Introduction: As a congenital and genetically related disease, many single nucleotide polymorphisms (SNPs) have been reported to be associated with the risk of HSCR. Our previous research showed that SNP rs2439302 (NRG1) interacted with rs2435357 (RET) to increase the risk of HSCR development. However, the underlying molecular mechanism is still not well understood. Methods: SNP rs2439302 (NRG1) and rs2435357 (RET) were genotyped in 470 HSCR cases. The expression of NRG1 and RET was investigated in the colon of HSCR patients. Knockdown of the NRG1 and RET homologs was performed in zebrafish to investigate their synergistic effect on ENS development. The effect of SNP rs2439302 and rs2435357 polymorphism on neuron proliferation, migration, and differentiation were investigated in SHSY-5Y cells and IPSCs. Results: Significant downregulation of NRG1 and RET expression was noticed in the aganglionic segment of HSCR patients and SHSY-5Y cells with rs2439302 GG/rs2435357 TT genotype. NRG1 and RET double mutants caused the most severe reduction in enteric neuron numbers than NRG1 single mutant or RET single mutant in the hindgut of zebrafish. SHSY-5Y cells and IPSCs with rs2439302 GG/rs2435357 TT genotype exhibited a decreased proliferative, migration, and differentiative capacity. CTCF showed a considerably higher binding ability to SNP rs2439302 CC than GG. NRG1 reduction caused a further decrease in SOX10 expression via the PI3K/Akt pathway, which regulates RET expression by directly binding to rs2435357. Discussion: SNP rs2439302 (NRG1) GG increases the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) to regulate RET expression via the PI3K/Akt/SOX10 pathway.

BACKGROUND:Robotics has been used safely and successfully in a variety of adult surgeries and is gradually gaining ground in pediatrics. While the benefits of robotic-assisted surgery in disease treatment are well recognized, its high cost has led to questions. To investigate whether robotic-assisted laparoscopic surgery (RALS) is cost-effective compared to conventional laparoscopic surgery (LS) in pediatric surgery, we attempted to construct a model to perform an analysis of these two surgical approaches using Python statistical analysis software.METHODS:We selected four common complex pediatric surgical conditions (choledochal cyst, Hirschsprung's disease, vesicoureteral reflux, and congenital hydronephrosis) from three systems (pediatric hepatobiliary, gastroenterology, and urology). Models were constructed using Python statistical software to compare hospital costs and surgical outcomes for RALS and LS. In addition, we performed a preferred strategy analysis for both surgical modalities while assessing model uncertainty using one-way sensitivity analysis.RESULTS:For the four diseases, the operative time decreased sequentially. The total inpatient costs of RALS were 10,816.72, 9145.44, 8414.29, 7973.58 dollars, respectively, yielding 1.789, 1.712, 1.749, 1.792 quality adjustment life years (QALYs) over two years post-operatively. The incremental cost of RALS relative to LS for each disease was 3523.44, 3200.20, 3049.79, 3043.66 dollars, respectively, with an incremental utility of 0.060, 0.054, 0.051, 0.050 QALYs. The incremental cost-effectiveness ratios (ICERs) for RALS for each of the four diseases were 58,724.01, 59,262.95, 59,799.79, 60,873.20 dollars/QALY, all less than 100,000 dollars/QALY. The cost of robot consumables was the main incremental cost of RALS and had the most significant impact on the model.CONCLUSION:For the four pediatric surgical conditions described above, RALS has higher inpatient costs than LS, but it has better postoperative outcomes, and all four RALS treatments are cost-effective. Children with complex diseases and long operative times appear to benefit more from RALS.

Objective:To explore the safety, efficacy and cosmetic outcomes of transumbilical enterostomy (TUE) and two-stage laparoscopic-assisted pull-through for Hirschsprung's disease (HSCR).Methods:From February 2014 to February 2019, 58 HSCR children (41 boys, 17 girls) undergoing enterostomy were reviewed, including rectosigmoid HSCR of severe enterocolitis or dilated colon (n=13), long-segment HSCR (n=27) and with total colonic aganglionosis (TCA, n=18). Enterostomy was performed at a mean age of (5.7±2.4) months. TUE (n=27) and conventional abdominal enterostomy (CAE, n=31) were performed. Short segment HSCR underwent laparoscopic Soave procedure while long segment HSCR or TCA laparoscopic Duhamel procedure. Demographics, complications and cosmetic outcomes were evaluated.Results:No significant inter-group differences existed in operation time of TUE, blood loss, length of stay or hospital costs ( P>0.05). Two cases in TUE group and 2 in CAE group developed stomal mucosal prolapse (7.41% vs. 6.45%, P>0.05). There was wound infection at stoma in 1 case in TUE group and 2 cases in CAE group (3.70% vs. 6.45%, P>0.05). Dermatitis around stoma occurred in 4 patients in TUE group and 8 in CAE group (14.81% vs. 25.81%, P>0.05). There was one case of obstruction in CAE group and none in TUE group. Enterocolitis occurred in 3 and 4 children in TUE and CAE groups respectively (11.11% vs. 12.90%, P>0.05) and both responded well to conservative measures. Operative duration for two-stage laparoscopic procedure was significantly shorter in TUE group than that in CAE group (143.0±27.1 vs. 158.9±29.4 min, P<0.05). The cosmetic outcomes using scar score was significantly better in TUE group than that in CAE group (6.51±0.86 vs. 14.12±1.29, P<0.05). Conclusions:Transumbilical enterostomy is both safe and effective for HSCR. And staged laparoscopy-assisted pull-through achieves cosmetic outcomes similar to primary laparoscopic pull-through.

