EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Preclinical study for treatment of hypospadias by advanced therapy medicinal products.

PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.

Evidence-based (S3) Guideline on (anogenital) Lichen sclerosus.

Lichen sclerosus (LS) is an inflammatory skin disease that usually involves the anogenital area. All patients with symptoms or signs suspicious of lichen sclerosus should be seen at least once initially by a physician with a special interest in the disease in order to avoid delay in diagnosis, as early treatment may cure the disease in some and reduce or prevent scarring. The diagnosis is made clinically in most cases. Biopsies should only be performed under certain circumstances. The gold standard for treatment remains potent to very potent topical steroids; however, mild and moderate disease in boys and men may be cured by circumcision. Certain triggers should be avoided. http://www.euroderm.org/images/stories/guidelines/2014/S3-Guideline-on-Lichen-sclerosus.pdf http://www.awmf.org/fachgesellschaften/mitgliedsgesellschaften/visitenkarte/fg/deutsche-gesellschaft-fuer-gynaekologie-und-geburtshilfe-dggg.html.

[Assessment of the specific characteristics of urethral stricture according to records of medical republican institution of Uzbekistan].

Urethral stricture in men is a common disorder, negatively affecting the health and therefore the quality of patients life. The aim of the study was to evaluate the nature of the stricture in various segments of male urethra and the incidence rate of urethral stricture in the Republic of Uzbekistan. The study presents the analysis of medical records of 195 men (mean age 40,6+/-13,1 years) who underwent urethroplasty in the Republican Specialized Centre of Urology between February 2013 and March 2015. 46.7% and 53.3% of patients had anterior and posterior urethral strictures, respectively. The most common causes of stricture were trauma (38.5%) and infections (22.6%); 18% of strictures were considered idiopathic, 19% - iatrogenic. In 13.3% of cases, stricture located within the pendulous urethra, in 42.7% - within the bulbar urethra, in 32% - within the posterior urethra. In 28.7% of patients the length of the stricture was more than 6 cm, in 25.6% - 2 cm or less.

Controversies in urethral reconstruction.

Urethral strictures are a frequent source of lower urinary tract symptoms in men. Open urethroplasty is regarded as the gold-standard treatment for urethral stricture disease. The treatment for urethral strictures is a continually evolving process and there is renewed controversy over the best approach to take in reconstructing the urethra, since the superiority of one approach over another has not yet been clearly defined. Anterior urethroplasty can be treated, with low morbidity, in an outpatient surgical setting, thus decreasing the impact of urethroplasty. In order to improve outcome in adult patients when the penile shaft is involved, reconstructive urethral surgeons have learned to apply the principles of delicate tissue handling, and the development of minimally invasive techniques. Genital or extra-genital skin has been used as a free graft or harvested as a flap for some time, thanks to its location, hairless skin and durability. Since the early 1990s, the use of oral mucosa was introduced in genital reconstructive surgery and has become popular for urethral reconstructions. Urethral reconstructive surgery is changing rapidly and this change has posed problems for surgeons who see the principles that previously defined their profession becoming obsolete or unworkable. New techniques and new engineered material are a part of our future.

Surgical challenge in patients who underwent failed hypospadias repair: is it time to change?

INTRODUCTION: Our purpose was to evaluate patients who underwent failed hypospadias repair. PATIENTS AND METHODS: We evaluated 4 different groups of patients who underwent failed hypospadias repair. Group 1: patients who underwent only urethral surgery; group 2: patients who underwent only corpora cavernosa surgery; group 3: patients who underwent urethral and corpora cavernosa surgery; group 4: patients who underwent complex reconstructive surgery. Success was defined as a functional urethra without fistula, with glandular meatus and acceptable esthetic appearance of the genitalia. RESULTS: Out of 1,176 patients, group 1 included 301 patients (25.5%), group two 60 patients (5.2%), group three 166 patients (14.1%) and group four 649 patients (55.2%). The mean follow-up was 60.4 months. Out of 1,176 cases, 1,036 (88.1%) were considered successful and 140 (11.9%) failures. CONCLUSION: In the majority of patients (55.2%) with failed hypospadias repair, urethral reconstruction is associated with complex surgical procedures to fully resurface glands, penile shaft and genitalia.

