A novel pathogenesis concept of biliary atresia approached by combined molecular strategies.

Cholestatic jaundice is one of the most common neonatal conditions. BA, a correctable cholangiopathy, presents with cholestatic jaundice within the first weeks of life. The inflammation of bile ducts leads to progressive fibrosclerosis involving biliary trees, followed by cirrhosis and liver failure. With the use of modern molecular studies, this research aimed to define a novel pathogenesis by exploring variations. We performed genetic discovery by using supervised and unsupervised approaches. Ultimately, a combination of genetic variations and survival data was analyzed to strengthen the novel concept in this study. In this study, coding regions were explored to identify rare deleterious variants within genes from the first analysis together with gene sets reported in PFIC, and diseases with hyperbilirubinemia. Our unsupervised prioritization was primarily designed to identify novel causal genes from nonsynonymous variants derived by three biostatistical algorithms: enrichment analysis, burden test, and trio study. Survival analysis was integratively evaluated with a combination of identified causal genes. The individuals with identified variants from the supervised approach were frequently related to the severity of cirrhosis and poor postoperative outcome. In the unsupervised approach, nonsynonymous variants were enriched. Cilium and muscle related pathways had a significant correlation. CCDC8 was statistically significant gene in which six cases carried mutations identified through burden analysis. Individuals who carried variants in corresponding genes and significant pathways had significantly lower native-liver survival than individuals in whom none of these variants were identified (log-rank p value 0.016). This study explored genetic variations by multiple strategies. Different pathways of cholestatic diseases have been found to be associated with BA. Therefore, BA may be characterized as a shared sequela of many cholestatic disorders. Susceptibility in those pathways suggested an association with BA and strengthened this proposed novel hypothesis. The results emphasized the consequences of many disruptive pathophysiologies.

Impact of EFEMP1 on the survival outcome of biliary atresia in Thai infants.

Genome-wide association studies (GWASs) have identified a genetic associated between EFEMP1 and biliary atresia (BA). To examine the susceptibility of single nucleotide polymorphisms (SNPs) in EFEMP1 in Thai BA patients, we performed an analysis of the genetic associations and biological interactions with previously reported key SNPs in ADD3, a key gene associated with BA. The study also used high-throughput sequencing to detect novel variants in both genes. In addition, the clinical impact of EFEMP1 SNPs in terms of survival association was also evaluated. The genotypes of 60 BA patients and 179 controls were evaluated using a TaqMan genotyping assay for rs2501577 and rs17095355 in ADD3 and rs6761893 and rs727878 in EFEMP1. The genotype frequencies were analyzed together with the SNP-SNP interactions. Fine mapping by whole-exome sequencing was performed to identify deleterious variants within both genes, and the survival analysis results were analyzed with the EFEMP1 SNPs. The recessive genotypes of rs2501577, rs17095355 and rs6761893 showed significantly higher frequencies in the BA patients than the controls, and a logistic regression showed that minor alleles of those SNPs increased the BA risk by ORs of 1.86, 1.67, and 1.84, respectively. Moreover, the SNP-SNP interference suggested that a combination of recessive alleles from the 2 genes resulted in an additive risk to BA. In addition, rare missense variants in the gene coding sequences were identified in 7 cases. Immunohistochemical studies revealed a pattern of ADD3 downregulation and EFEMP1 overexpression in the bile ducts of BA patients. Patients with the AA genotype of rs6761893 had significantly lower 5-year native liver survival (34.0%) than those with AT/TT (75.0%), with a log-rank p value of 0.041. Variants in EFEMP1 are associated with the occurrence of BA in Thai patients. In addition, these variants have an additive influence on BA risk when combined with ADD3 variants. Moreover, rs6761893 in EFEMP1 was indicative of survival in Thai BA patients.

Fecal microbiome alterations in pediatric patients with short bowel syndrome receiving a rotating cycle of gastrointestinal prophylactic antibiotics.

