Clinical characteristics and the prognosis of rhabdomyosarcoma - a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

AIM: There have been no nationwide group studies for patients with rhabdomyosarcoma in Japan. This study aims to assess the actual state of treatments and their outcome. PATIENTS AND METHODS: From 1982 to 1996, 79 rhabdomyosarcomas were registered by the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area. The prognostic factors and treatments were assessed based on the 5-year survival rate. The staging was done according to the Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification. RESULTS: The 5-year survival rate for all patients was 39.1 %. The survival rates for each factor were as follows, according to 1) group; 77.8 % for Group I, 51.9 % for Group II, 33.7 % for Group III, and 20.2 % for Group IV; 2) primary site: 56.3 % for the head and neck, 43.8 % for the parameningeal region, 12.5 % for the extremity, 58.3 % for the genitourinary region, and 30.5 % for the others; 3) histology: 35.8 % for the embryonal type, 36.8 % for the alveolar type. CONCLUSIONS: Altogether, the outcome of this study was poor. To improve outcomes, a new nationwide group study for rhabdomyosarcoma, which we belong to, has just started in Japan.

Improved survival outcome for hepatoblastoma based on an optimal chemotherapeutic regimen--a report from the study group for pediatric solid malignant tumors in the Kyushu area.

BACKGROUND/PURPOSE: The survival outcome for patients with hepatoblastoma normally depends on the resectability of the tumor. In Japan, the pre and/or postoperative chemotherapy protocol using a combination of cisplatin (CDDP) and tetrahydropyranyl-Adriamycin (THP-ADR) has been the standard treatment since 1991. This study aims to assess exactly what influence the establishment of this chemotherapy protocol has had on both the tumor resectability and the outcome of patients with hepatoblastoma. METHODS: From 1982 to 1997, 60 patients with hepatoblatoma were treated in the Kyushu area, Japan. Based on the pretreatment extent of disease (PRETEXT), the outcome and tumor resectability were compared between group A (1982 to 1990, n = 27, PRETEXT I:5, II:8, III:6, IV:8) and group B (1991 to 1997, n = 33, PRETEXT I:9, II:9, III:5, IV:10). RESULTS: The 5-year survival rates (group A and group B) were 33% and 73% for all cases (P <.01), 100% and 89% for PRETEXT I, 38% and 89% for II (P <.05), 17% and 80% for III (P <.01), and 0% and 40% for IV (P <.01), respectively. The 5-year survival rates for patients with metastases were 0% for group A (n = 5) and 57% for group B (n = 7; P <.01). The rates of a complete resection of primary tumor were 48% for group A and 67% for group B. In particular, a significant difference was found regarding the complete resection rate between groups A and B in the patients with PRETEXT III (17% for group A and 80% for group B; P <.01). In the patients with an incomplete tumor resection (14 for group A, 11 for group B), the 5-year survival rates were 0% for group A and 45% for group B (P <.01). CONCLUSIONS: The optimal chemotherapeutic regimen of CDDP and THP-ADR was thus found to greatly contribute to the improved survival rate of hepatoblastoma patients. Preoperative chemotherapy resulted in an increased resectability of the tumor, whereas postoperative chemotherapy played an important role in the increased cure rate of cases with either an incomplete tumor resection or metastasis. However, refractory cases with PRETEXT IV or metastasis may still require the development of an even more effective treatment modality, including the use of blood stem cell transplantation.

Characteristics and surgical outcomes of paediatric retinal detachment.

