Spectrum of MNX1 Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome

BACKGROUND: The major genetic cause of Currarino syndrome (CS), a congenital malformation syndrome typically characterized by sacral agenesis, anorectal malformation, and presence of a pre-sacral mass, is known to be pathogenic variants in motor neuron and pancreas homeobox 1 (MNX1), which exist in almost all familial cases and 30% of sporadic cases. Less commonly, a large deletion or a complex rearrangement involving the 7q36 region is associated with CS. We investigated the spectrum of MNX1 pathogenic variants and associated clinical features in the Korean patients with CS. METHODS: We enrolled 25 patients with CS, including 24 sporadic cases and one familial case. Direct sequencing of MNX1 and multiplex ligation-dependent probe amplification were performed. We also analyzed clinical phenotypes and evaluated genotype-phenotype correlations. RESULTS: We identified six novel variants amongst a total of six null variants, one missense variant, and one large deletion. The null variants included four frameshift variants (p.Gly98Alafs*124, p.Gly145Alafs*77, p.Gly151Leufs*67, and p.Ala216Profs*5) and two nonsense variants (p.Tyr186* and p.Gln212*). The missense variant, p.Lys295Gln, was located in the highly-conserved homeobox domain and was predicted to be deleterious. A large deletion involving the 7q36 region was detected in one patient. Pathogenic variants in MNX1 were detected in 28% of all CS cases and 25% of sporadic cases. The clinical phenotype was variable in patients with and without pathogenic variants; no significant genotype-phenotype correlation was observed. CONCLUSIONS: This study revealed the spectrum and phenotypic variability of MNX1 pathogenic variants in the Korean population.

Arteriovenous Malformation of the Distal Ileum in a 14-Year-Old Girl with Recurrent Abdominal Pain: A Case Report

Arteriovenous malformation (AVM) is a lesion involving a high-flow vascular malformation, which is one of the causes of massive gastrointestinal bleeding. In the pediatric population, AVM is quite rare in the gastrointestinal tract, and the most common primary site is the colon. A small bowel is a rare primary site of AVM, and only 1 case has been reported in Korea. Here, we report on a case of AVM found in the distal ileum of a 14-year-old girl who complained about recurrent lower abdominal pain only without a gastrointestinal hemorrhage. In the previous research literature, a small bowel AVM can be diagnosed through detecting the existence of an enhancing nidus of the intestinal wall at the arterial phase, accompanied by an early draining vein as it appeared on a dynamic contrast-enhanced abdominal computed tomography. In our case, the pathologically confirmed AVM of the distal ileum showed a dot-like enhancement within the thick low-attenuating submucosal layer of the terminal ileum.

Soft Tissue Hemangioendothelioma in Children / 소아외과

PURPOSE: Soft tissue hemangioendothelioma (STHE) is a rare vascular tumor, which has a similar prognosis to borderline malignancy. The disease is poorly understood in pediatric cases because of its low incidence; therefore, we investigated treatment strategies for STHE in children. METHODS: We retrospectively analyzed 8 patients with STHE, who were pathologically confirmed between January 1995 and June 2015. The median duration of follow-up was 72 months. RESULTS: Five were male and the median age at the time of surgery was 1.2 years. Six patients presented with a palpable mass, and 2 patients experienced facial paralysis. The median tumor size was 4.0 cm. The following tumor locations were observed head (2 patients), neck (2 patients), chest wall (1 patient), sacrococcyx (1 patient), upper limb (1 patient), and lower limb (1 patient). The patients underwent either microscopic complete resection (R0) (3 patients), macroscopic complete resection (R1) (2 patients), or macroscopic incomplete resection (R2) (3 patients). After histopathological examination, 6 patients were diagnosed with kaposiform hemangioendothelioma (HE), one with retiform HE, and one with epithelioid HE. Postoperative sequelae occurred as gait disturbance, hearing impairment, and vocal cord palsy. Tumor recurrence or regrowth occurred in 4 patients. These patients underwent reoperation and IFN therapy; however, in the patient with epithelioid HE, metastasis to the scalp occurred after these therapies. The patient with the head tumor who underwent R2 resection, underwent resection three more times, but died 11 months after the first surgery. CONCLUSION: When treating STHE in children, R0 resection should be first considered, but recurrence and metastasis should be monitored depending on the size, pathology, and location of the lesion. When major sequelae are expected, function-preserving surgery could be considered, depending on tumor location, size, and nearby organs.

