Background and objectives Cystinuria is a rare inherited renal stone disease. Mutations in the amino acid exchanger System b 0,+ , the two subunits of which are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. The work analyzed the epidemiology of cystinuria and the influence of mutations in these two genes on disease severity in a United Kingdom cohort.Design, setting, participants, & measurements Prevalent patients were studied from 2012 to 2014 in the northeast and southwest of the United Kingdom. Clinical phenotypes were defined, and genetic analysis of SLC3A1 and SLC7A9 combining Sanger sequencing and multiplex ligation probe-dependent amplification was performed.Results In total, 76 patients (42 men and 34 women) were studied. All subjects had proven cystine stones. Median age of presentation (first stone episode) was 24 years old, but 21% of patients presented after 40 years old. Patients had varied clinical courses, with 37% of patients having $10 stone episodes; 70% had evidence of CKD, and 9% had reached ESRD as a result of cystinuria and its complications. Patients with cystinuria received a variety of different therapies, with no obvious treatment consensus. Notably, 20% of patients had staghorn calculi, with associated impaired renal function in 80% of these patients. Genetic analysis revealed that biallelic mutations were present in either SLC3A1 (n=27) or SLC7A9 (n=20); 22 patients had only one mutated allele detected (SLC3A1 in five patients and SLC7A9 in 17 patients). In total, 37 different mutant variant alleles were identified, including 12 novel mutations; 22% of mutations were caused by large gene rearrangements. No genotypephenotype association was detected in this cohort.Conclusions Patients with cystinuria in the United Kingdom often present atypically with staghorn calculi at $40 years old and commonly develop significant renal impairment. There is no association of clinical course with genotype. Treatments directed toward reducing stone burden need to be rationalized and developed to optimize patient care.
Background: Balanitis Xerotica Obliterans (BXO) is a chronic, often progressive disease, which can lead to phimosis and urethral stenosis, affecting both urinary and sexual function. Steroid creams are usually the first-line treatment but have a limited role and surgical intervention is frequently necessary. Conservative surgical procedures (circumcision) are often preferred in the first instance with the premise that recurrence of disease will require a more definitive reconstruction. This study looked at patients with pathologically proven BXO referred to the Plastic Surgery Unit at James Cook University Hospital between 2005 and 2009. The aim was to look at their management in the past and subsequent management by us. We also looked at whether early referral of progressive and recurrent BXO patients to reconstructive surgery could have prevented unnecessary delay in resolving symptoms at an earlier stage. Materials and Methods: Data was collected retrospectively and information regarding the exact anatomical location affected, the extent of the disease, the referring specialty and any previous surgical interventions was obtained. Alterations in urinary and sexual function and relief of symptoms following reconstructive surgery were analysed. Results: Of the 23 patients in the study, 43% had previous surgery and 60% of those had undergone two or more procedures. Twenty-one percent of patients had a history of BXO for over five years. Forty-seven percent of patients had alteration in their urinary function and 48% alteration in their sexual function due to the disease, prior to referral. Early results showed remarkable improvement in urinary and sexual function following reconstructive surgery in this group. Conclusions: Steroid creams have been shown to limit the progression of the disease but do not offer a cure in the majority of cases. Circumcision can be a curative procedure in early disease. Although there is conflicting evidence for treatment of recurring urethral strictures, repeated urethrotomy or urethral dilatation has poor long-term outcome. In patients with recurrent disease and associated complications we propose early referral to a plastic surgeon with genitourinary interest or reconstructive urologist for definitive treatment.
Castration resistant prostate cancer remains a major clinical burden and novel therapeutic options are urgently required to improve survival. Tasquinimod is an orally administered quinoline-3-carboxamide with potent antiangiogenic and antitumorigenic action that has shown promise in the treatment of advanced prostate cancers. This review explores both preclinical and clinical findings to date. In summary, tasquinimod has been shown to demonstrate a potent in vitro and in vivo anticancer action and completed early phase clinical trials have demonstrated good drug tolerance and prolonged progression-free survival. Although Phase III clinical trials are on-going, the findings to date highlight the promise of this drug in the treatment of advanced prostate cancer.
Background:Balanitis Xerotica Obliterans (BXO) is a chronic, often progressive disease, which can lead to phimosis and urethral stenosis, affecting both urinary and sexual function. Steroid creams are usually the first-line treatment but have a limited role and surgical intervention is frequently necessary. Conservative surgical procedures (circumcision) are often preferred in the first instance with the premise that recurrence of disease will require a more definitive reconstruction. This study looked at patients with pathologically proven BXO referred to the Plastic Surgery Unit at James Cook University Hospital between 2005 and 2009. The aim was to look at their management in the past and subsequent management by us. We also looked at whether early referral of progressive and recurrent BXO patients to reconstructive surgery could have prevented unnecessary delay in resolving symptoms at an earlier stage.Materials and Methods:Data was collected retrospectively and information regarding the exact anatomical location affected, the extent of the disease, the referring specialty and any previous surgical interventions was obtained. Alterations in urinary and sexual function and relief of symptoms following reconstructive surgery were analysed.Results:Of the 23 patients in the study, 43% had previous surgery and 60% of those had undergone two or more procedures. Twenty-one percent of patients had a history of BXO for over five years. Forty-seven percent of patients had alteration in their urinary function and 48% alteration in their sexual function due to the disease, prior to referral. Early results showed remarkable improvement in urinary and sexual function following reconstructive surgery in this group.Conclusions:Steroid creams have been shown to limit the progression of the disease but do not offer a cure in the majority of cases. Circumcision can be a curative procedure in early disease. Although there is conflicting evidence for treatment of recurring urethral strictures, repeated urethrotomy or urethral dilatation has poor long-term outcome. In patients with recurrent disease and associated complications we propose early referral to a plastic surgeon with genitourinary interest or reconstructive urologist for definitive treatment.
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