[Profiling of Targeted miRNAs (8-nt) for the Genes Involved in Type 2 Diabetes Mellitus and Cardiac Hypertrophy].

Type 2 Diabetes Mellitus (T2DM) and cardiac hypertrophy (CH) are among the top ten leading cause of deaths, worldwide. T2DM and cardiac hypertrophy are the chronic diseases, have close association and direct life-threatening complications like stroke, myocardial infarction, retinopathy, nephropathy, and limb amputation. In addition to other medical approaches, miRNAs-based strategy is considered most efficient for early detection of chronic diseases and also has potential for the treatment of T2DM and cardiac hypertrophy like it is being used for cancer in clinical trials. MicroRNAs (miRNAs) are single stranded (non-coding) of 20 to 22 nucleotides sequences which bind to their target mRNA upon the complimentary basis, to silence the protein expression at post transcriptional level. Bioinformatic databases are used like online mendelian inheritance in man (OMIM), gene testing registry (GTR), TargetScan and ShinyGO for validation of disease linked genes and sorting the common miRNAs in both diseases, such as miR-30-5p/101-3p.2/190-5p/506-3p/9-5p/128-3p/137/96-5p/7-5p/107/101-3p.1/98-5p/124-3p.2/124-3p.116-5p/15-5p/497-5p/ 424-5p/195-5p/1271-5p, let-7-5p. Aforementioned databases were also used for the miRNAs which have more than one disease linked genes target in each pathological condition. Such miRNAs for cardiac hypertrophy are: miR-19-3p/183-5p.2/153-3p/372-3p/302-3p/520-3p/373-3p/129-5p/144-3p/139-5p and for T2DM are: miR-27-3p/206/1-3p/181-5p. This finding would be helpful for the appropriate selection of miRNAs and to design applicable research project in future. It will require more validation by using the miRNAs expression analysis, mimic, and anti-miRNA approach to check their potential against cardiac hypertrophy and T2DM.

A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years.

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results. MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic. RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good. CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service.

Long-term outcomes in primary male epispadias.

PURPOSE: The authors present a case series of 30 male patients who presented with primary epispadias between 1989 and 2002 and looked at their long-term outcomes. OBJECTIVES: (1) What procedures and operations did these patients require following their original surgery? (2) What were their outcomes as adults in terms of continence, cosmesis, and sexual function? MATERIALS AND METHODS: Primary male epispadias patients who had gone through transition into Adolescent and Adult Urology services were identified retrospectively from electronic patient records. RESULTS: The authors identified 30 male patients with a median follow-up of 18.5 years. Twenty-four had penopubic epispadias, and six had penile epispadias. All initial surgery took place between 9 and 48 months. Twenty-eight patients needed further surgery over the follow-up period, 26 had surgery for continence, and 12 required revision surgery. At follow-up, 15 patients were continent voiding per urethra, nine patients reported stress leakage with volitional urethral voiding, six patients were using a Mitrofanoff to void, and four of these had an ileocystoplasty. Nineteen patients had documentation on their feelings toward cosmetic outcome; 17 expressed concern. Twenty-one patients had documentation about sexual function; 20 had normal erections with six reporting chordee and nine reporting retrograde ejaculation. No patients were recorded to have fathered any children. DISCUSSION: There are only a few published studies looking at long-term outcomes of genitourinary reconstruction in primary male epispadias and their sexual function in adulthood. The majority of this patient cohort required surgery to improve their continence and had more than one continence procedure. There is limited data on continence outcomes in the literature with small cohorts and rates varying between 40 and 100% at 10-year follow-up. Despite corrective surgery, nearly all the patients were concerned about their genital appearance. Other studies have shown similar outcomes in terms of patient satisfaction and sexual function. The limitations of this work are that the information was gathered retrospectively from the electronic patient record and validated instruments on outcomes were not used. CONCLUSIONS: The study outcomes will be useful for clinicians who are counseling patients and parents regarding what to expect as adults.

Access for retroperitoneoscopic surgery.

Retroperitoneoscopic surgery is used for a variety of renal and adrenal procedures in the paediatric population. This can be a challenging procedure but has advantages over open and transperitoneal laparoscopic approaches. This VideoBank article aims to aid the surgeon in gaining safe and efficient access for retroperitoneal surgery by demonstrating key steps including patient positioning and optimal trocar placement.