BACKGROUND: Pediatric patients with short bowel syndrome (SBS) are at risk of developing small intestinal bacterial overgrowth (SIBO). Prevention of SIBO using cyclic enteric antibiotics has been implemented to control the balance in microbial ecosystems, although its effectiveness has not been well studied. PURPOSE: This study aimed to explore the change in the gut microbial composition in SBS patients during cyclic antibiotic phases and antibiotic-free period, and to compare the microbiota composition between healthy controls and SBS patients. METHOD: SBS patients taking oral metronidazole alternating with trimethoprim-sulfamethoxazole (TMP-SMT) and antibiotic-free conditions as a '10-day cyclic protocol' were involved in fecal microbiome study using Illumina 16S sequencing. RESULTS: When healthy control possessed the majority of Bacteroidetes spp. (54%) and Firmicutes spp. (33%), the microbial composition in SBS patients especially Firmicutes spp. and Proteobacteria spp. was prominently changed in each phase of treatment. In antibiotic-free period, SBS patients displayed 49% Firmicutes and 36% Proteobacteria. However, higher Proteobacteria than Firmicutes were detected at the commencement of metronidazole (58% versus 33%). Similarly, 56% Proteobacteria and 27% Firmicutes were found during TMP-SMT. Escherichia coli increased prominently during the antibiotic periods. CONCLUSION: Prophylactic antibiotics change the gut microbiota composition in an unfavorable direction, especially when repeatedly used for a long period. This practice should be reconsidered. LEVEL OF EVIDENCE: III.

Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand.

Biliary atresia (BA) is the most severe form of obstructive cholangiopathy occurring in infants. Definitive diagnosis of BA usually relies on operative findings together with supporting pathological patterns found in the extrahepatic bile duct. In infancy, overlapping clinical patterns of cholestasis can be found in other diseases including biliary hypoplasia and progressive familial intrahepatic cholestasis. In addition, BA has been reported as a phenotype in some rare genetic syndromes. Unlike BA, other cholangiopathic phenotypes have their own established genetic markers. In this study, we used these markers to look for other cholestasis entities in cases diagnosed with BA. DNA from 20 cases of BA, diagnosed by operative findings and histopathology, were subjected to a study of 19 genes associated with infantile cholestasis syndromes, using whole exome sequencing. Variant selection focused on those with allele frequencies in dbSNP150 of less than 0.01. All selected variants were verified by polymerase chain reaction-direct sequencing. Of the 20 cases studied, 13 rare variants were detected in 9 genes: 4 in JAG1 (Alagille syndrome), 2 in MYO5B (progressive familial intrahepatic cholestasis [PFIC] type 6), and one each in ABCC2 (Dubin-Johnson syndrome), ABCB11 (PFIC type 2), UG1A1 (Crigler-Najjar syndrome), MLL2 (Kabuki syndrome), RFX6 (Mitchell-Riley syndrome), ERCC4 (Fanconi anemia), and KCNH1 (Zimmermann-Laband syndrome). Genetic lesions associated with various cholestatic syndromes detected in cases diagnosed with BA raised the hypothesis that severe inflammatory cholangiopathy in BA may not be a distinct disease entity, but a shared pathology among several infantile cholestatic syndromes.

Single nucleotide polymorphisms within Adducin 3 and Adducin 3 antisense RNA1 genes are associated with biliary atresia in Thai infants.

BACKGROUND: A genome-wide association study in East Asians suggested a genetic association between biliary atresia (BA) and a cluster of variants within the Adducin 3 (ADD3) and ADD3 antisense RNA1 (ADD3-AS1) genes. Another study in Thai neonates reported an association between BA and rs17095355. To validate those findings, this study aimed to analyze the BA association with single nucleotide polymorphisms (SNPs) and the additive influence of ADD3 and ADD3-AS1 in Thai neonates. METHODS: DNAs from 56 BA cases and 166 controls were genotyped for rs2501577, rs11194981, rs12268910 (ADD3) and rs17095355 (ADD3-AS1), using TaqMan PCR. Genotype distributions were compared between the groups, and SNP-SNP interactions were analyzed by combination of allelotypes. RESULTS: The risk allele frequencies of rs2501577, rs11194981, and rs17095355 in the BA group were significantly higher than in the controls. Univariate analysis showed that recessive variants in the three SNPs were associated with BA risk at ORs of 1.81 (95% CI 1.32-2.50), 1.58 (95% CI 1.14-2.20) and 1.92 (95% CI 1.39-2.66), respectively. SNP-SNP interaction analysis showed that the SNP combination of the two genes rs17095355 and rs2501577 provided an additive increase in BA risk. CONCLUSION: ADD3 and ADD3-AS1 variants increased susceptibility to BA, suggesting that these genes may play an additive role in the pathogenesis of the disease. In addition, these interactions may give a clue to the overexpression of the ADD3 protein in the liver of BA patients.