Clinical Study of Congenital Esophageal Stenosis: Comparison according to Association of Esophageal Atresia and Tracheoesophageal Fistula / 대한소아소화기영양학회지

PURPOSE: Congenital esophageal atresia (CES) is a rare congenital disease. The severity of symptoms is variable; thus, diagnosis is difficult and tends to be delayed. CES is frequently accompanied by esophageal atresia (EA) with/without tracheoesophageal fistula (TEF). We investigated the characteristics of CES by reviewing our experience with CES patients and researched the differences between CES with EA-TEF and isolated CES. METHODS: A total of 31 patients underwent operations for CES were reviewed retrospectively. The patients were divided into two groups according to the association with EA-TEF, and compared the differences. RESULTS: Sixteen boys and 15 girls were included. The mean age at symptom onset was 8 months old, and the mean age at diagnosis was 21 months old. Nine patients with EA-TEF were included group A, whereas the other 22 patients were assigned to group B. There were no differences in sex, gestational age, associated anomalies and pathologic results between the groups. In group A, the age at diagnosis and age at surgery were younger than in group B despite the age at symptom occurrence being similar. Postoperative complications occurred only in group A. CONCLUSION: In this study, symptoms occurred during the weaning period, and vomiting was the most frequent symptom. CES patients with EA-TEF tended to be diagnosed and treated earlier despite the age at symptom occurrence being similar. CES patients with EA-TEF had more postoperative complications; therefore, greater attention should be paid during the postoperative period.

Thyroid Cancer in Pediatric Age: A Single Institution Experience / 소아외과

PURPOSE: Thyroid cancer is a rare disease in pediatric population, but its incidence rate is increasing. The aim of this report is to present a single institution experience of pediatric thyroid cancer and to identify clinical features, predisposing factors, and postoperative course of pediatric thyroid cancer. METHODS: We retrospectively reviewed 35 pediatric patients who underwent operation due to thyroid cancer at Seoul National University Children's Hospital between May 1997 and January 2017. The median follow-up period was 70 months (range, 5–238 months). RESULTS: The mean age at operation was 12.0±5.91 years and 27 patients were female. The underlying conditions in patients included history of chemoradiotherapy for previous other malignancies (n=4), hypothyroidism (n=3), history of chemotherapy (n=2), family history of thyroid cancer (n=1) and history of radiation therapy (n=1). The initial symptoms were palpable neck mass (n=21) and incidental findings (n=11). Total thyroidectomy (n=30) or unilateral lobectomy (n=5) were performed. There were 15 postoperative complications including transient hypocalcemia in 14 patients and Horner's syndrome in 1 patient. The most common pathologic cell type was papillary thyroid cancer (n=29). Extrathyroid extension and lymph node invasion were found in 25 patients and 27 patients, respectively. Thirteen patients showed multifocality. During follow-up period, 5 patients underwent additional operation because of tumor recurrence in lymph nodes. Lung metastasis was detected in 3 patients at the time of diagnosis and in 3 patients during follow-up period. The mortality rate was zero and mean disease-free survival was 83.7±47.9 months. CONCLUSION: Pediatric thyroid cancer has lower mortality rate and recurrence rate as seen in this study despite the advanced stage at diagnosis. A thorough follow-up of patients with an underlying condition such as history of chemoradiotherapy and understanding new pediatric guideline can be helpful to maximize patients' survival and prognosis.

Anterior Anorectocolonic Tubular Duplication Presenting as Rectovestibular Fistula in an Infant / 소아외과

Anorectal duplications account for only 5% of gastrointestinal duplications, and cases with involvement of the anal canal are much rarer. Nearly all anorectal duplications are posterior to the rectum; duplications located anterior to the normal rectum are highly unusual, and only a few cases have been reported. We report the case of an anterior anorectocolonic duplication presenting as a rectovaginal fistula in a 2-month-old infant. After diagnosis, the duplication was excised completely without further intestinal complications.

Currarino triad with Mullerian duct anomaly in mother and daughter without MNX1 gene mutation

The Currarino triad is a unique complex of congenital caudal anomalies, including anorectal malformation, sacral bony defect and presacral mass. This triad may be associated with Mullerian duct anomalies, such as duplication of the vagina and uterus. Each of these diseases has a familial tendency and sometimes coexist within families. But, when coexisting in familial cases, nearly all reported cases revealed mutations of the motor neuron and pancreas homeobox 1 (MNX1) gene. Familial cases of Currarino triad combined with Mullerian duct anomaly without MNX1 gene mutation are very rare. Here we report cases of mother and daughter, who had Currarino triad and Mullerian duct anomaly without MNX1 gene mutation, along with a brief literature review.

