The characteristics of mediastinal neuroblastoma.

The prognosis of mediastinal neuroblastoma has been reported to be better than for other neuroblastomas. The reason for this is however not clear. Furthermore, a comparison between mediastinal neuroblastoma and the other neuroblastomas has been rarely reported so far. In this study, the characteristics of mediastinal neuroblastoma (84 cases) are investigated and compared with those of other neuroblastomas (440 cases). Regarding clinical factors, the age distribution and the rate of cases detected at mass screening were similar in both groups. According to Evan's staging system, the rates of early stage (I, II) were 62% in the mediastinal neuroblastoma and 38% in the other neuroblastomas (p<0.001). Regarding the biological prognostic factors, a favorable histology based on Shimada's classification was found in 100% (35/35) of the mediastinal neuroblastoma cases and in 85% (112/132) of the other neuroblastoma cases (p<0.05). With regard to N-myc amplification, all of the examined 42 cases in mediastinal neuroblastoma had a N-copy number of less than 10 copies, while 32 of the examined 263 cases (12%) in the other neuroblastomas had an amplification of N-myc of more than 10 copies (p<0.05). The 5-year survival rates were 78% in the mediastinal neuroblastoma and 59% in the other neuroblastomas, respectively. Of the cases who underwent an incomplete resection of primary tumors in localized neuroblastoma, the 5-year survival rate of the mediastinal neuroblastoma cases was significantly more favorable than that of the other neuroblastomas. The majority of mediastinal neuroblastoma cases showed an early stage and favorable prognostic factors. It is likely that the clinical and biological prognostic factors of the tumor are therefore more closely correlated with the outcome of mediastinal neuroblastoma rather than the degree of the surgical resection. Regarding the treatment for mediastinal neuroblastoma, it is most important to evaluate the biology of the tumor after surgical resection.

Mass screening for neuroblastoma at 6 months of age: difficult to justify.

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS: These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.

Acetylcholinesterase (ACE) staining shows the abnormal innervation of a pulled-through rectum in a case of repaired anorectal malformation.

Abnormal innervation of the anorectum was noted in relation to anal incontinence in a case of repaired high-type anorectal malformation (ARM). A ten-year-old boy presented with anal incontinence after reconstructive surgery of ARM with a recto-urethral fistula. An anorectal manometrical examination revealed both an adequate tonus of the anal sphincter muscles and the absence of rectoanal reflex relaxation. And a barium enema showed a narrow region in the rectosigmoid colon, which was similar to that of Hirschsprung's disease (HD). Furthermore, an acetylcholinesterase (ACE) histochemical study of the rectal suction biopsies revealed an increased number of ACE-positive nerve fibers in the lamina propria mucosae and muscularis mucosae of the pulled-through colon. At the same time, however, some ganglia cells were also observed in the submucosa of the affected rectosigmoid colon and these cells could not be found in HD. Although the mechanism by which the abnormally innervated parasympathetic nerve fibers arose in the pulled-through colon remains unclear, this neuronal abnormality is considered to be the cause of anal incontinence in this case.

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

Management of traumatic pancreatic pseudocysts in children.

Eight children with pancreatic injuries after blunt abdominal trauma are presented. One patient with pancreatitis without complications was treated successfully with medication; seven (87.5%) developed pseudocysts, which resolved spontaneously with conservative treatment in four cases (57.1%). Non-resolving pseudocysts in 3 patients finally required surgical intervention. Pseudocysts that resolve spontaneously and those that require surgical intervention can be distinguished. The two groups showed different time sequences in both serum amylase values and pseudocyst size. Analyses of these clinical data revealed three factors with significant predictive value. On the basis of these findings, a new management strategy for traumatic pancreatic pseudocysts in children is proposed. The cyst is likely to resolve spontaneously in cases showing any two or more of the following factors: (1) cyst presentation after day 6; (2) maximum serum amylase below 1,600 IU/l; and (3) serum amylase below 600 IU/l on day 20. However, early surgical intervention is required in the presence of two or more of the following: (1) cyst presentation before day 4; (2) maximum serum amylase above 1,900 IU/l; or (3) serum amylase above 1,200 IU/l on day 20.