PURPOSE: To report the clinical features and surgical and visual outcomes of rhegmatogenous retinal detachment (RRD) in the paediatric population. METHODS: A retrospective review of children (aged 0-15 years) who underwent primary surgical repair for RRD at the Hiroshima University Hospital between 1988 and 2001. RESULTS: In all 53 eyes of 49 patients were identified; paediatric RRD accounted for 3.1% of 1779 eyes with RRD operated on during this period. The causes of RRD included blunt trauma (27%), myopia (25%), idiopathic (20%), familial exudative vitreoretinopathy (13%), and others. Among 55 eyes, 12 (22%) already had proliferative vitreoretinopathy (PVR) of grade C or D preoperatively. The median initial visual acuity (VA) was 0.3. Retinal reattachment was achieved with a single operation in 78%. Final retinal reattachment was achieved in 87%. Retinal reattachment rates with and without PVR were 42% and 100%, respectively (P<0.01). Median final VA was 0.7. Final VA was > or =0.1 in 73% and > or =0.5 in 53%; four eyes had a final VA of no light perception. The presence of preoperative PVR (P=0.03) and the initial VA (P<0.0001) significantly affected final VA. CONCLUSIONS: Paediatric RRD is characterised by a delay in diagnosis, as evidenced by the high rate of PVR at presentation. Retinal reattachment was adversely affected by the presence of PVR. Final VA correlated with the initial VA and was significantly affected by preoperative PVR. Early diagnosis may improve the visual prognosis of paediatric retinal detachment.

Malignant germ cell tumors: clinical characteristics, treatment, and outcome. A report from the study group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

PURPOSE: This study aims to assess the prognostic factors and optimal treatments for malignant germ cell tumors (MGCT) in childhood. METHODS: Among 117 MGCT, the clinical features were analyzed. Regarding the histology, there were 89 embryonal carcinomas, 13 dysgerminomas, 4 choriocarcinomas, and 11 others. The prognostic factors and treatments were assessed based on the 5-year survival rate. RESULTS: (1) Stage: 100% for stage I (n = 54), 75.0% for stage II (n = 4), 67.3% for stage III (n = 14), and 54.8% for stage IV (n = 33); Unknown: n = 12. (2) Primary site: 93.4% for the testis (n = 52), 86.7% for the ovary (n = 31), 56.9% for the sacrococcygeal (n = 21), and 60.6% for others (n = 12); unknown: n = 1. (3) Surgical intervention for primary tumor: 100% for stage I with a complete resection (n = 53), 78.4% for stage III, IV with a complete resection (n = 26), and 33.3% for stage III, IV with an incomplete resection (n = 21). (4) Type of chemotherapy for the stage III and IV: 83.9% for the PVB (cisplatin, vinblastin, bleomycin; n = 13), 66.7% for the VAC (vincristine, actinomycin D, cyclophosphamide; n = 6), and 47.1% for other regimens (n = 25). CONCLUSIONS: An early stage, a diagnosis under 1 year of age and a primary site in the gonads were favorable prognosis factors, whereas histologic findings of choriocarcinoma and liver or lung metastasis were unfavorable. Radical complete resection alone is a sufficient treatment for localized MGCT. The PVB regimen is optimal chemotherapy for advanced MGCT; however, high-risk cases still may require more aggressive treatment.

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification.

BACKGROUND/PURPOSE: In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens. METHODS: Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens. RESULTS: The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01). CONCLUSIONS: These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.

Capillary hemangioma of the liver with Kasabach-Merritt syndrome in a neonate: report of a case.

Hepatic hemangiomas are benign tumors, and therefore minimally invasive treatment such as irradiation or steroid therapy is often recommended. However, in patients who have a hemangioma complicated by Kasabach-Merritt syndrome, surgical intervention should also be considered because of its confirmative therapeutic effect. We present herein the case of a 32-day-old male infant in whom a huge hepatic hemangioma associated with Kasabach-Merritt syndrome was treated by surgical intervention together with strong antidisseminated intravascular coagulation therapy.

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.

Biliary tract duplication accompanied by choledocholithiasis: report of a case.

