Kinetics of HTT lowering in brain of YAC 128 mice following single and repetitive intranasal dosing of siRNA packaged in chitosan-based nanoparticle.

This report describes the kinetics of Huntington's Disease (HD) gene (HTT) lowering in brains of YAC 128 mice. Lowering (or "knock-down") of HTT mRNA expression was achieved by intranasal administration of specially designed siRNA loaded into chitosan nanoparticles. Kinetic patterns of HTT lowering observed in different brain regions allowed calculation of cumulative lowering effects that result from multiple consecutive administrations. Mathematical modeling generated dosing schedules for approaching a steady knock-down effect and for prediction of magnitude and duration of HTT lowering. Kinetic modeling of HTT lowering with our algorithm will be useful in determining intranasal dosing schedules to produce chronic, therapeutically significant lowering effect of gene expression.

Serum Levels of Incretin Hormones - GLP-1 and GIP in Patients with Type 1 Diabetes Mellitus.

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.

Chronic Treatment with Opiate Agonists in Bulgaria - Assessing the Quality of Life Using SF 36 v. 2.

INTRODUCTION: Drug addictions to psychoactive substances are disorders with a complex bio-psycho-social genesis, which are characterized with chronic relapses. Substance addiction causes multifactorial damage to the normal functioning of individuals and requires a multicenter approach for the treatment process. AIM: The aim of the study was to assess the quality of life of patients undergoing chronic treatment with the opiate agonist methadone using a standardized questionnaire method in Bulgarian. MATERIAL AND METHODS: The study included patients aged 18 to 40 years undergoing chronic treatment with methadone for at least six months. The study included 100 subjects. Seventy-six patients were from 5 clinical programs in Bulgaria; twenty- four clinically healthy age-matched subjects with no history of drug abuse, psychiatric and somatic diseases were the control group. RESULTS: We found significant differences between patients and controls in all components of the survey (P<0.05). The patients had lower scores than the control group in the SF-36 in terms of all eight components and both the physical and mental component summaries of the SF-36-survey. Patients compared between the groups by dose, duration of treatment with methadone and period of heroin abuse before initiating treatment did not show significant differences. There were no significant differences between patients with and without hepatitis C virus. CONCLUSIONS: Opiate addiction is a state associated with poor quality of life. The duration of treatment, the methadone dose, period of heroin abuse before initiating treatment and illness of hepatitis C virus does not correlate with lower results.

Current surgical management of severe peyronie's disease.

OBJECTIVES: To report the principles of penile resculpturing of different deformities caused by M. Peyronie: restoration of penile length, girth and shape with or without penile prosthesis implantation. METHODS: In the period between February 2007 and March 2009, we performed grafting surgery for M. Peyronie in 98 patients aged between 24 and 72 years (mean 52 years). Penile deformities were diferent: dorsal curvature in 54 (55%), lateral in 7 (7%), ventral in 11 (11%), and combined curvature in 21 (21%) associated corporal narrowing was present in 24 patients (24%). Four (4%) patients presented isolated penile shortening without other deformity. Isolated diffuse corporal narrowing without shortening was found in two (2%) patients. Severity of curvature ranges from 60 to 90 degrees, mean 72. Thirty one (31%) patients had associated ED. Surgical options for severe Peyronie's disease were: single grafting in 26 pts (26%), complex grafting including circular tunical incision in 36 pts (36%), and in patients with ED the same procedures combined with penile prosthesis implantation (37 pts, 38%). Surgical correction was based on measurement of the tunical defect and precise calculation of graft size and shape. Penile straightening and lengthening was achieved by equalizing of shortened penile side/s with the longest one (convex) and grafting. Penile width is reestablished with additional longitudinal incision/s and grafting; graft width is determined by measurement of difference in circumference between normal and narrowed part of the corpora. We used Intexen LP (AMS) as a grafting material in all cases. RESULTS: The mean follow-up was 15 months (6-25). Mean penile length gain without prosthesis was 2.8cm (1.5-4.2) and with prosthesis 3.2cm (2-4.5cm). Insuficient straightening was in 5 patients (>15 degree) where Neuro Vascular Bundle (NVB) was limiting factor. Twenty four patients reported hypoesthesia and reduced orgasmic sensitivity that recovered spontaneously after 3-6 months. De-novo ED occurred in 6 pts and progression of disease in 6 patients. Infection occurred only in one patient with penile prosthesis implantation. Overall patients' satisfaction was 95%. CONCLUSIONS: Complete tunical reconstruction in IPP can be performed as a safe procedure by transversal, longitudinal and circular grafting with or without simultaneous penile prosthesis implantation. Maximum penile length, girth and shape restoration can be achieved using geometrical calculation, regardless of type of deformity.

