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.

[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.

[Use of human fibrinogen and human thrombin for urethral reconstructive surgery].

The objective of the present study is to test the use of a haemostatic sponge for urethral reconstructive surgery and to assess the relevant benefits. METHODS. The haemostatic sponge is made up of collagen with human fibrinogen and human thrombin. When the sponge gets in contact with fluids, such as blood, lymph or saline solution, the fibrinogen and thrombin are activated and form a fibrin net able to achieve local haemostasis and tissue regeneration. This kind of product was used in 30 selected patients (pts.), aged 19 - 70 (mean age: 35), who underwent single-stage anastomotic urethroplasty from January 2006 to March 2007: 22 bulbar end-to-end anastomoses and 8 bulbo- prostatic anastomoses. All operations were performed due to post-traumatic stricture of bulbar and posterior urethra. The main selection criterion for the use of the haemostatic sponge has always been the tendency to and/or the presence of bleeding in the different surgical stages. The sponge imbibed in saline solution and suitably modeled for all specific requirements was differently placed: sleeve-shaped in the case of bulbar anastomoses (16 pts.); as a "patch" in the centre of spongioplasty in bulbo-prostatic anastomoses (8 pts.), and within the widening incisions of the urethral roof performed between the two cavernous bodies at level of the intercrural septum (5 pts.). In 1 case (obese patient) a single sponge was placed after the deep perineal reconstruction on the bulbo-cavernous muscle- subcutaneous layers because of massive bleeding. RESULTS. In all cases a perfect control of haemostasis could be achieved, with immediate end of bleeding in the points where the haemostatic sponges were used. The dressings performed on day 3 upon removal of the compressive scrotum-perineal bandages did not show any late post-operative bleeding. The follow-up visits at month 1 and 3 yielded positive outcomes for all 30 patients, who achieved complete wound healing by first intention, and a perfect anastomosis especially in the bulbar end-to-end urethroplasty, confirmed by urethrografy at one month. CONCLUSIONS. The association of human fibrinogen and human thrombin in haemostatic sponges represents a manageable, useful product, apparently sure, not negatively interfering in repairing and regenerating tissue processes, and allowing a simple and direct control of important bleeding events occurring during urethral reconstructive surgery as well as other operations. It is therefore advisable to more widely use the product after a suitable followup period.

History and evolution of dorsal onlay urethroplasty for bulbar urethral stricture repair using skin or buccal mucosal grafts.

OBJECTIVES. To illustrate the history and the evolution over time of bulbar dorsal onlay urethroplasty, comparing outcomes when using buccal mucosa or skin grafts. MATERIALS AND METHODS. Ninety-four patients underwent bulbar urethral reconstruction using two dorsal onlay techniques, namely augmented anastomotic urethroplasty and dorsal onlay graft urethroplasty. Preoperative evaluation included clinical history, physical examination, urine culture, residual urine measurement, uroflowmetry and urethrography. Thirty-four patients underwent augmented anastomotic urethroplasty using penile skin (10 cases) or buccal mucosa (24 cases) grafts. Sixty patients underwent dorsal onlay graft urethroplasty using penile skin (38 cases) or buccal mucosa (22 cases) grafts. Forty-eight out of 94 patients received skin grafts and 46 buccal mucosal grafts. RESULTS. Sixty-four (68%) out of 94 cases were successful, whereas 30 (32%) failed. The 34 augmented anastomotic urethroplasties provided successful outcomes in 24 cases (70.6%), but poor outcomes in 10 (29.4%) cases. The 60 dorsal onlay graft urethroplasty proved to be successful in 42 cases (70%), failing in 18 (30%) cases. Twenty-eight (58.3%) out of 48 penile skin grafts were successful and 20 (41.7%) failed. Thirty-six (78.3%) out of 46 buccal mucosa grafts were successful and 10 (21.7%) failed. The 30 failed cases were then treated with internal urethrotomy in 14 cases (46.7%), perineal urethrostomy in 8 cases (26.7%), two-stage repair in 4 cases (13.3%), and one-stage repair in 4 cases (13.3%). CONCLUSIONS. The dorsal onlay technique used for bulbar urethral stricture repair has changed over time. In our experience, the buccal mucosa seems to be the best substitute graft material for bulbar urethroplasty using dorsal approach.

