Successful Treatment for Hepatoblastoma in Trisomy 18: A Case Report.

Children with trisomy 18 tend to develop hepatoblastoma. Since the introduction of appropriate management for organ malfunction, individuals with trisomy 18 have come to have a longer life expectancy. However, the predisposition to hepatoblastoma becomes a significant issue for the quality of a case. Here, we present a rare multifocal hepatoblastoma involving predominantly Couinaud segments 5 and 7 in a 10-month-old boy with trisomy 18. Though the first-line cisplatin monotherapy resulted in unsatisfactory tumor shrinkage, the second-line neoadjuvant chemotherapy administrating irinotecan and vincristine gave rise to significant tumor reduction in volume, leading to the completion of partial resection of the liver without the microscopic residual disease. The patient has been free from recurrence for 44 months. Because anatomical right hepatectomy can cause circulatory instability, including acute onset of pulmonary hypertension in trisomy 18 patients, physicians should balance treatment benefits and potential adverse effects. Our successful experience utilizing a combination of efficacious and less cardiotoxic neoadjuvant chemotherapy followed by the partial hepatectomy encourages physicians to treat a patient with trisomy 18 and tackle hepatoblastoma with a genetic background.

Successful laparoscopic-assisted partial splenectomy and splenopexy with umbilical approach to wandering spleen with an enlarged cyst in a pediatric patient.

A 10-year-old girl with a wandering spleen with an enlarged cyst was successfully treated by laparoscopic-assisted partial splenectomy and splenopexy. The patient visited our hospital with a complaint of a lower abdominal mass. Abdominal computed tomography showed malposition of the spleen and the presence of a 10 cm diameter splenic cyst (SC) in the lower pole. In surgery, the navel was opened with an inverted Y-shaped incision. The SC was punctured and aspirated the contents of the cyst, the migrating spleen was pulled out of navel and the partial splenectomy was done. The residual spleen was laparoscopically fixed by creating an extraperitoneal pocket. Pathologically, the cyst was covered with a vitrified fibrotic capsule and was diagnosed as a pseudocyst. We considered it a traumatic cyst. The postoperative course was uneventful. This minimally invasive laparoscopic procedure was feasible and effective for treating wandering spleen with a large SC in a pediatric patient.

Recovery of bowel function after transperitoneal or retroperitoneal laparoscopic pyeloplasty. A multi-center study.

AIM: To document the recovery of bowel function (BF) in children after transperitoneal (TP) or retroperitoneal (RP) laparoscopic pyeloplasty. METHODS: Data were obtained retrospectively from four centers between 2008 and 2019 for TP (n = 51) and RP (n = 58). Each surgeon chose which technique to perform. RESULTS: Subject demographics were not significantly different. Differences in operative times were not significant (RP: 241 min versus TP: 225 min). Mean duration/requirement for postoperative epidural/intravenous analgesia were not significantly different (TP: 1.4 days versus RP: 1.3 days) and (TP: 66.7% versus RP: 67.2%), respectively. Postoperative nasogastric (NG) intubation was more common in RP (TP: 19.6% versus RP: 44.8%; p < .05). NG aspiration (TP: 0.15 mL/kg/hr versus RP: 0.16 mL/kg/hr), nausea (TP: 31.4% versus RP: 17.2%), and vomiting (TP: 19.6% versus RP: 15.5%) were not significantly different. There were no perioperative complications (including ileus). Abdominal distention was problematic in one case per group (TP: 2.0% versus RP: 1.7%). Times for oral liquid (TP: 0.69 day versus RP: 0.83 day), solid food (TP: 0.88 day versus RP 1.07 days), and the first bowel movement (TP: 2.86 days versus RP: 2.79 days), were not significantly different. CONCLUSIONS: BF recovery would appear to be consistent, independent of technique.

Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease.

PURPOSE: Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. METHODS: The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. RESULTS: The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. CONCLUSION: DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.

Diagnostic laparoscopy for neonatal perforated Meckel's diverticulum.

