Rapunzel syndrome in children: a retrospective review of ten cases combined with literature review in a tertiary referral center.

PURPOSE: Rapunzel syndrome is an uncommon condition in children, and its clinical features remain unclear. This study presents the largest single-center series of pediatric cases to date, with the objective of documenting the clinical characteristics and treatment approaches for children with Rapunzel syndrome. METHODS: A retrospective study was conducted in children with Rapunzel syndrome from 2019 to 2023. We recorded age, gender, symptoms, locations of bezoar, complications, and treatment options. RESULTS: Ten patients with Rapunzel syndrome were included. The median age was 9.1 years, with all of whom were female. The most common clinical symptoms were upper abdominal mass (90%), abdominal pain (80%), and nausea and vomiting (50%). Complications occurred in six cases (60%), including small bowel obstruction (20%), severe gastric dilatation (10%), intestinal perforation (10%), choledochodilation (10%), acute pancreatitis with cholecystitis (10%). Preoperative ultrasonography suggested low-echoic foreign bodies continuing to the jejunum or ileocecal region in five cases (50%). Preoperative gastroscopy attempted in four cases (40%) to remove the foreign bodies, all of which failed. All patients underwent surgical treatment, with nine cases undergoing gastric incision foreign body removal, and one case undergoing gastric incision foreign body removal combined with intestinal perforation repair. All patients recovered well. No recurrence was observed during follow-up. CONCLUSION: The accuracy of ultrasound diagnosis in identifying Rapunzel syndrome is high; however, it may lead to misdiagnosis if not complemented with the patient's medical history. Endoscopic presents a heightened treatment risk and a reduced success rate. The condition commonly presents with severe complications, thus making laparotomy a safe and effective option for intervention.

Clinical features of intussusception in children secondary to small bowel tumours: a retrospective study of 31 cases.

BACKGROUND: Summarizing the clinical features of children with intussusception secondary to small bowel tumours and enhancing awareness of the disease. METHODS: Retrospective summary of children with intussusception admitted to our emergency department from January 2016 to January 2022, who underwent surgery and were diagnosed with small bowel tumours. Summarize the types of tumours, clinical presentation, treatment, and prognosis. RESULTS: Thirty-one patients were included in our study, 24 males and 7 females, with an age of onset ranging from 1 m to 11y 5 m. Post-operative pathology revealed 4 types of small intestinal tumour, 17 lymphomas, 10 adenomas, 4 inflammatory myofibroblastomas and 1 lipoma. The majority of tumours in the small bowel occur in the ileum (83.9%, 26/31). Abdominal pain, vomiting and bloody stools were the most common clinical signs. Operative findings indicated that the small bowel (54.8%, 17/31) and ileocolic gut were the main sites of intussusception. Two types of procedure were applied: segmental bowel resection (28 cases) and wedge resection of mass in bowel wall (3 cases). All patients recovered well postoperatively, with no surgical complications observed. However, the primary diseases leading to intussusception showed slight differences in long-term prognosis due to variations in tumor types. CONCLUSIONS: Lymphoma is the most common cause of intussusception in pediatric patients with small bowel tumours, followed by adenoma. Small bowel tumours in children tend to occur in the ileum. Therefore, the treatment of SBT patients not only requires surgeons to address symptoms through surgery and obtain tissue samples but also relies heavily on the expertise of pathologists for accurate diagnosis. This has a significant impact on the overall prognosis of these patients.

Accidental ingestion of multiple magnetic beads by children and their impact on the gastrointestinal tract: a single-center study.

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates. METHODS: Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points. RESULTS: The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2-E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1-E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point. CONCLUSIONS: Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.

Surgical resection of chemotherapy-insensitive pulmonary metastases in children with hepatoblastoma in China: A single-center experience.