Experience with fibrin glue in bulbar urethral reconstruction using dorsal buccal mucosa graft.

Buccal mucosa dorsal onlay graft urethroplasty represents a widespread method for bulbar urethral stricture repair. We describe a modified procedure with the use of fibrin glue applied on the receiving bed before graft location.

Penile carcinoma in patients with genital lichen sclerosus: a multicenter survey.

PURPOSE: In this observational descriptive study we reviewed the histology and the clinical records of 130 patients with LS involving the male genitalia to determine the presence of premalignant or malignant lesions. MATERIALS AND METHODS: A total of 130 male patients (from 1991 to 2001) with genital LS were treated at our centers. Mean patient age at diagnosis was 42.5 years. In all patients with a clinical diagnosis of LS, the histology was reexamined to look for evidence of LS, applying strict histological criteria. All cases of histologically proven epithelial malignancy, namely SCC, VC and EQ, were reviewed to confirm the presence of neoplastic changes and ascertain the degree of SCC differentiation. RESULTS: Of 130 men 11 (8.4%) with genital LS showed premalignant or malignant histopathological features including 7 (64%) with SCC, 2 (18%) with VC, 1 (9%) with EQ and 1 (9%) with SCC associated with VC. In 6 of 11 patients (55%) the histological study showed the presence of epithelial dysplasia. CONCLUSIONS: Survival of patients with penile carcinoma depends on early diagnosis and treatment, and all patients with genital LS should be observed closely to detect the development of neoplastic or preneoplastic lesions as early as possible.

Interim outcomes of dorsal skin graft bulbar urethroplasty.

PURPOSE: We update our interim results of bulbar urethroplasty using a skin graft placed on the dorsal urethral surface. MATERIALS AND METHODS: A total of 45 patients with an average age of 45 years underwent dorsal onlay skin graft urethroplasty between January 1994 and December 2000. Of the patients 23 had undergone an average of 2.6 prior endoscopic procedures (range 1 to 14). Preoperative evaluation include clinical history, physical examination, retrograde and voiding urethrography, and ultrasonography. In all patients the bulbar urethra was opened along its dorsal surface, the graft was sutured, splayed and quilted to the corpora cavernosa, and the urethra was rotated to cover the graft. In all patients was used penile skin as substitution material. Mean graft length was 4.7 cm (range 2.5 to 11). Three weeks after surgery voiding cystourethrography was performed. RESULTS: Average followup was 71 months (range 41 to 110). Clinical outcome was considered a failure when postoperative instrumentation was needed, including dilation. Of 45 cases 33 (73%) were classified as successful and 12 (27%) were failures. The 12 failures were treated with internal urethrotomy (1), end-to-end-anastomosis (1), skin graft urethroplasty (2) and 2-stage urethroplasty (6). Six of the 12 initial failures had a satisfactory final outcome. The remaining 6 patients refused further surgical procedures and received a definitive perineal urethrostomy. CONCLUSIONS: Penile skin grafts used as a dorsal onlay for bulbar urethral reconstruction in a homogeneous series of patients showed a tendency to deteriorate with time. Longer followup is required to compare penile skin with buccal mucosa as substitute materials for bulbar urethral reconstruction.

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.

Anterior urethral strictures.

The surgical treatment of adult anterior urethral strictures has developed continuously. Recently considerable changes have been introduced, involving the cause of the urethral disease and surgical techniques. The criteria for selecting the reconstructive surgical technique are presented according to the cause and a new classification of urethral strictures. The main surgical procedures are presented and fully illustrated, with an updated and comprehensive review of recent publications.