Mid- to long-term outcomes of the 'anatomical approach' to congenital megaprepuce repair.

INTRODUCTION: The understanding of the aetiopathogenesis and the long-term outcomes of correctional repair of congenital megaprepuce (CMP) remains unestablished. Different techniques have been described; however, optimum results have been difficult to achieve. OBJECTIVE: The aim of our study was to review our experience of the 'anatomical approach' to the correction of CMP. MATERIAL AND METHODS: This is a retrospective review of boys who underwent CMP repair between 2003 and 2014. All of them had the anatomical approach: A curved incision is made between the scrotal and penile skin. Circumferential dissection superficial to Buck's fascia frees the penis and allows the scrotum to assume a more caudal position. The dissection distally lifts the preputial sac that is opened ventrally. The redundant inner preputial skin is excised. After full degloving, the dorsal flap of skin is thinned. The base of the flap is anchored, and the rectangle of skin is wrapped around the shaft. The remaining diamond-shaped incision is closed in a vertical line. Postoperatively, foam dressings and urethral catheter are left in place. Symptomatology, hospital stay, postoperative complications, redosurgery, voiding and cosmesis were evaluated. RESULTS: Sixty-one patients had surgery at 5-151 months (median 17 months). Median hospital stay was 24 h (12-168 h). Foam dressings and urethral catheter were used in 47 boys and removed in outpatient clinic after 3-7 days. There were two immediate postoperative complications requiring surgery. One due to severe oedema and constriction ring, and the other had wound infection with wound breakdown, both in patients with no dressings (P < 0.05). Follow-up was available for 58 patients, with a median of 22 months (3-79 months). Two required redosurgery (3.5%), one with poor cosmetic result and one recurrence. In all patients, a normal circumcised appearance had been achieved and in 47, cosmetic result was excellent (81%). Five patients have residual suprapubic fat, and four, excess ventral skin. One with residual suprapubic fat has reached puberty and it has resolved. All declared good stream. The same technique was used for six patients with poor cosmetic result after surgery elsewhere. The outcome is excellent for all, with median follow-up of 20.5 months (5-31 months). CONCLUSION: The 'anatomical' repair provides the ability to create the appearance of a standard circumcision, which is generally accepted as normality. Apart from the penis itself, this technique facilitates correction of the penoscrotal transposition, giving the external genitalia the best appearance. It seems to provide good functional and cosmetic outcomes, and it holds true at mid- to long-term follow-up. Dressings and catheter can potentially prevent postoperative complications. However, a prospective study with standardised parameters is required to confirm these findings.

Retroperitoneoscopic lower pole heminephrectomy.

INTRODUCTION: Retroperitoneoscopic heminephrectomy is a challenging procedure but with advantages over open and transperitoneal laparoscopic approaches. Lower pole heminephrectomy is less commonly undertaken compared with the upper pole.s OBJECTIVE: This VideoBank article aims to aid the surgeon in reducing the associated risks by demonstrating key steps including patient positioning, access and demonstrating key critical views. MATERIALS AND METHODS: This is a video article with audio commentary of a pediatric patient undergoing a retroperitoneoscopic lower pole heminephrectomy. CONCLUSION: Lower pole heminephrectomy can be safely undertaken via a retroperitoneoscopic approach.

Laparoscopic ureterocalicostomy in children: The technique and feasibility.

Ureterocalicostomy is a salvage technique commonly used for failed pyeloplasties; it has also been reported as a primary procedure in ureteropelvic junction obstruction (UPJO). This video describes the technique of laparoscopic ureterocalicostomy for primary UPJO in a child with a malrotated kidney and parenchymal thinning. A 13-year-old girl with symptomatic UPJO was found to have a malrotated kidney with a high posterior insertion of the ureter. A laparoscopic dependent ureterocalicostomy over a double-J stent was performed. The postoperative course was uneventful, with excellent clinical and radiological outcomes. Literature review revealed only two reports of this laparoscopic procedure as a primary surgery in children (one with intrarenal pelvis associated to urolithiasis and the other with a malrotated kidney). Laparoscopic ureterocalicostomy is a safe and feasible option in selected cases with parenchymal thinning due to atypical UPJ anatomy or failed pyeloplasty.

Paediatric cystolitholapaxy through the Mitrofanoff/Monti channel.

