[Malignant primary tumors of the liver in childhood]. / I tumori maligni primitivi del fegato in età pediatrica. Esperienza di un singolo centro.

Twenty-one children (16 males, 5 females) with malignant primary hepatic tumors were admitted to the Pediatric Clinic of the University of Bologna between June 1973 and July 2001. The diagnosis was hepatoblastoma (HBL) in 16 cases; hepatocellular carcinoma (HCA) in 3 cases; undifferentiated sarcoma in 1, malignant rhabdoid tumour of the liver in 1. Median age at diagnosis was 1.8 year (1 mounth-13 years). As to intrahepatic tumor's extension, patients were classified in groups (from I to IV) according to International Society of Pediatric Oncology staging. 2 patients were ascribed to group I; 9 to group II; 9 to group III and I to group IV. At diagnosis 3 pts presented lung metastases. Seventeen patients (81%) were treated with surgery, in 11 cases as first approach to the tumor. In 10 patients, initially with unresesectable tumor, chemotherapy was started first. Drugs used were mostly Cisplatinum or Carboplatinum with Doxorubicin. Sussequently 6 patients were submitted to surgery. At a median follow up of 12.5 years, 52.3% of patients is alive without disease. This percentage rises to 58% taking into consideration only HBL and HCA cases (alive 11/19). We conclude that excluding metastases at diagnosis (3 deaths), the main prognostic factor is resectability and radical surgery: in our experience 4 patients with unresectable tumor died, as 2 patients with microscopical residual after surgery.

Italian Cooperative Study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience.

BACKGROUND: In 1991, the Italian Association for Pediatric Hematology-Oncology and the National Council of Research (CNR) initiated an Italian Cooperative Study (SE 91-CNR Protocol) with the main objective of improving the overall survival (SUR) and the event free survival (EFS) of children and young adults with localized Ewing sarcoma and primitive neuroectodermal tumors of bone compared with a previous study (IOR/Ew2 Protocol). METHODS: Between November 1991 and November 1997, 165 patients were enrolled in this study, 160 of whom were evaluable. The patients were treated with a multimodal approach characterized by intensified chemotherapy, hyperfractionated and accelerated radiation therapy, and the addition of ifosfamide and etoposide to standard chemotherapy with vincristine, actinomycin-D, doxorubicin, and cyclophosphamide. RESULTS: After a median follow-up of 37 months, 126 of the 160 evaluable patients remained free of disease recurrence. Thirty-one patients developed a disease recurrence (20 with disseminated disease). CONCLUSIONS: The 3-year SUR and EFS rates found in the current study (83.6% and 77.8%, respectively) may be considered satisfactory. Only age at diagnosis < or =14 years and a good histologic response appeared to affect the outcome of patients with localized Ewing sarcoma positively. These results appear to demonstrate the efficacy of the addition of ifosfamide in induction chemotherapy to four-drug standard combination chemotherapy, as confirmed by the improved outcome in terms of 3-year EFS reported in the SE 91-CNR Protocol compared with the IOR/Ew2 Protocol (77.8% vs. 60.7%). In addition, the better outcome also could be explained by the change in treatment strategy with a trend toward the use of more surgery than radiation therapy compared with the authors' previous protocol.

Predictive factors of histological response to primary chemotherapy in Ewing's sarcoma.

Clinicopathologic variables associated with a good histological response to primary chemotherapy in Ewing's sarcoma are identified. The histological response to preoperative chemotherapy in 243 cases of Ewing's sarcoma treated with neoadjuvant chemotherapy was analyzed in relation to different clinicopathological features (sex and age of the patients, tumor size, serum lactate dehydrogenase (LDH) levels, tumor site) and to the type and schedule of anticancer drugs delivered preoperatively according to three consecutive chemotherapy regimens. A higher rate of good responses was achieved with the use of ifosfamide and dactinomycin in addition to a conventional three-drug VAC regimen, suggesting that these drugs should be included from the beginning in neoadjuvant regimens for the treatment of Ewing's sarcoma. The analysis of event-free survival in 158 patients with a 4-year minimum follow-up confirmed that histological response to preoperative chemotherapy is a reliable predictor of outcome in Ewing's sarcoma.

Abnormal insulin response to glucose following treatment for Wilms' tumor in childhood.

