Fabry disease: a review

Fabry disease is an inherited deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha GalA) due to mutations in the Gal gene at Xq22. The result is intralysosomal accumulation of glycosphingolipids. In males who carry the mutation (1/40,000), severe multisystem disease develops in childhood or adolescence. Attacks of acute pain lasting a few minutes to a few days occur in the hands and feet, joints, muscles, and abdomen, sometimes with a fever. Highly suggestive skin lesions called angiokeratomas develop, as well as cornea verticillata characterized by corneal deposits without visual impairment. Stroke, seizures, heart disorders (conduction disturbances, valve disease, and left heart failure) and kidney disorders (proteinuria and chronic renal failure) develop in the third or fourth decade of life. Women who are heterozygous for the Gal gene can transmit the disease to their sons but are usually free of symptoms, although many have cornea verticillata. However, they may have moderate or severe disease related to uneven chromosome X inactivation. Late-onset variants with predominant neurological, cardiac, or renal manifestations have been described. The diagnosis is difficult when the family history is negative for Fabry disease. Tests on plasma and leukocytes show very low levels of alpha GalA activity in affected men, confirming the diagnosis. The Gal gene mutation should be looked for to detect heterozygous women. Symptomatic treatments include analgesics, antihypertensives, antiplatelet agents or anticoagulants to treat ischemic events, and hemodialysis or kidney transplantation to treat chronic renal failure. The recent introduction of enzyme replacement therapy with recombinant agalsidase alpha or beta has been a major breakthrough in the treatment of Fabry disease. Enzyme replacement therapy relieves the pain and decreases the risk of complications. The safety profile is good. Given the high cost of agalsidase therapy (about 160,000 euro/year/patient) and the low incidence of Fabry disease, patients should be referred to highly specialized centers (see addresses on the France Orphanet web site).     

The Vista system: a new bipolar resection device for endourological procedures: comparison with conventional resectoscope

OBJECTIVE: Conventional transurethral resection of the prostate (TURP) uses a monopolar electrocautery system in which the current passes from the active electrode through the patient's body towards the return plate and may cause distant negative effects. In this study a new developed resection device, the Vista system, using a bipolar electrocautery system and 0.9% sodium chloride solution for irrigation, was evaluated in an ex-vivo model. METHODS: The modified model of the isolated blood perfused kidney was used to determine cutting qualities, ablation rate, blood loss and coagulation depth of the bipolar resectoscope. After ablating the renal tissue of a perfused kidney in a surface area, blood loss was semiquantitatively determined. Afterwards samples were taken and processed for histological evaluation of the coagulation depth. We compared the new bipolar resection device against a conventional monopolar resectoscope. RESULTS: We found good cutting qualities of the bipolar resectoscope although it is more difficult to start a cut. The ablation rate is determined by the width of the electrode and is similar to the standard device (30 cm(2)/min). The bleeding is reduced with increasing output powers (26.13 +/- 6.15 g/min (level 5); 20.49 +/- 5,47 g/min (level 6); 13.16 +/- 5,47 g/min (level 7); 10.43 +/- 4.76 g/min (level 8) and lower compared to a conventional monopolar resectoscope (17.08 +/- 4.47 g/min). The coagulation depth increases with higher output powers but is reduced compared to the standard device (118 +/- 22 microm (level 5); 121 +/- 23 microm (level 6); 141 +/- 62 microm (level 7); 163 +/- 30 microm (level 8) versus 287 +/- 57 (monopolar resectoscope)). CONCLUSION: Our results with the bipolar resection device for TURP suggest that it may offer an alternative to conventional TURP. As active and the return electrode are placed on the resectoscope, high current densities are achieved locally and complications caused by distant negative effects of the current are theoretically reduced in vivo. Furthermore the risk of TUR syndrome is theoretically eliminated by using physiological sodium chloride solution for irrigation. To prove the clinical significance of our ex-vivo findings, clinical studies including large numbers of patients have to be performed.     

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

Background

Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.

Methods

Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.

Results

Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).

Conclusions

This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.     

Volumetric MR-guided high-intensity focused ultrasound versus uterine artery embolisation for treatment of symptomatic uterine fibroids: comparison of symptom improvement and reintervention rates

Purpose

To compare the effectiveness of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) with that of uterine artery embolisation (UAE) for treatment of uterine fibroids.