Objective: The objective of this study is to investigate the operation timing, methods, and outcome of pulmonary metastases of hepatoblastoma (HB) in children. Methods: The clinical and follow-up data of 53 children with pulmonary metastases of HB that were admitted to our hospital from January 2012 to December 2018 were retrospectively analyzed. The pediatric patients, 36 male and 17 female, aged 13-124 months with the median age of 41 months, and all underwent routine thoracotomy. Results: In the 53 cases, 77 lung metastatic tumors were resected. Further, 37 patients received only one operation, 10 received two operations, 4 received 3 operations, and 2 received 4 operations. Based on Kaplan-Meier analysis, the accumulative overall survival (OS) rates at 1, 3, and 5 years were 86.8%, 69.0%, and 57.0%, respectively (median OS time: 60 months; 95% CI: 50.675-69.709 months), and accumulative EFS (vent-free survival) rates at 1, 3, and 5 years were 86.8%, 67.0%, and 55.4%, respectively (median EFS time: 59 months; 95% CI: 49.519-68.578 months). According to univariate analysis, OS was significantly altered for patients with no more than 5 nodules (p = 0.023), lung metastases without extrapulmonary metastases (p = 0.000), and laterality (p = 0.029). Gender and age (less than three years) were not significantly related to survival. According to univariate analysis, lung metastases with extrapulmonary metastases could be considered as individual factor contributing to poorer prognosis. Conclusion: In this pediatric group, patients with residual nodules after chemotherapy of HB could benefit from surgical treatment, but the appropriate surgical indication of metastasectomy needs to be further investigated.

The role of preserved bowel and mesentery fixation in apple-peel intestinal atresia.

OBJECTIVE: This study explored the feasibility of mesoplasty with end-to-side anastomosis in the treatment of different apple-peel mesenteric defects with high jejunal atresia. METHODS: A retrospective analysis was performed on 42 premature infants admitted to the hospital between 2014 and 2021. Prenatal ultrasound scans revealed bowel dilatation. The patients experienced vomiting after birth and produced white or no meconium. Plain radiography showed double or triple bubble signs and the patients underwent emergency laparotomy. High jejunal atresia with different apple-peel atresia appearance was discovered intraoperatively, involving mobilization of the ileocecal region. Patients received end-to-side anastomosis between the enlarged blind pouch and atretic bowel, as well as mesoplasty. A jejunal feeding tube was placed trans-nasally. Patients were discharged after achieving full enteral feeding. We also reviewed the literature on the subject. RESULTS: Three patients died and 39 survived. The discharged patients were followed up for 12 months, and none showed post-operative complications such as intestinal obstruction, malnutrition, or chronic diarrhea. All surviving patients reached the expected height and weight for children of the same age. CONCLUSION: For cases of high jejunal atresia with apple-peel intestinal atresia, mesoplasty may be a good option to avoid postoperative volvulus.

Analysis of Factors Influencing Outcomes in Preterm Infants With Necrotizing Enterocolitis.

Background: To explore the surgical outcomes between patients with perforated and non-perforated neonatal necrotizing enterocolitis (NEC) and identify indications for surgical intervention. Methods: The surgical outcomes of 271 children with NEC admitted to the Seventh Medical Center of Chinese PLA General Hospital between August 2009 and August 2020 were retrospectively analyzed. The patients were divided into the non-perforated and perforated groups. The preoperative factors, including gestational age, birth weight, intrauterine infection, cholestasis, platelet change, white blood cell count, and C-reactive protein level were compared between the two groups, along with postoperative factors including infection status, complications, enteral and parenteral nutrition time, ICU time, ventilator use time, and intestinal necrosis length. Bell staging was performed for the two groups and the mortality of different Bell stages was explored. The risk of death and predisposing factors of patients with NEC were analyzed. Results: In total, 271 children undergoing surgery were included in this study. A total of 188 children were observed without perforation, including 57 deaths (30.3%), and 83 children with perforation, including 24 deaths (28.9%). Preoperative cholestasis and time from NEC diagnosis to surgery were significantly different between the two groups (P < 0.05). Postoperative factors, including parenteral nutrition time (32 [3-94] days vs. 23 [1-53] days), enteral nutrition time (27 [0-86] days vs. 18 [0-81] days), NICU time (44 [5-125] days vs. 29 [1-92] days), and length of intestinal necrosis (15 [0-92] cm vs. 10 [2-70] cm), were significant. The mortality rate of patients with Bell stage IIIA was higher than that of patients with Bell stage IIIB. A total of 81 patients had 30-day postoperative mortality (57 non-perforated cases). Multivariate Cox regression analysis showed that non-perforation was a poor prognostic factor for survival outcome (hazard ratio 2.288, 95% confidence interval [1.329-3.940], P = 0.003). Conclusions: Preterm infants in the non-perforated group had more serious complications and had a longer recovery time after surgery. Bell staging is not accurate in diagnosing severe NEC that needs surgical intervention.