Duplication of the biliary tract is extremely rare. In fact, to the best of our knowledge, only four previous reports of pediatric patients with this disease have been documented in the Japanese literature. This anomaly was diagnosed by perioperative endoscopic retrograde cholangiopancreatography (ERCP) in three of these patients, and incidentally during surgery for congenital biliary dilatation in the other one. We report herein a case of biliary tract duplication which was diagnosed by T-tube cholangiography, only in the oblique view, after cholecystectomy and choledochotomy with T-tube drainage. The patient was a 13-year-old girl who was initially diagnosed as having choledocholithiasis based on the results of preoperative and intraoperative cholangiography; however, a postoperative T-tube cholangiography revealed residual stones. At this point, duplication of the biliary tract was diagnosed only in the first oblique view. Reoperation was carried out 26 days after the first operation. The biliary tract was dissected completely from the pancreaticobiliary junction to the left and right hepatic ducts in the porta hepatis and found to be duplicated from the level of porta hepatis to the suprapancreatic area. We report our experience of this case, followed by a discussion on the relevant literature.

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.

Involvement of CD8+ RT1.B+ and CD4+ RT1.B+ cells of cervical lymph nodes in the immune response after corneal transplantation in the rat.

Graft rejection reactions have been observed with concomitant lymphocyte infiltrations after allogenic corneal transplantation, although the cornea is considered to be relatively protected from the systemic immune response. In order to characterize the lymphocytes that accumulate in cervical lymph nodes following transplantation, we used a model of orthotopic penetrating keratoplasty in inbred rats. After grafting, the time course of the pathological scoring was monitored, and subpopulations of CD4+ RT1.5+ and CD8+ RT1.B+ cells were analyzed in the cells harvested from the cervical lymph nodes. The number of CD8+RT1.B+ cells increased 1 week after grafting, reaching the maximum at 3 weeks; whereas CD4+ RT1.B+ cells were induced 1 week after the grafting and remained constant during the next 3 weeks. There were four times as many CD4+ RT1.B+ cells as CD8+ RT1.B+ cells 1 week after grafting when there was no rejection. Therefore, it appears that CD8+RT1.B+ and CD4+RT1.B+ cells in the cervical lymph nodes do participate in ocular immunologic responses.

Ultrasound biomicroscopy in the diagnosis of persistent hypotony after vitrectomy.

PURPOSE: To describe a case of persistent hypotony after an otherwise successful vitreous surgery for epiretinal membrane, in which ciliochoroidal detachment was detected by ultrasound biomicroscopy but not by ophthalmoscopy. METHOD: We used ultrasound biomicroscopy to determine the cause of persistent postoperative hypotony. RESULTS: Ultrasound biomicroscopy clearly disclosed ciliochoroidal detachment. In an attempt to resolve ciliochoroidal detachment, we performed vitrectomy and fluid-gas exchange combined with diathermy around the sites of sclerotomy. Postoperatively, the regression of ciliochoroidal detachment was confirmed by ultrasound biomicroscopy. CONCLUSIONS: Using ultrasound biomicroscopy, we were able to visualize ciliochoroidal detachment and its regression clearly, which we had not observed during ophthalmoscopy.

Postoperative posterior retinal holes after pars plana vitrectomy for primary retinal detachment.

BACKGROUND: Although retinal breaks occur frequently during vitrectomy, the postoperative occurrence of new retinal holes close to the vascular arcade after vitrectomy for rhegmatogenous retinal detachment rarely has been reported. METHODS: Three patients with rhegmatogenous, retinal detachment were treated by vitrectomy. More than 49 days after vitrectomy, posterior retinal holes with no retinal detachment occurred halfway between the vascular arcade and the chorioretinal scar around the extrusion hole or the primary retinal tear. RESULTS: These new holes were effectively managed with photocoagulation. CONCLUSION: New hole formation could be caused by the technique of the internal drainage, the contraction of the photocoagulation scar, or epiretinal membrane contraction. Another possibility is that new holes occur through two opposite tangential traction contractile forces: one induced by the contraction of the photocoagulation scar, the other caused by the contraction of the premacular cortical vitreous attached to the vascular arcade.