Mesenchymal Hamartoma of the Liver and DICER1 Syndrome.

Mesenchymal hamartoma of the liver (MHL) is a benign tumor affecting children that is characterized by a primitive myxoid stroma with cystically dilated bile ducts. Alterations involving chromosome 19q13 are a recurrent underlying cause of MHL; these alterations activate the chromosome 19 microRNA cluster (C19MC). Other cases remain unexplained. We describe two children with MHLs that harbored germline DICER1 pathogenic variants. Analysis of tumor tissue from one of the children revealed two DICER1 "hits." Mutations in DICER1 dysregulate microRNAs, mimicking the effect of the activation of C19MC. Our data suggest that MHL is a new phenotype of DICER1 syndrome. (Funded by the Canadian Institutes of Health Research and others.).

End-stage renal disease due to ARPKD in the first months of life: transplantation or dialysis?--two case reports.

ARPKD with renal insufficiency during the first months of life is a clinical challenge. We report on two children with ARPKD with massively enlarged kidneys requiring renal replacement therapy in early infancy. Patient 1 developed pulmonary insufficiency due to massively enlarged kidneys. At the age of six months the girl was listed for KT as "high urgency" on the Eurotransplant waiting list. A kidney from a deceased donor was pre-emptively transplanted and simultaneous nephrectomy performed. No postoperative complications were observed, and the patient was discharged from in-patient care 42 days after transplantation. Unexpectedly, she died at the age of one yr due to cerebral vascular spasms of unknown origin. Patient 2 was transferred at the age of three months to our clinic with life-threatening pulmonary insufficiency. Pre-emptive KT was not possible; therefore, bilateral nephrectomy was performed and PD begun. The boy is still doing well on PD one yr later. Pre-emptive KT and bilateral nephrectomy followed by PD are two options for infants with ARPKD and excessive kidney enlargement. PD could be complicated and in some cases become impossible by peritoneal damage during nephrectomy. On the other hand, KT covers a high risk of infections caused by immunosuppression. The decision, which method to choose, should be driven by the individual situation of the patient and the expertise of the center.

Urinary proteome analysis identifies infants but not older children requiring pyeloplasty.

One out of every five children suffering from ureteropelvic junction obstruction (UPJO) requires pyeloplasty. This prevalence indicates an urgent necessity to identify high-grade UPJO as early as possible to avoid renal damage. A novel non-invasive proteomic urine test has recently been introduced that is able to detect these patients at an early stage. In the study reported here, we tested this approach to assess its use in our centre and to expand its application to older children. Twenty-seven children (median age 0.4 years, range 0.1-8.8 years) with hydronephrosis who had been scheduled a nuclear diuretic renal scan (DR) to identify urodynamically relevant UPJO were included in our prospective study. Patients with prior surgery of the urinary tract were excluded. The urinary proteome pattern was analysed using capillary electrophoresis coupled to mass spectrometry. Of the 27 children, 11 had a relevant UPJO diagnosed by the DR. In 19 children <1 year of age, urinary proteome analysis predicted obstruction with a sensitivity of 83% (5/6) and a specificity of 92% (12/13). However, in older patients, the sensitivity decreased to 20% (1/5) and specificity to 66% (2/3). Based on our results, the proteome pattern established by Decramer and co-workers predicts the need for surgery in infants but not in older children with UPJO.

Dysplastic kidney and not renal agenesis is the commonly associated anomaly in infants with seminal vesicle cyst.

OBJECTIVE: To determine whether the association of seminal vesicle cyst (SVC) and renal anomaly in young children correlates with previously reported cases of SVCs in adolescent and adult patients, as congenital SVCs, although rare, are frequently described in association with ipsilateral renal agenesis, mainly in adolescent and adult patients, whereas reports on SVCs in younger children are sparse. PATIENTS AND METHODS: We report on nine infants (median age 4 months) with congenital SVCs, all of them associated with ipsilateral dysplastic kidneys. All patients had ultrasonography of the renal system and voiding cysto-urethrography. Magnetic resonance imaging was used in two patients. RESULTS: The SVCs were found incidentally during ultrasonography for the renal anomaly. Three patients had dysplastic and six had multicystic dysplastic kidneys. In previous reported adult cases of SVCs the most common associated renal anomaly was agenesis of the ipsilateral kidney (25 of 44 cases), whereas only one case of dysplastic kidney was reported. CONCLUSION: As the appearance of renal agenesis might result from a former congenital dysplastic kidney, our findings indicate that cases of ipsilateral renal agenesis in adult patients with congenital SVCs might represent former dysplastic or multicystic dysplastic kidney.

