Improved outcomes after technical modifications in tubularized incised plate urethroplasty for mid-shaft and proximal hypospadias.

PURPOSE: To investigate and compare the outcomes after tubularized incised plate (TIP) urethroplasty in mid-shaft and proximal hypospadias using a standard and a modified technique. METHODS: We conducted a retrospective study in 104 consecutive children who underwent mid-shaft or proximal TIP repairs from Jan 2007 to Sept 2015. Patients in Cohort One had dorsal dartos (DD) neourethral coverage while patients in Cohort Two had either de-epithelialized split preputial (DESP) or tunica vaginalis (TV) flap coverage. TV flap was used only when DESP flap was not sufficient to cover the neourethra. RESULTS: There were 52 patients each in Cohort One (DD, n = 52) and Cohort Two (DESP, n = 38; TV, n = 14) with no difference in ratio of mid-shaft/proximal between the two cohorts. At a median follow-up of 28 months, 36 patients (34.6 %) developed 47 complications including fistula (n = 19; 18.3 %) and neourethral dehiscence (n = 4; 3.8 %). Cohort One patients had significantly more fistula (28.8 vs 7.7 %; p = 0.005) and neourethral dehiscence (7.7 vs 0 %; p = 0.04) than Cohort Two. There was no difference between the two cohorts in the complication rates of meatal stenosis, recurrent ventral curvature and neourethral stricture. CONCLUSIONS: Both DESP and TV flap appear to be superior to DD in preventing fistula and neourethral dehiscence in non-distal TIP repairs.

From laparoscopic to open Kasai portoenterostomy: the outcome after reintroduction of open Kasai portoenterostomy in infant with biliary atresia.

PURPOSE: Apparently superior result was observed after open Kasai portoenterostomy in infant with biliary atresia. Our institute stopped performing laparoscopic portoenterostomy since 2007. We aimed to investigate the outcome after reintroduction of open portoenterostomy. METHODS: 27 non-syndromic infants underwent open Kasai portoenterostomy from 2007 to 2012. The age and the sex of the patient, the bilirubin level before the operation, the early clearance of jaundice (total bilirubin <20 µmol/L within 6 month of portoenterostomy), the native liver survival at 2 years after the operation were reviewed. The results were retrospectively compared with all 16 infants who underwent laparoscopic Kasai portoenterostomy before 2007. RESULTS: All infants had type III biliary atresia. No statistical difference was observed regarding the age at operation and the pre-operative bilirubin level. The early clearance of jaundice rate was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). At 2 years after the operation, the native liver survival was 81% (22/27) after open operation and was 50% (8/16) after laparoscopic operation (p = 0.03). CONCLUSION: Reintroduction of open Kasai portoenterostomy was associated with superior early clearance of jaundice rate and 2-year native liver survival rate.

Impact of Age of Patient and Experience of Surgeon on the Outcome after Kasai Portoenterostomy: Can We Delay the Surgery?

INTRODUCTION: Age of patient and experience of biliary atresia (BA) center are well-known factors associated with early jaundice clearance (EJC) after Kasai portoenterostomy (KPE) in infants with BA. This study focused on the impact of age and surgeon factor on the short-term outcome after KPE within a single center. MATERIALS AND METHODS: Fifty-four consecutive infants (18 boys and 36 girls) who underwent KPE from January 2010 to January 2020 were reviewed. KPE was performed in the earliest available operative session once the initial work-up was completed. In group A (n = 41), KPE was performed by surgeon A. In group B (n = 13), KPE was performed by specialists under the supervision of surgeon B (who is the mentor of surgeon A) when surgeon A was not available for operation. The demographics of patients, the EJC (total bilirubin <20 µmol/L within 6 months of KPE), and 2-year native liver survival (NLS) between the two groups were studied. RESULTS: The median age at operation was 52 days (range 26-135 days). The overall EJC rate and 2-year NLS were 85.2 and 89.4%, respectively. Group A (p = 0.015) and male gender (p = 0.029) were statistically associated with EJC but not the age at operation (p = 0.101). Group A was also statistically associated with superior 2-year NLS (p = 0.047). CONCLUSION: Balancing between the impact of age at operation and the experience of surgeon on the outcome after KPE, our result suggested that KPE may be deferred until a more experienced surgeon to operate.