Complete disruption of the main pancreatic duct: a case successfully managed by percutaneous drainage.

The authors report on a 7-year-old boy who sustained blunt abdominal trauma on a bicycle handlebar. A large traumatic pancreatic pseudocyst developed, for which percutaneous external drainage under ultrasound guidance was performed. Both the catheter fistulogram and endoscopic retrograde cholangiopancreatogram showed complete disruption of the main pancreatic duct. During continuous external drainage, the pseudocyst disappeared. The drainage flow decreased gradually and ceased. The patient is well, with normal endocrine and exocrine pancreatic functions, 2 years after discharge.

CT manifestations of pediatric intrathoracic desmoid tumors.

We describe the CT findings in two pediatric cases of intrathoracic desmoid tumor arising from the chest wall. In both cases, CT showed heterogeneously enhanced intrathoracic masses with destruction of the ribs.

Yolk sac tumor in a case of testicular feminization syndrome.

A 17 month old who had been diagnosed as having testicular feminization syndrome (noted during inguinal herniorrhaphy) was operated on because of an abdominal mass that had a high serum level of alpha-fetoprotein. Histologically, the lesion was a yolk sac tumor. The alpha-fetoprotein level normalized within 2 months of the surgery, through the administration of adjunctive chemotherapy containing cisplatinum. The patient is disease-free 4 years postoperatively. When performing inguinal herniorrhaphy in a girl, the surgeon should be prepared to deal with testicular feminization syndrome. If gonadal neoplasm is deniable at the time of diagnosis, careful follow-up examinations are needed until completion of the development of secondary sex characteristics.

Vibrio trachuri sp. nov., a new species isolated from diseased Japanese horse mackerel.

A new species, Vibrio trachuri sp. nov., was isolated from the cultured Japanese horse mackerel (Trachurus japonicus). These Vibrio were Gram negative, motile rods and formed yellow colonies on BTB teepol and TCBS plate, turned TSI medium to yellow and was sensitive to 150 microM O/129 (2,4-diamino-6,7-diisopropyl pteridine phosphate) like Listonella anguillarum which has been described as Vibrio anguillarum. However, the results of VP test and decarboxylation of lysine or dihydrolation of arginine suggested that these Vibrio are rather closely related to V. parahaemolyticus. DNA similarity determined by the microplate hybridization technique revealed that these Vibrio are genetically quite distant from Listonella anguillarum or V. parahaemolyticus and rather close to V. harveyi, although there was no Vibrio species which had more than 70% similarity value. From these results we propose to nominate Vibrio trachuri sp. nov. for this new Vibrio species.

Rapid and sensitive PCR detection of Vibrio trachuri pathogenic to Japanese horse mackerel (Trachurus japonicus).

A polymerase chain reaction (PCR) method was performed for rapid and sensitive detection of pathogenic Vibrio trachuri isolated from cultured Japanese horse mackerel. A set of primers was selected from the base sequence of the Pst I fragment of T9210 chromosomal DNA and used for PCR detection of T9210. This PCR specifically amplified the DNAs from V. trachuri T9210, T9213, and T9216 but not of those other bacterial strains. PCR using a Pst I-1 primer set made it possible to detect 100 fg of T9210 DNA. The PCR method reported here may be useful for detection and identification of V. trachuri pathogenic to Japanese horse mackerel.

Management of colorectal polyps in children.

Forty-two patients each with a colorectal polyp have been treated in our hospital over the past 10 years. In twenty-two cases the polyps were noted in the rectum, nine in the sigmoid colon, seven in the descending colon and four in the transverse colon. Each patient had only one polyp. Hematochezia was the main symptom in 29 patients, prolapse of the polyp from the anus in 10, abdominal pain due to intussusception in two and no symptoms were observed in one. Auto-amputation of the polyp was considered to have occurred in five patients. Twelve rectal polyps were resected from a transanal operation, and another 25 polyps were removed endoscopically with electric cautery. We have had no experience of endoscopic complications such as bleeding or perforation. A histological examination revealed an adenoma in one patient. Other polyps were non-neoplastic and were classified as juvenile, inflammatory and hyperplastic in 30, two and four patients, respectively. There have been no recurrences of polyps to date.