INTRODUCTION: Bladder calculi are a known complication of bladder augmentation. Open cystolithotomy remains the preferred option for treating large or multiple stones. Increasingly, however, minimal access techniques have been used. Reports of Mitrofanoff cystolitholapaxy are rare and have been limited to adults. This study presented a two centre series of children treated by cystolitholapaxy via the Mitrofanoff/Monti channel. MATERIALS AND METHODS: With institutional approval the current study retrospectively reviewed and identified 14 patients, on a prospective database, who underwent Mitrofanoff cystolitholapaxy to treat bladder calculi at two independent institutions in the UK and Chile between 2004 and 2016. It looked at patient demographics, surgical technique, stone clearance and recurrence, as well as leak or catheterisation difficulties of the Mitrofanoff/Monti channel post-procedure. RESULTS: Fourteen patients underwent Mitrofanoff cystolitholapaxy during the period 2004-2016. One patient was excluded due to lack of follow-up. The remaining 13 patients were aged 5-22 (median 14) years at the time of the procedure. Their underlying diagnoses were four neuropathic bladders, four bladder exstrophy, four cloacal exstrophy and one posterior urethral valve. Patients underwent augmentation cystoplasty at a median age of 5 (range 1-15) years, using ileum in 10 and sigmoid colon in three. The channel for clean intermittent catheterisation was an appendix Mitrofanoff in nine and a Monti channel in four. An Amplatz sheath was placed through the Mitrofanoff to allow safe access to the bladder for treating the stones (see Summary Table). Recurrent stones were treated using the same technique. Stone and channel outcomes were analysed for each procedure. There were 22 procedures in 13 patients; five (38%) patients had recurrent stones. Median time to recurrence was 6 months. There were no immediate complications. Stone clearance was confirmed by ultrasound and abdominal x-ray at 3-6 months after the procedure. Median follow-up was 15 (range 3-53) months. There were no leaks or difficulties catheterising the channel on follow-up. DISCUSSION: This was the first series of Mitrofanoff/Monti cystolitholapaxy for the treatment of calculi in augmented bladders of paediatric patients. Previous concerns about damaging the continence mechanism of the conduit appeared to be unwarranted. The use of an Amplatz sheath protected the continence system from repeated instrumentation, and permitted free backflow of irrigation and rapid clearance of stone fragments. Recurrence of stones occurred in 38%, which was in keeping with rates reported in the wider literature. CONCLUSION: Mitrofanoff cystolitholapaxy was safe, and with appropriate care did not result in leakage or difficulty catheterising.

Retroperitoneoscopic heminephrectomy.

Retroperitoneoscopic heminephrectomy has multiple potential benefits in both infants and children. This article reviewed technical aspects of the procedure, and provided illustrations and an operative video demonstration. The vital first step is a 'critical view' of the collecting system/vascular supply of both upper/lower moieties. Dividing the lateral renal attachments later in the dissection allows passive retraction of the hilum, facilitating this dissection.

Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery.

BACKGROUND: Surgical removal of mandibular third molars results in some degree of post-operative pain, swelling and trismus. These can be controlled by proper administration of local anesthesia, careful bone removal, minimal trauma to adjacent soft tissues and administration of methylprednisolone and serratiopeptidase drugs. The aim of the present study was to compare the efficacy of methylprednisolone and serratiopeptidase in controlling post-operative pain, swelling and trismus after surgical removal of impacted mandibular third molars. MATERIAL AND METHODS: The subjects were divided into two groups of 50 patients each undergoing surgical removal of mandibular third molars. Group A was given methylprednisolone 4mg orally every 8th hourly and Group B was given serratiopeptidase 10 mg every 12th hourly orally. Post-operatively pain, swelling and trismus were evaluated at the end of 1st, 3rd and 5thday. RESULTS: The results of this study showed that methylprednisolone is an effective analgesic, while serratiopeptidase has moderate analgesic activity. Serratiopeptidase is more effective than methylprednisolone in controlling post surgical swelling and trismus. Hence combination of these two drugs would be very effective than individual drug when widespread post-operative sequelae are expected after surgical removal of impacted lower third molars. CONCLUSIONS: We conclude that methylprednisolone affords better pain relief while serratiopeptidase exerts better anti-inflammatory and anti-swelling effects in the post-operative period. Synergistic combinations of these two drugs would however prove to be more effective when extensive post-operative sequelae are expected. Key words:Methylprednisolone, serratiopeptidase, pain, swelling, trismus, third molar.