Meckel diverticulum in exomphalos minor

A congenital hernia into the base of the umbilical cord is known as an exomphalos and when the size of the defect is 5 cm or less and containing only bowel, it is called as exomphalos minor. We present a case of a newborn with an exomphalos minor within a Meckel diverticulum. He underwent surgical resection of the Meckel diverticulum and repair of the abdominal wall defect. To our knowledge, this is the first reported case of Meckel diverticulum in an exomphalos minor in Korea.

Immunohistochemical and Molecular Markers Associated with Differentiated Thyroid Carcinoma / 대한갑상선학회지

In the last decade, conventional diagnosis of thyroid nodules largely depended on fine-needle aspiration (FNA) and ultrasound. However, FNA has a limited ability to distinguish between benign and malignant lesions, especially in cases with indeterminate cytology. Although the clinical course of differentiated thyroid carcinoma is believed to be favorable, delayed diagnosis can make its clinical management difficult. Many immunohistochemical (IHC) or molecular adjunctive markers have been tested to improve the diagnostic accuracy for thyroid nodules. The common IHC markers galectin-3, Hector Battifora mesothelial-1, and cytokeratin-19 are used alone or as part of panels for both FNA and analysis of surgical specimens. A novel IHC marker, podoplanin, was recently introduced as an adjunctive marker for thyroid cancer diagnosis and prognosis and is associated with the progression of papillary thyroid carcinoma (PTC). Several researchers have identified molecular markers to increase the diagnostic accuracy of thyroid lesions of undetermined significance. Four promising molecular markers have been proposed and thoroughly investigated: B-type Raf kinase (BRAF) and RAS, rearranged in transformation/PTC (RET/PTC), paired box gene 8 (Pax8)/peroxisome proliferator-activated receptor gamma (PPARgamma). BRAF mutations can be measured by immunohistochemistry using an antibody specific to the mutated protein. In this review, we focused on the limitations of current diagnostic tools and on determining the application of the above-mentioned markers to thyroid nodule diagnosis.

How Should the Pyloric Submucosal Mass Coexisting with Hypertrophic Pyloric Stenosis Be Treated?: A Case of Pyloric Ectopic Pancreas with Hypertrophic Pyloric Stenosis / 대한소아소화기영양학회지

Co-existing pyloric submucosal masses with hypertrophic pyloric stenosis (HPS) are very rare and treating these lesions is always a problem. A 20-day-old boy presented with recurrent episodes of projectile non-bilious vomiting lasting for 5 days. HPS was suspected due to the presenting age and the symptoms. The sonography demonstrated not only circumferential wall thickening of the pylorus, but also a pyloric submucosal mass. At laparotomy, a 0.8 cm sized pyloric submucosal mass was identified along with a hypertrophied pylorus. Pyloric excision was performed due to the possibility of sustaining the symptoms and malignancy. The pathological report of the submucosal mass was ectopic pancreas. Coexisting pyloric lesions can be diagnosed along with HPS, and surgical excision, not just pyloromyotomy, should be considered in these circumstances. To the best of our knowledge, this is the first case report of pyloric ectopic pancreas and HPS to be diagnosed concurrently.

Long Term Outcomes of Pediatric Liver Transplantation According to Age

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.

Gastrointestinal hemangioma in childhood: a rare cause of gastrointestinal bleeding / 소아과

Gastrointestinal (GI) hemangiomas are relatively rare benign vascular tumors. The choice of an appropriate diagnostic method depends on patient age, anatomic location, and presenting symptoms. However, GI hemangiomas are not a common suspected cause of GI bleeding in children because of their rarity. Based on medical history, laboratory results, and imaging study findings, the patient could be treated with either medication or surgery. Herein, we report 3 cases of GI hemangioma found in the small bowel, rectum, and GI tract (multiple hemangiomas). Better knowledge and understanding of GI hemangioma could help reduce the delayed diagnosis rate and prevent inappropriate management. Although rare, GI hemangiomas should be considered in the differential diagnosis of GI bleeding.