Digital camera image analysis of faeces in detection of cholestatic jaundice in infants.

BACKGROUND: Stool colour assessment is a screening method for biliary tract obstruction in infants. This study is aimed to be a proof of concept work of digital photograph image analysis of stool colour compared to colour grading by a colour card, and the stool bilirubin level test. MATERIALS AND METHODS: The total bilirubin (TB) level contents in stool samples from 17 infants aged less than 1 year, seven with confirmed cholestatic jaundice and ten healthy subjects was measured, and outcome correlated with the physical colour of the stool. RESULTS: The seven infants with cholestasis included 6 cases of biliary atresia and 1 case of pancreatic mass. All pre-operative stool samples in these cases were indicated as grade 1 on the stool card (stool colour in healthy infants ranges from 4 to 6). The average stool TB in the pale stool group was 43.07 µg/g compared to 101.78 µg/g in the non-pale stool group. Of the 3 colour channels assessed in the digital photographs, the blue and green light were best able to discriminate accurately between the pre-operative stool samples from infants with cholestasis and the samples from the healthy controls. With red, green, and blue (RGB) image analysis using wave level as the ANN input, the system predicts the stool TB with a relationship coefficient of 0.96, compared to 0.61 when stool colour card grading was used. CONCLUSION: Input from digital camera images of stool had a higher predictive capability compared to the standard stool colour card, indicating using digital photographs may be a useful tool for detection of cholestasis in infants.

Comparison of Cleaning up Eyelids after Taking off False Eyelashes between Eye Makeup Remover Alone and Eye Makeup Remover with Ocusoft®.

Background: Hirschsprung's disease (HD) is the most common intestinal obstruction in newborn. The Transanal Endorectal Pull -Through (TERPT) is a new surgical procedure that has rapidly replaced traditional ones. Objective: We have reviewed early post-operative complications after TERPT of childhood HD in Thailand. Material and Method: The clinical course and a 1 year outcome of all pediatric HD undergoing TERPT from 5 pediatric surgical centers in Thailand between 2008 and 2011 were reviewed. Results: Seventy-six patients (66 males and 10 females) of HD were included. The average age of diagnosis and surgery are 199 (0-4,015) and 297 (9-4,075) days, respectively, where ages and classification of HD are not related. The associated conditions are Down syndrome (DS) 6.6% and congenital heart disease (CHD) 5.3%. The most common presented symptom was intestinal obstruction. Other symptoms were Hirschsprung, which are associated with enterocolitis (HAEC) 13.1% and intestinal perforation 2.6%. The patients were diagnosed by barium enema (BE) 93.4%, rectal biopsy (RB) 6.6% and anorectal manometry (ARM) 6.6%. HAEC is the most common both pre- and post-operative complications (23.7% and 22.4%). Other post-operative complications are incontinence 13.2%, perianal excoriation 9.2%, anastomosis stricture 7.9%, anastomosis leakage 2.6%, retained aganglionic segment 2.6%, anastomosis volvulus 1.3% and anovaginal fistula 1.3%. One patient died due to anastomosis leakage (1.3%). Five patients were associated with DS, 3 patients (60%) were incontinent, 1 patient had anastomosis stricture (20%) and 2 patients (40%) was HAEC. Conclusion: Most of HD were diagnosed and treated in the newborn period. TERPT is safe and also feasible in all pediatric age groups. The associated DS are related to have more morbidity. HAEC is the most common complication. Even though there are limitations in the diagnostic investigation those did not achieve the standard diagnosis of HD in this study; but the outcomes are not different from the reviews. The improvement in laboratories and pathological investigation services will reflect the surgical service and outcome of pediatric HD in this region. The awareness of post-operative complications will lead to the prevention and early management in the postoperative period.

