Guo-qing Cao

10 years of experience with laparoscopic-assisted endorectal Soave pull-through procedure for Hirschsprung's disease in China.

OBJECTIVE To report early and late results of laparoscopic-assisted endorectal Soave pull-through (LAEPT) with a short and V-shaped partial resection muscular cuff for Hirschsprungs disease (HD) over a 10-year period. METHODS The clinical courses of 218 patients who underwent modified LAEPT for HD were reviewed. LAEPT was described by the Georgeson technique. The main modifications included less dissection of the bottom of the pelvis, rectal mucosa dissection with a long cuff, coloanal anastomosis with a short cuff, and a V-shaped partial resection in the posterior wall of the muscular cuff. RESULTS From September 1999 to July 2009, 218 patients were operated on by the same surgeon. Ages ranged from 15 days to 12 years old. The aganglionic segment was located in the rectum or sigmoid colon in 176 patients, in the left colon in 38 children, and in the transverse colon in 4 patients. The median operating time was 176 minutes. Conversion to open surgery was required in 2 patients. Bleeding of the left iliac vein occurred in 1 patient, and a 180° twist of the neorectum occurred in 2 cases. Median first bowel movement time was 23 hours, and median postoperative hospital stay was 10.4 days. Median daily defecation frequency was 4.6 within 2 weeks and 2.3 at 3 months postoperatively. The immediate postoperative complications included intestine herniation from the trocar site in 2 patients, perianal excoriation in 32 patients, and anastomotic leakage in 3 patients. Follow-up ranging from 6 to 120 months was obtained for 182 patients. Late postoperative complications included postoperative adhesive bowel obstruction (1.1%), enterocolitis (7.7%), anasomostic stenosis (2.2%), constipation (1.6%), and soiling (3.6%). Eighty-seven percent had excellent and good bowel function. CONCLUSION LAEPT with a short muscular cuff with a V-shaped partial resection in the posterior wall is a safe and effective procedure for HD.

Clinical value of pelvic 3-dimensional magnetic resonance image reconstruction in anorectal malformations

OBJECTIVE The study aimed to build a 3-dimensional (3D) reconstruction of pelvic magnetic resonance images and evaluate the clinical value in anorectal malformations (ARMs). METHODS Magnetic resonance imaging (MRI) examinations were performed on a 1.5-T magnet. Sagittal, coronal, and transverse turbo spin-echo T1-weighted and fast spin-echo T2-weighted images of the pelvic region were obtained in 22 children. A 3D reconstruction was made on a computer and assisted by the 3D-Doctor software (Trial Version, Able Software Corp). The level and type of ARM and the developmental state of the striated muscle complex (SMC) were analyzed with 3D reconstruction image. RESULTS The 3D images of the pelvic were confirmed in 22 cases. Three-dimensional reconstructed images perfectly displayed the anatomical relationships of the SMC and the rectal atresia in these spaces. The 3D configuration of the SMC was different in each of the high- and low-type cases. The high-type malformation of SMCs differed particularly from the descriptions. CONCLUSIONS Pelvic magnetic resonance 3D reconstructed images were able to show the dimensional anatomical relations of pelvis, bladder, urethra, rectum, and SMC. Both a 3D image and positional information with MRI offers the surgeon a simulated operative profile of the SMC superior to MRI slices alone, which will help in providing morphological data for image diagnosis and operation of the ARM.

Noscapine Induced Apoptosis via Downregulation of Survivin in Human Neuroblastoma Cells Having Wild Type or Null p53

Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein expression. The Noscapine treatment increased levels of total and Ser15-phosphorylated p53 protein in SK-SY5Y cells, but the proapoptotic response to this agent was maintained even after knockdown of the p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in a marked decrease in protein and mRNA level of survivin as early as 12 hours after treatment. Ectopic expression of survivin conferred statistically significant protection against Noscapine-mediated cytoplasmic histone-associated apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in both cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated with activation of caspase-3 and cleavage of PARP. In conclusion, the present study provides novel insight into the molecular circuitry of Noscapine-induced apoptosis to indicate suppression of survivin expression as a critical mediator of this process.