Gene expression of endothelin-1, endothelin-converting enzyme-1, and endothelin receptors in human epididymis.

We have previously reported the presence of endothelin-1 (ET-1) and its receptors in the human testis. In the present study we extended our investigations to human epididymis. The rationale of our study originated from the fact that sperm appear to be immotile during their transit through the epididymis. Hence, it is conceivable that specific factors, unknown to date, are present in this organ, capable of inducing smooth muscle contractions, thus forcing sperm transport. In this paper it is shown that ET-1 messenger ribonucleic acid and protein are readily detectable in the epithelial compartment of the human epididymis, and that ET-converting enzyme-1, which converts the precursor pro-ET-1 into the active peptide ET-1, is expressed in the epididymis, thus indicating an active processing of the prohormone. In addition, two classes of ET receptors were characterized and located in the muscle cells of the epididymis. These receptors correspond, in terms of affinity constants and capacity, to the ETA and ETB receptors previously characterized. These receptors mediate the contractile activity of the epididymis in vitro, thus suggesting that ET-1 can be responsible of sperm progression through this organ, acting via a paracrine mode of action.

Caval extension of renal cell carcinoma. Results of surgical treatment.

Twenty-eight patients with renal cell carcinoma extending to the vena cava underwent surgical treatment consisting of radical nephrectomy and removal of tumor thrombus, which was at the level of the renal veins in 23 cases, the hepatic veins in 4, and extending above the diaphragm in 1 case. In 7 patients lymph nodes were invaded, and 8 had both positive nodes and extrarenal tumor diffusion discovered at surgery. The mean survival was 41.7 months for patients with only venous extension of the tumor, 16 months for patients with positive nodes, and 10.2 months for those with both nodal and extrarenal tumor diffusion.

Retroperitoneal germ cell tumor in postmenopausal woman.

A fifty-four-year-old woman presented with right renal colic and three months later a retroperitoneal tumor was diagnosed. After explorative laparotomy with biopsy, which showed a germ cell tumor, the patient received external beam radiotherapy, but died of metastatic diffusion nine months later. We believe this is a rare occurrence of a germ cell tumor in a postmenopausal woman.

Endothelin-1 is synthesized and biologically active in human epididymis via a paracrine mode of action.

In a previous study, we reported the presence of endothelin-1 and endothelin receptors in the human testis. We have now extended our investigations to the human epididymis. Since sperm appear to be immotile during their transit through the epididymis, it is conceivable that specific local factors promote smooth muscle contraction, enabling sperm transport. In this paper, we show that endothelin-1 mRNA and protein are readily detectable in the epithelial compartment of the human epididymis, and that endothelin converting enzyme- 1, which converts the precursor pro-endothelin-1 into active endothelin-1, is expressed in the epididymis, consistent with active processing of the prohormone. In addition, two classes of endothelin receptors were characterized and located in the muscle cells of the epididymis. These receptors correspond, in terms of affinity constants and capacity, to the previously characterized endothelinA and endothelinB receptor. These receptors appear to be biologically active and mediate the contractile activity of the epididymis in vitro. Our data suggest that endothelin-1, via a paracrine mode of action, may be responsible for sperm progression through this organ.

Weekly epidoxorubicin therapy in hormone-refractory metastatic prostate cancer.