Manejo quirúrgico actual de la enfermedad de le Peyronie grave / Current Surgical Management of Severe Peyronie’s Disease

OBJETIVO: Informar sobre los principios de la cirugía reconstructiva de diferentes deformidades del pene causadas por la enfermedad de Peyronie: restauración de la longitud, perímetro y forma con o sin implante de prótesis de pene.MÉTODOS: En el período comprendido entre febrero 2007 y marzo de 2009, se realizó cirugía con par-che por enfermedad de Peyronie en 98 pacientes con edades comprendidas entre 24 y 72 años (media 52 años). Las deformidades en el pene eran diferentes: curvatura dorsal en 54 (55%) pacientes, lateral en 7 (7%), ventral en 11 (11%), y curvatura combinada en 21 (21%); 24 pacientes presentaban estrechamiento en el cuerpo cavernoso (reloj de arena) (24 %). Cuatro (4%) pacientes presentaban acortamiento de pene aislado, sin otras deformidades, y en dos (2%) pacientes se encontró un estrechamiento cavernoso difuso aislado sin acortamiento. La gravedad de la curvatura varió de 60º- 90º, media 72. Treinta y un (31%) pacientes pade-cían disfunción eréctil asociada. Las opciones quirúrgi-cas para los casos graves de enfermedad de Peyronie fueron: injerto simple en 26 (26%) pacientes, injertos complejos incluyendo incisión circular de la túnica albugínea en 36 (36%), y los mismos procedimientos en pacientes con disfunción eréctil combinados con implante de prótesis de pene en 37 pacientes (38%). La corrección quirúrgica se basó en la medición del defecto de la túnica y el cálculo preciso del tamaño del injerto y la forma. El enderezamiento y alargamiento del pene se logró, mediante la nivelación del lado/s acortados del pene con el más largo (convexo) y el injerto. El ancho del pene se restablece con incisión/es longitudinal/es adicionales e injertos; el ancho del injerto se determina mediante la medición de la diferencia en la circunferencia entre las partes normal y reducida del cuerpo cavernoso. En todos los casos, se utilizó InteXen LP (AMS) como material de injerto(AU)

RESULTADOS: El seguimiento medio fue de 15 meses (6-25). El incremento de longitud del pene fue de 2,8 cm sin prótesis (1,5-4,2 cm) y 3,2 cm (2-4,5cm) con prótesis. En 5 pacientes (<15 grados), la corrección de la curvatura fue insuficiente, debido a que el haz neurovascular fue un factor limitante. Veinticuatro pacientes informaron de hipoestesia y sensibilidad orgásmica reducida que se recuperó espontáneamente al cabo de 3-6 meses. Seis pacientes presentaron una disfunción eréctil de novo y 6 pacientes progresión de la enfermedad. Sólo un paciente con implante de prótesis de pene sufrió infección. El índice de satisfacción general de los pacientes fue del 95%.CONCLUSIONES: La reconstrucción de la túnica albu-gínea completa en la enfermedad de Peyronie puede realizarse como un procedimiento seguro por medio de injertos transversales, longitudinales y circulares con o sin implante simultáneo de prótesis de pene. Se puede lograr, mediante el cálculo geométrico, la longitud máxi-ma del pene, el grosor y la recuperación de la forma, independientemente del tipo de deformidad(AU)