Effects of RET, NRG1 and NRG3 Polymorphisms in a Chinese Population with Hirschsprung Disease.

The RET proto-oncogene was identified as a major locus involved in Hirschsprung disease (HSCR). A genome-wide association study (GWAS) and whole exome sequencing identified NRG1 and NRG3 as additional HSCR susceptibility loci. We investigated the effects of RET (rs2506030 and rs2435357), NRG1 (rs2439302, rs16879552 and rs7835688) and NRG3 (rs10748842, rs10883866 and rs6584400) polymorphisms in a Chinese population with HSCR. We assessed single nucleotide polymorphisms (SNPs) in the RET, NRG1 and NRG3 genes in a cohort of 362 sporadic HSCR patients and 1,448 normal controls using a TaqMan genotyping assay. Significant associations were found between HSCR risk and rs2506030, rs2435357, rs2439302 and rs7835688 (odds ratio [OR] 1.64, P = 1.72E-06; 2.97, P = 5.15E-33; 1.84, P = 9.36E-11; and 1.93, P = 1.88E-12, respectively). Two locus analyses of SNPs indicated increased disease risks of HSCR between NRG1 rs2439302 and RET rs2435357 or rs2506030. RET rs2506030 (GG genotype) and rs2435357 (TT genotype), in combination with NRG1 rs2439302 (GG genotype), were strongly associated with the highest risk of HSCR (OR = 56.53, P = 4.50E-07) compared with the two loci or a single SNP of either RET or NRG1. Our results support the association between genetic variation of RET and NRG1 and susceptibility to HSCR in the Chinese population.

Dendritic Cells Regulate Treg-Th17 Axis in Obstructive Phase of Bile Duct Injury in Murine Biliary Atresia

Several cell types are considered to be effector cells in bile duct injury in rhesus rotavirus (RRV)-induced experimental biliary atresia (BA). Here, we identified an increased T helper 17 (Th17) cell population in a BA mode. By depleting the Th17 cells, the BA symptoms (onset of jaundice, acholic stools and retarded growth) were attenuated and the survival rate was improved. Furthermore, we found that in mice with BA, the percentage of CD4+CD25highFoxp3+ T regulatory (Treg) cells decreased along with the increased percentage of Th17 cells. However, the absolute numbers of Treg and Th17 cells were both increased in liver of RRV-injected mice compared to saline-injected mice. The proportion of Th17 cells at 7 days post-infection was decreased if Treg cells isolated from normal adult mice, but not Treg cells from the livers of mice with BA, were intraperitoneally transferred on day 5 of life. In vitro experiments also showed that Treg cells from mice with BA had a diminished suppressive effect on Th17 cell generation. To determine the mechanisms, we investigated the production of cytokines in the liver. The level of IL-6, which has been shown to be abundantly secreted by activated dendritic cells (DCs), was remarkably elevated. Importantly, in a Treg/Th17 cell suppression assay, IL-6 was demonstrated to paralyze the Treg cells’ suppressive effect on Th17 cells and eventually the unrestrained increase of Th17 cells contributed to bile duct injury. In conclusion, the DC-regulated Treg-Th17 axis, probably in conjunction with other effector T cells, aggravates progressive inflammatory injury at the time of ductal obstruction.

