Paratesticular rhabdomyosarcoma in children and adolescents-Outcome and patterns of relapse when utilizing a nonsurgical strategy for lymph node staging: Report from the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumour 89 and 95 studies.

PURPOSE: To report the results from International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors studies (MMT 89 and 95) of males with nonmetastatic paratesticular rhabdomyosarcoma. METHODS: From 1989 to 2003, 159 patients were included. Radical inguinal orchidectomy was recommended, but retroperitoneal lymph node (LN) assessment was based on imaging alone. The treatment was stratified by stage (SIOP tumor-node-metastasis staging system) and histology. RESULTS: Median age at presentation was 5.6 years (range 0.3-17.6) and 120 patients were of <10 years (75%). Patients ≥10 years had tumors of >5 cm more frequently compared to patients of <10 years (54% vs. 22%, P = 0.0004). The 5- year overall and progression-free survivals were 94% and 83%, respectively. Seventy-eight percent of relapses occurred in the retroperitoneal LN. Thirty-one percent of stage N0 patients of age ≥10 years developed node relapse, compared with 8% of N0 patients aged <10 years (P = 0.0005). CONCLUSIONS: Older patients with paratesticular rhabdomyosarcoma have a significant risk of LN relapse. These results support a surgical approach to LN staging in this subgroup of patients.

Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology--SIOP Malignant Mesenchymal Tumor 89.

PURPOSE: To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy. PATIENTS AND METHODS: Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage. RESULTS: Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy. CONCLUSION: Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).

Treatment of children with nonmetastatic paratesticular rhabdomyosarcoma: results of the Malignant Mesenchymal Tumors studies (MMT 84 and MMT 89) of the International Society of Pediatric Oncology.

PURPOSE: To report the results of the Malignant Mesenchymal Tumors studies (MMT 84 and 89) of the International Society of Pediatric Oncology (SIOP) in males with nonmetastatic paratesticular rhabdomyosarcoma. PATIENTS AND METHODS: From 1984 to 1994, 96 males were treated in SIOP protocols. Radical inguinal orchidectomy was recommended, but initial retroperitoneal lymph node dissection was not performed. Disease was staged according to the SIOP tumor-node-metastasis staging system. Treatment was stratified by stage. In the MMT 89 study, males with completely resected tumors at diagnosis received less chemotherapy (vincristine and dactinomycin) than patients in the MMT 84 study (ifosfamide, vincristine, and dactinomycin). RESULTS: Median age at diagnosis was 65 months. Thirty-one tumors were larger than 5 cm, and 13 males were older than 10 years with a tumor larger than 5 cm. At a median follow-up of 7 years, 87 patients were alive; 79 were in first complete remission and eight were in second complete remission. Relapse occurred in 16 patients (17%). At 5 years, the overall survival (OS) rate was 92%, with an event-free survival (EFS) rate of 82%. OS and EFS were significantly worse for males with tumors greater than 5 cm and for males older than 10 years at diagnosis. CONCLUSION: Males with paratesticular RMS have an excellent prognosis except for a selected group of patients older than 10 years or with tumor greater than 5 cm. Intensified chemotherapy incorporating alkylating agents for this subgroup may be preferred to the use of systematic lymphadenectomy to improve survival while minimizing the burden of therapy.

Neonatal sarcoma.

Though some neonatal soft tissue tumours have identical biology and natural history to the same tumours in older children many tumours in this age group have a distinct and more favourable behaviour and mandate less aggressive treatment; many being curable by surgical resection alone. Accurate histological diagnosis is essential. In those instances where adjunctive chemotherapy is indicated it is essential to modify paediatric chemotherapy dosages and regimes to minimise the risk of serious adverse effects. Radiotherapy should be avoided due to its severe adverse effects on growth and the risk of inducing secondary malignancies.

Polytetrafluoroethylene patch repair of a saccular abdominal aortic aneurysm in a 5-year-old boy.

A 5-year-old boy presented with acute abdominal pain and was subsequently found to have an abdominal aortic aneurysm. The aetiology remains obscure. Repair was accomplished with a PTFE patch and he remains well on follow up.

Intestinal alpha beta T cells differentiate and rearrange antigen receptor genes in situ in the human infant.

Intestinal Ag exposure during neonatal life influences appropriate adult immune responses. To define the mechanisms shaping the T cell repertoire during this period, we examined T cell differentiation and receptor diversity in the intestine of human infants. Developmental phenotypes of intraepithelial and lamina propria intestinal T cells from infants aged 1 day to 2 years were assessed ex vivo by flow cytometry and in situ by triple-fluorescent immunohistochemistry. Gene recombination-specific enzymes were assessed by PCR. TCR beta-chain V region gene diversity was determined by sequencing. Several different early lineage T cell populations were present neonatally: CD3(+)4(-)8(-) T cells were present at birth and numbers decreased during the neonatal period; CD3(+)4(+)8(+) T cells were present in low numbers throughout infancy; and CD3(+)4(+)8(-) or CD3(+)4(-)8(+) T cells increased with age. Very early lineage T cells, CD3(-)2(-)7(+) and CD3(-)2(+)7(+), were present neonatally, but were essentially absent at 1 year. Most lamina propria T cells differentiated rapidly after birth, but maturation of intraepithelial T cells took place over 1 year. Intestinal samples from infants less than 6 mo old contained transcripts of T early alpha and TdT, and 15 of 19 infant samples contained mRNA for RAG-1, some coexpressing RAG-2. TCR beta-chain repertoires were polyclonal in infants. Immature T cells, pre-T cells, and genes involved in T cell recombination were found in the intestine during infancy. T cell differentiation occurs within the neonatal human intestine, and the TCR repertoire of these developing immature T cells is likely to be influenced by luminal Ags. Thus, mucosal T cell responsiveness to environmental Ag is shaped in situ during early life.