Society (CROES) Percutaneous Nephrolithotomy Global Study

Whats known on the subject? and What does the study add?

The Methylation of the TSC2 Promoter Underlies the Abnormal Growth of TSC2 Angiomyolipoma-Derived Smooth Muscle Cells

Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that is caused by mutations in either the TSC1 or TSC2 gene. Smooth muscle-like cells (ASMs) were isolated from an angiomyolipoma of a patient with TSC. These cells lacked tuberin, were labeled by both HMB45 and CD44v6 antibodies, and had constitutive S6 phosphorylation. The cells bear a germline TSC2 intron 8-exon 9 junction mutation, but DNA analysis and polymerase chain reaction amplification failed to demonstrate loss of heterozygosity. Testing for an epigenetic alteration, we detected methylation of the TSC2 promoter. Its biological relevance was confirmed by tuberin expression and a reduction in HMB45 labeling and S6 constitutive phosphorylation after exposure to the chromatin-remodeling agents, trichostatin A and 5-azacytidine. These cells were named TSC2(-/meth) ASMs. Their proliferation required epidermal growth factor in the medium as previously described for TSC2(-/-) ASMs. Blockade of epidermal growth factor with monoclonal antibodies caused the death of TSC2(-/meth) ASMs. In addition, rapamycin effectively blocked the proliferation of these cells. Our data show for the first time that methylation of the TSC2 promoter might cause a complete loss of tuberin in TSC2 cells, and that the pathogenesis of angiomyolipomas might also originate from epigenetic defects in smooth muscle cells. Additionally, the effect of chromatin-remodeling agents in these cells suggests a further avenue for the treatment of TSC as well as lymphangioleiomyomatosis.

Postoperative Infection Rates in Low Risk Patients Undergoing Percutaneous Nephrolithotomy With and Without Antibiotic Prophylaxis: A Matched Case Control Study

PURPOSE Current guidelines recommend prophylactic antibiotic therapy for all patients undergoing percutaneous nephrolithotomy. We examined the effects of antibiotic prophylaxis in patients undergoing percutaneous nephrolithotomy with negative preoperative urine cultures. MATERIALS AND METHODS Of the 5,803 patients in the CROES (Clinical Research Office of the Endourological Society) Percutaneous Nephrolithotomy Global Study database, a group of 162 patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture who did not receive antibiotic prophylaxis were matched on preoperative nephrostomy, the presence of staghorn calculi and diabetes status with an equal number of patients who received antibiotic prophylaxis. Comparisons were made between the 2 groups in terms of operative and postoperative outcomes, including the incidence of fever and other complications. RESULTS Patients who received antibiotic prophylaxis had a lower mean (SD) age at 44.9 (14.2) vs 50.1 (14.4) years (p = 0.001). They were also more likely to be in the prone position during the procedure (71.6% vs 39.5%, p <0.001) but less likely to receive postoperative stenting (17.3% vs 32.7%, p = 0.002) than those who did not receive prophylaxis. The 2 groups were comparable in terms of all other baseline characteristics and operative factors. Patients who received antibiotic prophylaxis were less likely to experience fever (2.5% vs 7.4%, p = 0.040) and other postoperative complications (1.9% vs 22.0%, p <0.0001), and had a higher stone-free rate after percutaneous nephrolithotomy (86.3% vs 74.4%, p = 0.006). CONCLUSIONS Antibiotic prophylaxis of patients undergoing percutaneous nephrolithotomy with a negative baseline urine culture is associated with a significant reduction in the rate of postoperative fever and other complications.

Long-term followup after extracorporeal shock wave lithotripsy treatment of kidney stones in solitary kidneys

A total of 64 treatments by the Dornier HM3 lithotriptor was performed on 52 solitary kidneys with stones. A slight increase but no significant variations in serum creatinine was noted in 15 patients without obstruction just after treatment (p greater than 0.05). No significant increases in serum creatinine were found even at the short-term, mid-term and long-term followup. After 12 to 56 months hypertension developed in only 1 previously normotensive patient. Of 37 patients at mid-term followup (12 to 24 months) 62% were stone-free, 24% had passable fragments, 8% had recurrent stones and 5% had regrowth of the residual fragments. At long-term followup (24 to 56 months) 50% of 26 patients were stone-free, 19% had dust or passable fragments, 19% had recurrences and 11% had regrowth of the residual fragments. The demonstrated effectiveness, small number of complications at the short-term followup, lack of sequelae at the long-term followup and relatively small number of recurrences confirm that extracorporeal lithotripsy is not only effective but also safe. It can be proposed as the treatment of first choice even when the stone is in a single remaining kidney.