Comparison of outcomes according to the operation for type A esophageal atresia

PURPOSE: The purpose was to evaluate outcomes according to different operative strategies of type A esophageal atresia (EA). METHODS: All patients who underwent surgery for type A EA between 1980 and 2011 were included. Patients were divided into 2 groups: E-E group included patients who received esophageal end-to-end anastomosis, whereas E-G group included patients who received esophago-gastric tube anastomosis. RESULTS: Twenty-two patients were included. The median gestational age was 37.5 weeks. The median birth weight was 2.5 kg. Twenty-one patients underwent gastrostomy as initial procedures, and one patient underwent primary esophageal end-to-end anastomosis. The median gap between both esophageal ends was six vertebral distance (VD). Seven patients underwent primary anastomosis of the esophagus, and 14 patients underwent gastric replacement. Three patients (13.6%) had anastomotic leakage and 10 patients (45.5%) had anastomotic stenosis. Most of the patients (90.9%) had gastroesophageal reflux, but only two patients required antireflux surgery. The median VD was significantly shorter in E-E group than in E-G group (3 VD vs. 6 VD). Stenosis was significantly more often in E-E group, but there was no significant difference in leakage and reflux symptoms. CONCLUSION: The treatment for type A EA can include E-E anastomosis or E-G anastomosis, depending on the length of the end-to-end interval after performing gastrostomy. Appropriate tension and blood flow in the anastomosis site are essential for preventing postoperative stenosis and leakage, and esophageal replacement with gastric tube is believed to be feasible and safe in cases where excessive tension is present.

Clinical Feature of Neonatal Neuroblastoma: Comparison of Outcome between Diagnosed Prenatally and at Postpartum Group / 소아외과

PURPOSE: Neonatal neuroblastoma (NBL) is the most common malignant tumor in neonates, but there have been few studies about it. The purpose of this study was to investigate the clinical features of NBL and to compare prenatal and postnatal diagnosed groups. METHODS: Nineteen patients who were diagnosed with NBL prenatally or within 28 days after birth from February 1986 to February 2013 in Seoul National University Hospital were enrolled in the study. The patients were categorized according to the International Neuroblastoma Staging System (INSS) and Children's Oncology Group (COG). Retrospective medical-record reviews were performed on these patients. The operative date, complication, pathological stage, and overall survival of the prenatally diagnosed group and the postpartum diagnosed group were compared. RESULTS: Tumor was detected via prenatal ultrasonography in 8 patients (42.1%), and 11 patients (57.9%) were diagnosed within 28 days after birth. Based on INSS, the patients were divided into the stage I (n=8), stage II (n=1), stage III (n=3), stage IV (n=4), and stage IVs (n=3) groups, respectively. Based on COG, on the other hand, the patients were divided into the low-risk (n=8), intermediate-risk (n=8), and high-risk (n=3) groups. The postoperative complication rate was 29%. One patient died from complications from chemotherapy. The other 18 patients' mean follow-up period was 77.7 months. The differences between the postoperative complication rate, proportion of early-stage tumor, and overall survival of the prenatal and postnatal groups were not statistically significant (p=0.446, p=0.607, p=0.414). CONCLUSION: NBL showed favorable outcomes but relatively higher postoperative complications. There seem to be no significant statistical differences in the postoperative complications, proportion of early-stage tumor, and overall survival between the prenatally diagnosed group and the postpartum diagnosed group.

Simultaneous Rhabdoid Tumor of the Chin and an Adrenal Gland in a Neonate / 임상소아혈액종양

Herein, we report a neonatal case of an extra-renal non-cranial malignant rhabdoid tumor with simultaneous tumor in the adrenal gland, which was initially diagnosed with hemangioma. The patient showed a soft tissue mass on the chin at birth which grew rapidly with invasion of lower lip. Despite multimodal treatment including surgery, chemotherapy and high dose chemotherapy followed by autologous stem cell transplantation, the patient died of disease progression at the age of 20 months finally. The clinical presentation, diagnosis, pathology, treatment, and prognosis for this case are discussed.

Early experience of laparoscopic choledochal cyst excision in children / 대한외과학회지

PURPOSE: Laparoscopic choledochal cyst excision with Roux-en-Y hepaticojejunostomy (LCE) in children is being attempted more frequently around the world, and although it has been performed in Korea, no publication has been published on it. However, cholangitis and/or pancreatitis are limitations that make open conversion more likely. The aims of this study, through a retrospective clinical analysis, were to prove the efficacy of LCE in children and to validate that preoperative management expands its indications. METHODS: From May 2011 to November 2012, 13 pediatric LCEs were performed. Demo graphics, preoperative findings, management, operative and postoperative outcomes were reviewed. RESULTS: The mean age at operation was 48.5 months and mean bodyweight 19.0 kg. Ultrasonography was conducted in all patients followed by either magnetic resonance cholangiopancreatography (8 cases) or computed tomography (5 cases). The mean diameter of the cysts was 30.2 mm. Eight patients with cholangitis and/or pancreatitis were given antibiotics preoperatively. Four had their condition resolved by administration of antibiotics, 3 underwent additional endoscopic retrograde biliary drainage or percutaneous transhepatic biliary drainage, and one, due to aggravating tenderness, underwent surgery after 4 days of administrating antibiotics without improvement of the inflammation. Two faced open conversions, one because of a very narrow bile duct, and the other because of remnant inflammation after inadequate preoperative management already mentioned above. Patients were discharged on the eighth postoperative day. There were no complications. CONCLUSION: Pediatric LCE is a feasible option for choledochal cyst. Proper preoperative management such as antibiotics and drainage procedures enhances its efficacy by broadening its indications, even with concomitant cholangitis and/or pancreatitis.