Pneumoperitoneum in a neonate is a serious condition for which bowel perforation is indicated in most cases. Because the transdiaphragmatic air dissection could occur in some ventilated neonates without peritonitis, making the right diagnosis is sometimes difficult, and exploratory laparotomy is often necessary. Here, we report the first case of neonatal pneumoperitoneum caused by a perforated Meckel's diverticulum in which diagnostic laparoscopy was useful in achieving minimal access surgery. Using a multiuse single-site port on the umbilicus could enable the extraction of a certain length of a small intestine with good cosmetic results. This method would decrease the hurdles of early surgical interventions for the suspected perforation of unknown aetiology and shorten the fasting period, which is beneficial for the neurodevelopment of small neonates.

Pyrrole-imidazole polyamide-mediated silencing of KCNQ1OT1 expression induces cell death in Wilms' tumor cells.

KvDMR (an intronic CpG island within the KCNQ1 gene) is one of the imprinting control regions on human chromosome 11p15.5. Since KvDMR exists within the promoter region of KCNQ1OT1 (antisense transcript of KCNQ1), it is likely that genomic alterations of this region including deletion, paternal uniparental disomy and de-methylation in maternal allele lead to aberrant overexpression of KCNQ1OT1. Indeed, de-methylation of KvDMR accompanied by uncontrolled overexpression of KCNQ1OT1 occurs frequently in Beckwith-Wiedemann syndrome (BWS), and around 10% of BWS patients developed embryonal tumors (Wilms' tumor or hepatoblastoma). These observations strongly suggest that silencing of KCNQ1OT1 expression might suppress its oncogenic potential. In the present study, we designed two pyrrole-imidazole (PI) polyamides, termed PI-a and PI-b, which might have the ability to bind to CCAAT boxes of the KCNQ1OT1 promoter region, and investigated their possible antitumor effect on Wilms' tumor-derived G401 cells. Gel retardation assay demonstrated that PI-a and PI-b specifically bind to their target sequences. Microscopic observations showed the efficient nuclear access of these PI polyamides. Quantitative real-time PCR analysis revealed that the expression level of KCNQ1OT1 was significantly decreased when treated with PI-a and PI-b simultaneously but not with either PI-a or PI-b single treatment. Consistent with these results, the combination of PI-a and PI-b resulted in a significant reduction in viability of G401 cells in a dose-dependent manner. Furthermore, FACS analysis demonstrated that combinatory treatment with PI-a and PI-b induces cell death as compared with control cells. Taken together, our present observations strongly suggest that the combinatory treatment with PI polyamides targeting KCNQ1OT1 might be a novel therapeutic strategy to cure patients with tumors over-expressing KCNQ1OT1.

Influence of surgical intervention on neurodevelopmental outcome in infants with focal intestinal perforation.

BACKGROUND: Intestinal perforation is known to correlate with neurodevelopmental outcome in very low-birthweight (VLBW) infants, and its two major causes are necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP). Infants with FIP are reported to have better neurodevelopmental outcome than infants with NEC, but outcome has not been compared with that in infants without diseases that require surgery. The aim of this study was to compare neurodevelopmental outcomes between FIP survivors and infants without diseases that require surgery. METHODS: Records of VLBW infants with FIP and infants without surgical diseases were retrospectively analyzed. Neurodevelopmental outcome was compared between eight infants with FIP and 24 case-matched control infants without surgical diseases using the Kyoto Scale of Psychological Development. Control group members were individually matched with FIP survivors for sex, gestational age, birthweight, and intraventricular hemorrhage (IVH) grade. Those with an episode of sepsis or severe IVH (grade 3-4) that occurred irrespective of FIP were excluded. RESULTS: Three FIP survivors and 12 infants without surgical diseases were classified as neurodevelopmentally normal (37.5% vs 50%, P = 0.69) at a corrected age of 18 months-3 years. All neurodevelopmentally normal FIP survivors were born at a gestational age ≥ 26 weeks. CONCLUSION: Excluding the influence of sepsis or severe IVH, no significant difference was found in neurodevelopmental outcome between FIP survivors and infants without surgical diseases. None of the FIP infants born before 26 weeks of gestation, however, had normal neurodevelopment, suggesting that longer gestation might be needed to overcome the stress associated with FIP.