Descriptive Profile Outcomes between Closed and Open Drainage Systems Following Urethroplasty.

BACKGROUND: An indwelling urinary catheter or urethral stent are standardly used following a urethroplasty to prevent post-operative urinary retention. There are both closed drainage system (CDS) and open drainage system (ODS) available. OBJECTIVE: The study was designed to determine the outcomes between post-operative CDS and ODS. MATERIAL AND METHOD: Fifty-seven hypospadias patients with 66 urethroplasties, performed by a single surgeon, were assessed. During the 40-month study period, the operative outcomes relative to the technique of both urinary catheter drainage systems were evaluated for length of hospital stay (LOS), cost of hospitalization, and post-operative complications. RESULTS: CDS and ODS drainage systems were performed in 32 and 34 operations, respectively. The patient characteristics, the surgical profiles, and post-operative complications were not statistically significant. The CDS/ODS group had median LOS (range) of 9 (1 to 22) 12 (1 to 6) days, respectively, and cost of hospitalization (SD) of 22,908 (4,455)/18,408 (3,848) Bahts respectively. Both had statistical significance, p < 0.001. The subgroup of 26 posterior hypospadias and TIP urethroplasties were also evaluated. CONCLUSION: Patients with hypospadias given an open drainage system after urethroplasty have a higher rate of early discharge, lower cost of hospitalization, and a lower rate of wound infection.

Functional and manometric outcomes after a congenital pouch colon reconstruction: report of a case.

Congenital pouch colon is a form of anorectal malformation, rarely reported outside north India. Hallmarks of this malformation are a short colon containing a large distal pouch with a fistula connecting to the urinary system. Herein, the authors report the case of a Thai male neonate with a congenital pouch colon type II who was initially misdiagnosed as a common imperforate anus. As a result, urinary tract infection and metabolic acidosis developed after a colostomy. A definitive surgery consisting of a tabularized coloplasty and an abdominoperineal pull-through was performed at one month of age. After closure of the colostomy, the child experienced transient loose stool with perineal excoriation for about three months and then gradually improved. At three years of age, the patient had normal bowel movements and adequate sensation, and a contrast enema showed a normal sized neorectum. An anal endosonogram revealed good localization of the rectum. A rectal manometry showed spontaneous rectal contraction and a complete rectoanal inhibitory reflex. The present case provides evidence suggesting that preservation of the native pouch colon is not contraindicated in this type of congenital pouch colon syndrome.

Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients.

Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric nervous system known to be associated with the RET-protooncogene and other candidates. Recently, a genome-wide association study has added NRG1, a regulator of the development of the enteric ganglia precursors, as a new candidate gene. The aim of this study is to validate the association of the RET-protooncogene and the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide polymorphism (SNP) genotyping and PCR-restriction fragment length polymorphism for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene) and rs2439305 (NRG1) showed the strongest associations with the disease at P-values of 8.17E-09 (odds ratio (OR)=6.43, 95% confidence intervals (CI)=3.33-12.40) and 6.94E-03 (OR=3.28, 95% CI=1.28-8.38), respectively. The RET-protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG genotype) was strongly associated with an increased risk of HSCR with a P-value of 1.99E-04 (OR=20.34, 95% CI; 2.54-162.78) when compared with a single SNP of the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and NRG1 is involved in the risk of HSCR development in the Thai population. Moreover, the study also detected a combined effect of SNPs by SNP-SNP interaction, which may help in predicting HSCR risk.

Surgery in management of snake envenomation in children.