In a pilot trial, we treated thirty-three hormone resistant metastatic prostate cancer patients with a combination of androgen blockade plus weekly cytotoxic therapy and determined both response and toxicity in 32 of them. Their median Karnofsky performance status at the time of entry was 65. We administered Epidoxorubicin (EpiDx) intravenously, at a dose of 35 mg/m2, every week for 4 months. Initially, all patients had only hormonal therapy and chemotherapy was added once they progressed. In terms of W.H.O. criteria, 9 patients (28%) had a partial response, the disease was stable in 14 (44%), and progressive in 9 (28%); even in this last group, 6 patients with bone metastases experienced lasting relief from pain. No patients had to interrupt treatment due to leukopenia or cardiotoxicity. Other toxicities, including nausea and vomiting, mucositis and alopecia, were mild. Pretreatment prostate-specific antigen (PSA) levels decreased significantly (p < 0.05) in 26 patients (81%) after treatment. In our view, weekly EpiDx administration serves as an active regimen in hormone-refractory prostate cancer.

Impairment of antipyrine metabolism in urinary tract cancer.

The metabolism of antipyrine was studied in 13 patients with cancer and bladder papillomas and in 11 control subjects, matched for interfering factors like smoking, diet, age and sex. The mean antipyrine half-life was significantly longer in patients with urinary tract cancer (14.7 +/- 1.32 h SE) than in control subjects (11 +/- 0.55 h SE) (P less than 0.025); other clinical parameters did not vary.

When and how to use buccal mucosa grafts in penile and bulbar urethroplasty.

The surgical treatment of adult anterior urethral strictures has been a constantly evolving process, and renewed controversy exists over the best means of reconstructing the anterior urethra. Recently, considerable changes have been introduced: the wider use of buccal mucosa graft versus the use of genital or extragenital skin, and the use of dorsal onlay urethroplasties, also named Barbagli procedures. Moreover, in the penile urethra the dorsal placement of the graft is now combined with the incision and the augmentation of the urethral plate, as suggested for childhood hypospadias surgery. In adult male patients, the urethral strictures involving the penile and bulbar urethra are due to failed hypospadias repair, ischemia, lichen sclerosus, congenital anomalies of the mucosal membrane, traumatic scar after blunt perineal trauma. Buccal mucosa is receiving increased attention in the urological literature for penile and bulbar urethroplasty. We present here, step by step, 4 different surgical techniques for penile and bulbar urethroplasty, using buccal mucosa grafts. The surgical procedures are selected according to the current and updated literature and to the new classification of anterior urethral diseases. The ideal surgical technique should be simple, safe, reliable and reproducible in the hands of any surgeon, as well as being based on sound anatomical principles. We believe the technique we present here fulfil all these criteria.

[Granulomatous prostatitis]. / Le prostatiti granulomatose.

Granulomatous prostatitis is a rare chronic inflammation and its etiology is not well understood. There is difficulty in differential diagnosis with prostatic cancer. But RMN and ultrasound guided biopsy can confirm the diagnosis. The authors report 15 cases and discuss etiological, clinical and diagnostic aspects.

[Oncocytoma in a horseshoe kidney]. / L'oncocitoma in rene a ferro di cavallo.

Oncocytoma is a neoplasm that constitutes 4-5% of tumors located in the renal parenchyma. It was studied for the first time by Zippel in 1942 and since than nearly 150 cases have been described. The association between neoplasm and horseshoe kidney is extremely rare. The horseshoe kidney is a malformation which often becomes complicated by infection, hydronephrosis and calculosis, but very rarely by a neoplasm (only 113 cases). The Authors report a case of oncocytoma in the horseshoe kidney and discuss the diagnostic, clinical and therapeutical aspects.

[Perineal urethrostomy in complex anterior urethral stricture]. / Die perineale Urethrostomie bei komplexer vorderer Harnröhrenstriktur.

Staged urethroplasty is a well-known procedure for urethral reconstruction that had already been described by Russell in 1914 and was later popularized by Johanson, Turner-Warwick, Blandy, and Schreiter. It lends itself to the treatment of complex anterior urethral stricture in combination with lichen sclerosus, failed correction of hypospadias, fistula, via falsa, abscess, carcinoma, or previously unsuccessful urethroplasty. Perineal urethrostomy can be performed as a temporary or definitive measure. Some patients even decline further urethral reconstruction because they perceive subjective satisfaction after perineal urethrostomy that was originally intended to be temporary.