Effectiveness of Interval Appendectomy After Conservative Treatment of Pediatric Ruptured Appendicitis with Abscess.

The management of patients with acute perforated appendicitis with abscess is controversial. The aim of the present study was to assess the outcomes of treatment in patients with this condition. We retrospectively analyzed 31 patients (16 men and 15 women with a mean age of 8.4 years) with appendicitis presenting with abscess. Patients were divided into two groups (emergency operation group and interval operation group), and clinical characteristics and outcomes of treatment were investigated. On presentation, no differences in gender, age, body weight, duration of symptoms, temperature, white blood cell count, C-reactive protein level, or maximum size of the abscess in the axial view were detected between the two groups. Fifteen patients (48.4 %) underwent emergency surgery. The remaining 16 patients (51.6 %) were initially treated conservatively with antibiotics. All 16 patients underwent planned operations after receiving conservative treatment, and two (12.5 %) of these patients underwent appendectomy before the planned operation day because of recurrent appendicitis without abscess. There were no differences in the length of hospital stay. In the emergency operation group, six (40 %) patients presented with wound infection and four (26.7 %) developed a postoperative intra-abdominal abscess. No infective complications were reported in the interval operation group. Interval appendectomy after conservative treatment of pediatric ruptured appendicitis with abscess significantly reduced postoperative infection rates.

Laparoscopic partial nephrectomy for the treatment of large cystic nephroma in children.

UNLABELLED: Abstract Background: Cystic nephroma (CN) is a rare benign renal neoplasm. The differential diagnosis of cystic partially differentiated nephroblastoma is only possible with pathological findings. Therefore, surgical resection is necessary to diagnose suspected CN lesions. Because CN is usually well demarcated and has a good prognosis, partial nephrectomy is recommended for its treatment. However, to our knowledge, laparoscopic treatment of CN has not been reported. We describe 2 cases of large CNs successfully treated: Case 1 was a 9-month-old boy with a lower polar mass in the right kidney, which occupied two-thirds of the kidney, and Case 2 was a 9-month-old boy with an upper polar mass in the left kidney, which occupied three-fourths of the kidney. MATERIALS AND METHODS: Using the transperitoneal approach, the lesion was detected by a laparoscopic ultrasound probe, and vessels in the affected region were dissected. After the renal artery was clamped with bulldog clips, the parenchyma of the affected region was divided with an ultrasonically activated scalpel. The partly cut pelvis was closed by suturing, and the resected stump was coated with hemostatic agents and covered with the pediculate peritoneum. RESULTS: The lesion was not exposed during surgery, and the microscopic features were consistent with CN in both cases. Residual renal function was good, and no residual tumor was found in both cases for over a year. CONCLUSIONS: Laparoscopic partial nephrectomy is a feasible approach to treat large CNs. When it is difficult to close the resection stump by parenchymal suturing, covering the stump with hemostatic agents and pediculate peritoneum is feasible.

Urethroscopic holmium: YAG laser ablation for acquired posterior urethral diverticulum after repair of anorectal malformations.

Two patients with acquired posterior urethral diverticulum that is a complication of laparoscopic assisted anorectoplasty underwent urethroscopic holmium: YAG laser ablation. After the ablation therapies, the size of the diverticulum markedly decreased in both patients. Holmium: YAG laser is safe and easy to handle in the small pediatric urethra.

Laparoscopic excision of urachal remnants is a safe and effective alternative to open surgery in children.

BACKGROUND: An infected urachal remnant is an uncommon benign condition that usually recurs and has the potential to become malignant. This study aimed to review our experience in laparoscopic excision of urachal remnants and report the efficacy and outcomes of the procedure in children. PATIENTS AND METHODS: Between January 2010 and January 2012, five children with a median age of 35 months presented with urachal remnants at our institute. The data and treatment outcomes of all the patients were retrospectively reviewed. Laparoscopic surgery was performed using three ports, including the umbilical port. In all five children, the urachal remnant was excised from the umbilicus to the bladder dome by electrocauterization, and the stump on the bladder was ligated with endoloop sutures and some absorbable sutures. RESULTS: All the five procedures were completed successfully. The median pneumoperitoneum time was 75 minutes. The boundary between the normal bladder wall and the urachal remnant was clearly identified using a laparoscope, allowing excision of the remnant and muscle layer of the bladder wall. No intraoperative or postoperative complications were reported at a median follow-up of 16 months. Complete resection of the urachal remnant was confirmed by pathological evaluation. No symptom recurrences were encountered. Laparoscopic resection had good cosmetic outcomes. CONCLUSIONS: Laparoscopic resection of urachal remnants in children allows for better anatomical visualization and may be considered as a safer, more effective, and more cosmetically beneficial alternative to open surgery.

