Frank d'Ancona

Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density

Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 × 10−12 for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).

Current Status of Thermotherapy of the Prostate

PURPOSE We reviewed the available data on transurethral microwave thermotherapy in the treatment of patients with benign prostatic hyperplasia (BPH). Furthermore we provide a perspective of this minimally invasive treatment modality. MATERIALS AND METHODS To our knowledge all previously reported data from clinical trials of transurethral microwave thermotherapy for BPH are reviewed. RESULTS Transurethral microwave thermotherapy was designed to apply microwave energy deep within lateral prostatic lobes while simultaneously cooling the urethral mucosa, thus enabling an outpatient based anesthesia-free procedure. Lower energy protocols using the Prostraton device provide significant symptomatic improvement and improvement in maximum flow of approximately 35% over baseline. Similar changes are being documented with other transurethral microwave thermotherapy devices. Higher energy protocols using the Prostatron device result in symptomatic improvement similar to that of lower energy protocols, while improvement in uroflowmetry is much more pronounced. However, the latter effect is achieved at the expense of increased morbidity. Second generation protocols have not yet been documented by users of the other thermotherapy devices. CONCLUSIONS Numerous studies unequivocally support the efficacy and safety of transurethral microwave thermotherapy for treatment of symptomatic BPH. Significant improvement in objective and subjective parameters has been realized with transurethral microwave thermotherapy at multiple centers in the United States and Europe.

Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5).

High energy thermotherapy versus transurethral resection in the treatment of benign prostatic hyperplasia : results of a prospective randomized study with 1 year of followup

PURPOSE We compared the outcome of transurethral resection of the prostate and high energy microwave thermotherapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS Of 52 patients with symptomatic benign prostatic hyperplasia 21 (mean age plus or minus standard deviation 69.6 +/- 8.5 years) were treated with transurethral resection of the prostate and 31 (mean age 69.3 +/- 5.9 years) were treated with high energy microwave thermotherapy. Patients were assessed using the Madsen symptom score, measurements of voiding parameters, transrectal ultrasound and cystometry, including pressure-flow analyses. Examinations were repeated at fixed intervals for up to 12 months after treatment. RESULTS After transurethral resection and thermotherapy there was significant improvement in all clinical parameters. At 1 year of followup symptomatic improvement was 78% in the transurethral resection group versus 68% in the thermotherapy group, with improvements in free flow rate of 100 and 69%, respectively. Both groups had significant relief of bladder outlet symptoms. No serious complications occurred in either group, while 1 patient in each group required repeat treatment. CONCLUSIONS Satisfactory results were obtained after both treatments, with improvements following high energy microwave thermotherapy being in the same range as those after transurethral resection of the prostate.

SEXUAL FUNCTION FOLLOWING HIGH ENERGY MICROWAVE THERMOTHERAPY: RESULTS OF A RANDOMIZED CONTROLLED STUDY COMPARING TRANSURETHRAL MICROWAVE THERMOTHERAPY TO TRANSURETHRAL PROSTATIC RESECTION

PURPOSE We evaluate changes in sexual function in patients treated with high energy transurethral microwave thermotherapy compared to transurethral resection of the prostate. MATERIALS AND METHODS A total of 147 patients randomized to undergo transurethral microwave thermotherapy or transurethral resection of the prostate were asked to complete a self-administered questionnaire evaluating sexual function before, and 3 and 12 months after treatment. The questionnaire dealt with such items as social status, libido, quality of erection, ejaculation and overall satisfaction of sexual functioning. RESULTS There was a statistically significant improvement of micturition in both groups. The improvement in the transurethral prostatic resection group was significantly better than in the transurethral microwave thermotherapy group. Antegrade ejaculation occurred at 3 months following treatment in 27% of the transurethral prostatic resection group compared to 74% of the transurethral microwave thermotherapy group and at 1 year in 37 and 67%, respectively. Significantly more patients undergoing transurethral prostatic resection (36%) had changes in sexual function compared to the transurethral microwave thermotherapy group (17%). The transurethral microwave thermotherapy group was more satisfied with the sex life. Of these patients 55% graded sex as very satisfying compared to 21% in the transurethral prostatic resection group. The severity of symptoms was not correlated with sexual function in this study. In general, older patients had sexual dysfunction more often, while younger patients had pain during sexual activities more frequently. CONCLUSIONS Although clinically less effective, high energy transurethral microwave thermotherapy is a better therapeutic option than surgery for patients who want to preserve sexual function. In particular ejaculation is often preserved after transurethral microwave thermotherapy while there is significant deterioration following transurethral prostatic resection. In general, older patients have greater sexual dysfunction.

Randomized controlled trial comparing hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy

Background Laparoscopic donor nephrectomy (LDN) has become the gold standard for live-donor nephrectomy, as it results in a short convalescence time and increased quality of life. However, intraoperative safety has been debated, as severe complications occur incidentally. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative approach, combining the safety of hand-guided surgery with the benefits of endoscopic techniques and retroperitoneal access. We assessed the best approach to optimize donors’ quality of life and safety. Methods In two tertiary referral centers, donors undergoing left-sided nephrectomy were randomly assigned to HARP or LDN. Primary endpoint was physical function, one of the dimensions of the Short Form-36 questionnaire on quality of life, at 1 month postoperatively. Secondary endpoints included intraoperative events and operation times. Follow-up was 1 year. Results In total, 190 donors were randomized. Physical function at 1 month follow-up did not significantly differ between groups (estimated difference, 1.79; 95% confidence interval, −4.1 to 7.68; P=0.55). HARP resulted in significantly shorter skin-to-skin time (mean, 159 vs. 188 min; P<0.001), shorter warm ischemia time (2 vs. 5 min; P<0.001) and a lower intraoperative event rate (5% vs. 11%, P=0.117). Length of stay (both 3 days; P=0.135) and postoperative complication rate (8% vs. 8%; P=1.00) were not significantly different. Potential graft-related complications did not significantly differ (6% vs. 13%; P=0.137). Conclusions Compared with LDN, left-sided HARP leads to similar quality of life, shorter operating time, and warm ischemia time. Therefore, we recommend HARP as a valuable alternative to the laparoscopic approach for left-sided donor nephrectomy.