Surgical technique: Retroperitoneoscopic approach for adrenal masses in children.

Laparoscopic adrenalectomy is considered to be the standard of care for the surgical excision of adrenal masses. The transperitoneal laparoscopic and retroperitoneoscopic approaches are described. Both are safe and as effective as open adrenalectomy, with the added benefit of the minimally invasive approach. It can be utilized for patients requiring surgery for a phaeochromocytoma, adrenal adenoma, adrenal adenocarcinoma, Cushing's syndrome, neuroblastoma, and an incidentaloma. Relative contraindications include previous surgery of the liver or kidney, large tumours (>8-10 cm in diameter) or coagulation disorders. Although the transperitoneal route is used more widely, the retroperitoneal approach provides direct access to the adrenal gland and easy visualization of the adrenal vein. It avoids also colonic mobilization, minimizes the risk of injury to hollow viscera, and the potential risk of adhesion formation. However, the reversed orientation of the kidney and hilum, combined with a significantly smaller working space, may make this approach difficult to master.

Primary bladder exstrophy closure in neonates: challenging the traditions.

PURPOSE: We describe a novel approach to neonatal bladder exstrophy closure that challenges the role of postoperative immobilization and pelvic osteotomy. MATERIALS AND METHODS: We reviewed the primary management of bladder exstrophy at our institutions between 2007 and 2011. In particular we compared postoperative management in the surgical ward using epidural analgesia to muscle paralysis and ventilation in the intensive care unit. Clinical outcome measures were time to full feed, length of stay, postoperative complications and redo closure. Cost-effectiveness was also evaluated using hospital financial data. Data are expressed as median (range). Significance was explored by Fisher exact test and unpaired t-test. RESULTS: A total of 74 patients underwent primary closure without osteotomy. Successful closure was achieved in 70 patients (95%). A total of 48 cases (65%) were managed on the ward (group A) and 26 (35%) were transferred to the intensive care unit (group B). The 2 groups were homogeneous for gestational age (median 39 weeks, range 27 to 41) and age at closure (3 days, 1 to 152). Complications requiring surgical treatment were noted in 4 patients (8.3%) in group A and 3 (11.5%) in group B (p = 0.609). Length of stay was significantly shorter for the group managed on the ward (11 vs 18 days, p <0.0001). Median costs were $42,732 for patients admitted to the intensive care unit and $16,214 for those admitted directly to the surgical ward (p <0.0001). CONCLUSIONS: Primary closure of bladder exstrophy without lower limb immobilization and osteotomy is feasible. Postoperative care on the surgical ward using epidural analgesia results in shorter hospitalization.

Clinical and gonadal features and early surgical management of 45,X/46,XY and 45,X/47,XYY chromosomal mosaicism presenting with genital anomalies.

OBJECTIVE: The 45,X/46,XY and 45,X/47,XYY group of patients includes some of those previously diagnosed with 'mixed gonadal dysgenesis'. Our aim was to establish the clinical and gonadal spectrum, and early surgical management, of patients with chromosomal mosaicism presenting with genital anomalies. PATIENTS AND METHODS: We performed a retrospective review of patients with 45,X/46,XY or 45,X/47,XYY mosaicism presenting with genital ambiguity between 1988 and 2009. At least one gonadal biopsy or gonadectomy specimen was available for each patient. Gonadal histology was re-evaluated by a paediatric pathologist. RESULTS: Of 31 patients with 45,X/46,XY (n = 28) or 45,X/47,XYY (n = 3) mosaicism and genital anomalies, 19 (61%) were raised male. Histology of 46 gonads was available from patients who had undergone a gonadectomy or gonadal biopsy, at a median age of 9.5 months. 18 gonads were palpable at presentation, including 5 (28%) histologically unremarkable testes, 2 streak gonads, and 1 dysgenetic gonad with distinct areas of testicular and ovarian stroma but no oocytes. All intra-abdominal gonads were found to be dysgenetic testes (of which 2 were noted to have pre-malignant changes) or streaks, apart from 1 histologically unremarkable testis. 15 (48%) patients had other anomalies, most commonly cardiac and renal; 4 (13%) had a Turner phenotype. CONCLUSION: The anatomy and gonadal histology of 45,X/46,XY and 45,X/47,XYY individuals with genital ambiguity do not conform to a set pattern, and hence management of each patient should be individualized according to detailed anatomical and histological assessment.