UNLABELLED: To determine whether beta-cell function could be impaired by the treatment for Wilms' tumour (WT) in childhood. We investigated the insulin secretion of 44 survivors of WT (22 males) with a median off-treatment follow up of 8.3 years (range 1-19.8). All patients had an intravenous glucose tolerance test (IVGTT) (0.5 gm/kg, max 25 g) to determine the first-phase insulin response (FPIR) (sum of the 1- and 3-min insulin concentrations). Median age at the time of the study was 12.7 years (range 4.2-22.7). Eight subjects (7 males) had a FPIR value below the 3rd percentile, and 7 (3 males) above the 97th centile. Among the 22 patients who received radiotherapy. 7 (6 males) showed a FPIR < 3rd percentile versus only 1 (a male) of the 22 patients who received no radiation (31.8% vs 4.5%; P < 0.05). Analysis of variance showed that the time elapsed since therapy had a significant role on the development of low FPIR only in males. The 7 patients with an insulin release > 97th percentile did not show any significant difference compared to subjects with lower insulin values for weight, age at diagnosis, sex, time elapsed since treatment, radiotherapy and chemotherapy protocol. CONCLUSION: An impaired insulin response is evident in some patients treated for WT in childhood, mainly in male patients who received abdominal radiotherapy and were examined a longer time after therapy. We hypothesize that this decreased insulin release is related to damage due to radiotherapy and therefore a careful follow up is recommended in adulthood in these patients.

Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities.

PURPOSE: This study was performed to assess the prognostic value of the proposed histopathologic method to evaluate the response of the primary tumor to preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients, who were preoperatively treated by chemotherapy alone. Responses were graded I to III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor cells, respectively). Follow-up data were available for all patients, with a mean follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically highly significant difference was observed in outcome among the three groups of patients. For patients with total necrosis (grade III response), the estimated 5-year disease-free survival rate was 95%, in contrast to 68% for grade II responders and 34% for grade III responders (P < .0001). This difference was also confirmed when any single group was compared with the other groups. Among the parameters tested, patient age and the size of tumor had some prognostic value. CONCLUSION: The proposed histopathologic grading, to evaluate the effect of chemotherapy on the primary tumor, had the strongest correlation to clinical outcome. This method could therefore be used to identify patients with a high risk of recurrent disease. These patients could be randomized to receive alternative postoperative treatments to investigate whether more aggressive therapies will improve outcome.

Response of previously untreated metastatic rhabdomyosarcoma to combination chemotherapy with carboplatin, epirubicin and vincristine.

This study aimed to assess the response to a novel combination chemotherapy containing carboplatin plus epirubicin in previously untreated children with metastatic rhabdomyosarcoma. 81 children (< or = 18 years) were treated between 1989 and 1994 with a combination of carboplatin, epirubicin and vincristine, given as initial therapy as part of a multicentre European trial (SIOP Intergroup Study of Stage IV Malignant Mesenchymal Tumours in Children). The chemotherapy regimen (CEV) was: carboplatin 500 mg/m2 plus epirubicin 150 mg/m2 administered on day 1, and vincristine 1.5 mg/m2 administered on days 1 and 7. Response was evaluated at day 21. 2 patients achieved complete remission and 41 patients partial remission, with an overall response rate of 53% (95% confidence interval 45-76%). Three patients showed progressive disease (4%). Toxicity was mainly haematological, with 52% experiencing grade IV neutropenia and 34% grade IV thrombocytopenia. Mucositis and infections were not severe. There were no toxic deaths. The combination of carboplatin, epirubicin and vincristine is effective and well tolerated in patients with metastatic rhabdomyosarcoma.

[Inflammatory pseudotumor of the urinary bladder. Study of 4 cases and review of the literature]. / Pseudotumore infiammatorio della vescica urinaria. Studio di 4 casi e revisione della letteratura.

INTRODUCTION: Inflammatory pseudotumour (IPT) of the urinary bladder is a benign proliferative lesion which can simulate clinically and histologically a sarcoma. Aim of this study is to report four new cases and to review the literature. CASES: Two patients were male, aged 2 and 4 years respectively (cases 1 and 2); cases 3 was a 26 year old woman and case 4 was a 40 year old man. Three patients presented with gross haematuria. One patient (case 4) presented with abdominal pain. On cystoscopy all the lesions presented as polypoid masses, ranging from 0.5 to 3 cm. in greatest axis. All patients were treated with conservative surgery. Case 1 died of unrelated causes 7 years later; at autopsy no evidence of residual bladder lesion was found. All the remaining three patients are alive and free of disease 8, 4, and 3 years respectively. RESULTS: On histology all the lesions had similar features. They were characterized by a submucosal growth of spindle cells with little pleomorphism, immersed in abundant myxoid stroma. In all cases immunoreactivity with vimentin was obtained; smooth muscle actin was focally positive in two cases and cytokeratin in one case. Bladder muscular wall was involved in three cases. CONCLUSION: The present four cases showed same histological and immunohistochemical feature of the IPTs previously described in the literature. IPT of the urinary bladder must be differentiated from malignant lesions such as rhabdomyosarcoma, leiomyosarcoma, inflammatory fibrosarcoma, sarcomatoid carcinoma. Differential diagnosis is based mainly on the characteristic histological picture of IPT. Immunohistochemistry can be misleading as IPT shares in common with those malignant conditions, positivity with some markers, such as desmin with rhabdomyosarcoma and cytokeratin with sarcomatoid carcinoma.