BACKGROUND: Snakebite is common in children especially in the developing countries. This study was undertaken to determine the role of surgery in the treatment of venomous snake bite in pediatric patients. METHODS: The clinical data of 58 pediatric patients aged 0-16 years who had been treated for venomous snakebite from January 1999 to December 2008 were analyzed. RESULTS: Of the 58 patients, 43 (74.6%) were male. Peak age incidence was around 2-3 years (28.8%). The majority of envenomations occurred in the summer and rainy seasons, especially in the latter, during flooding. The bites occurred during 6 pm to 12 pm in 27 patients (49.0%). The main bite site was the lower extremities in 49 patients (83.9%). The main species of the snake were Malayan pit viper (Calloselasma rhodostoma) in 28 patients (47.5%) and cobra (Ophiophagus hunnah or Naja spp.) in 21 patients (35.6%). Soft tissue necrosis occurred more in cobra bites (47.6%) than viper bites (3.6%). The most common organism identified in necrotic tissue was Morganella morgagnii. Four patients with cobra bite had respiratory failure that required ventilatory support. Compartment syndrome was suspected in 2 patients. Surgical intervention was necessary in 13 patients. Most procedures involved serial wound debridement, followed by skin grafting. One case needed a toe amputation because of necrosis. The average length of hospital stay in patients who needed surgical management was 18.8 days (range: 12.1-25.5 days). There were no mortalities. CONCLUSIONS: Surgery plays an important role in the management of snakebite patients, especially for those with cobra bite with tissue necrosis.

Peripheral precocious puberty in a male caused by Leydig cell adenoma harboring a somatic mutation of the LHR gene: report of a case.

While a germline activating mutation of the luteinizing hormone receptor (LHR) gene is known to cause autonomous production of testosterone from testicular Leydig cells in male-limited precocious puberty, only a few studies have addressed the role of somatic LHR mutation in testicular pathology. The authors report a case of a 6-year-old boy who developed secondary sex characteristics including facial acne, enlarging genitalia, and aggressive behavior, for which serial biochemical evaluation confirmed the status of peripheral precocious puberty. Examination revealed asymmetrical testicular volume, following which a left testicular tumor was detected through ultrasonography. A left orchiectomy was performed, and histopathology revealed a well-circumscribed Leydig cell tumor Molecular study of the exon 11 of the LHR gene revealed a missense mutation at the nucleotide position 1,732, leading to a substitution of histidine for aspartic acid at codon 578. Interestingly, the substitution was consistent with all previously reported LHR alteration in pediatric Leydig cell adenoma, but which had never before been reported in male-limited precocious puberty, suggesting that the mutation is a molecular signature of the adenoma.

Immunohistological evidence for Wnt-signaling activation in Peutz-Jeghers polyposis.

OBJECTIVE: Molecular pathogenesis of gastrointestinal polyposis in Peutz-Jegher's syndrome (PJS) has been linked to the loss-of-function mutation of LKB1. Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps. This study aimed to look for immunohistochemical evidence of Wnt-signaling activation in PJS polyps. METHOD: Beta-catenin immunohistochemistry patterns were evaluated in gastrointestinal polyps from five cases of PJS. All patients were also evaluated for germline mutations of LKB1 and somatic mutations of beta-catenin in the polyps. RESULTS: Four of the five cases had germline mutations of LKB1, including two novel mutations, a one-base insertion at codon 53 and a large deletion encompassing exon 3 (codon 136-155). PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium. Polyps from two cases with LKB1 mutations revealed moderate-intensity nuclear staining in approximately 20 and 70% of the polyps. CONCLUSION: The study offers additional evidence of Wnt-signaling activation in PJS polyp development at the tissue level, although the degree of up-regulation was not as high as has been found in Wnt-associated neoplasms.

Papillary carcinoma of the thyroid gland in a child of thyrotoxicosis patient receiving radioactive iodine therapy: report of a case.

