Jeong-Meen Seo

A Genome-Wide Association Study Identifies Potential Susceptibility Loci for Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of intramural nervous plexuses along variable lengths of the hindgut. Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus. To discover additional risk loci, we performed a GWAS of 123 sporadic HSCR patients and 432 unaffected controls using a large-scale platform with coverage of over 1 million polymorphic markers. The result was that our study replicated the findings of RET-CSGALNACT2-RASGEF1A genomic region (rawP = 5.69×10−19 before a Bonferroni correction; corrP = 4.31×10−13 after a Bonferroni correction) and NRG1 as susceptibility loci. In addition, this study identified SLC6A20 (adjP = 2.71×10−6), RORA (adjP = 1.26×10−5), and ABCC9 (adjP = 1.86×10−5) as new potential susceptibility loci under adjusting the already known loci on the RET-CSGALNACT2-RASGEF1A and NRG1 regions, although none of the SNPs in these genes passed the Bonferroni correction. In further subgroup analysis, the RET-CSGALNACT2-RASGEF1A genomic region was observed to have different significance levels among subgroups: short-segment (S-HSCR, corrP = 1.71×10−5), long-segment (L-HSCR, corrP = 6.66×10−4), and total colonic aganglionosis (TCA, corrP>0.05). This differential pattern in the significance level suggests that other genomic loci or mechanisms may affect the length of aganglionosis in HSCR subgroups during enteric nervous system (ENS) development. Although functional evaluations are needed, our findings might facilitate improved understanding of the mechanisms of HSCR pathogenesis.

Experience with laparoscopic-assisted anorectal pull-through in 25 males with anorectal malformation and rectourethral or rectovesical fistulae: postoperative complications and functional results

INTRODUCTION LAARP (laparoscopic-assisted anorectal pull-through) has become an established operation for anorectal malformation (ARM) with rectourethral or rectovesical fistula. The aim of this study was to review post-LAARP operation complications and midterm functional results. METHODS Between 2003 and 2010, we performed 28 LAARPs in ARM patients with rectourethral or rectovesical fistula. We retrospectively analyzed the clinical outcomes in 25 male patients with rectourethral or vesical fistulae. RESULT The mean age of the patients at the time of LAARP was 2.7 ± 1.4 months. The most common ARM type was rectoprostatic urethral fistula (n=16). Few immediate postoperative complications (urinary tract infection (1), ileus (1), and one case of pneumonia) occurred. Rectal mucosal prolapse developed and was excised 6 months later in 13 (52%) patients. Urethral diverticulum occurred in one patient with a rectobulbar urethral fistula. Immediate postoperative high rectal tone developed in six patients during the early study period (2003-2004). Six of the 12 patients older than 3 years had voluntary bowel movement and no soiling. CONCLUSION LAARP was a safe procedure. Shorter dissection of rectum in the intra-abdominal space may be helpful in preventing rectal mucosal prolapse. Intermittent rectal tube insertion may be useful for the patient with high rectal tone in the immediate postoperative period. LAARP is not recommended for the bulbar fistula with a long common wall.

Reversal of Intestinal Failure–Associated Liver Disease by Switching From a Combination Lipid Emulsion Containing Fish Oil to Fish Oil Monotherapy