Surgical Treatment of Pancreatic Trauma in Children

Debates exist about the appropriate treatment for pancreatic trauma in children. We intended to examine the safety of the operation of pancreatic trauma in children. This is a retrospective study of 13 patients, younger than 15, who underwent surgery for pancreatic trauma, between 1993 and 2011 in Seoul National University Children's Hospital. Medical records were reviewed for mechanism of trauma, clinical characteristics, radiological findings, operation and outcomes. Organ injury scaling from the AAST (American Association for Surgery of Trauma) was used. All injuries were caused by blunt trauma. Patients with grade III, IV, and those who were difficult to distinguish grade II from IV, underwent surgery due to severe peritonitis. Three patients with grade II were operated for reasons of mesenteric bleeding, tumor rupture of the pancreas, and progression of peritonitis. Distal pancreatectomy was performed in 10 patients and subtotal pancreatectomy and pylorus preserving pancreaticoduodenectomy in 1 patient each. The remaining one underwent surgical debridement because of severe adhesions. The location of injury, before and after operation, coincided in 83.3%. The degree of injury, before and after the operation, was identical in all the patients except for those who were difficult to tell apart grade II from grade IV, and those cannot be graded due to severe adhesion. Postoperative complications occurred in 23.1%, which improved with conservative treatment. Patients were discharged at mean postoperative 12(range 8~42) days. Even though patients with complications took longer in time from diagnosis to operation, time of trauma to operation and hospital stay, this difference was not significant. In conclusion, When pancreatic duct injury is present, or patient shows deterioration of clinical manifestation without evidence of definite duct injury, or trauma is accompanied by other organ injury or tumor rupture, operative management is advisable, and we believe it is a safe and feasible method of treatment.

Risk Factors for Malignancy of Pheochromocytoma and Abdominal Paraganglioma in Children: Clinicopathologic Perspectives

No abstract available.

Prevalence and Significance of Immature Ganglion Cell in Hirschsprung's Disease

Immature ganglion cell (IGC) is known for its relationship with intestinal motility and its impact on postoperative functional outcomes of Hirschsprung's disease (HD). There are few studies on the relationship between intestinal dysmotility and IGC in HD patients. 67 patients pathologically diagnosed with HD and who received definitive operation in Seoul National University Children's Hospital from 2010 to 2011 were included. 10 patients were excluded due to inadequate immunohistochemical staining results. The proximal end of resected ganglionic segment was evaluated with immunohistochemistry examination with MAP-2, a marker of ganglionic cells and bcl-2, a marker of IGCs The median age at operation was 155 (15-4678) day-old. 55 (96.5%) patients positive for bcl-2, were regarded as having IGC, and 2 (3.5%) patients positive for MAP-2 but negative for bcl-2, were regarded as having only mature ganglion cells. In the bcl-2 positive group, there were 7 patients (12.7%) with constipation, 15 patients (27.3%) with soiling, 3 patients (5.5%) with perianal excoriation and 6 patients (10.9%) with medication use. In bcl-2 negative group, intestinal dysmotility was not seen. There was no statistical significance in the two groups. Considering that HD is diagnosed at a young age, the rate of IGC present is very high and it might be inappropriate to relate IGC to functional outcome at young ages.

Xanthogranulomatous cholecystits in 2-month-old infant / 대한외과학회지

Xanthogranulomatous cholecystitis (XGC) is a rare form of chronic cholecystitis that is accompanied by xanthomatous histiocytes and chronic inflammation. A 2-month-old boy presented with a right upper abdominal palpable mass. Cholecystectomy with liver wedge resection was done, under the impression that the mass might be a hepatic tumor or liver abscess. Pathologic examination showed XGC with abscess formation. Most cases of XGC were observed in adult and only a few cases were reported in children. We describe a very rare case of XGC in infancy.