OBJECTIVES: To report the principles of penile re-sculpturing of different deformities caused by M. Peyronie: restoration of penile length, girth and shape with or without penile prosthesis implantation.METHODS: In the period between February 2007 and March 2009, we performed grafting surgery for M. Peyronie in 98 patients aged between 24 and 72 years (mean 52 years). Penile deformities were diferent: dorsal curvature in 54 (55%), lateral in 7 (7%), ventral in 11 (11%), and combined curvature in 21 (21%); associated corporal narrowing was present in 24 patients (24%). Four (4%) patients presented isolated penile shortening without other deformity. Isolated diffuse corporal narrowing without shortening was found in two (2%) patients. Severity of curvature ranges from 60 to 90 degrees, mean 72. Thirty one (31%) patients had associated ED. Surgical options for severe Peyronie’s disease were: single grafting in 26 pts (26%), complex grafting including circular tunical incision in 36 pts (36%), and in patients with ED the same procedures combined with penile prosthesis implantation (37 pts, 38%). Surgical correction was based on measurement of the tunical defect and precise calculation of graft size and shape. Penile straightening and lengthening was achieved by equalizing of shortened penile side/s with the longest one (convex) and grafting. Penile width is reestablished with additional longitudinal incision/s and grafting; graft width is determined by measurement of difference in circumference between normal and narrowed part of the corpora. We used Intexen LP (AMS) as a grafting material in all cases(AU)

RESULTS: The mean follow-up was 15 months (6-25). Mean penile length gain without prosthesis was 2.8cm (1.5-4.2) and with prosthesis 3.2cm (2-4.5cm). Insuficient straightening was in 5 patients (>15 degree) where Neuro Vascular Bundle (NVB) was limiting factor. Twenty four patients reported hypoesthesia and reduced orgasmic sensitivity that recovered spontaneously after 3-6 months. De-novo ED occurred in 6 pts and progression of disease in 6 patients. Infection occurred only in one patient with penile prosthesis implantation. Overall patients’ satisfaction was 95%. CONCLUSIONS: Complete tunical reconstruction in IPP can be performed as a safe procedure by transversal, longitudinal and circular grafting with or without simultaneous penile prosthesis implantation. Maximum penile length, girth and shape restoration can be achieved using geometrical calculation, regardless of type of deformity(AU)

Penile enhancement using autologous tissue engineering with biodegradable scaffold: a clinical and histomorphometric study.

INTRODUCTION: Autologous tissue engineering with biodegradable scaffolds is a new treatment option for real penile girth enhancement. AIM: The aim of this article is to evaluate tissue remodeling after penile girth enhancement using this technique. METHODS: Between June 2005 and May 2007, a group of 12 patients underwent repeated penile widening using biodegradable scaffolds enriched with expanded autologous scrotal dartos cells. Clinical monitoring was parallel to histological investigation of tissue remodeling. During second surgical procedure, biopsies were obtained 10-14 months after first surgery (mean 12 months, N=6) and compared with those obtained after 22-24 months (mean 23 months, N=6), and control biopsies from patients who underwent circumcision (N=5). Blind evaluation of histomorphometrical and immunohistochemical finding was performed in paraffin sections. MAIN OUTCOME MEASUREMENTS: Penile girth gain in a flaccid state ranged between 1.5 and 3.8 cm (mean 2.1 ± 0.28 cm) and in full erection between 1.2 and 4 cm (mean 1.9 ± 0.28 cm). Patients' satisfaction, defined by a questionnaire, was good (25%) and very good (75%). RESULTS: In biopsies obtained 10-14 months after first surgery, highly vascularized loose tissue with collagen deposition associated with small foci of mild chronic and granulomatous inflammation surrounding residual amorphous material was observed. Fibroblast-like hyperplasia and small vessel neoangiogenesis occurred intimately associated with the progressive growth of vascular-like structures from accumulation of CD34 and alpha-smooth muscle actin-positive cells surrounding residual scaffold-like amorphous material. Capillary neoangiogenesis occurred inside residual amorphous material. In biopsies obtained after 22-24 months, inflammation almost disappeared and tissue closely resembled that of the dartos fascia of control group. CONCLUSIONS: Autologous tissue engineering using expanded scrotal dartos cells with biodegradable scaffolds is a new and promising method for penile widening that generates progressive accumulation of stable collagen-rich, highly vascularized tissue matrix that closely resemble deep dartos fascia.