Herein we present the case of a 9-year-old girl who had an enlarged right lobe of the thyroid gland and sub-clinical hypothyroidism (thyroid stimulating hormone at 9.24 mIU/L). The patient had a history of unintentional exposure to radiation while her mother was receiving radionuclide therapy for diffuse toxic goiter. Ultrasonography of the young girl showed right lobe enlargement with diffuse coarse heterogenous echogenicity, compatible with a microcalcification pattern identified in both lobes of the thyroid gland. Histopathology of the tissue from a thyroidectomy revealed papillary thyroid carcinoma in the right lobe and chronic lymphocytic thyroiditis in the remaining tissue. Molecular pathology demonstrated an RET/PTC1 rearrangement in both tumor and non-tumorous tissue harboring thyroiditis. Considering the history of exposure and the characteristics of the thyroid pathology together, the PTC in this patient was likely a secondary-to-genetic alteration induced by external radiation. This case emphasizes the importance of stringent restrictions when giving radioactive iodine therapy to a patient with small children.

Infectious complications in infants with gastroschisis: an 11-year review from a referral hospital in southern Thailand.

UNLABELLED: MAIN PURPOSES: The study aimed to (1) examine the incidence of infectious complications (ICs) in our referral hospital in southern Thailand in infants with gastroschisis, with analysis of the impact of these complications on outcomes, and (2) identify associated factors to improve the practice at our institution for dealing with this condition. METHODS: A retrospective review of consecutive gastroschisis cases at the major teaching and referral hospital in southern Thailand was conducted for an 11-year period (1996-2006). Cases referred after a primary operation at other hospitals were excluded. The study focused on postoperative nosocomial infections as identified by Centers for Disease Control and Prevention criteria. RESULTS: Sixty-eight patients with gastroschisis were operated on. Twenty-seven patients (39.71%) underwent primary closure. Mortality was 4 of 68 patients (5.9%). Infectious complication occurred in 43 patients (63.2%). The complications significantly increased mechanical ventilation days (10.8 vs 3.8 days in noncomplicated cases), need for parenteral nutrition (25.3 vs 14.5 days), and postoperative stay (33.7 vs 21.1 days). Common ICs were wound infection (32.35%), isolated septicemia (19.1%), and pneumonia (13.24%). Univariate analysis identified an association between the occurrence of IC and birth order (multigravida), time from birth until arrival at our center (5 hours or more), hypoalbuminemia, hypoglycemia, type of operation (staged closure), use of central venous line, and prolonged use of ventilator. On multiple logistic regression, prolonged referral time, use of a central venous line, multigravida, and staged closure independently predicted the risk of IC. CONCLUSION: Infectious complication was significantly related to outcome in gastroschisis cases and should not be overlooked. Our data suggest that prompt referral, limiting central line practice on a selective basis, and an attempt to reduce wound infection in cases that require a temporary silo may improve the overall outcomes.

Outcomes of pediatric nephroblastoma in southern Thailand.

BACKGROUND AND AIMS: The outcomes of nephroblastoma (Wilms tumor, WT) in our institute and other developing countries are notably below results in most developed countries. The objective of this study was to review treatment outcomes of pediatric nephroblastoma in southern Thailand during the past decade and attempt to isolate factors associated with a poor prognosis. PATIENTS AND METHODS: The records of 34 WT patients, aged less than 16 years, who were operated on in Songklanagarind Hospital, Thailand, during the period from January 1996 to December 2007 were reviewed. The management protocol followed the scheme of the US National Wilms Tumor Study Group (NSWTG). RESULTS: Thirteen cases (38.2%) were diagnosed as stage I, 4 (11.8%) as stage II, 13 (38.2%) as stage III and 2 (5.9%) as stage IV. Two cases with bilateral disease (stage V) had stage I tumors in both kidneys. Four-year overall survival (OS) and event free survival (EFS) rates were 65.2% and 52.7%, respectively. Univariate analysis by Log-rank test revealed statistically significant associations between OS and nodal status (p-value <0.01), manifestation of gross hematuria (p-value 0.02), and tumor size of 10 centimeters or more (p-value 0.02). Multivariate analysis found only the nodal status to be independently associated with OS at a Hazard Ratio of 16.6 (p-value <0.01). Eight of 13 stage I cases and 6/13 stage III cases had relapsed, with two-year post-relapse survival of 42.8%. Significantly poorer outcome was found in cases with early relapse within 200 days after enrolment (p-value 0.02). CONCLUSION: The poor outcome of pediatric nephroblastoma in southern Thailand seems to be related at least in part to failures in primary treatment in stage I patients. Large tumor size and gross hematuria were associated with risk of a poorer outcome.