Intestinal failure-associated liver disease (IFALD) is a serious complication of parenteral nutrition (PN). Studies have shown that the amount and content of intravenous lipid emulsions (LEs) used is closely related to the development of IFALD. We report 2 cases of IFALD reversed by switching from a combination lipid emulsion containing fish oil to fish oil monotherapy (Omegaven; Fresenius Kabi Austria Gmbh, Graz, Austria). Patients initially received PN containing SMOFlipid 20% (SMOF; Fresenius Kabi Austria Gmbh, Graz, Austria), 2.0-3.0 g/kg/d, over 24 hours. When IFALD developed, LE was switched from SMOF to Omegaven starting at 1.0 g/kg/d over 12 hours. Case 1 was an 11-month-old girl with a diagnosis of extensive Hirschsprung disease up to the proximal jejunum. She developed direct bilirubinemia at 3 months, and the patients LE was switched to Omegaven. A decrease in direct bilirubin was observed after 60 days on Omegaven, and IFALD was completely resolved after 90 days. Case 2 was a 1-month-old boy with a history of gastroschisis diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome. He could not tolerate any oral feeds and was kept on full PN. He had elevated direct bilirubin and developed IFALD since 5 weeks. Omegaven treatment was initiated at 5 months. Direct bilirubin rose to 8 mg/dL during the first month on Omegaven. Then a gradual decrease in direct bilirubin was observed, and after 5 months on Omegaven, IFALD was completely resolved. In conclusion, 2 infants with advanced IFALD showed reversal of cholestasis by switching from SMOF to Omegaven monotherapy.

Posteromedial diaphragmatic hernia following pediatric liver transplantation.

Moon S‐B, Jung S‐M, Kwon C‐H, Kim S‐J, Joh J‐W, Seo J‐M, Lee S‐K. Posteromedial diaphragmatic hernia following pediatric liver transplantation.

Hepatoblastoma: 15-year experience and role of surgical treatment

Purpose Hepatoblastoma is the most common malignant liver tumor in children. The aim of this study was to review our results of hepatoblastoma treatment and to determine the role of surgical treatment in hepatoblastoma. Methods This is a retrospective clinical study. The medical records of patients with hepatoblastoma, treated between October 1994 and October 2009, were reviewed. The patients were classified according to the pretreatment extent of disease (PRETEXT) grouping system. The main outcome variable was survival. Secondary outcome variables were complete, partial and no response to chemotherapy and surgery, when indicated. Results Twenty-seven patients were treated during the observation period. Eighteen were males. Five were PRETEXT group I, 8 group II, 13 group III and 1 group IV. Complete excision was achieved in all patients except in one case that underwent liver transplantation (group IV). Median follow-up and survival rate were 2.3 years and 100%, 6.6 years and 75%, 5.8 years and 92%, 7.7 years and 100%, for groups I to IV, respectively. Twenty patients are currently considered to be in complete response status and three patients are receiving postoperative chemotherapy. Four patients died; the causes of death were cytomegalovirus hepatitis, bone marrow suppression during adjuvant chemotherapy, primarynonfunction after the transplantation for recurrent tumor and metachronous rectal cancer, respectively. Conclusion Favorable long-term outcome could be expected for hepatoblastoma with complete tumor excision and adjuvant chemotherapy.

Graft rotation and late portal vein complications in pediatric living donor liver transplantation using left‐sided grafts: Long‐term computed tomography observations

Right‐side rotation of the graft is an uncommon event after pediatric living donor liver transplantation (LDLT) with a left‐sided graft. However, graft rotation might lead to gradual portal vein (PV) stretching and late portal vein complications (PVCs). The goal of this study was to quantify the degree of graft rotation (R) by computed tomography (CT) and to determine the effect of graft rotation on the development of late PVCs. One hundred ten patients underwent LDLT with left‐sided grafts between 1996 and 2009; CT images were available and were reviewed for 66 of these patients. To quantify R, the following variables were measured with CT: the longest distance between the midline and the extrahepatic PV at the level of the hepatic hilum (A), the distance between the midline and the center of the superior mesenteric vein at the level of the confluence of the splenic vein and superior mesenteric vein (B), and the inner transverse diameter of the body cavity at the level at which A was measured (C). R was calculated as (A − B)/C. In patients with a patent PV (n = 59) and in patients with late PVCs (n = 7), the median R values were 0.16 (range = 0.03‐0.38) and 0.25 (range = 0.13‐0.39), respectively; there was a significant difference between the 2 groups (P = 0.003). Multivariate analysis showed that R ≥ 0.2 was the only independent risk factor for the development of late PVCs (P = 0.021). In conclusion, the gradual stretching of the PV after right‐side rotation of left‐sided grafts might play an important role in the development of late PVCs. PV patency should be closely monitored when graft rotation is noted during clinical follow‐up. Liver Transpl 17:717‐722, 2011.