Conversion of a neonatal hepatic hemangioma to focal nodular hyperplasia.

Hepatic hemangioma and focal nodular hyperplasia are both frequently observed benign lesions of the liver. Whereas hepatic hemangioma is the most frequent benign liver tumor in children, focal nodular hyperplasia occurs predominantly in adult patients. Concomitance of both entities has been described in adults, suggesting a similar pathogenesis. We report on a 6-month-old child with a continuously shrinking hepatic hemangioma after interventional therapy and a growing hepatic mass 5 years later, which emerged as focal nodular hyperplasia at the site of the former hemangioma. Diagnostic and therapeutic strategies regarding this patient are discussed. The present case supports the theory that these two entities may share a similar pathomechanism.

Stem-like cells in human hepatoblastoma.

Hepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma.

Thoracoscopy versus thoracotomy improves midterm musculoskeletal status and cosmesis in infants and children.

BACKGROUND: It has been postulated that video-assisted thoracoscopic surgery (VATS) achieves a better biometric and aesthetic outcome than conventional thoracic surgery (CTS), but data are lacking. We aimed to compare the midterm effects of both approaches in children. METHODS: Sixty-two infants and children, who underwent VATS (34; 55%) or CTS (28; 45%) for benign thoracic conditions, were evaluated at follow-up after a mean of 3.8 years (1 to 7 years). The patients underwent standardized clinical assessment of the skeletal system and function. The intercostal spaces were investigated for rib fusion by ultrasound. Patients (+/- parents) themselves, as well as clinicians, subsequently assessed the scars. RESULTS: Comparing the operated versus nonoperated sides, chest asymmetry was significantly less frequent after VATS versus CTS in the horizontal plane (mean relative difference 0.996 +/- 0.003 vs 0.964 +/- 0.008, p < 0.001) and in nipple location (mean relative difference 0.985 +/- 0.008 vs 0.949 +/- 0.013, p = 0.047). The ranges of motion of the shoulder joints did not differ significantly. However, the incidence of scoliosis was lower in VATS patients (9% vs 54%, p < 0.001) and the intercostal spaces of the operated hemithoraces were narrower after CTS (p < 0.001). The Manchester scar assessment scores were in favor of VATS (mean 7.5 vs 13.1, p < 0.001). The visual analog scale scores recorded by patients-parents and independent observers were also significantly better after VATS. Patient satisfaction was less with CTS as 10% wanted to have the scar revised, compared with none in the VATS group. CONCLUSIONS: The thoracoscopic versus conventional approach to the thoracic cavity in children is associated with significantly less midterm musculoskeletal sequelae and a better cosmetic outcome.

Carbon dioxide does not affect the methylation status of prognostic important oncogenes Rassf1A and DCR2 in neuroblastoma cells.

PURPOSE: The aim of the current study was to investigate effects of CO(2) atmosphere, mimicking conditions of the pneumoperitoneum during laparoscopy, on epigenetic conditions of Rassf1A and DCR2 oncogenes in neuroblastoma cells. METHODS: SH-SY5Y neuroblastoma cells were exposed to 100% CO(2) for 4 h. Cells were lysed 4, 8 and 168 h after exposure. After methylation analysis of Rassf1A and DCR2 with polymerase chain reaction, results were compared to those of physiologically incubated neuroblastoma cells. RESULTS: No significant changes were found after exposure to carbon dioxide compared to the control. Values of methylated Rassf1A were 12.6 +/- 1.1 versus 13.2 +/- 1.4 ng/microl in the controls, respectively (4 h after incubation), 12.6 +/- 1.2 versus 15.1 +/- 0.9 ng/microl (8 h) and 14.2 +/- 1.5 versus 11.7 +/- 1.3 ng/microl (168 h). DCR2 showed values of 4.6 +/- 0.5 versus 3.7 +/- 0.5 ng/microl (4 h), 3.8 +/- 0.5 versus 4.1 +/- 0.4 ng/microl (8 h) and 3.6 +/- 0.4 versus 3.8 +/- 0.5 ng/microl (168 h). CONCLUSION: Exposure of neuroblastoma cells to 100% CO(2) does not alter methylation of two prognostic relevant index genes. It seems therefore unlikely that effects on methylation levels within CO(2) pneumoperitoneum lead to epigenetic changes in neuroblastoma.

Thoracoscopic biopsy in children with diffuse parenchymal lung disease.

