Unusual presentation of bladder neuroblastoma in a child: A case report.

BACKGROUND: Neuroblastoma is an extracranial malignant tumor in children that is most often located in the adrenal gland and sympathetic ganglion. Here, we present a rare case of neuroblastoma originating from the urinary bladder. CASE SUMMARY: A 3-year-old girl presented with lower abdominal pain with micturition. Ultrasound revealed a lower abdominal mass. Abdominal computed tomography scan displayed a solitary mass at the top of the urinary bladder. Blood levels of neuron-specific enolase and lactate dehydrogenase were elevated. We treated the child with partial cystectomy and six courses of chemotherapy, and the outcome at 4-year follow-up was unremarkable. CONCLUSION: Neuroblastoma should be considered when tumors are located in the urinary bladder, especially in the dome; although this presentation is rare, the prognosis is very good.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for treatment of clear cell sarcoma of the kidney in children.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children. METHODS: Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy. RESULTS: No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases. CONCLUSIONS: Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study. THE TYPE OF STUDY: A case series with no comparison group. LEVEL OF EVIDENCE: Level IV.

Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.

BACKGROUND: Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated. OBJECTIVE: This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma. METHOD: In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro. RESULTS: In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved. CONCLUSION: Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.

Serum and urinary thioredoxin concentrations are associated with severity of children hydronephrosis.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in children. This study was to assess the relationship between serum thioredoxin (S-Trx) and urinary thioredoxin (U-Trx) concentrations and severity of children hydronephrosis caused by UPJO. METHODS: This study included 156 hydronephrosis children with unilateral UPJO and 80 healthy children. S-Trx and U-Trx concentrations were measured using enzyme-linked immunosorbent assay. U-Trx/creatinine (cr) ratio was calculated. RESULTS: S-Trx and U-Trx concentrations and U-Trx/cr ratio were significantly higher in hydronephrosis children than in healthy children. They were significantly correlated with split renal function, anterior-posterior diameter and Society for Fetal Urology classification, as well as were independently related to the split renal function <39.2%, anterior-posterior diameter>30mm and Society for Fetal Urology grade IV. Under receiver operating characteristic curves, U-Trx/cr ratio showed the higher predictive value compared to S-Trx and U-Trx concentrations. CONCLUSION: Increased S-Trx and U-Trx concentrations, especially U-Trx/cr ratio, are closely associated with the severity of children hydronephrosis, substantializing Trx as a promising biomarker for the progression of children hydronephrosis.

Neoadjuvant Intraarterial Chemotherapy for Treatment of Malignant Vaginal Tumors in Children: A Single-Center Experience.

Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.

Preoperative Interventional Therapy for Childhood Undifferentiated Embryonal Liver Sarcoma: Two Retrospective Cases from a Single Center.

Background Undifferentiated embryonal liver sarcoma (UELS) accounts for only 9 to 15% of all malignant liver tumors in children. Typically, UELS occurs in older children and presents as an abdominal mass. Most UELS are unresectable because of the later diagnosis. The outcome of UELS is very poor, with a 5-year overall survival of < 37.5%. Transarterial chemoembolization (TACE) has been reported to be an effective modality for unresectable liver tumors. To investigate the effects of TACE on UELS in children, we present two cases of children with UELS who underwent TACE and surgical resection in our center within the past 10 years. Methods In this study, two children with UELS were treated using TACE with cisplatin, doxorubicin, and iodized oil. The size of the tumors was measured before and after TACE using ultrasonography. Routine was also given before and after surgical resection. Side effects were recorded. Both patients had follow-up. Results After interventional therapy, both patients presented with vomiting, fever, and transient liver dysfunction without cardiac or renal dysfunction. One patient had bone marrow depression. The size of the tumors was reduced by 23% to 31% after TACE. The tumors were completely removed by surgical procedures after 4 weeks of TACE in both patients. One patient survived free of disease for 1 year, and the other survived free of disease for 9 years. Conclusion TACE yielded satisfactory results for unresectable UELS in children, with lower dosage of chemotherapy and fewer side effects. It may be applied as a preoperative therapy for children with unresectable UELS.

Congenital duodenal obstruction in neonates: a decade's experience from one center.

BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common anomalies in newborns, and accounting for nearly half of all cases of neonatal intestinal obstruction. This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes. METHODS: We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012. We analyzed demographic criteria, clinical manifestations, associated anomalies, radiologic findings, surgical methods, postoperative complications, and final outcomes. RESULTS: The study comprised 287 newborns (193 boys and 94 girls). Birth weight ranged from 950 g to 4850 g. Fifty-three patients were born prematurely between 28 and 36 weeks' gestation. Malrotation was diagnosed in 174 patients, annular pancreas in 66, duodenal web in 55, duodenal atresia or stenosis in 9, preduodenal portal vein in 2, and congenital band compression in 1. Twenty patients had various combinations of these conditions. Presenting symptoms included bilious vomiting, dehydration, and weight loss. X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64% of patients, and confirmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%. Multiple associated abnormalities were observed in 50.52% of the patients. Various surgical approaches were used, including Ladd's procedure, duodenoplasty, duodenoduodenostomy, duodenojejunostomy, or a combination of these. Seventeen patients died postoperatively and 14 required re-operation. CONCLUSIONS: Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders. Timely diagnosis and aggressive surgery are key to improving prognosis. Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery.

A retrospective study of the preoperative treatment of advanced Wilms tumor in children with chemotherapy versus transcatheter arterial chemoembolization alone or combined with short-term systemic chemotherapy.

PURPOSE: To evaluate the therapeutic effect of preoperative transcatheter arterial chemoembolization (TACE) combined with short-term systematic chemotherapy in the treatment of advanced Wilms tumor. MATERIALS AND METHODS: This was a retrospective study on 66 patients with unilateral advanced Wilms tumor, age 5 months to 11 years (median, 2.9 years; 30 boys and 36 girls), treated at our institution between 1995 and 2007. Characteristics of the patient population were maximal tumor diameter > 10 cm, or involvement of periaortic lymph nodes, or inferior vena cava invasion, or distal metastasis, or tumor with anaplastic histology. Patients were divided into three groups. Twenty patients were treated with conventional preoperative chemotherapy (PC group) using vindesine, actinomycin D, and pirarubicin for 4 weeks; 21 patients were treated in the TACE group with preoperative renal arterial chemoembolization using Lipiodol-pirarubicin-vindesine emulsion; and 25 patients were treated with preoperative chemoembolization combined with short-term systematic chemotherapy (T+S) for 2 weeks. RESULTS: No drug-induced cardiotoxicity, nephrotoxicity, or hepatic dysfunction was observed. Complete surgical removal of the tumor was achieved in 12 (65.0%), 17 (80.9%), and 22 (88.0%) patients in the PC, TACE, and T+S groups, respectively (T+S group vs PC group, P = .030). The 2-year relapse-free survival rates were 65.0%, 80.9%, and 100.0% in the PC, TACE, and T+S groups, respectively (T+S vs PC, P = .001). CONCLUSIONS: From our experience, preoperative chemoembolization combined with short-term systematic chemotherapy is able to achieve higher rates of complete tumor resection and relapse-free survival in the treatment of advanced Wilms tumor.

Childhood undifferentiated embryonal liver sarcoma: clinical features and immunohistochemistry analysis.

PURPOSE: The aim of the study was to report on 3 cases of childhood undifferentiated embryonal liver sarcoma (UELS) and to highlight the clinical features, laboratory findings, diagnosis, and management of this rare disease. METHODS: The patients' age, sex, clinical features, laboratory findings, pathologic results, and therapy were reviewed. Immunohistochemistry analysis was performed on the resected mass sections. RESULTS: In this study, 2 cases were female (aged 8 and 12 years) and 1 was male (aged 9 years). The causes of hospitalization were mainly abdominal pain, mass, or fever. An elevated erythrocyte sedimentation rate was noted in 2 available cases, and alpha fetoprotein (AFP) was within the normal range. Imaging findings indicated a well-defined heterogeneous large mass in the right lobe. Histopathologic evaluation of the mass confirmed the diagnosis of UELS. Immunohistochemical staining showed that vimentin and CD68 antigen were positive in all samples, whereas desmin was positive in one sample. Surgery with chemotherapy was performed in 2 cases. CONCLUSION: The diagnosis of UELS depends mainly on the pathologic findings. Undifferentiated embryonal liver sarcoma should be included in the differential diagnosis of mass in the liver, especially with well-defined heterogeneous imaging findings and normal AFP. Diagnosis and management should be made early as UELS is a potentially treatable tumor.