Single-incision laparoscopic versus conventional laparoscopic endorectal pull-through for Hirschsprung's Disease: A comparison of short-term surgical results ☆

BACKGROUND Single-incision laparoscopy has recently become a popular procedure in pediatric surgery. The current series is the largest study to evaluate the operative complications and results of single-incision laparoscopic endorectal pull-through (SILEP) for the treatment of HD through a retrospective comparison with conventional laparoscopic endorectal pull-through (CLEP). METHODS Twenty eight patients who underwent single-incision laparoscopic endorectal pull-through for HD between July 2010 and August 2011 were compared to thirty patients who underwent CLEP. Patient age, gender, transitional zone, operative time, blood loss, intraoperative and postoperative complications, as well as short-term results, were assessed. RESULTS A total of 28 patients were included for SILEP, and historical reported 30 patients were completed by CLEP. The SILEP and CLEP groups were similar in regard to age, gender, transition zone, operative time, blood loss, hospital stay, and intraoperative complications. Postoperative results were not different, including equal daily defecation frequency and early postoperative complications. No patients with recurrent constipation were seen. Two patients with the transitional zone in the descending colon in the SILEP group had a 3mm trocar added in the left abdomen, and there were no conversions in the conventional laparoscopic group. CONCLUSION We have shown that in selected HD patients, the SILEP technique was safe and technically feasible in experienced hands. It results in similar operative results compared with conventional laparoscopic endorectal pull-through. However, the operation is more difficult if the transition zone was higher than the rectosigmoid.

Hybrid Nuss Procedure for Pectus Excavatum With Severe Retrosternal Adhesions After Sternotomy

BACKGROUND The most striking feature of pectus excavatum (PE) after previous congenital heart disease (CHD) surgery through a median sternotomy is the postsurgical adhesions between the sternum and heart. For patients with severe adhesions, passing the introducer can be difficult and hazardous when performing a Nuss repair. We describe a hybrid Nuss procedure using a small subxiphoid incision for blunt and sharp anterior mediastinal dissection and using a thoracoscope to ensure the whole process of dissection is under direct visualization. METHODS A retrospective case review was conducted of PE patients (previous CHD operation) who had undergone the hybrid Nuss procedure between January 2012 and June 2015. Demographic, treatment, and outcome variables were recorded. RESULTS Eleven patients were included. The mean age was 4.7 ± 1.7 years (range, 3.2 to 8.9). The mean Haller index based on computed tomography was 4.15 ± 0.78 (range, 3.2 to 5.8). All cases were the symmetric type. Mean operating time was 95.5 ± 8.4 minutes (range, 80 to 110); mean blood loss was 15 ± 2.3 mL; and mean length of hospitalization was 6.0 ± 1.4 days (range, 4 to 8). There was no pneumothorax, cardiac injury, wound infection, discomfort requiring removal, or bar rotation at the average 27-month (range, 9 to 50) follow-up. Two patients had the bars removed. No reoperations were performed owing to recurrence. CONCLUSIONS The hybrid Nuss procedure is a safe, simple modification of the Nuss repair for patients with severe retrosternal adhesions. This procedure achieves dissection with direct visualization. Hence, the risk of death due to cardiac perforation can be prevented.

Endoscopic transaxillary approach for congenital muscular torticollis

BACKGROUND Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. Open operative techniques all leave noticeable scars. We proposed a modified endoscopic 1-trocar transaxillary and neck microincision approach for the treatment of CMT. METHODS Endoscopic release of the sternocleidomastoid (SCM) muscle was performed in 45 infants and children aged 6 months to 15 years. One 5-mm incision was made in the anterior axillary fold, and a subcutaneous tunnel over the clavicular and sternal heads of the SCM muscle was made. A subcutaneous space was established by CO₂ inflation at a pressure of 8 mm Hg and then endoscopically using a 5-mm endoscope. Two additional 1.5- to 2-mm supraclavicular mini-incisions were made beside the SCM muscle for the introduction of miniforceps and electrocautery, respectively. The sternal and clavicular attachments were dissected and divided by electrocautery. Clinical evaluation was performed using the Lee scoring system. RESULTS The operation was successfully completed endoscopically in all 45 children. The mean operative time was 40 minutes. No injuries of major blood vessels or nerves were encountered. A small bleed was noted in 1 child owing to reoperation. Follow-up for 6 months to 3 years in 42 patients showed complete muscular release and satisfactory cosmetic appearance with no recurrence. The results were classified as excellent in 88.1% (37/42), good in 9.5% (4/42), fair in 2.4% (1/42), and poor in 0 using the Lee scoring system. The neck scars were not visible 1 month after the procedure. CONCLUSIONS The subcutaneous endoscopic transaxillary and micro-neck incision approach for the treatment of CMT is a safe, practical procedure that provides good functional and cosmetic outcomes without vascular or neural injury.