Genetic variants of IL‐11 associated with risk of Hirschsprung disease

Hirschsprung disease (HSCR) is a congenital and heterogeneous disorder characterized by the absence of enteric ganglia during enteric nervous system (ENS) development. Our recent genome‐wide association study has identified a variant (rs6509940) of interleukin‐11 (IL‐11) as a potential susceptible locus for HSCR. As interleukins play important roles in the ENS, we further studied associations with HSCR of nine common single nucleotide polymorphisms (SNPs) on IL‐11.

Postoperative adjuvant OK-432 sclerotherapy for treatment of cervicofacial lymphatic malformations: An outcomes comparison

OBJECTIVES Surgical treatment of extensive cervicofacial lymphatic malformations is often challenging due to a high rate of postoperative fluid re-accumulation and lesion recurrence resulting from incomplete resection. This study suggests a combined treatment of surgical resection and postoperative adjuvant OK-432 sclerotherapy via closed suction drainage. Using comparative analysis, this study aims to evaluate the efficacy of adjuvant sclerotherapy. METHODS A retrospective chart review was performed on patients who underwent surgical resection of cervicofacial lymphatic malformations between January 2009 and July 2013. Patients were divided into two groups based on whether or not adjuvant OK-432 sclerotherapy was administered via closed suction drainage after surgery. Both surgery-related and adjuvant sclerotherapy-related complications were assessed, and treatment effectiveness was measured based on the change in Cologne Disease Score (CDS) or the need for further treatment. RESULTS A total of 17 patients underwent surgical resection. Nine of these patients underwent surgical resection only, while the other eight underwent surgical resection with adjuvant OK-432 sclerotherapy. The increase in total Cologne Disease Score (CDS) and change of progression parameters were significantly higher for the adjuvant sclerotherapy group compared to the surgery-only group. Additionally, there were no cases of postoperative lymphatic fluid retention among the adjuvant sclerotherapy group. The two groups exhibited similar complication rates with no statistically significant difference. CONCLUSIONS Adjuvant OK-432 sclerotherapy via closed suction drainage is a safe and effective treatment modality. The combination of surgical resection and post-operative adjuvant sclerotherapy via closed suction drainage should be integrated into the treatment algorithm of extensive cervicofacial lymphatic malformation.

Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: Overcoming the learning curve

BACKGROUND/PURPOSE We describe our initial experience of thoracoscopic esophageal atresia with distal tracheoesophageal fistula (EA/TEF) repair. METHODS Twenty-three consecutive cases of thoracoscopic repair of EA/TEF were performed between October 2008 and March 2013. The medical records of 22 patients were retrospectively reviewed, excluding one case of early postoperative mortality. RESULTS The study period was divided into two sections: from 2008 to 2011 (13 cases) and from 2012 to 2013 (9 cases). Patient characteristics did not differ between the two study periods. Mean operation time was significantly shorter in period 2 compared to period 1 (p<0.01). There was one case that was converted to open repair via thoracotomy during period 1. Anastomosis leakage was seen in two cases during period 1, while no cases of leakage were encountered in period 2. Ten of 13 cases (76.9 %) in period 1 had clinically significant esophageal strictures requiring one or more sessions of balloon dilatations. No cases of esophageal strictures were seen in period 2 (p<0.01). CONCLUSIONS When the initial learning curve was endured, surgical outcomes of thoracoscopic repair of EA/TEF were superior to the outcomes of earlier cases, and comparable to past experiences with open thoracotomy.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.

Background Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. Methods A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. Results The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). Conclusion Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.