[Effect of preoperative transcatheter arterial chemo-embolization on activity of cell proliferation in Wilms; tumor].

OBJECTIVE: To investigate the effect of preoperative transcatherter arterial chemo-embolization (TACE) on the cell proliferation in Wilms; tumor. METHODS: Forty-one cases of Wilms; tumor diagnosed by histopathology were divided into two groups: in TACE group, 23 patients received TACE first and were operated 2 weeks later; in control group, 18 patients were operated alone. A comparative analysis of the pathological finding was made in two groups, and the expression of PCNA and VEGF in tumor tissue was detected by immunohistochemistry. RESULT: The degeneration of tumor tissue such as tumor cell necrotic, broken, disappearance occurred in 17 cases of TACE group and in 4 cases of control group, respectively (P <0.01). The expression of PCNA in TACE group and in control group was 1/23 (4.3 %) and 9/18(50.0 %), respectively (P <0.01). VEGF was expressed in 7/23 (30.4 %) of TACE group and 9/18 (50.0 %) of control group (P=0.283). CONCLUSION: TACE can significantly inhibit proliferation and enhance degeneration of Wilms; tumor cells.

[Surgical approaches to the correction of congenital penile curvature].

OBJECTIVE: To evaluate some currently used surgical approaches to the correction of congenital penile curvature. METHODS: Seventy-six patients with congenital penile curvature underwent surgical correction, of whom 67 were accompanied with hypospadias, 5 with epispadias and 4 with normal urethral meatus. The methods for straightening the phallus included 5-week preoperative hCG treatment, complete degloving of penile skin, release of periurethral fibrous bands extending proximally to the meatus, plication of dorsal or ventral tunica albuginea, and embedding of dermis and tunica vaginalis grafts. RESULTS: All the cases were followed up for 2 months to 2 years, and the mean follow-up time was 9.3 months. Satisfactory phallus straightening was achieved in 67 cases (88%), mild residual chordee remained in 6 (8%), which needed no reoperation for the time being unless warranted by follow-up, and relapse occurred in 3 (4%), which needed further operation. CONCLUSION: Most cases of congenital penile curvature can be corrected sufficiently with the above methods.

[The relationship between postoperative complication and pathological features of 324 patients with neuronal intestinal malformations].

OBJECTIVE: To investigate the relationship between the morphological features of different types of neuronal intestinal malformations (NIM) and their postoperative complications. METHODS: The data of morphological and clinical features of 324 cases with NIM were analyzed retrospectively. RESULTS: In all 324 patients, 210 cases were Hirschsprung's disease (HD), 38 intestinal neuronal dysplasia (IND), 45 mixed HD/IND, 8 hypoganglionosis, 22 combined HD/hypoganglionosis and 1 immaturity of ganglion cells. The percentages of normal neuron in bowel of different NIM were 88.1%, 24.4%, 18.4%, 4/8, 27.7% and 0/1 in HD, HD/IND, IND, hypoganglionosis, HD/hypoganglionosis and immaturity of ganglion cells respectively. There were totally 46 cases complicated with recurrent postoperative enterocolitis (EC). Incidence of recurrent postoperative EC in HD patients was 6.7% while in IND/HD and IND patients was 35.6% and 28.9%, respectively. Incidences of EC in cases with the residual IND margins and with the normal margins were 38.2% and 8.7%, respectively. Incidence of EC in cases with transanal endorectal pull-through procedure and with transabdominal procedure was 18.0% and 8.3%, respectively. Nine cases underwent another procedure because of severe persistent constipation or EC after operation, including 4 cases HD/IND, 1 case IND, 3 cases HD and 1 case HD/hypoganglionosis. CONCLUSIONS: Neuron distribution is inconsistent with pathology of NIM. Postoperative EC are rare in the patients only with isolated HD. Furthermore, margins with residual IND and transanal endorectal pull-through procedure are risk factors to recurrent EC. However, the extension of excision about IND is uncertain and need further study.

Mutation of RET proto-oncogene in Hirschsprung's disease and intestinal neuronal dysplasia.