Combined laparoscopic and cystoscopic injection sclerotherapy for bladder venous malformation: a novel technique.

Treatment of vascular malformations of the urinary bladder can be challenging. We report a case of bladder venous malformation treated with sodium tetradecyl sulphate (STS 3%) sclerotherapy, using a combined cystoscopic and percutaneous transperitoneal laparoscopy guided approach. When cystoscopic views are poor, the laparoscopic approach is a useful adjunct to aid sclerotherapy of bladder venous malformation. This technique has not been previously described.

Outcomes and fate of the remnant moiety following laparoscopic heminephrectomy for duplex kidney: a multicenter review.

PURPOSE: To evaluate outcomes following laparoscopic heminephrectomy (LHN) in duplex kidneys in the pediatric population, focusing on the fate of the remnant moiety. METHODS: 142 patients underwent laparoscopic heminephrectomy for duplex kidney across 4 different institutions in the U.S. and Europe. Median age at surgery was 11.4 months. A retroperitoneoscopic approach was used in all patients, with 82 (57.7%) patients placed in posterior prone position (PPR), and 60 (42.3%) in lateral retroperitoneal (LRP). Follow up included routine ultrasound, and DMSA was performed in the event of abnormalities in ultrasound or postoperative course. RESULTS: Median operative time was 120 min. 11 patients (7.7%) required open conversion, the majority of which (8/11) occurred prior to 2000. Median hospital stay was 2 days and no major complications were observed. 7 patients (4.9%) developed a postoperative urinoma, and 1 patient required ureterectomy for urinary tract infection. With a median follow-up of 4.5 years, 7 children (4.9%) experienced significant loss of function in the remaining moiety, with 3 patients requiring completion nephrectomy. Of patients losing their remaining moiety, median age at surgery was 9 months [4 - 42], and all except 1 (6/7) had an upper pole heminephrectomy. Three patients in this group (42%) experienced an immediate postoperative complication (hematoma, UTI, urinoma). No consistent preoperative or technical factors were consistent in the renal loss group. CONCLUSIONS: LHN for duplex kidney produces satisfactory outcomes in the pediatric population. With a median follow up of 4.5 years, we demonstrate a non-functioning renal moiety rate of 5%. We did not identify any clinical predictors of this outcome in our series, although upper pole heminephrectomy, patient age, and postoperative complications may be contributing factors.

Understanding cloacal anomalies.

Persistent cloaco is the most severe type of anorectal malformation encountered in children. Patients with cloacal anomalies have a high incidence of associated anomalies most commonly: urinary tract and spinal. Persistent cloaca remains a difficult reconstructive challenge but it is now possible to anatomically correct the defect with surgery in the majority of patients. This review discusses embryology, prenatal diagnosis, neonatal physical and radiological findings. A summary of early management and investigation is provided and the commonest surgical reconstruction techniques are discussed. The main goals of surgical reconstruction are the achievement of bowel and bladder control for the child and normal sexual function in adult life. Although the majority of cloaca patients can achieve faecal and urinary continence with the surgical reconstructive procedures performed today, many require additional/multiple urological procedures to achieve continence, treat bladder dysfunction and to protect renal function. One half of patients will develop renal failure, so regular and life long surveillance is mandatory. Due to the high number of associated gynaecological problems all patients should be assessed by a paediatric gynaecologist at puberty.

Experience with oral mexiletine in primary erythromelalgia in children.

Primary erythromelalgia is characterized by burning pain, redness, and warmth in the extremities. We present two cases of primary erythromelalgia both of whom presented with a history of several months of severe burning pain in both hands and feet. Both patients had received multiple pain medications with no improvement in symptoms. Pain was relieved by putting affected parts in ice cold water, which resulted in immersion injury of the affected parts. Both patients stopped taking part in school and social activities. We tried oral mexiletine, a class Ib antiarrythmic agent, in view of its reported role in various chronic painful conditions. Dramatic improvement was observed with its use. Both patients improved after several weeks of use, and there were fewer soaking episodes. We observed no adverse effects with mexilitine therapy.