Methods

Between January 2010 and January 2013, 51 women with symptomatic uterine fibroids underwent MR-HIFU. Follow-up and MR imaging were compared to 68 women treated with UAE, who fulfilled eligibility criteria for MR-HIFU – e.g., size (≤ 12 cm) and number (≤ 5) of fibroids. We compared median symptom severity (tSSS), total health-realted quality of life (HRQoL) scores, and reintervention rates. The adjusted effect on symptom relief and HRQoL improvement was calculated using multivariable linear regression. Cox regression was applied to calculate the adjusted risk of reintervention between both treatments.

Results

Median tSSS improved significantly from baseline to three-month follow-up (P?P?P?P?=?0.002) times higher risk of reintervention within 12 months (18/51 vs. 3/68).

Conclusion

Both MR-HIFU and UAE result in significant symptom relief related to uterine fibroids. However, MR-HIFU is associated with a higher risk of reintervention.

Key Points

? This study compared outcomes between volumetric MR-HIFU and UAE for uterine fibroids. ? Both MR-HIFU and UAE result in significant symptom relief and quality of life improvement. ? UAE had a stronger positive effect on the clinical outcomes. ? Reintervention rate after MR-HIFU ablation was significantly higher than after UAE.     

Three-Dimensional Reconstruction of Basal Cell Carcinomas

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer. One of the main problems with BCC is the risk of local recurrence of the tumor after treatment. This is mainly due to its irregular outgrowths, which cannot be detected clinically. OBJECTIVE: To better understand the tumor morphology and growth pattern of BCC, we tried to develop a method that provides a precise three-dimensional model of the tumor. METHODS: Because Mohs surgery provides the best overview of the tumor and the tumor margins (both lateral and in depth), the reconstruction was based on slides from Mohs surgery. After digitization and processing of the slides, the tumor was then surrounded by a Mohs surgeon on a computer screen. These selections (lines) were used for a three-dimensional reconstruction of the tumor using MedSurf3D software. RESULTS: This method allows three-dimensional reconstruction of any given BCC. The MedSurf3D software enables visualization of a three-dimensional model of the tissue, which is removed during the surgical procedure. CONCLUSIONS: Three-dimensional reconstruction is a fascinating tool that might improve our understanding of the behavior, growth pattern, and tumor morphology of BCCs. This technique might also be useful in other fields of cutaneous oncology, such as the calculation of the tumor volume of melanomas.     

Is there a place for virtual reality simulators in assessment of competency in percutaneous renal access?

Objective

To assess competency of urology post-graduate trainees (PGTs) in percutaneous renal access (PCA).

Methods

Upon obtaining ethics approval and informed consents, PGTs between post-graduate years (PGY-3 to PGY-5) from all four urology programs in Québec were recruited. PCA competency of each participant was assessed objectively by performing task 4 on the PERC Mentor? simulator, where they had to correctly access and pop 7 balloons in 7 different renal calyces and subjectively by the validated Percutaneous Nephrolithotomy—Global Rating Scale (PCNL-GRS).

Results

A total of 26 PGTs with a mean age of 29.2 ± 0.7 years participated in this study. When compared with the 21 PGTs without practice, all 5 PGTs who had practiced on the simulator were competent (p = 0.03), performed the task with significantly shorter operative time (13.9 ± 0.7 vs. 4.4 ± 0.4 min; p < 0.001) and fluoroscopy time (9.3 ± 0.6 vs. 3.4 ± 0.4 min; p < 0.001), and had significantly higher PCNL-GRS scores (13 ± 0.6 vs. 20.6 ± 1; p < 0.001) and successful attempts to access renal calyces (23 ± 5 vs. 68.7 ± 11; p = 0.001). According to a pass score of 13/25, thirteen PGTs were competent. Competent PGTs performed the task with significantly shorter fluoroscopy time (9.8 vs. 6.5 min; p = 0.01) and higher percentage of successful attempts to access renal calyces (p < 0.001), higher PCNL-GRS scores (p < 0.001), and lower complications (p = 0.01).