Long-Term Results of One-Stage Laparoscopic-Assisted Endorectal Pull-Through for Rectosigmoid Hirschsprung's Disease in Patients Aged Above 5 Years.

Purpose: Despite the fact that the laparoscopic-assisted endorectal pull-through (LAEPT) for Hirschsprung's disease (HD) was introduced over 20 years ago, published outcomes in older children and adolescent are lacking. To address this, we studied the long-term results of LATEP for rectosigmoid HD in patients above 5 years of age. Materials and Methods: A retrospective review was conducted on all nonsyndromic patients above 5 years of age and who underwent one-stage LAEPT for rectosigmoid HD between January 2002 and December 2017. Late Hirschsprung-associated enterocolitis (HAEC) was defined as HAEC occurring 1 year after the pull-through operation. Postoperative bowel function was assessed using the Krickenbeck classification. Results: Forty-one patients (37 males and 4 females) were included in this study with a median follow-up of 9.0 years. The median age at surgery was 55 days. Two patients had anastomotic leakage. No patient had late HAEC, rectal prolapse, anastomotic stricture, or intestinal obstruction. According to the Krickenbeck classification, all patients had voluntary bowel movements without constipation. Overall, 65.8% of patients had no soiling. However, on subgroup analysis, only 45.4% of patients younger than 11 years of age had no soiling compared with 89.5% in patients at or older than 11 years of age (P = .003). Conclusions: Our results showed that LAEPT for rectosigmoid HD was a safe procedure. Nearly 90% of patients had normal bowel function by puberty. Further studies are needed to address the problem of soiling in patients younger than 11 years of age.

Comparison of Characteristics and Outcomes in Antenatally and Postnatally Detected Choledochal Cyst in Infants and Young Children in a Laparoscopic Surgery Center.

Purpose: The aim of this study was to compare the characteristics and the outcome between infants and young children with antenatally (AN) and postnatally (PN) detected choledochal cyst (CC) in a laparoscopic surgery center. Methods: A retrospective review was conducted for all children who underwent excision of CC and hepaticojejunostomy (HJ) before 36 months of age between October 2004 and October 2019. Results: Thirty-nine children (28 girls and 11 boys) were included in this study. Twenty-one children had AN detected CC and 18 had PN detected CC. The median age at operation (AN vs. PN; 3 months vs. 15.5 months, P < .001) and body weight (AN vs. PN; 5.6 kg vs. 10.5 kg, P < .001) were significantly different between the two groups. Children in PN group has an increased risk of being symptomatic (AN vs. PN; 6 vs. 18, P < .001) and having intervention before operation (AN vs. PN; 0 vs. 4, P = .037). Laparoscopic excision was performed in all children in AN group and in 12 children (66.7%) in PN group (P = .006). Conversion to open HJ was performed in 4 children in AN group but none in PN group (P = .146). There was no statistical differences in success in laparoscopic operation (P = .257), median operative time (P = .094), postoperative complication (P = .576), and median length of hospital stay (P = .749). Conclusions: Despite younger age at operation, the outcome of laparoscopic excision of AN detected CC was comparable with PN detected CC. Earlier detection and operation decreased the risk of preoperative intervention.

Ten-Year Native Liver Survival Rate After Laparoscopic and Open Kasai Portoenterostomy for Biliary Atresia.