Can histopathology predict treatment outcome following high-energy transurethral microwave thermotherapy of the prostate? Results of a biopsy study

Despite good results of high‐energy transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia, it is still difficult to predict the response to treatment on an individual basis. Besides clinical baseline parameters, intrinsic histological parameters are suggested to play a role in the response variance after TUMT. In this study we analyzed histological parameters (vessel density and epithelium‐stroma (E/S) ratio) in patients who were selected for high‐energy TUMT and related these parameters to clinical outcome.

QUALITY OF LIFE ASSESSMENT IN PATIENTS TREATED WITH LOWER ENERGY THERMOTHERAPY (PROSTASOFT 2.0): RESULTS OF A RANDOMIZED TRANSURETHRAL MICROWAVE THERMOTHERAPY VERSUS SHAM STUDY

PURPOSE We evaluated the impact of lower energy transurethral microwave thermotherapy on quality of life and quality of sexual function in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS A total of 50 patients with BPH were randomized to receive either lower energy transurethral microwave thermotherapy treatment (Prostasoft 2.0) or placebo treatment and followed for 26 weeks after treatment. All patients completed a Madsen symptom score and quality of life questionnaire to assess acceptability, daily activities, psychological well-being, social activities and improvement in quality of life. A sexual function questionnaire was used to assess changes in sexual function after microwave thermotherapy. RESULTS A significant difference in voiding parameters and symptom score was found between the transurethral microwave thermotherapy and sham groups. Maximum uroflow changed from 9.6 ml. per second at baseline to 13.9 ml. per second and from 9.9 ml. per second at baseline to 9.6 ml. per second at 26 weeks for transurethral microwave thermotherapy and sham groups, respectively. Madsen score improved from 13.2 to 5.3 for the transurethral microwave thermotherapy group and from 11.9 to 9.1 for the sham group. For quality of life measures, a statistically significant difference in favor of the transurethral microwave thermotherapy group was found only for the acceptability item. At baseline and after 26 weeks no statistically significant difference was observed between the 2 groups for Quality of Life measures documenting sexual function. However, almost 20% of patients treated by either transurethral microwave thermotherapy or sham claimed at 26 weeks after treatment that treatment had influenced sexual function. CONCLUSIONS Although significant changes in objective and subjective parameters were found in patients after lower energy microwave thermotherapy, the change in quality of life was minimal. In addition to the minimal invasiveness of transurethral microwave thermotherapy, preservation of sexual function is appealing.

Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial

BackgroundTransplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donors safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other.Methods/designThe HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donors safety and comfort while reducing donation related costs.DiscussionThis study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy.Trial RegistrationDutch Trial Register NTR1433

Case selection for high-energy transurethral microwave thermotherapy

Abstract Transurethral microwave thermotherapy (TUMT) is a minimally invasive outpatient procedure for the treatment of benign prostatic hyperplasia (BPH). Different devices and operating software have been used in various clinical trials. The objective of this study was to identify the possible baseline parameters that could be used to identify the best responders to different microwave devices and treatment programs. Data on three different high-energy thermotherapy devices (Urowave, Prostalund, and Prostatron) were collected and analyzed. At 1 year of follow-up, 166 patients were available for the Prostatron system. In all, 52 had a ≥ 50% change in both symptom score and peak flow rate, whereas 114 patients were considered nonresponders. Responders were characterized at baseline by a lower peak flow rate (8.80 versus 10.48 ml/s, P ≤ 0.0001) and a larger degree of outlet obstruction as measured by the URA parameter (45.33 versus 36.70 cmH2O, P ≤ 0.0300); a larger energy dose was delivered to this group during treatment (173.36 versus 156.40 kJ, P ≤ 0.0258). A total of 19 patients were available from the Prostalund cohort. No significant difference was found in the values recorded for baseline parameters between responders (5 patients) and nonresponders (14 patients). Stratification of 143 patients treated with the Urowave resulted in 29 responders ( ≥ 50% improvement in both Qmax and AUA score) at 6 months of follow-up, with a significant difference being found in the baseline value recorded for peak flow rate (7.0 versus 8.0 ml/s, P ≤ 0.026). At 12 months, however, this significance difference could no longer be found. In conclusion, baseline parameters with significant predictive value for a clinical response could be identified for the Prostatron device only. The results of this study further confirm the importance of an extensive laboratory and clinical research program for a fuller understanding of the clinical response obtained with a certain microwave device and a particular treatment software and for provision of the greatest possible advantage from these new alternative treatments. Further exploratory work is required for a better understanding of the role of other parameters such as prostate tissue architecture and vascularity, the microwave frequency, the applicator design, the intraprostatic temperature, and the treatment duration in the clinical response to microwave thermotherapy.