AIM: To investigate the genetic relationship between Hirschsprung's disease (HD) and intestinal neuronal dysplasia (IND) in Chinese population. METHODS: Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,17 of RET proto-oncogene were amplified by polymerase chain reaction (PCR). The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism (SSCP) and sequencing of the positive amplified products was performed. RESULTS: Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G-->A (G667S), 2 frameshift mutations in exon 13 at nucleotide 18974 (18974insG), 1 missense mutation in exon 13 at nucleotide 18919 A-->G (K756E) and 1 silent mutation in exon 15 at nucleotide 20692 G-->A(Q916Q) were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G-->A and 1 silent mutation in exon 13 at nucleotide 18888 T-->G (L745L) were detected. No mutation was found in IND patients and controls. CONCLUSION: Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of RET proto-oncogene mutation is quite different between IND and HD in Chinese population. IND is a distinct clinical entity genetically different from HD.

[Treatment of advanced Wilms' tumor].

OBJECTIVE: To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery. METHODS: Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology. RESULTS: In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively. CONCLUSION: The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.

[Tubularized incised plate urethroplasty for children's hypospadias].

OBJECTIVE: To evaluate a new method of urethroplasty. METHODS: A total of 212 patients with hypospadias aged from 4 months to 9 years (glans type, n = 8; penis type, n = 181, penoscrotal type, n = 23) underwent tubularized incised plate urethroplasty. RESULTS: Followed up for 2 approximately 34 months, 188 cases obtained optimal functional and cosmetic results, 22 developed small fistulae and 16 were cured after a second operation 6 months later, 6 waited to be operated again, 2 cases of neourethra dehiscence were cured by second tubularized incised plate urethroplasty one year later. CONCLUSION: With its simplicity, low complication rate and reliable creation of a normal-appearing glanular meatus, tubularized incised plate urethroplasty can particularly be applied to boys with proximal hypospadias absent of severe penile curvature.

Polymerase chain reaction-single strand conformational polymorphism analysis of rearranged during transfection proto-oncogene in Chinese familial Hirschsprung's disease.

AIM: To investigate the relationship between mutations of rearranged during transfection (RET) proto-oncogene and Chinese patients with Hirschsprung's disease (HD), and to elucidate the genetic mechanism of familial HD patient at the molecular level. METHODS: Genomic DNA was extracted from venous blood of probands and their relatives in two genealogies. Polymerase chain reaction (PCR) products, which were amplified using specific primers (RET, exons 11, 13, 15 and 17), were electrophoresed to analyze the single-strand conformational polymorphism (SSCP) patterns. The positive amplified products were sequenced. Forty-eight sporadic HD patients and 30 normal children were screened for mutations of RET proto-oncogene simultaneously. RESULTS: Three cases with HD in one family were found to have a G heterozygous insertion at nucleotide 18,974 in exon 13 of RET cDNA (18,974insG), which resulted in a frameshift mutation. In another family, a heterozygosity for T to G transition at nucleotide 18,888 in the same exon which resulted in a synonymous mutation of Leu at codon 745 was detected in the proband and his father. Eight RET mutations were confirmed in 48 sporadic HD patients. CONCLUSION: Mutations of RET proto-oncogene may play an important role in the pathogenesis of Chinese patients with HD. Detection of mutated RET proto-oncogene carriers may be used for genetic counseling of potential risk for HD in the affected families.

[Clinicopathologic features of kaposiform hemangioendothelioma].

OBJECTIVE: To explore the clinicopathologic features of kaposiform hemangioendothelioma (KHE). METHODS: The clinicopathologic data were studied in three cases of KHE and review the literatures. RESULTS: Two cases were female and one was male. All cases occurred in infancy. Two tumor located in axillary chest wall and one in lumbar region. All of the three patients had Kasabach-Merritt syndrome. Histologically, the tumor was composed of spindle-shaped cells. in all cases nodular growth pattern was seen. Immunohistochemically, Neoplastic spindled cells expressed CD34 and CD31. Associated lymphangiomatosis was present in two cases. Two tumors were resected completely, one was resected partly. the follow-up period ranged from 6 months to 3 years, and all were alive. CONCLUSIONS: Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor that mainly occurred in early infancy. It is frequently complicated by Kasabach-Merritt syndrome, and it has features common to both capillary hemangioma and Kaposi sarcoma. The prognosis of KHE is determined by the size, location and the hemorrhage degree of vascular tumor. Better outcome might be achieved in patients with KHE of the skin and in the soft tissues under the skin. It appears that the main treated measure should be wide local excision.