PURPOSE: Laparoscopic Kasai portoenterostomy (LKP) remains controversial in the management of infants with biliary atresia (BA). There are no data reporting the 10-year native liver survival rate after LKP. The study aims to present the 10-year native liver survival rate after LKP and complications in native liver survivors after Kasai portoenterostomy (KP). METHODS: A retrospective review was conducted for 31 consecutive infants with BA who underwent KP by day 75 of life in our institute from January 1993 to December 2007. The demographics and outcomes of patients after LKP and open KP (OKP) were compared. RESULTS: Eleven patients underwent LKP and 20 patients underwent OKP. No statistical difference was observed in the age at operation and the preoperative bilirubin level. The operative time for LKP was significantly longer than that for OKP (mean 314.5 minutes versus 271.5 minutes, P = .03). The 10-year native liver survival rate was 45% (5/11) after LKP and was 85% (17/20) after OKP (P = .03). Forty percent (2/5) of the native liver survivors in the LKP and 71% (12/17) in the OKP developed complications within 10 years after KP (P = .23). CONCLUSIONS: The 10-year native liver survival rate in patients who underwent LKP by 75 days of life was 45%. With superior 10-year liver survival rate and comparable complication rate after OKP, OKP is still the treatment of choice for BA in our institute.

Gatifloxacin affects GLUT1 gene expression and disturbs glucose homeostasis in vitro.

Gatifloxacin may induce life-threatening dysglycemia. The facilitated glucose transporter type 1 (GLUT1) protein is ubiquitously expressed in many tissues. Disturbed GLUT1 protein function weakens the systemic glycemic control and may cause dysglycemia. In this study we demonstrate that gatifloxacin modulates the transcription and reduces the expression and function of GLUT1 gene in HepG2 cells. When treated with gatifloxacin at concentrations of 3.4 mug/ml (8.4 muM) and 17 mug/ml (42 muM), GLUT1 promoter activity was stimulated by 2.8 and 3.8 folds, GLUT1 mRNA expression was decreased by 41% and 31%, and glucose uptake was decreased by 41% and 52%, respectively. Our findings imply that disturbed GLUT1 gene expression and protein function may underlie the dysglycemic effect of gatifloxacin.

Three Japanese patients with glucose transporter type 1 deficiency syndrome.

We report three Japanese patients with glucose transporter type 1 deficiency syndrome (Glut1DS). Two patients had a normal erythrocyte 3-O-methylglucose (3OMG) uptake, one with a previously reported T295M substitution and the other with a novel 12-bp insertion at nt 1034-1035, ins CAGCAGCTGTCT. The third patient, with deficient 3OMG uptake, had a previously reported hot-spot mutation, R333W. All three patients responded to a ketogenic diet. All patients showed a significant improvement in ataxia, with blood beta-hydroxybutyrate (BOHB) levels ranging from 0.1 to 3mM. BOHB levels of at least 3mM were necessary to control seizures, and higher ketone levels are recommended to meet brain energy needs during development. FDG-PET scan, performed before and after a ketogenic diet in the R333W patient, did not change despite a clinical improvement. This clinical condition is treatable and early diagnosis is important.

Cystic meconium peritonitis with jejunoileal atresia: Is it associated with unfavorable outcome?

AIM: To compare the outcome between patients with jejunoileal atresia (JIA) associated with cystic meconium peritonitis (CMP) and patients with isolated JIA (JIA without CMP). METHODS: A retrospective study was conducted for all neonates with JIA operated in our institute from January 2005 to January 2016. Demographics including the gestation age, sex, birth weight, age at operation, the presence of associated syndrome was recorded. Clinical outcome including the type of operation performed, operative time, the need for reoperation and mortality were studied. The demographics and the outcome between the 2 groups were compared. RESULTS: During the study period, 53 neonates had JIA underwent operation in our institute. Seventeen neonates (32%) were associated with CMP. There was no statistical difference on the demographics in the two groups. Patients with CMP had earlier operation than patients with isolated JIA (mean 1.4 d vs 3 d, P = 0.038). Primary anastomosis was performed in 16 patients (94%) with CMP and 30 patients (83%) with isolated JIA (P = 0.269). Patients with CMP had longer operation (mean 190 min vs 154 min, P = 0.004). There were no statistical difference the need for reoperation (3 vs 6, P = 0.606) and mortality (2 vs 1, P = 0.269) between the two groups. CONCLUSION: Primary intestinal anastomosis can be performed in 94% of patients with JIA associated with CMP. Although patients with CMP had longer operative time, the mortality and reoperation rates were low and were comparable to patients with isolated JIA.