Identification of Genes Associated With Hirschsprung Disease, Based on Whole-Genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development.

BACKGROUND & AIMS: Hirschsprung disease, or congenital aganglionosis, is believed to be oligogenic-that is, caused by multiple genetic factors. We performed whole-genome sequence analyses of patients with Hirschsprung disease to identify genetic factors that contribute to disease development and analyzed the functional effects of these variants. METHODS: We performed whole-genome sequence analyses of 443 patients with short-segment disease, recruited from hospitals in China and Vietnam, and 493 ethnically matched individuals without Hirschsprung disease (controls). We performed genome-wide association analyses and gene-based rare-variant burden tests to identify rare and common disease-associated variants and study their interactions. We obtained induced pluripotent stem cell (iPSC) lines from 4 patients with Hirschsprung disease and 2 control individuals, and we used these to generate enteric neural crest cells for transcriptomic analyses. We assessed the neuronal lineage differentiation capability of iPSC-derived enteric neural crest cells using an in vitro differentiation assay. RESULTS: We identified 4 susceptibility loci, including 1 in the phospholipase D1 gene (PLD1) (P = 7.4 × 10-7). The patients had a significant excess of rare protein-altering variants in genes previously associated with Hirschsprung disease and in the ß-secretase 2 gene (BACE2) (P = 2.9 × 10-6). The epistatic effects of common and rare variants across these loci provided a sensitized background that increased risk for the disease. In studies of the iPSCs, we observed common and distinct pathways associated with variants in RET that affect risk. In functional assays, we found variants in BACE2 to protect enteric neurons from apoptosis. We propose that alterations in BACE1 signaling via amyloid ß precursor protein and BACE2 contribute to pathogenesis of Hirschsprung disease. CONCLUSIONS: In whole-genome sequence analyses of patients with Hirschsprung disease, we identified rare and common variants associated with disease risk. Using iPSC cells, we discovered some functional effects of these variants.

Combination of plasma white blood cell count, platelet count and C-reactive protein level for identifying surgical necrotizing enterocolitis in preterm infants without pneumoperitoneum.

PURPOSE: To evaluate whether plasma white blood cell count (WBC), platelet count (PLT), and C-reactive protein level (CRP) can be used to differentiate surgical necrotizing enterocolitis (NEC) from medical NEC. METHODS: Preterm infants admitted between January 1, 2011 and July 31, 2015 were stratified by the need of surgery as surgical NEC (n = 41) and medical NEC (n = 43). The values of WBC, PLT and CRP were collected at time before NEC occurred (T0), at onset of NEC (T1) and when surgical assessment was required (T2). Patients admitted between August 1, 2015 and March 1, 2018 (n = 53) were collected for further verification. RESULTS: Variables identified in logistic regression analysis predicting surgical NEC were WBC and PLT at T2 (WBC2 and PLT2). The predictive probability of surgery (P) could be calculated by the equation [Formula: see text]. The area under curve of P was 0.84 and the ideal cutoff value was 0.55, with sensitivity and specificity of 85 and 81%, respectively. This cutoff value got an sensitivity of 80% and specificity of 79% in the verification group. CONCLUSION: Combination of WBC and PLT can effectively differentiate surgical NEC from medical NEC infants when surgical assessment was required.

Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population.