Different genomic and metabolic patterns between mass screening-positive and mass screening-negative later-presenting neuroblastomas.

The mass screening of neuroblastoma has been undertaken in Japan by measuring urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) in all infants at the age of 6 months. This program may not only improve the prognosis but also provide important insights into the biology and evolution of human neuroblastoma. The authors studied and discuss the clinical significance of the N-myc oncogene, catecholamine metabolism, and other tumor markers in 43 patients with neuroblastoma who underwent the urinary screening test at 6 months of age. Thirty patients were found by the screening, and 13 were negative at the screening but later had a tumor. In the former group, the tumors were mostly in early stages (Stage I, 12; Stage II, 11; Stage III, seven), no amplification of N-myc was observed, and all patients are alive without disease. Although two patients whose urine at the screening showed elevated VMA and HVA levels and accidentally were not treated for 13 and 17 months, there was no change in the values of VMA and HVA during that time. However, in the latter group, the tumors were mostly in advanced stages (Stage I, one; Stage III, four; Stage IV, eight) and N-myc amplification was observed in seven of 13. Only two of these 13 are alive without disease. The age at diagnosis of the screening-negative group was 23 months compared with 8 months in the patients identified by screening, and the pattern of catecholamine metabolites in the screening-negative group tended to be dopaminergic with a low VMA-HVA ratio, especially in cases with N-myc amplification. These data suggest that the screening-positive patients with neuroblastoma may have favorable characteristics, and the biology of these tumors may be different from that of screening-negative later-presenting tumors. They also suggest that there may be at least two distinct subsets of neuroblastoma. For the early detection of the poor prognostic neuroblastomas, the measurement of urinary dopamine with VMA and HVA at later ages, such as 1 to 2 years, should be considered.

Remnants of urachus in infants and children--the problems of diagnosis and treatment.

A total of 17 cases of remnants of urachus were examined between 1981 and 1989, including 2 cases of patent urachus, 5 of urachal cyst, 9 of urachal sinus, and 1 of urachal diverticulum. A long urachal sinus was considered to be caused by the self-destruction of a cyst. While patent urachus was diagnosed in neonates with urine discharge from the umbilicus, cysts or sinuses accompanied by infection were more often found in older children. Imaging of the burrows was diagnostic in 8 out of 11 cases, ultrasound examination in 9 out of 12, and CT examination in all of 3 cases. Since this condition is frequently accompanied by malformations of the urinary system, attention must be paid to locating the accompanying anomalies. Although primary extraction was performed in 13 cases, the primary treatment of cases with highly infected cysts should be drainage, followed by secondary extraction. Furthermore, caution must be exercised to avoid hemorrhage in cases with dilation of the umbilical artery.

An infantile case of infiltrating lipoma in the buttock.

This paper presents a rare case of infantile infiltrating lipoma in the buttock. The usefulness of magnetic resonance imaging of the tumor in the follow-up study is discussed.

The fate of swallowed button batteries in children.

The method of treatment and fate of 41 button batteries ingested by 34 children were analysed; 31 batteries were in the stomach and 10 beyond the pylorus. In 31 batteries situated in the stomach, removal by magnet tube technique was attempted in 30 batteries, 25 being successfully taken out, while 5 failed passing through the pylorus at the duodenum. One was removed endoscopically, since a magnet tube was not available. The remaining 10 batteries in 10 children were found at different levels from the duodenum to the rectum. In addition, 5 batteries were pushed down from the stomach during magnet tube removal. These 15 batteries, located in the intestine were excreted during 35 hours. In contrast to other asymptomatic foreign bodies that are allowed to pass through the GI tract spontaneously, we feel that button batteries should be removed by magnet tube technique to avoid complications such as GI tract perforation with associated bleeding, possible mercury poisoning and burns. Magnet tube removal is a simple and safety method requiring neither anaesthesia nor admission.