Early Reoperations after Primary Repair of Jejunoileal Atresia in Newborns.

Aim: To review nine-year experience in managing jejuno-ileal atresia (JIA) by primary resection and anastomosis and identify factors associated with reoperations. Methods: From April 2006 to May 2015, all consecutive neonates who underwent bowel resection and primary anastomosis for JIA were analyzed retrospectively. Patients with temporary enterostomy were excluded. Patient demographics, types of atresia, surgical techniques, need for reoperations, and long-term outcomes were investigated. Results: A total of forty-three neonates were included, in which nineteen (44.2%) of them were preterm and fourteen (32.6%) were of low birth weight. Thirteen patients (30.2%) had jejunal atresia whereas thirty patients (69.8%) had ileal atresia. Volvulus, intussusception and meconium peritonitis were noted in 12, 8, and13 patients, respectively. Eight patients (18.6%) had short bowel syndrome after operation. Ten patients (23.3%) required reoperations from 18 days to 4 months after the initial surgery due to anastomotic stricture (n=1), adhesive intestinal obstruction (n=1), small bowel perforation (n=2) and functional obstruction (n=6). Prematurity and low birth weight were associated with functional obstruction leading to reoperation (p=0.04 and 0.01 respectively). The overall long-term survival was 97.7%. All surviving patients achieved enteral autonomy and catch-up growth at a median follow-up of 4.7 years. Conclusion: Long-term survival of JIA after primary resection and anastomosis are excellent. However, patients have substantial risk of early reoperations to tackle intraabdominal complications.

Tumor risk of children with 45,X/46,XY gonadal dysgenesis in relation to their clinical presentations: Further insights into the gonadal management.

OBJECTIVE: To investigate the risk of gonadal germ cell neoplasms (GCN) in children with 45,X/46,XY gonadal dysgenesis and its relation to the clinical presentations. METHODS: We conducted a retrospective study reviewing the clinical and gonadal features of all consecutive children with 45,X/46,XY gonadal dysgenesis who received gonadal management in a tertiary center from 1985 to 2015. Study subjects were divided into Group I(significant genitalia anomaly), Group II(female phenotype) and Group III(male phenotype). RESULTS: 21 children were studied (Group I=8; Group II=11; Group III=2). All 19 children of Group I and II eventually underwent bilateral gonadectomy. One patient of Group III underwent gonadal biopsy which showed increase in fibrous tissue in the testes without any GCN. 3/8(37.5%) and 6/11(54.5%) of patients in Group I and II respectively had either gonadoblastoma (GB) or carcinoma-in-situ (CIS) or both affecting one or both gonads. Among Group I patients, the 4 dysgenetic testes affected by CIS in 3 patients were intraabdominal (n=1), inguinal (n=1) and scrotal (n=2) in positions. Among Group II patients, 6/20 streak gonads had GB and 2/2 dysgenetic testes had GB or CIS. CONCLUSIONS: 45,X/46,XY children with significant genitalia anomaly or female phenotype are both at high risk of gonadal GCN.

The effects of phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin on cellular glucose transport.