BACKGROUND: Biliary atresia (BA) is a major neonatal cholestatic disease and main indication for pediatric liver transplantation in the world. Recently, GPC1 has been implicated as a risk gene for BA by genetic studies and follow-up functional experiments on zebrafish. METHODS: Two common genetic variants of GPC1, rs2292832 and rs3828336, were selected systematically through 'SNPinfo', and were examined using TaqMan Genotyping Assays for association studies in a Chinese population containing 134 cases and 618 controls. RESULTS: Of the two single nucleotide polymorphisms (SNPs), we found a significantly decreased BA risk associated with rs2292832 (additive model: OR=0.638, 95% CI: 0.467-0.873, P=0.005), and a marginal effect for rs3828336 (heterozygous model: OR=0.564, 95% CI: 0.312-1.020, P=0.058). The haplotype analysis indicated that either Crs2292832-Crs3828336&Trs3828336 or Trs2292832-Trs3828336 conferred a protective effect from BA (OR=0.569, 95% CI=0.414-0.783, P<0.001; OR=0.528, 95% CI: 0.301-0.926, P=0.026). Moreover, bioinformatics analysis suggested that rs2292832 altered GPC1 expression via effect on transcription-factor-binding sites (TFBS) of upstream binding transcription factor (UBTF), as a regulatory DNA variation in Deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). CONCLUSION: Common variants of GPC1 gene were genetically involved in BA risk.

Common genetic variants regulating ADD3 gene expression alter biliary atresia risk.

BACKGROUND & AIMS: Biliary atresia (BA) is a rare and most severe cholestatic disease in neonates, but the pathogenic mechanisms are unknown. Through a previous genome wide association study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 genes, which was replicated in Chinese and Thai populations. This study aims to fully characterize the genetic architecture at 10q24.2 and to reveal the link between the genetic variants and BA. METHODS: We genotyped 107 single nucleotide polymorphisms (SNPs) in 10q24.2 in 339 Han Chinese patients and 401 matched controls using Sequenom. Exhaustive follow-up studies of the association signals were performed. RESULTS: The combined BA-association p-value of the GWAS SNP (rs17095355) achieved 6.06×10(-10). Further, we revealed the common risk haplotype encompassing 5 tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [p=5.32×10(-11); odds ratio, OR: 2.38; confidence interval, CI: (2.14-2.62)]. Through Sanger sequencing, no deleterious rare variants (RVs) residing in the risk haplotype were found, dismissing the theory of "synthetic" association. Moreover, in bioinformatics and in vivo genotype-expression investigations, the BA-associated potentially regulatory SNPs correlated with ADD3 gene expression (n=36; p=0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences in the population, and, positive selection (favoring the derived alleles that arose from mutations) was evident at the ADD3 locus, suggesting a possible role for the BA-associated common variants in shaping the general population diversity. CONCLUSIONS: Common genetic variants in 10q24.2 can alter BA risk by regulating ADD3 expression levels in the liver, and may exert an effect on disease epidemiology and on the general population.

RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.

Laparoscopic cholecystocholangiography for diagnosis of prolonged jaundice in infants, experience of 144 cases.

PURPOSE: Cholangiography is often crucial for establishing the definitive diagnosis in infants with prolonged jaundice. Here, we describe our protocol of using the two-hole laparoscopic technique and discuss its benefits. METHODS: 144 consecutive patients with suspected biliary atresia were included in this retrospective study. A 5-mm umbilical port is introduced for a 30 degrees laparoscope. An additional 5-mm trocar was inserted at right subcostal incision. A liver biopsy was performed first if needed. The fundus of gallbladder was then exteriorized through the incision of the working port after pneumoperitoneum was released and a catheter is inserted into the gallbladder for cholangiography. RESULTS: The average duration of operation was 34 min (range 20-55 min). Laparoscopic cholangiography failed in 21 cases (14.6%) where atrophic gallbladder was found and BA was confirmed by subsequent laparotomy. For the remaining 123 cases, biliary atresia were diagnosed in 88 (71.5%), biliary hypoplasia in 14 (11.4%), and cholestasis in 21 (17.1%), respectively. There was no bleeding or any other complications intraoperatively. CONCLUSION: The technique of laparoscopic cholecystocholangiography is simple, safe and efficient. It can provide an accurate diagnosis. Furthermore, for patients without biliary atresia, unnecessary laparotomy can be avoided.

Further evidence of the anti-inflammatory effects of silver nanoparticles.