Primary pull-through with modified Duhamel technique: 1 institution's experience.

BACKGROUND/PURPOSE: Primary pull-through for Hirschsprung disease has been reported to give comparable surgical outcomes to staged operations with less morbidity. The aim of this study was to review the early experiences in our institution with the primary pull-through option. METHODS: Medical records of 50 consecutive patients with Hirschsprung disease who underwent a modified Duhamel pull-through operation from 2001 to 2004 were retrospectively reviewed. For analysis, cases were divided into 2 groups: primary pull-through (group I, 30 patients), and patients with a previously established colostomy who underwent a staged operation (group II, 20 patients). Comparisons were made regarding operating time, operative morbidity, and medium-term functional outcomes. RESULTS: There was no difference between the groups with respect to median age and weight at time of surgery, sex ratio, presenting symptoms, and extent of aganglionosis. Seventy-four percent of the procedures were performed on infants (group I, 21 [70%] of 30 patients; group II, 16 [80%] of 20 patients). Acute postoperative complications were experienced by 4 (13.3%) of 30 patients in group I and 4 (20%) of 20 patients in group II (P <.05). Postoperative enterocolitis occurred in 11 (36.7%) of 30 patients in group I and in 7 (41.2%) of 17 patients in group II. CONCLUSIONS: Our experience indicates that the primary pull-through using a modified Duhamel technique gave neither difference in functional outcomes nor medium-term complications compared to a staged procedure. Considering a sparing of colostomy and a potential economic benefit, the procedure should be considered in selected patients.

Circumumbilicus incision for bleeding Meckel's diverticulectomy.

BACKGROUND/OBJECTIVE: With regard to the recent interest in minimally invasive surgery, the authors report on a technique of transumbilical incision for Meckel s diverticulum and appendectomy, which provides better cosmetic results and no increase in complications. MATERIAL AND METHOD: The case records of 18 consecutive Meckel's diverticulum (MD) patients who were treated at Songklanagarind Hospital in Thailand between 1996 and 2005 were reviewed. RESULTS: The male-female ratio was 14-4 (3.5:1). Of the 15/18 (83.3%) symptomatic cases, presenting symptoms were bleeding 10/15 (66.7%), gut obstruction 2/15 (13.3%), peritonitis 2/15 (13.3%), and intussusception 1/15 (6.7%). All bleeding patients were children (age 1-15 years), 9/10 (90%) Meckel scan positive and 10/10 (100%) ectopic-gastic tissue. Four children underwent a circumumbilical incision. There were no perioperative or long-term complications related to the transumbilical approach. CONCLUSION: The umbilical incision has all the benefits of a minimal access approach. Umbilical incision is a safe, inexpensive, cosmetically pleasing, and easy technique. This minimally invasive surgery does not require long-term specialized training or special equipment.

Novel mutation of Endothelin-B receptor gene in Waardenburg-Hirschsprung disease.

Homozygous mutations of EDNRB in human have been reported to result in Waardenburg-Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance. We investigated a case of WS4 together with all members of her nuclear family for the alteration of the EDNRB gene by using PCR-SSCP and direct sequencing technique. The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.

Incomplete duplication of the esophagus: a case report.

A case of incomplete duplication of the esophagus diagnosed in a 20-month-old girl with an esophageal perforation is presented. X-ray films of the chest showed pneumomediastinum and subcutaneous emphysema. A water soluble contrast esophagogram revealed a contrast leakage from the cervical esophagus to the thoracic inlet. The endoscopic findings are described. Complete resection of the esophageal duplication was effective.