Single-incision laparoscopic-assisted appendectomy in children: exteriorization of the appendix is a key component of a simple and cost-effective surgical technique.

PURPOSE: Single-incision laparoscopic appendectomy was recently introduced as a less-invasive surgical technique than existing methods, and is increasingly being performed worldwide. We have started to perform transumbilical laparoscopic-assisted appendectomy (TULAA) in children. In this study, we assessed its feasibility, efficacy, and cost-effectiveness compared with conventional multiport laparoscopic appendectomy (MLA). METHODS: We retrospectively reviewed all of the patients who underwent MLA or TULAA between August 2009 and December 2012. Patient characteristics, operative time, length of hospital stay, postoperative complications, cost-effectiveness, and cosmetic results were analyzed. RESULTS: A total of 88 patients underwent laparoscopic appendectomy, with MLA in 48 patients and TULAA in 40 patients. TULAA was successful in 36/40 patients. There were no significant differences in mean operative time or mean length of stay between the two groups of patients. There were no postoperative complications in the TULAA group. The cost of TULAA was much lower than that of MLA. TULAA also provided nearly scarless surgery. CONCLUSION: TULAA, in which the appendix is exteriorized via a combination of open and laparoscopic techniques, is a safe and effective procedure for treating appendicitis in children. TULAA is a cost-effective treatment that provides excellent cosmetic results.

External stabilization for severe tracheobronchomalacia using separated ring-reinforced ePTFE grafts is effective and safe on a long-term basis.

PURPOSE: Tracheobronchomalacia is a respiratory disorder that results from abnormal cartilage development. Since 2003, we have performed external stabilization for severe tracheobronchomalacia using separated ring-reinforced expanded polytetrafluoroethylene (ePTFE) grafts. The aim of this study was to analyze the short- and long-term outcomes of our procedure. METHODS: We reviewed the charts of patients who underwent external tracheobronchial stabilization from January 2003 through December 2012. Separated ring-reinforced ePTFE grafts were fixed to the anterior and posterior lesions of malacia independently, with confirmation of a well-opened lumen by bronchoscopy. RESULTS: Five children with severe tracheobronchomalacia underwent six operations. The median follow-up period was 43 months (range 11-109 months). There was no operative mortality associated with the procedure. One patient required removal of a section of the graft owing to the development of bronchial granulation tissue at the site of fixation. All patients showed improved respiratory function, and tracheal growth was confirmed by follow-up computed tomography. CONCLUSIONS: External stabilization with separated ring-reinforced ePTFE grafts for severe tracheobronchomalacia is effective, less invasive than alternatives and preserves the growth potential of the affected airway segment.

Complete thoracoscopic versus video-assisted thoracoscopic resection of congenital lung lesions.

BACKGROUND: Minimally invasive surgery is recognized as a safe and feasible technique for resecting congenital lung lesions. In our hospital, video-assisted thoracoscopic surgery (VATS) was initially performed through a 5-6-cm incision with several trocars under differential lung ventilation (assisted-VATS). Complete thoracoscopic surgery (complete-VATS) with artificial pneumothorax was introduced in 2009 and allowed surgery in smaller infants. The aim of this study was to compare the outcomes of complete-VATS and assisted-VATS for congenital lung lesions. PATIENTS AND METHODS: Between January 2004 and October 2012, 22 children underwent pulmonary lobectomy by complete-VATS or assisted-VATS at our hospital. We retrospectively reviewed the intraoperative and early postoperative results of these patients. RESULTS: Of the 22 children, 10 underwent assisted-VATS, and 12 underwent complete-VATS to treat various diseases, including congenital cystic adenomatous malformation, sequestration, and bronchial atresia. The age, body weight, and mean operative time were not significantly different between the two groups. Four patients in the complete-VATS group, but none in the assisted-VATS group, weighed <10 kg. Intraoperative bleeding was significantly less, and hospital stay was significantly shorter, in the complete-VATS group. One patient in the assisted-VATS group had intraoperative bleeding and required conversion to open surgery. Postoperative complications included transient paralysis of the affected arm and transient atelectasis in 1 patient each in the complete-VATS group. CONCLUSIONS: Complete-VATS can be safely performed with less bleeding and shorter hospital stay than assisted-VATS. As differential lung ventilation is not essential during complete-VATS, complete-VATS can be performed in small infants.