Lung biopsy is necessary for establishing the diagnosis in patients with otherwise unclassified diffuse or localized parenchymal lung disease. This study aimed to assess the safety and accuracy of video-assisted thoracoscopic (VATS) lung biopsy in children with diffuse parenchymal lung disease (DPLD). In addition we aimed to evaluate the value of this technique with respect to the spectrum of diseases encountered, correlating histological diagnosis with treatment decisions and subsequent clinical outcome. Data from all patients (n = 21) who underwent surgical lung biopsy for suspected DPLD between March 2001 and August 2006 were collected prospectively. Median age was 3 years, 8 months (range 11 days to 15 years, 2 months). All lung biopsies were performed by VATS under general anesthesia. Median operative time was 45 min (range 25-100 min). Conversion to minithoracotomy due to cardiorespiratory difficulties was necessary in two young infants. There were no further intraoperative complications. In 8/21 children, a chest tube was inserted postoperatively for a median of 2 days (range 1-5 days). In one patient, prolonged air-leakage was managed thoracoscopically on postoperative day 9. There were no other postoperative complications. The specimens were of adequate volume and quality and a histopathological diagnosis was obtained for all patients. There was a broad spectrum of different diagnoses which led to specific therapeutic decisions. Subsequent medical treatment was beneficial in the majority of the patients. In conclusion, VATS is a safe and effective procedure for diagnosis of children with suspected DPLD. Diagnostic accuracy is high, morbidity rates are low, and patients may benefit from avoiding thoracotomy.

Laparoscopic repair of neonatal gastric perforation.

BACKGROUND: Gastric perforation is a rare, life-threatening condition in neonates. To avoid deterioration, prompt surgical treatment is mandatory. PATIENTS: We report on 2 neonates (1 and 8 days old) with feeding tube associated gastric perforation managed laparoscopically by single layer suture repair. Both children suffered from severe peritonitis. Operative time was 60 minutes in both cases. Oral feeding was started on postoperative day 3 and 7, respectively. No complications regarding the gastric perforation were encountered on follow-up (11 and 8 months, respectively) in both cases. CONCLUSIONS: We recommend laparoscopic suture repair as a safe and feasible method for surgical treatment of gastric perforation in neonates. These appear to be the first reported cases using this procedure for treatment of neonatal gastric perforation.

Exposure to carbon dioxide and helium reduces in vitro proliferation of pediatric tumor cells.

BACKGROUND: Minimally invasive techniques are increasingly applied to children with malignant tumors. We showed previously that CO(2) used for pneumoperitoneum modulates the function of macrophages and polymorphonuclear cells via direct effects and via acidification. Numerous in vitro and small animal model studies also confirmed an alteration of the behavior of several types of adult tumor cells by CO(2). The impact of CO(2) and other gases used for pneumoperitoneum on the behavior of various pediatric tumors has not yet been determined. METHODS: Cell lines of neuroblastoma (IMR 32, SK-N-SH, Sy5y), lymphoma (Daudi), hepatoblastoma (Huh 6), hepatocellular carcinoma (Hep G2), and rhabdomyosarcoma (Te 671) were incubated for 2 h. Incubation was performed with 100% CO(2), 100% helium, and 5% CO(2) as control. Cell proliferation was determined by the MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] by actively growing cells to produce a blue formazan product. The MTT-assay was performed before, directly after incubation, and daily for 4 days. Vitality of the cells was determined by trypan blue. The extracellular pH during incubation was measured during gas exposition every 10 min using Bayer Rapid Lab 855. RESULTS: CO(2) for 2 h significantly decreased the proliferation of neuroblastoma, lymphoma, hepatoblastoma, and hepatocellular carcinoma cells. This decrease persisted over 4 days in neuroblastoma, lymphoma, and hepatocellular carcinoma cells. The CO(2) had no impact on hepatoblastoma and rhabdomyosarcoma cells. Helium had a similar effect on neuroblastoma cells. After 4 days, a significant decrease of cell activity was found in two neuroblastoma cell lines and in hepatoblastoma cells. Helium had no effect on lymphoma and hepatocellular carcinoma cells. The extracellular pH was 6.2 during incubation with CO(2), and 7.6 during incubation with helium. CONCLUSION: CO(2) and helium may affect the proliferation of some pediatric tumor cell lines in vitro. However, some of these effects and the impact on the extracellular pH are differential. The role of pH modulation, hypoxia and direct effects of gases remain to be investigated before a general recommendation on the use of minimally invasive techniques in pediatric oncology can be given.

Thoracoscopic resection of intra- and extralobar pulmonary sequestration in the first 3 months of life.