The production of pure silver in nanoparticle size has opened new dimensions in the clinical use of this precious metal. We and others have demonstrated previously that silver nanoparticles (nAg) possess efficient antimicrobial activity. Herein we show they may also have significant anti-inflammatory effects in a postoperative peritoneal adhesion model. This finding provides further insight into the biological actions of nAg as well as a potentially novel therapy for peritoneal adhesions in clinical surgery.With the advent of nanoscience, pure silver can now be made into nanometer-sized particles. As a result, we are able to explore the potentially beneficial properties of pure silver. In our previous study using a burn wound model in mice, we demonstrated that besides antibacterial action, silver nanoparticles (nAg) appear to have anti-inflammatory properties. Herein we further confirm the anti-inflammatory effects of nAg and explore their potential clinical application through a postoperative peritoneal adhesion model. We also elucidate the potential mechanism of action of silver. Our in vitro and in vivo experimental findings show that nAg are effective at decreasing inflammation in peritoneal adhesions without significant toxic effects. This study thus provides further evidence for and contributes to the understanding of the anti-inflammatory properties of nAg and may also give a novel therapeutic direction for the prevention of postoperative adhesions.

Laparoscopic excision of choledochal cyst and Roux-en-Y hepaticojejunostomy in symptomatic neonates.

PURPOSE: Choledochal cysts require surgical excision, preferably before the onset of cholangitis. Recently, it has become feasible to accomplish the excision laparoscopically in adults and older children. Yet, whether laparoscopic excision of choledochal cyst can be performed safely in symptomatic neonates with choledochal cyst is unclear. We herewith reviewed our experience of laparoscopic excision of choledochal cysts in neonates. METHODS: We managed 9 neonates with choledochal cysts between April 2003 and February 2007. The choledochal cysts were excised laparoscopically. The Roux-en-Y hepaticojejunostomy was fashioned extracorporeally by exteriorizing the jejunum through the extended umbilical port site. End-to-side anastomosis between the common hepatic duct stump and Roux loop was carried out intracorporeally. The patients were followed up for an average of 26 months. RESULTS: The patients presented with jaundice, pale stool, and deranged liver function tests. The diagnosis was confirmed with ultrasonography postnatally. The median operation time was 3.6 hours. There was no operative complication and no conversion. The blood loss was minimal. The recovery was uneventful, and the median hospital stay was 6 days. The liver function tests normalized 3 to 16 weeks postoperatively. No complication was detected at the follow-up visits. CONCLUSIONS: Our preliminary results show that laparoscopic excision of choledochal cyst and Roux-en-Y hepaticojejunostomy in neonates is both feasible and safe. It curtails further complication of the cysts and reverses the derangement of liver function. In addition, the laparoscopic approach minimizes surgical trauma.

Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.

Hirschsprung's disease (HSCR), or aganglionic megacolon, is a congenital disorder characterized by the absence of enteric ganglia in variable portions of the distal intestine. RET is a well-established susceptibility locus, although existing evidence strongly suggests additional loci contributing to sporadic HSCR. To identify these additional genetic loci, we carried out a genome-wide association study using the Affymetrix 500K marker set. We successfully genotyped 293,836 SNPs in 181 Chinese subjects with sporadic HSCR and 346 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Aside from SNPs in RET, the strongest overall associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI(95%):(1.40, 2.00), P = 1.80 x 10(-8)] and 1.98 [CI(95%):(1.59, 2.47), P = 1.12 x 10(-9)], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (P = 0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote, indicating that NRG1 is a modifier of HSRC penetrance. Our highly significant association findings are backed-up by the important role of NRG1 as regulator of the development of the enteric ganglia precursors. The identification of NRG1 as an additional HSCR susceptibility locus not only opens unique fields of investigation into the mechanisms underlying the HSCR pathology, but also the mechanisms by which a discrete number of loci interact with each other to cause disease.

Laparoscopic hepatojejunostomy for biliary atresia.