Non-promoter DNA hypermethylation of Zygote Arrest 1 (ZAR1) in neuroblastomas.

BACKGROUND: The comprehensive methylation analysis of tumor-specific differently methylated regions in malignant melanomas and brain tumors has led to the identification of non-promoter hypermethylation of zygote arrest 1 (ZAR1). To search the non-promoter ZAR1 hypermethylation in neuroblastomas, we analyzed the levels of the methylation and transcript expression of ZAR1. METHODS: The MassARRAY® EpiTYPER (Sequenom Inc., San Diego, CA, USA) system was optimized to determine the quantitative methylation levels of ZAR1 for 12 neuroblastoma cell lines, 23 neuroblastoma samples and four adrenal samples. ZAR1 expression levels were evaluated through a quantitative, real-time reverse transcription-polymerase chain reaction. The quantitative methylation levels of ZAR1 were subjected to correlation studies with the established markers of progressive disease and outcome. RESULTS: Strikingly, the hypermethylation of ZAR1 regions and ZAR1 expression levels was observed in the neuroblastoma cell lines and neuroblastoma samples, compared to the adrenal samples. Somatic changes in ZAR1 methylation and ZAR1 expression were found in all three neuroblastoma patients. In the ZAR1 regions, poor-outcome tumors that were MYCN-amplified and/or Stage 3 or 4 and/or the age at diagnosis was≥18months, and/or showed an unfavorable histology were frequently hypermethylated. CONCLUSION: Our results indicate that the hypermethylation of ZAR1 regions is extremely frequent in neuroblastomas and correlates with established markers of progressive disease and outcome.

Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.

BACKGROUND: The identification of tissue-specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process. PROCEDURE: We used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets. RESULTS: Screening of 12 tDMRs revealed 2 genomic regions (SLC16A5 and ZNF206) with frequent aberrant methylation patterns in NB. The methylation levels of SLC16A5 and ZNF206 were low compared to the control adrenal medullas. The SLC16A5 methylation level (cut-off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not with MYCN amplification. The ZNF206 methylation level (cut-off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono-variant analysis, patients with both hypomethylation of SLC16A5 and hypermethylation of ZNF206 had a significantly prolonged event-free survival, when these two variables were analyzed together. CONCLUSIONS: We demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome.

Long-term survival with cloacal dysgenesis sequence.

Cloacal dysgenesis sequence (CDS) is a rare and lethal malformation. We report such a case of long-term survival, currently to 12 years of age. In the fetal period, she received a timely placement of vesico-amniotic shunt for a megabladder due to a severe urethral obstruction. Postnatally, cystostomy and colostomy were created because of no perineal opening of urethra, vagina, and anus. Anorectoplasty, construction of efferent conduit, and colostomy closure were performed at 4 years of age. Ileovaginoplasty and ileovesicostomy which was a Mitrofanoff-type of conduit, and labioplasty were performed at the age of 11 years. To the best of our knowledge, only five survivors with CDS over 1 year of age have been reported.

Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

OBJECTIVES: The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. METHODS: The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. RESULTS: The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. CONCLUSION: Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

Application of high-dose rate (60)Co remote after-loading system for local recurrent neuroblastoma.

The local control of neuroblastoma is a very important treatment consideration. We describe a patient who received high-dose rate 60Co remote after loading system treatment for local control of recurrent neuroblastoma and discuss the efficacy of high-dose rate 60Co remote after loading system treatment.