BACKGROUND: Thoracoscopic techniques have gained increasing acceptance in pediatric surgery, but experience with newborns and small children is limited. To our knowledge, a series of minimally invasive resection of pulmonary sequestration in newborns has not yet been reported in the literature. We report on 5 patients with pulmonary sequestration thoracoscopically. METHODS: From November 2000 to November 2002, 5 patients underwent thoracoscopic resection of pulmonary sequestration. Ages ranged from 4 to 91 days. Two patients had postnatal pulmonary symptoms. Preoperative diagnosis was dubious in 4 children. There were 4 extralobar and 1 intralobar pulmonary sequestrations. RESULTS: Thoracoscopy was performed with 3-mm instruments and 3 to 5 ports. All procedures were completed successfully. The median duration of the operation was 95 minutes (range, 63-117 minutes), and visualization was excellent. Anomalous blood vessels were clipped and/or ligated. Four patients were extubated immediately after the operation, 1, the day after. The postoperative course was uneventful in all children. At follow-up after 14 months (mean; range, 10-19 months), all patients were free of symptoms and had normal chest x-rays. CONCLUSION: Thoracoscopy is feasible for resection of intra- and extralobar pulmonary sequestrations during the first 3 months of life.

Surgical repair of combined gastroschisis and sternal cleft.

We present a case of prenatally diagnosed gastroschisis combined with a sternal cleft, as well as the successful surgical management of this unusual condition. Successful management of gastroschisis combined with sternal cleft has not been reported before in the literature.

Family cases of gastroschisis.

The etiology of gastroschisis is still unclear. To the authors' knowledge, there are only 14 cases of familial gastroschisis in the literature. The authors add the second case of mother-and-son occurrence and a case of siblings occurrence, thereby updating the current literature for family gastroschisis.

Thoracoscopic resection of extralobar sequestration in a neonate.

The authors report a case of extralobar pulmonary sequestration (ELS) located at the right costophrenic recessus and resected thoracoscopically in a 22-day-old girl. Prenatally, spontaneous resolution of a cystic adenomatoid lung lesion (CCAM) occurring independently in the upper right hemithorax was observed. ELS with preceding complete resolution of CCAM in the ipsilateral hemithorax has not been reported before. This is the first neonate reported with ELS treated by thoracoscopy.

Colon atresia, facial hemiaplasia, and anophthalmia: a case report.

A case of a newborn with atresia of the transverse colon and right facial hemiaplasia, anophthalmia, and cerebral dysfunction is reported. Colon atresia is a rare cause of congenital bowel obstruction and often associated with other malformations such as abdominal wall defects, gastrointestinal, cardiac, urogenital, and musculosceletal lesions. Facial hemiaplasia may arise in frame of chromosomal defects or as a result of neurovascular compromise caused by congenital amniotic bands. However, the combination of colon atresia and facial hemiaplasia has not been reported before.

Laparoscopic fenestration of posttransplant lymphoceles in children.

BACKGROUND/PURPOSE: Lymphoceles are frequently observed as a surgical complication after renal transplantation. Whereas the frequency, pathogenesis, diagnosis, and treatment of lymphoceles has been well described in adult patients, no data are available for the pediatric age group. METHODS: Since December 2000; 5 children (2 boys and 3 girls; median age, 6 years; range, 6 to 15 years) of a total of 21 (10 boys and 11 girls; median age, 13 years; range, 2 to 19 years) children undergoing kidney transplantation had a posttransplant lymphocele. The clinical course, renal function, and ultrasonographic appearance of the transplanted kidney of all children were observed in a prospective manner. RESULTS: The lymphoceles became obvious between day 13 and 48 (median, 20 days) posttransplantation. Lymphocele size ranged from 2.0 x 3.0 cm to 11.0 x 15.0 cm. They were localized at any site (superior, inferior, lateral, medial, and dorsal) around the transplanted kidney. Four patients had a significant decrease of renal function, in 2 children mild urinary tract obstruction occurred, and 1 patient suffered from considerable abdominal pain. Diagnosis was established by ultrasound scan in all cases. All patients were treated by laparoscopic fenestration of the lymphocele immediately after diagnosis, except 1 patient, in whom fenestration was not done until 10 months later. Operating time ranged from 45 to 90 minutes (median, 62 minutes). No intraoperative or postoperative complication occurred. Renal function, urinary tract obstruction, and pain recovered soon after operation in all patients. After 3 to 10 months (median, 8 months) postoperatively, no relapse has been observed. CONCLUSIONS: Our data emphasize laparoscopic fenestration as the treatment of choice for children with posttransplant lymphoceles, because it is safe, effective, and technically easy to perform. If done early after diagnosis, renal function will recover immediately.