PURPOSE: The aim of this study was to evaluate the feasibility of laparoscopic hepatojejunostomy for types I and II biliary atresia (BA). MATERIALS AND METHODS: Between April 2003 and July 2007, 10 children with "correctable" types I and II BA were enrolled for the study. They presented with progressive jaundice, pale stools, and elevated aspartate transferase and alanine transferase levels. There were 6 girls and 4 boys, with ages ranging from 23 to 160 days (median,53). All BA had cysts of extrahaptic bile ducts. There were 6 type I and 4 were type II BA. The median diameter of the cysts was 1.5 cm (range, 1.0-1.8). All 10 children underwent laparoscopic cyst excision with Roux-en-Y hepatojejunostomy. Four trocars were inserted. The distal end of the cyst was resected.and a Rouxen-Y hepatojejunostomy was fashioned. The patients were followed up on median for 26 months (range, 4-51). RESULTS: The median duration of the operation was 3.0 hours (range, 2.4 - 3.2). There were no intraoperative complications. The blood loss was between 5 to 10 mL. Postoperatively, patients passed flatus after 18 hours(range, 16-28), and resumed oral intake in 20 hours (range, 16-30). Normal colored stools were passed after 3 days (range, 2-4). Jaundice started to disappear on postoperative day 10 (range, 7-16). In 6 cases, the total and the direct bilirubin were normalized on postoperative day 14-3 in 3 weeks. One patient had a persistent elevation of bilirubin. The postoperative course was uneventful in all patients. The median postoperable hospital stay was 7 days (range, 5-9). No postoperative complication was found at the follow-up visits. CONCLUSIONS: The laparoscopic Kasai' operation for children with type I or II biliary atresia is feasible, safe, and effective.

Total extrapleura sternal elevation for the correction of pectus excavatum in children.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of the thoracoscopic total extrapleural approach of the Nuss procedure for the correction of pectus excavatum in children. MATERIALS AND METHODS: Under thoracoscopic guidance, an extrapleural tunnel was created by using a blunt dissector via a right thoracic incision. A steel bar was inserted in the entirely extrapleural tunnel. The bar was turned and fixed as in the standard Nuss procedure. RESULTS: The operations were completed successfully in all patients. The operating time ranged from 35 to 50 minutes (median, 45). The intraoperative blood loss was 2 to 3 mL. There was no pneumothorax or hydrothoraxin our series. All patients were followed up for 2-6 months, and the surgical outcomes were excellent. CONCLUSIONS: The extrapleura Nuss procedure under thoracoscopic guidance is a safe and less traumatic procedure for the correction of pectus excavatum.

Mutational analysis of SHH and GLI3 in anorectal malformations.

BACKGROUND: Anorectal malformations (congenital absence of the anal opening) are among the most common pediatric surgical problems and carry a significant chronic morbidity. METHODS: Direct sequencing was used to screen 88 anorectal malformations patients for mutations and polymorphisms in SHH and GLI3. These genes were chosen according to the phenotype presented by mutant mice and their expression patterns. RESULTS: We report on 10 GLI3 variants (IVS3+141C>G, T183A, IVS4+124T>C, IVS7+17G>A, IVS8+1 G>C, N503N, P941P, P998L, A1005A, A1039A) and four SHH mutation/variants (IVS1-49C>T, IVS2+111A>C, L214L, G290D). CONCLUSIONS: These variants are not over-represented in the healthy population and most are predicted to be benign. This study conveys the problematic assessment of the pathogenic role in disease of rare point mutations and variants.

Mapping of a Hirschsprung's disease locus in 3p21.

Hirschsprung's disease (HSCR) is a congenital disorder in which ganglion cells are absent in variable portions of the lower digestive tract according to which patients are classified. The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required. An unidentified RET-dependent modifier on 3p21 appears to be necessary for transmission of the short HSCR (S-HSCR) phenotype. We investigated 6 Mb of the 3p21 region on a quest for the HSCR-susceptibility locus. Fifty-eight S-HSCR case-parent trios were genotyped using Sequenom technology for 214 tag single nucleotide polymorphisms (SNPs) distributed along 6 Mb of the 3p21 region. A five-marker haplotype, spanning a 118 kb gene-rich region, was found to be overtransmitted to affected offspring. The associated haplotype encompasses three genes involved in neurological phenotypes. Importantly, this association was replicated in an independent sample of 172 S-HSCR cases and 153 unrelated controls. Ranking markers by proximity to candidate genes or by expected functional consequences could be used in follow-up studies to finally pinpoint this HSCR locus.