Complex case of urethral duplication with megalourethra.

Urethral duplication and megalourethra are very rare anomalies and their concomitant presence is extremely rare, with only a few published cases. We present a complex case of complete urethral duplication with dorsal megalourethra that was severely stenotic in its bulbar part and meatus, with the ventral urethra atretic distally and dilated proximally. Both the corpus spongiosum and the cavernosum were missing. He had associated upper urinary tract abnormalities. Urethral patency was restored successfully by meatoplasty, staged buccal mucosa graft urethroplasty, and tailoring of the megalourethra. This report is unique regarding the use of a buccal mucosa graft for urethral reconstruction in patients with associated urethral duplication and megalourethra.

Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice.

Granulocyte colony stimulating factor (G-CSF) is a multi-modal hematopoietic growth factor, which also has profound effects on the diseased CNS. G-CSF has been shown to enhance recovery from neurologic deficits in rodent models of ischemia. G-CSF appears to facilitate neuroplastic changes by both mobilization of bone marrow-derived cells and by its direct actions on CNS cells. The overall objective of the study was to determine if G-CSF administration in a mouse model of Alzheimer's disease (AD) (Tg APP/PS1) would impact hippocampal-dependent learning by modifying the underlying disease pathology. A course of s.c. administration of G-CSF for a period of less than three weeks significantly improved cognitive performance, decreased beta-amyloid deposition in hippocampus and entorhinal cortex and augmented total microglial activity. Additionally, G-CSF reduced systemic inflammation indicated by suppression of the production or activity of major pro-inflammatory cytokines in plasma. Improved cognition in AD mice was associated with increased synaptophysin immunostaining in hippocampal CA1 and CA3 regions and augmented neurogenesis, evidenced by increased numbers of calretinin-expressing cells in dentate gyrus. Given that G-CSF is already utilized clinically to safely stimulate hematopoietic stem cell production, these basic research findings will be readily translated into clinical trials to reverse or forestall the progression of dementia in AD. The primary objective of the present study was to determine whether a short course of G-CSF administration would have an impact on the pathological hallmark of AD, the age-dependent accumulation of A beta deposits, in a transgenic mouse model of AD (APP+ PS1; Tg). A second objective was to determine whether such treatment would impact cognitive performance in a hippocampal-dependent memory paradigm. To explain the G-CSF triggered amyloid reduction and associated reversal of cognitive impairment, several mechanisms of action were explored. (1) G-CSF was hypothesized to increase activation of resident microglia and to increase mobilization of marrow-derived microglia. The effect of G-CSF on microglial activation was examined by quantitative measurements of total microglial burden. To determine if G-CSF increased trafficking of marrow-derived microglia into brain, bone marrow-derived green fluorescent protein-expressing (GFP+) microglia were visualized in the brains of chimeric AD mice. (2) To assess the role of immune-modulation in mediating G-CSF effects, a panel of cytokines was measured in both plasma and brain. (3) To test the hypothesis that reduction of A beta deposits can affect synaptic area, quantitative measurement of synaptophysin immunoreactivity in hippocampal CA1 and CA3 sectors was undertaken. (4) To learn whether enhanced hippocampal neurogenesis was induced by G-CSF treatment, numbers of calretinin-expressing cells were determined in dentate gyrus.