Glucose is the principal fuel for brain metabolism and its movement across the blood-brain barrier depends on Glut1. Impaired glucose transport to the brain may have deleterious consequences. For example, Glut1 deficiency syndrome (Glut1DS) is the result of heterozygous loss of function Glut1 mutation leading to energy failure of the brain and subsequently, epileptic encephalopathy. To preserve the integrity of the energy supply to the brain in patients with compromised glucose transport function, consumption of compounds with glucose transport inhibiting properties should be avoided. Phenytoin is a widely used anticonvulsant that affects carbohydrate metabolism. In this study, the hypothesis that phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) affect cellular glucose transport was tested. With a focus on Glut1, the effects of phenytoin and HPPH on cellular glucose transport were studied. Glucose uptake assay measuring the zero-trans influx of radioactive-labeled glucose analogues showed that phenytoin and HPPH did not exert immediate effects on erythrocyte Glut1 activity or glucose transport in Hs68 control fibroblasts, Glut1DS primary fibroblasts isolated from two patients, or in rat primary astrocytes. Prolonged exposure to the two compounds could stimulate glucose transport by up to 30-60% over the control level (p <0.05) in Hs68 and Glut1DS fibroblasts as well as in rat astrocytes. The stimulation of glucose transport by HPPH was dose-dependent and accompanied by an up-regulation of GLUT1 mRNA expression (p <0.05). In conclusion, phenytoin and HPPH do not compromise cellular glucose transport. Prolonged exposure to these compounds can modify carbohydrate homeostasis by up-regulating glucose transport in both normal and Glut1DS conditions in vitro.

Use of laparoscopy as the initial surgical approach of impalpable testes: 10-year experience.

AIM: To review the experience in the management of impalpable testes using laparoscopy as the initial approach and the need for inguinal exploration. METHODS: From January 2004 to June 2014, 339 patients with undescended testes underwent operation in our institute. Fifty patients (15%) had impalpable testes. All children with impalpable testes underwent initial laparoscopy. A retrospective review was conducted on this group of patients and the outcome was analyzed. RESULTS: Forty children had unilateral impalpable testis. Ten children had bilateral impalpable testes. Thirty-one children (78%) in the unilateral group underwent subsequent inguinal exploration while 4 children (40%) in the bilateral group underwent inguinal exploration (P < 0.05). Orchidopexy was performed in 16 children (40%) in the unilateral group and 9 children (90%) in the bilateral group (P < 0.05). Regarding the 24 children with unilateral impalpable testis and underwent orchidectomy for testicular nubbin (n = 19) or atrophic testes (n = 2) or has vanishing testes (n = 3); contralateral testicular hypertrophy was noticed in 10 (41%). No intra-operative complication was encountered. Two children after staged Fowler-Stephens procedure and 1 child after inguinal orchidopexy had atrophic testes. CONCLUSION: The use of laparoscopy in children with impalpable testes is a safe procedure and can guide the need for subsequent inguinal exploration. Children with unilateral impalpable testis were associated with an increased need for inguinal exploration after laparoscopy. Orchidopexies could be performed successfully in 90% of children with bilateral impalpable testes.

Outcome of patients after single-stage repair of perineal fistula without colostomy according to the Krickenbeck classification.

PURPOSE: The aim of the study is to assess the characteristics and outcome of anorectal malformation (ARM) patients who underwent single-stage repair of perineal fistula without colostomy according to the Krickenbeck classification. METHODS: From 2002 to 2013, twenty-eight males and four females with perineal fistula who underwent single-stage repair without colostomy in our institute were included in this study. Patients with perineal fistula who underwent staged repair were excluded. Demographics, associated anomalies, and operative complications were recorded. The type of surgical procedures and functional outcome were assessed using the Krickenbeck classification. RESULTS: Six patients had associated anomalies, including two patients with renal, two with cardiac, one with vertebral, and one with limb abnormalities. Thirteen patients underwent perineal operation, and fourteen patients underwent anterior sagittal approach in the neonatal period. One patient underwent anterior sagittal approach, and four patients underwent PSARP beyond the neonatal period. One patient had an intra-operative urethral injury and one a vaginal injury. Complications were not associated with the type of surgical procedure (p=0.345). All perineal wounds healed without infection. By using the Krickenbeck assessment score, all sixteen children older than five years of age had voluntary control. One patient had grade 1 soiling, and no patient had constipation. CONCLUSIONS: Single-stage operation without colostomy was safe with good outcomes in patients with perineal fistula. The use of Krickenbeck classification allows standardization in assessment on the surgical approach and on functional outcome in ARM patients.

