A phase II JN-I-10 efficacy study of IDRF-based surgical decisions and stepwise treatment intensification for patients with intermediate-risk neuroblastoma: a study protocol.

BACKGROUND: Few clinical trials have been reported for patients with intermediate-risk neuroblastoma because of the scarcity of the disease and the variety of clinical and biological characteristics. A multidisciplinary treatment that consists of multidrug chemotherapy and surgery is expected to lead to a good prognosis with few complications. Therefore, a clinical trial for patients with intermediate-risk tumors was designed to establish a standard treatment that reduces complications and achieves good outcomes. METHODS: We planned a prospective phase 2, single-arm study of the efficacy of image-defined risk factors (IDRF)-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. For the localized tumor group, IDRF evaluations will be performed after each three-course chemotherapy, and surgery will be performed when appropriate. For patients with metastatic tumors, a total of five chemotherapy courses will be performed, and primary lesions will be removed when the IDRF becomes negative. The primary endpoint is 3-year progression-free survival rate, and the secondary endpoints include 3-year progression-free survival rates and overall survival rates of the localized group and the metastasis group and the incidence of adverse events. From international results, 75% is considered an appropriate 3-year progression-free survival rate. If this trial's expected 3-year progression-free survival rate of 85% is statistically greater than 75% in the lower limit of the 95.3% confidence interval, with an accuracy 10% (85 ± 10%), both groups require more than 65 patients. DISCUSSION: This study is the first clinical trial on the efficacy of IDRF-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. We expect that this study will contribute to the establishment of a standard treatment for patients with intermediate-risk neuroblastoma. TRIAL REGISTRATION: UMIN000004700, jRCTs051180203; Registered on December 9, 2010.

A novel PAX3 rearrangement in embryonal rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft tissue tumor seen in children and young adults, and it can be classified into 2 major histological subtypes, alveolar and embryonal. In the alveolar subtype, 2 recurrent chromosomal translocations, t(2;13)(q35;q14) and its variant t(1;13)(p36;q14), have been identified as the specific cytogenetic abnormalities. These translocations produce the PAX3-FOXO1 and PAX7-FOXO1 fusion genes, respectively. In the embryonal subtype, however, no recurrent chromosomal abnormalities have been identified. In this study, we analyzed the complex chromosomal translocation in one case with embryonal rhabdomyosarcoma by means of spectral karyotyping (SKY) and identified a novel translocation involving chromosome band 2q35, which is the locus of PAX3 gene. Furthermore, we identified the novel PAX3 rearrangement using fluorescence in situ hybridization (FISH) analysis. Additional identification of the partner gene may help disclose the molecular mechanism of the development of this embryonal subtype.

Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy.

Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans cell histiocytosis (LCH), usually presents in young children as spontaneously regressing cutaneous lesions. However, the systemic type of JXG is difficult to treat in newborn infants, and fatal cases have been reported. In the patient described here, solid masses were discovered by fetal sonography during the 38th gestational week. At birth she had multiple tumors on the back, cheek, and hip as well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy. Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with systemic JXG by histopathologic findings of the hip mass. The LCH-based multiagent chemotherapy including cytarabine, vincristine, methotrexate, and prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and is currently doing well as a normally developing 2-year-old.

Results of retroperitoneal lymphadenectomy in the treatment of abdominal neuroblastoma.

HYPOTHESIS: Adequate locoregional surgical treatment prevents local relapse of abdominal neuroblastoma. DESIGN: A retrospective review of a consecutive series of patients who underwent surgical excision for abdominal neuroblastoma. SETTING: University hospital. PATIENTS: Forty-seven patients with abdominal neuroblastomas whose primary tumor site was restricted to the adrenal gland or the adjoining sympathetic ganglia. INTERVENTION: Complete excision of the primary tumor and retroperitoneal lymphadenectomy. MAIN OUTCOME MEASURES: Surgical intervention, postoperative complications, survival, and local recurrence. RESULTS: The average duration of surgery was 5 hours 28 minutes; the mean intraoperative blood loss was 27.7 g/kg of body weight. We had no intraoperative major complications leading to visceral insufficiency or perioperative deaths. The following 15 postoperative complications were observed in 12 patients; these complications included diarrhea (8 patients), renal atrophy (3 patients), intestinal obstruction (2 patients), chylous ascites (1 patient), and wound infection (1 patient). The mean follow-up period for the entire patient population was 8.5 years. All 30 patients with Evans stage I, II, III, or IV-S and 8 of the 17 patients with Evans stage IV were alive without evidence of disease. Eight patients died of progressive disease; 1 died of cytomegalovirus infection. No local recurrence was detected within the lymphadenectomy field in any of the patients. CONCLUSION: Complete excision of the primary tumor and retroperitoneal lymphadenectomy can be done safely and provides excellent locoregional control for patients with abdominal neuroblastoma.

Cyclooxygenase-2 expression in the gallbladder of patients with anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is frequently associated with gallbladder carcinoma. Cyclooxygenase (COX) is a key enzyme in the synthesis of prostaglandins, and 2 isoforms have been identified: COX-1 and COX-2. Overexpressed in several precancerous lesions, the COX-2 isoform is thought to be involved in chronic inflammation and carcinogenesis. To determine whether COX expression correlates with biliary histology in patients with AAPBD, the authors investigated the expression of COX-1 and COX-2 in the gallbladder of patients with AAPBD. METHODS: Gallbladder specimens were obtained from 31 patients with AAPBD (mean age, 5.0 years), and from 7 patients with other hepatobiliary diseases as controls (mean age, 2.0 years). The authors quantified levels of COX-1 and COX-2 by the extent and intensity of staining after immunohistochemistry using anti-COX-1 and anti-COX-2 antibodies. RESULTS: Mucosal hyperplasia of the gallbladder was identified in 18 of 31 patients with AAPBD. The gallbladder epithelium of all specimens expressed COX-2. Marked expression of COX-2 was noted in specimens with mucosal hyperplasia, the mean immunoreactive score of which was significantly higher than that of specimens without mucosal hyperplasia (7.50 +/- 1.86 and 5.62 +/- 2.26, respectively; P =.021). In contrast, COX-1 expression was not detected in any specimen. CONCLUSIONS: Enhanced expression of COX-2 is related to mucosal hyperplasia of the gallbladder in patients with AAPBD. Thus, COX-2 may play a regulatory role in the proliferation of gallbladder epithelium, which may lead to carcinogenesis in patients with AAPBD.