Severe penile injuries: a problem of severity and reconstruction.

OBJECTIVES: To report our experience of treating severe penile injuries with different causes and treatments, as penile trauma presents a difficult physical and psychological problem, and the type and extent of injury varies from mild to severe, sometimes even with total amputation. PATIENTS AND METHODS: We analysed retrospectively 43 patients (mean age 28 years, range 5-52 years) with severe penile injuries referred to us from March 1999 to August 2007. The causes of penile injuries differed, including iatrogenic trauma (20), traffic accidents (11), burns (three), self-amputation (two), ritual circumcision (two), penile fracture (two), gunshot trauma (two) and electrocution (one). The management required a wide variety of surgical techniques tailored to each patient depending on the type and extent of injury. RESULTS: The mean (range) follow-up was 47 (10-108) months. The aesthetic and functional results, including satisfactory sexual intercourse were good in 35 patients. There were complications in seven patients; infection after implanting an inflatable penile prosthesis in one, protrusion of a semirigid prosthesis in one, urethral complications (one stenosis and two fistulae) in three and partial skin flap necrosis in two. CONCLUSIONS: Severe penile injuries should be treated on an individual basis, applying different techniques. However, treatment can be effective and safe only in specialized centres.

Metoidioplasty as a single stage sex reassignment surgery in female transsexuals: Belgrade experience.

INTRODUCTION: Metoidioplasty represents one of the variants of phalloplasty in female transsexuals. Its main characteristic is that it is a one-stage procedure. It involves lengthening and straightening of hypertrophied clitoris to create a neophallus, urethral lengthening to enable voiding while standing, and scrotal reconstruction with insertion of testicle prostheses. AIM: Our aim is to describe our technique and highlight its advantages. METHODS: Between September 2002 and April 2007, 82 female transsexuals, aged 18-54 years (mean age 31) underwent one-stage metoidioplasty. Clitoris is lengthened and straightened by division of clitoral ligaments and short urethral plate. Urethroplasty is done with combined buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora in which two testicle prostheses are inserted. Simultaneously, female genitalia are removed. MAIN OUTCOME MEASURES: Patients' personal satisfaction about sensitivity and length of neophallus, possibility to void in standing position, real length of reconstructed urethra as well as complication rate comparing to other published data. RESULTS: The median follow-up was 32 months (range 14-69). The mean neophallic length was 5.7 cm (range 4-10). Voiding in standing position was reported in all patients, while dribbling and spraying were noticed in 23 cases and solved spontaneously. There were two urethral strictures and seven fistulas that required secondary minor revision. All patients reported preserved sensation and normal postoperative erection. Testicle prostheses rejection was not observed in any of the patients. CONCLUSIONS: Metoidioplasty is a single-stage and time-saving procedure. It could be an alternative to total phalloplasty in female transsexuals who do not wish to have sexual intercourse. Also, it represents a first step in cases where additional augmentation phalloplasty is required.

Buccal mucosa grafts for repair of stenotic catheterizable continent stoma.

PURPOSE: Different tubular structures have been used to create cutaneous catheterizable continent urinary stomas. The most common complication is stomal stenosis on the cutaneous end of the tubes. We present a variant of stomal stenosis repair that uses a buccal mucosa graft. MATERIALS AND METHODS: Between January 2000 and March 2006 stenotic stomal repair was performed in 10 patients between 3 and 17 years old (mean age 6). A Mitrofanoff channel was created from a bladder tube in 4 patients, from appendix in 3, from ileum in 2 and from the ureter in 1. The procedure involved the removal of scar tissue and the creation of well vascularized dermal beds by skin de-epithelialization (epidermis removal). After that we formed 2 elliptical dermal flaps. Two elliptical buccal mucosa grafts were quilted to the recipient bed (the dermal flap) and anastomosed with the mucosa of the normal part of the channel. The flaps were joined, tubularized and sutured to the skin. An indwelling catheter was left in the channel for 2 weeks. Postoperatively the buccal mucosa was wetted with saline solution for 4 consecutive days. RESULTS: Followup was between 12 and 39 months (mean 22). There was no partial or total graft necrosis. None of the patients experienced repeat stenosis. The stoma was visible (uncovered) and the esthetic appearance was satisfactory in all patients. CONCLUSIONS: Repair of Mitrofanoff stomal stenosis using a buccal mucosa graft is a minor procedure. It is a good salvage procedure that excludes the need to create a new channel.