Laparoscopic excision of Meckel's diverticulum in children: what is the current evidence?

Complications aroused from Meckel's diverticulum tend to developed in children. Children presented with abdominal pain, intestinal obstruction, intussusception or gastrointestinal bleeding may actually suffered from complicated Meckel's diverticulum. With the advancement of minimally invasive surgery (MIS) in children, the use of laparoscopy in the diagnosis and subsequent laparoscopic excision of Meckel's diverticulum has gained popularity. Recently, single incision laparoscopic surgery (SILS) has emerged as a new technique in minimally invasive surgery. This review offers the overview in the development of MIS in the management of children suffered from Meckel's diverticulum. The current evidence in different laparoscopic techniques, including conventional laparoscopy, SILS, the use of special laparoscopic instruments, intracorporeal diverticulectomy and extracorporeal diverticulectomy in the management of Meckel's diverticulum in children were revealed.

Laparoendoscopic single-site nephrectomy and heminephroureterectomy in children using standard laparoscopic setup versus conventional laparoscopy.

OBJECTIVE: To investigate the safety and effectiveness of laparoendoscopic single-site surgery (LESS) using standard laparoscopic setup in pediatric nephrectomy/heminephroureterectomy (HN) by comparing with conventional laparoscopy (CL). METHODS: Twelve consecutive children who underwent LESS (nephrectomy = 8, HN = 4) from 2009 to 2012 were compared with a matched cohort of 18 children who underwent CL (nephrectomy = 12, HN = 6) at the same institution. Data were reviewed retrospectively. RESULTS: There was no difference between the 2 groups in the age of patients, body weight, gender distribution, laterality of pathology, postoperative analgesic requirement, and hospital stay. Eleven of the 12 children in the LESS group underwent the procedure successfully without additional trocar placement. The only open conversion happened in the case of LESS of the lower moiety HN. LESS nephrectomy took longer operative time than CL (mean 156 +/- 45 vs 99 +/- 35 minutes, median 155 vs 90 minutes, P <.01). Wound infection occurred in 1 patient after CL nephrectomy. No postoperative complication or access site hernia was noted in the children in the LESS group at follow-up. CONCLUSION: LESS nephrectomy and HN in the pediatric population is safe and effective with a minimally invasive nature comparable to CL. Learning curve factors may contribute to the reported longer operative time in LESS. Further studies are required to investigate the implication of patient selection and the cosmetic benefits of LESS, which may potentially require longer operative time.

Sodium valproate inhibits glucose transport and exacerbates Glut1-deficiency in vitro.

Anticonvulsant sodium valproate interferes with brain glucose metabolism. The mechanism underlying such metabolic disturbance is unclear. We tested the hypothesis that sodium valproate interferes with cellular glucose transport with a focus on Glut1 since glucose transport across the blood-brain barrier relies on this transporter. Cell types enriched with Glut1 expression including human erythrocytes, human skin fibroblasts, and rat astrocytes were used to study the effects of sodium valproate on glucose transport. Sodium valproate significantly inhibited Glut1 activity in normal and Glut1-deficient erythrocytes by 20%-30%, causing a corresponding reduction of Vmax of glucose transport. Similarly, in primary astrocytes as well as in normal and Glut1-deficient fibroblasts, sodium valproate inhibited glucose transport by 20%-40% (P < 0.05), accompanied by an up to 60% downregulation of GLUT1 mRNA expression (P < 0.05). In conclusion, sodium valproate inhibits glucose transport and exacerbates Glut1 deficiency in vitro. Our findings imply the importance of prudent use of sodium valproate for patients with compromised Glut1 function.