Conclusion

The PCNL-GRS in combination with the PERC Mentor? simulator was able to differentiate between competent and non-competent PGTs.

     

Impact of an autotransfusion system during endoluminal repair of abdominal aortic aneurysms: does it decrease the use of allogeneic blood?

Endoluminal repair of abdominal aortic aneurysms (AAA) is associated with decreased blood loss and transfusion requirements when compared to open AAA repair. We evaluated the use of an intraoperative autotransfusion system during endoluminal exclusion of AAAs. Fifty endoluminal AAA procedures selected at random were reviewed retrospectively. Patients were divided into 4 groups according to their estimated blood loss: Group I, 20 patients (0-500 cc); Group II, 18 patients (501-1,000 cc); Group III, 7 patients (1,001-1,500 cc); and Group IV, 5 patients (1,501-3,400 cc). The average blood loss was 327 cc for Group I, 728 cc for Group II, 1,217 for Group III, and 2,125, for Group IV. The overall blood loss was 834 cc, but 75 per cent was recovered. Hematuria was always present when greater than 1,000 cc of blood was retransfused, but renal function was not affected even with the concomitant administration of radiographic contrast. Only one patient required an autologous blood transfusion. The use of an autotransfusion device is safe, efficacious, and appears to further limit the need for homologous blood transfusion in patients undergoing endoluminal AAA repair.     

Thulium:yttrium‐aluminium‐garnet laser prostatectomy in men with refractory urinary retention

OBJECTIVE

To evaluate the feasibility and efficacy of thulium:yttrium‐aluminium‐garnet (YAG) laser prostatectomy in patients with an indwelling transurethral catheter due to recurrent urinary retention secondary to benign prostatic obstruction.

PATIENTS AND METHODS

Preoperative data and postoperative outcome, as well as complications, were recorded in 65 patients with a history of recurrent urinary retention before surgery (group A), who were compared with a group of 143 men with no recurrent urinary retention (group B).

RESULTS

The mean (sd ) volume of the prostate was 45.6 (22.5) and 43.1 (24.5) mL in groups A and B, respectively. The respective preoperative prostate‐specific antigen levels were 3.6 (7.8) and 2.8 (6.4) ng/mL, the surgical duration 72.4 (28.9) and 65.6 (28.6) min, the mean laser time and energy 32.5 (11.8) min/140.7 (42.1) kJ and 29.4 (11.6) min/117.6 (11.6) kJ, the maximum urinary flow rate after surgery 19.6 (11.2) and 19.1 (9.6) mL/s, and the postvoid residual urine volume 26.7 (36.3) and 20.6 (27.3) mL. Recorded complications were: bleeding, at 3% in group A and 1.4% in group B; urinary tract infection 15.4% and 4.2%; and a second procedure, 3% and 2.3%. Overall, complications were more frequent in group A (P = 0.02).

CONCLUSION

Thulium:YAG prostatectomy is feasible and effective, even in patients with potentially impaired detrusor function. The long‐term durability of these promising results has yet to be confirmed.     

Novel everting urologic access sheath: decreased axial forces during insertion

BACKGROUND: Advancement of urologic instruments through the genitourinary tract is associated with significant axial forces that likely contribute to patient discomfort, even after injection of a local anesthetic, and may lead to mucosal trauma, postprocedural dysuria and hematuria, and increased susceptibility to infection and strictures. Placing an everting urethral sheath prior to instrumentation may decrease these problems. Materials and METHODS: Two 7-cm-long, 5-mm diameter urethral luminal models were created, one with and one without an artificial stricture. We measured the forces generated during advancement of a novel everting access sheath (Cystoglide; Percutaneous Systems, Mountain View, CA) through the models in comparison with a representative cystoscope and a urologic dilator simulating a traditional access sheath. RESULTS: The mean force generated during advancement of the everting sheath was significantly less than that of both the representative cystoscope (P<0.01) and the traditional access sheath (P<0.01). This held true for the urethral models both with and without an artificial stricture (P<0.01) and with and without lubrication (P<0.01). CONCLUSIONS: This novel introduction sheath markedly decreased the axial forces applied to an artificial urethral luminal wall. It is possible that the clinical use of this technology will decrease the discomfort and potential complications associated with lower urinary-tract endoscopy.