Effects of NRG1 Polymorphisms on Hirschsprung’s Disease Susceptibility: A Meta-analysis

Substantial resources have been devoted to evaluate the relationship between NRG1 variants rs7835688 and rs16879552 and Hirschsprung’s Disease (HSCR) but no consistency exists. This meta-analysis aimed to assess the association between the two SNPs and HSCR. PubMed, EMBASE, and Chinese Biological Medicine databases were searched for studies potentially eligible up to March, 2017. The summary odds ratios (ORs) with 95% CIs were calculated from different genetic models. Nine case-control studies (8 for both and 1 for rs16879552 only) involving 1984 HSCR patients and 4220 controls were identified. The combined results showed a significant association between HSCR risk and rs7835688 in all genetic models (per-allele model: OR = 1.66, 95% CI = 1.35–2.05; P = 1.940E-06). Rs16879552 was significantly associated with HSCR in per-allele (OR = 1.50, 95% CI = 1.27–1.76; P = 1.087E-06), additive and recessive model, except for dominant model. Stratified analysis by ethnicity showed that rs7835688 and rs16879552 were only causative for Asians, but not risk locus for Caucasians. Furthermore, pooled data based on segment length indicated that individuals with rs7835688 experienced a significantly higher risk for short-segment HSCR in all genotypes; but rs16879552 was only found to be associated with long-segment HSCR/ total colonic aganglionosis at the allele level.

Clinical outcomes and ergonomics analysis of three laparoscopic techniques for Hirschsprung's disease

AIM To report the clinical outcomes and ergonomics analysis of three laparoscopic approaches in the management of Hirschsprungs disease (HD). METHODS There were 90 pediatric patients (63 boys, 27 girls; mean age: 3.6 ± 2.7 mo; range: 1.0-90.2 mo) who underwent laparoscopic endorectal pull-through Soave procedures for short- and long-segment HD in our hospital. Three laparoscopic approaches were used: conventional laparoscopic pull-through (CLP) in 30 patients between 2009 and 2013, single-incision laparoscopic pull-through (SILP) in 28 patients between 2010 and 2013, and hybrid single-incision laparoscopic pull-through (H-SILP) in 32 patients between 2011 and 2013. We applied the hybrid version of the single-incision approach in 2011 to preserve the cosmetic advantage of SILP and the ergonomic advantage of CLP. We retrospectively analyzed the clinical data, cosmetic results, and ergonomics of these three approaches to have a better understanding of the selection of one approach over another. RESULTS The CLP, SILP, and H-SILP groups were similar in regard to age, sex, transition zone, blood loss, hospital stay, and intraoperative complications. Early and late postoperative results were not different, with equal daily defecation frequency and postoperative complications. No conversion to open technique was needed and none of the patients had recurrent constipation. With proper training, the ergonomics challenges were overcome and similar operative times were registered for the general operative time in the patients < 1 year of age and the short-segment HD patients. However, significantly shorter operative times were registered compared to SILP for patients > 1 year of age (CLP and H-SILP: 120 ± 15 min and 119 ± 12 min, respectively, vs 140 ± 7 min; P < 0.05) and for long-segment HD patients (152 ± 3.5 min and 154 ± 3.6 min, respectively, vs 176 ± 2.3 min; P < 0.05). The best cosmetic result was registered with the SILP (scarless), followed by the H-SILP (near scarless appearance) and the CLP (visible scars) procedures. CONCLUSION Based on the results, we believed that the laparoscopic approach should be selected according to the age, transition zone, and desired cosmetic result.