Re: a new technique of vaginal reconstruction with the deep inferior epigastric perforator flap: a preliminary report.

Wang and colleagues described the use of fasciocutaneous flap based on deep inferior epigastric perforator (DIEP) vessels for vaginal reconstruction. They presented four patients with congenital vaginal agenesis and one with vaginal tumor. The rhombus-shaped abdominal flap was designed according to the location of deep inferior epigastric vessels perforators. The size of the flap ranged from 9 x 12 to 11 x 12 cm. The flap was elevated without underlying muscle, dissecting perforators together with the pedicle-deep inferior epigastric vessels up to their origin. The fully mobilized flap was tabularized, transposed paravesically to the previously prepared vaginal bed, and anastomosed to vaginal introitus. Primary donor-site closure was accomplished in all patients with conspicuous scars. All flaps survived and the authors reported a normal appearance of external genitalia with sufficient neovaginal depth and width. During the short follow-up (6-14 mo), two patients reported satisfactory sexual intercourse.

Combined buccal mucosa graft and dorsal penile skin flap for repair of severe hypospadias.

OBJECTIVES: Urethral reconstruction in severe hypospadias presents a great challenge. We have designed a method of combining a longitudinal dorsal island skin flap and buccal mucosa graft to create a neourethra in most severe hypospadias. METHODS: Between January 2003 and March 2007, 17 patients (aged from 9 to 23 months) underwent severe hypospadias repair (13 penoscrotal and 4 scrotal hypospadias). Short urethral plate was divided in all cases and remaining curvature repaired by dorsal plication. We harvested and fixed a buccal mucosa graft to the ventral side of corpora cavernosa to be the first half of a neourethra. A longitudinal dorsal island skin flap was created and buttonholed ventrally. We sutured it together with the buccal mucosa graft to form the neourethra. We fixed the abundant flap pedicle laterally to cover all suture lines of the neourethra. We performed penile skin reconstruction using available penile skin. RESULTS: The mean (range) follow-up was 25 (7 to 58) months. We achieved satisfactory, functional, and aesthetic results in 14 patients. In 3 cases urethral fistula (2) and distal stricture (1) required secondary treatment. CONCLUSIONS: Combined longitudinal island skin flap and buccal mucosa graft could be a good choice for urethral reconstruction in most severe hypospadias repairs.

New insight into surgical anatomy of epispadiac penis and its impact on repair.

PURPOSE: Surgical anatomy of the epispadiac penis is still not fully described. Using our complete disassembly technique, we discovered some anatomical features of epispadiac penis that may have significant impact on surgical outcome. MATERIALS AND METHODS: A total of 52 patients 2 days to 19 years old (mean age 43 months) underwent primary repair of epispadias between October 1996 and December 2006. After complete penile disassembly, ie full mobilization of the corporeal bodies, neurovascular bundles and urethral plate, reassembly of the penile entities was done. The urethral plate is tubularized and ventralized. The corporeal bodies are straightened and lengthened by 2 transverse incisions and grafting, joined medially and fixed to the glans cap. The glans is reconstructed, and the neurovascular bundles are moved dorsally and joined. The skin is reconstructed using different local flaps. RESULTS: Investigating the anatomical features of the epispadiac penis, we discovered several distinguishing features. The corporeal bodies are separated and triangular in shape. They represent the main substrate of dorsal curvature due to the significant disproportion in length between the long ventral and short wedge-shaped dorsal sides. The length of the neurovascular bundles is determined by their course-they are longer if they overlie the ventral side of the corpora and shorter if positioned over the dorsal side. The skin between the scrotum and penis has characteristics similar to penile skin. A good functional and esthetic outcome was achieved in 46 patients. Erection and glanular sensitivity were preserved in all patients. There was no necrosis of the glans or corporeal bodies. Complications included urethral fistula in 4 patients, stenosis in 2 and mild residual curvature in 2. CONCLUSIONS: New insights into the anatomical features of the epispadiac penis can have a significant impact on surgical outcomes.