Longitudinal growth and final height in long-term survivors of childhood leukaemia.

Survival of children with acute lymphoblastic leukaemia (ALL) has increased considerably in recent years and data on the spontaneous growth and final height of these children are conflicting. Therefore, we analysed the longitudinal growth and final height in 52 survivors (33 females, 19 males) of childhood ALL. These children were diagnosed and treated in a single institution, all remained in first remission and were submitted to cranial irradiation with either 2400 or 1800 cGy. None of the patients received testicular or spinal irradiation. Median age at diagnosis was 4.2 (range 1.3-9.6) years in the first group (2400 cGy) and 3.9 (0.8-10.5) years in the second (1800 cGy). Standing height was measured at diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24 months after the end of treatment, and finally at the completion of growth. In girls a significant decrease of mean height standard deviation score (SDS) during treatment and a catch up in growth after the end of therapy was followed by a second period of reduced growth. Mean final height SDS was significantly lower than the value at diagnosis in both groups of girls, but only in males treated with 2400 cGy. Mean overall loss in height SDS from diagnosis to final height was higher in females (-1.24) than in males (-0.40) (P = 0.009). Females < or = 4 years of age at diagnosis showed a higher loss in final height than females > 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of stage 4 neuroblastoma patients by means of MIBG and 99mTc-MDP scintigraphy.

In a group of 22 patients with a stage 4 neuroblastoma, MIBG and 99mTc-MDP scintigraphy and radiological skeletal survey were performed at diagnosis to assess the presence of metastatic skeletal disease. In 20 out of 22 patients the MIBG scan was repeated during follow-up at a time when maximum tumoral regression was expected, i.e. after 3-4 cycles of chemotherapy; scan results were correlated to clinical and laboratory data. At diagnosis MIBG scan showed bone involvement in 19/22 patients, 99mTc-MDP in 20/22 and radiological skeletal survey in 11/22. In 1 patient only marrow aspirate revealed diffusion of disease beyond the primitive lesion. A total of 117/161 (72%) bone lesions were detected by MIBG, 89/161 (55%) by 99mTc-MDP and 47/161 (29%) by radiological skeletal survey. MIBG scintigraphy revealed bone marrow involvement in 11/22 patients in whom either marrow aspirate or bone biopsy were positive. In 5 patients 14 soft tissue lesions were also discovered and all but one primitive lesion accumulated MIBG. Although MIBG scan detected a greater number of bone lesions than 99mTc-MDP, in two patients in whom MIBG scan was negative 99mTc-MDP revealed the presence of bone involvement. Therefore we conclude that 99mTc-MDP scan is necessary to fully assess bone involvement in neuroblastoma at diagnosis. When MIBG scan was repeated after chemotherapy there was a general reduction of the number of detected lesions and in 8/17 patients both bone metastases and marrow involvement could no longer be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion.

OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary.

Wilms' tumor with transient dermolysis of the newborn: recurrence of skin lesions during chemotherapy.

Transient bullous dermolysis of the newborn consists of congenital skin defects and a tendency for blistering of the skin and mucous membranes during the neonatal period. A case of transient bullous dermolysis of the newborn associated with Wilms' tumor is reported. Transient bullous dermolysis of the newborn does not represent an obstacle to administering appropriate chemotherapy when simple precautions are taken.

Vertebral histiocytosis.

Thirty-five cases of vertebral histiocytosis are examined for a total of 52 vertebrae affected. The study is conducted on the radiographic picture at the onset and at long-term follow-up in 32 cases (24-223 months, average 45). Diagnosis may be based on radiology only in typical cases, otherwise there may be errors in differential diagnosis with malignant neoplastic lesions. Radiotherapy does not seem to influence the volumetric reconstruction of the vertebral body, which is inversely proportional to age. In those cases submitted to chemotherapy, the morphological results, in the absence of other types of local treatment, are often excellent. Orthesic or surgical treatment must be chosen based on the extent of the lesion and on its ability to progress; CT scan may be useful to this purpose, but initial orientation may be suggested by multiple adjacent lesions or by radiographic images such as osteolysis of the pedicles.