Management of pediatric patients who have swallowed foreign objects.

The clinical management of children who have swallowed foreign bodies presents a great challenge for both pediatricians and pediatric surgeons. Our 7-year experience of treating 141 patients with a history of foreign body ingestion is reported. In 114 patients, there were 122 foreign bodies present in areas from the esophagus to the rectum, as located by plain chest and abdominal x-ray examination. In two patients, a plastic toy and the plastic cap of a razor were passed with stool a few days later. In the remaining 25 patients, nothing was found. In babies under one year of age, button batteries were the most commonly swallowed foreign bodies, while coins were the most frequently swallowed objects in children over the age of three years. Seventeen foreign bodies in the esophagus were removed: seven by balloon catheter, four endoscopically, and one by a magnet tube. Four were dislodged into the stomach. Twenty nine of the 78 items present in the stomach were button batteries and 23 of the items were removed using a magnet tube. One was removed endoscopically and 5 batteries that had moved beyond the pylorus were excreted within 48 hours. Twenty four coins in the stomach were managed conservatively. Surgical intervention was required in two patients; one patient had a previous history of pyloromyotomy, and a magnet tag measuring 1.5 cm in diameter did not pass through the pylorus for 7 weeks. The other patient had swallowed a sewing needle that moved into the descending colon and abdominal pain ensued.

Heterogenous expression of endothelial cell markers in infantile hemangioendothelioma. Immunohistochemical study of two solitary cases and one multiple one.

Three cases of infantile hemangioendothelioma were immunohistochemically studied with the use of antibodies against von Willebrand factor (vWF), Ulex europaeus I lectin (UEA I), vimentin, thrombomodulin (TM), and actin, as endothelial cell (EC) markers. Because of a broad variety of histologic features, the growth pattern of the tumor cells was subclassified into the following four subtypes: capillary, sinusoidal, cavernous, and myxomatous parts. The solitary tumor from patients 1 and 2 was composed of these four components, but the multiple tumor in the patient 3 consisted of capillary and sinusoidal parts. Immunohistochemically, vWF and vimentin were dominantly expressed in the ECs of the cavernous and myxomatous parts. UEA I had strongly positive results in all histologic types, except the myxomatous part. Expression of vWF and vimentin in neoplastic EC suggests that functional differentiation of the tumor tissue occurs in the myxomatous and cavernous parts and may be related to the spontaneous regression of the infantile hemangioendothelioma.

Improved survival rates in children over 1 year of age with stage III or IV neuroblastoma following an intensive chemotherapeutic regimen.

Combined chemotherapeutic regimens of (1) cyclophosphamide (40 mg/kg x two days), (2) cisplatinum (20 mg/m2 x five days) plus VM-26 (100 mg/m2), and (3) Adriamycin (60 mg/m2) plus DTIC (250 mg/m2 x five days) were prescribed for 42 Japanese children greater than 1 year of age with stage III or IV neuroblastoma. The protocol was separated into three forms (A, B, and C) from the combination pattern of three such high-dose courses. The cumulative survival rates for those with stages III and IV 48 months after initiation of therapy were 76.2% and 20.1%, respectively, and the overall rate was 36.7%. The tumor disappeared during the course of treatment in 25 of 42 children (59.5%). The 48-month survival rate was superior in patients greater than 5 years of age than younger patients (P less than .01). Even in patients with a tumor originating in the suprarenal region, the 48-month survival rate was 30.5%. Among 12 patients in whom the N-myc oncogene was measured, one of five with one to ten copies of amplification died, whereas all seven with greater than ten copies died or had a recurrence. Thus, the present chemotherapeutic regimens, in particular alternate administration of each high-dose course, considerably improved the survival of patients with stage III neuroblastoma. More aggressive protocols are needed for those with stage IV neuroblastoma who are greater than 1 year of age, particularly in those with an amplified N-myc oncogene.