Background Reported recurrence rates using jumping purse-string suturing in laparoscopic hernia repair (LH) are higher than that of intact purse-string. This study aims to compare the outcomes of LH using transabdominal jumping purse-string suturing (TJS) with those using transabdominal intact purse-string suturing (TIS) and percutaneous extraperitoneal intact purse-string suturing (PEIS). Methods A total of 3340 patients from three centers who have undergone laparoscopic hernia repair from January 2016 to June 2019 were retrospectively reviewed. Of these, 1460 patients received TJS, 724 patients received TIS, and 1006 patients received PEIS. One hundred and fifty patients were excluded due to the loss of follow-up. Demographic characteristics, intraoperative findings, and postoperative complications were analyzed. Results The hernia distribution characteristics and mean length of hospital stay were similar among the three groups (p > 0.05, p > 0.05). While the overall complication rates were similar among the three groups (0.34% in TJS vs. 0.41% in TIS vs. 0.50% in PEIS, TJS & TIS p = 0.502; TJS & PEIS p = 0.813), the incidence of intraoperative hematoma in TIS group and postoperative subcutaneous knot in PEIS group was significantly higher ((0.83% in TIS and 0.34% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.018; TJS & PEIS p = 0.163), (0% in TIS and 0% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.415; TJS & PEIS p = 0.025)). There were no differences in the recurrent rate in both unilateral and bilateral cases. Conclusions Transabdominal jumping purse-string suturing is not associated with a higher recurrence rate and is the recommended surgical approach.

Background: Anastomotic leak (AL) rates gradually decreased with surgical skills and perioperative management progression, but it is still inevitable. As the traditional management of AL after the pull-through procedure of Hirschsprung's disease (HD), enterostomy could lead to multiple surgeries, repeated hospitalizations, increased costs, and enterostomy-associated complications. This study aimed to explore the safety and feasibility of resuturing without enterostomy treating early AL after the laparoscopic Soave procedure. Methods: From October 2014 to June 2019, 10 patients who had AL after the laparoscopic Soave procedure were included. Six patients underwent simply resuturing with presacral drainage; the reoperation time was 1-5 days after primary surgery. Four patients who had diffused peritonitis or severe inflammations received resuturing with an ileostomy, and the reoperation time was 6-11 days. Results: Common early symptoms of AL included persistent fever, sacrococcygeal pain, and abdominal pain. The median delay to reoperation was 1.0 (0-2.25) day. Five patients had leaks at the 3-6 o'clock position, two had leaks at the 6-9 o'clock, and the other three had leaks at the 6 o'clock. The median postoperative fever durations were similar in patients without or with an ileostomy, and the median length of intensive care unit (ICU) stays, duration of antibiotic use, and postoperative length of stay were significantly longer in patients with ileostomy. The mean follow-up time was 38.5 +/- 16.7 months (15-69 m). As of the time of writing, no reoccurrence was identified. Conclusion: For patients without diffuse peritonitis, severe inflammations, early diagnosis and timely resuturing of AL within 5 days after the laparoscopic Soave procedure of HD could be a safe, effective, and pleasing treatment.

BACKGROUND:Robotic-assisted surgery (RAS) is becoming more popular because of the excellent performance in anastomosis and knot tying, especially in complex surgical procedures such as hepaticojejunostomy. As for operative time and costs, laparoscopic-assisted surgery (LAS) seem to be more advantageous. To date, there are only limited studies focusing on the comparison between RAS and LAS. This study aims to investigate differences in intraoperative and postoperative outcomes between robotic and laparoscopic approaches.METHODS:We performed a retrospective case-control study of 140 patients operated via mini-invasive approaches for choledochal cyst (CC) excision and hepaticojejunostomy at the Wuhan Union Hospital from Jun 2014 to Dec 2019. A multivariable logistic regression model for odds to having complications was built.RESULTS:The two groups were similar in age, sex, follow-up time, and Todani modification of the Alonso-Lej classification distribution. Patients undergoing RAS had longer overall operative time, shorter cyst excision time, shorter hepaticojejunostomy time, less estimated blood loss, a smaller postoperative high fever rate, shorter postoperative LOS, and a lower postoperative complication rate. Moreover, the intraoperative anatomy structures were more explicit in group RAS, such as the exposure of left or right hepatic duct opening and intrapancreatic bile duct. Multivariable logistic regression showed that longer hepaticojejunostomy time was the only risk factor of postoperative complications.CONCLUSION:Robotic-assisted CC excision and hepaticojejunostomy was associated with better intraoperative and short-term postoperative outcomes when compared to laparoscopic-assisted surgery.