School-related behavior in children with cancer.

Ninety-one children with cancer (thirty-seven with leukemia and fifty-four with solid tumors)--school aged (elementary and middle school), residing in Emilia-Romagna Region (Italy), and receiving treatment at the Department of Pediatrics (III), University of Bologna, from August 1973 to April 1987--took part in a study of school behavior as perceived by the teacher. The research was carried out through a 29-item forced-choice questionnaire based on the questionnaire proposed by Deasy-Spinetta for a similar study in the U.S.A. Results revealed that children with cancer have a school behavior scoring at levels significantly lower than controls. There are more difficulties for children attending middle than elementary school, for children on therapy than off therapy, and for children with leukemia than with solid tumors. In conclusion, the main obstacle to school performance seems to be lower attendance, which is mainly due to treatment and clinic visits and probably in part to an overprotection and an excessive concern on the part of physicians and parents.

Cystic nephroma in children. Report of a case.

A case of cystic nephroma is described in a 20-month-old female. The diagnosis of this rare renal pathologic lesion is essentially based on its pathologic features. The treatment consisted of nephrectomy followed by a brief course of chemotherapy. The literature is reviewed with regard to the pathologic features and treatment of this lesion, which has a favorable prognosis.

Childhood non-Hodgkin's lymphoma and "leukemia-lymphoma syndrome": long-term results with the modified LSA2-L2 protocol.

From June 1976 to December 1984, 48 previously untreated children with non-Hodgkin's lymphoma (NHL) were treated according to the LSA2-L2 protocol, modified by inclusion of cranial irradiation for patients in stage III and stage IV disease. According to the staging system proposed by Wollner, 4 patients were in stage I, 8 in stage II, 11 in stage III, 8 in stage IVA (less than or equal to 25% blasts in the bone marrow), 15 in stage IVB (greater than 25% blasts in the bone marrow), and 2 in stage IV central nervous system disease. The complete remission rate was 95.8%. The relapse-free survival (RFS) rate of 46 complete responders was 76% after a median observation time of 47+ months. Only 1 of 35 high-risk responder patients developed CNS relapse after prophylactic treatment. Clinical stages were related to the RFS: 100% in stage I-II vs. 69% in stage III-IV. All 8 patients in stage IV were alive without evidence of disease with a median observation time of 59+ months. Fifteen patients in stage IVB who had leukemia-lymphoma syndrome attained 59% RFS with a median observation time of 39+ months. After a median observation time of 38+ months, 29 of 37 patients are off therapy. The results emphasize the value of both the histologic and immunologic features and the stage of disease in predicting the outcome of NHL in children. The LSA2-L2 regimen appears to be a very effective protocol for children with lymphoblastic lymphoma, although it may be less efficacious for patients with large bone marrow involvement.

Relationship between smooth muscle and cytoskeleton antibodies in neuroblastoma.

The previously reported high prevalence of smooth muscle antibodies in neuroblastoma has been found to be associated with a similarly elevated prevalence of anti-cytoskeleton antibodies. The most relevant finding is related to anti-microfilaments (anti-actin) and anti-microtubules antibodies, which were detected with highly significantly different prevalences when compared with a disease control group (p less than 0.001 and p less than 0.000001, respectively). The correspondence between smooth muscle antibodies and anti-cytoskeleton antibodies is incomplete, and it is more relevant for anti-microfilaments. It is concluded that antigen specificities of smooth muscle antibodies in neuroblastoma are as complex as documented in other diseases. Possible pathogenetic and clinical implications emerging from these data are discussed.

[Neuroblastoma metastatic to the skull. Radiologic aspects and therapeutic problems]. / Neuroblastoma metastatico al cranio. Aspetti radiologici e problemi terapeutici.

Clinical-radiological findings, treatment and prognosis of cranial involvement in 19 cases of neuroblastoma stage IV have been considered. The most frequent clinical features were periorbital ecchymosis and intracranial hypertension. The radiographic aspects, graduated according to the type of the lesion, showed a close correlation with clinical findings and sometimes preceded them. Computerized tomography, carried out in 12 cases, was more reliable than plain films in identifying the site and extent of cranial lesions and the presence of cerebral extensions, as occurred in 2 patients. The presence of cranial involvement at diagnosis was an unfavorable prognostic sign. The 19 children were treated in various ways so that firm conclusions cannot be drawn, but cranial radiotherapy in combination with chemotherapy appeared to be more efficacious than chemotherapy alone.