Sacrospinous ligament fixation for neovaginal prolapse prevention in male-to-female surgery.

OBJECTIVES: To report our experiences of vaginal sacrospinous ligament fixation after vaginoplasty in male transsexual patients with the aim of preventing its postoperative prolapse. METHODS: From August 1997 through November 2005, a total of 62 male transsexual patients (mean age 26 years, range 18 to 58) underwent sacrospinous ligament fixation for neovaginal prolapse during male-to-female sex reassignment surgery. The neovagina was created from a penile skin tube flap combined with a urethral flap. A deep and wide perineal cavity between the urethra, bladder, and rectum was created by dissection of the tendineous center and rectourethral muscle. The right pararectal space was opened by penetrating the right pararectal fascia (rectal pillar) and right ischial spine was palpated. Using the ischial spine as a prominent landmark, the sacrospinous ligament was palpated. Long-handled Deschamps ligature was used to pierce the ligament medially to the ischial spine. Vaginopexy to the sacrospinous ligament was performed, and the neovagina was placed deep in the perineal cavity. RESULTS: The median follow-up was 32 months (range 7 to 102). Sacrospinous ligament fixation was successfully performed in all patients. The mean vaginal length was 10.7 cm (range 9.5 to 16). Of the 62 patients, 42 (76%) were able to have normal sexual intercourse. The appearance of the neovagina was aesthetically acceptable in 52 patients. In 3 cases, a minor bulge of the anterior vaginal wall was easily resolved by simple excision. CONCLUSIONS: Vaginal sacrospinous fixation is feasible in male transsexuals for neovaginal prolapse prevention. However, extensive experience with male pelvic surgery is required to avoid possible complications.

Total phalloplasty using a musculocutaneous latissimus dorsi flap.

OBJECTIVE: To present total phalloplasty in children and adults using a musculocutaneous latissimus dorsi (MLD) free flap to create a large neophallus, that allows easy urethroplasty and implantation of a prosthesis. PATIENTS AND METHODS: From April 1999 to January 2006, 16 patients (mean age 24 years, range 10-34) had a total phalloplasty; the indications were congenital anomalies of the penis in 12, iatrogenic in two and accidental penile trauma in two. The MLD flap is mobilized on a subscapular artery and vein, and a thoracodorsal nerve. The neophallus is created on-site and after dividing the neurovascular pedicle, transferred to the pubic region, where it is anastomosed with the femoral artery, saphenous vein and ilio-inguinal nerve. The donor site was closed directly in 15 patients while in one a split-thickness skin graft was used to cover the defect. In the following stages, two- or three-stage buccal mucosa urethroplasty was used in 11 patients; a penile prosthesis was implanted in seven. RESULTS: The mean (range) follow-up was 31 (12-74) months; the penis was 14-18 cm long and 11-15 cm in circumference. There was no partial or total flap necrosis; the donor site healed satisfactorily in 13 patients while in the remaining three there was moderate scarring. The patency of the urethra was good in all patients. Two urethrocutaneous fistulae developed; one closed spontaneously and the other was successfully treated with minor surgery. The function of the implanted penile prostheses was satisfactory in all patients. CONCLUSIONS: The MLD flap allows the creation of a neophallus of good size and with a good aesthetic appearance; it allows urethroplasty and safe implantation of a penile prosthesis, and it can also be used in children.