Langerhans cell histiocytosis in childhood--results of the DAL-HX 83 study

Owing to the unclear and mostly unknown etiology of Langerhans' cell Histiocytosis (LCH) and the unsatisfactory results in treating disseminated LCH a prospective multicentric study DAL-HX 83 was commenced, including 45 different clinics of West-Germany, Austria and Netherlands. From June 1st, 1983 to October 31st, 1986, 97 patients (pts) were involved in this study. 35 pts (9 females, 26 males, medium age 6 2/12 years, age range 0/12-14 2/12 years) suffering from localized disease (28x unifocal bone, 6x isolated skin, 1x isolated lymphnode involvement) were treated by surgery and/or radiation or were just kept in observation. 2 children (1 pt with primary localized bone lesion, 1 child with isolated skin rash) developed a new bone lesion after 1/2 year and 1 1/2 years respectively. 62 pts (33 females, 29 males, medium age 2 years, range 0/12-17 1/2 years) with previously untreated disseminated disease were assigned to 3 different risk groups (A, B and C) and were treated according to a standardized induction and risk adapted maintenance protocol. The whole treatment period was limited to 1 year. 19 pts with multifocal bone involvement (group A, medium age 6 1/2 years) were allocated to regimen A, 30 pts with bone and soft tissue involvement or soft tissue involvement alone (group B, medium age 1 8/12 years) to regimen B and 13 pts with dysfunction of the liver, lungs and/or haematopoietic system (group C, medium age 1 year) to regimen C. So far, 1 pt of group A (19 available pts) developed a new bone lesion after 10 months, another pt a suspicious bone involvement 16 months after diagnosis. A 4 months old girl of group B (27 available pts) died 11 months after diagnosis with progressive organ dysfunction, 2 pts are still alive with recurrent multifocal bone lesions and 1 pt achieved stable 2nd clinical remission after a local relapse (mediastinum). 4 pts of group C (11 available pts) died because of progressive disease between 5 days and 3 years after diagnosis, 3 pts are in partial remission after persistent and recurrent disease episodes. All the others are in clinical remission. The medium observation time of the whole group of pts with disseminated LCH is 1 9/12 years (range 0/12-3 5/12 years). The worst prognostic criteria were found to be the presence of organ dysfunction at diagnosis or its development during the course of disease and the age under two years.(ABSTRACT TRUNCATED AT 400 WORDS)     

Renal failure in Wilms' tumor patients: A report from the National Wilms' Tumor Study Group

This report defines the incidence and determines the etiology of renal failure (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the National Wilms' Tumor Study (NWTS) was searched to identify all children reported to have developed chronic renal failure. There were 55 patients found to have RF. Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one with a WT in a solitary kidney. The median interval from diagnosis to the onset of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in unilateral WT remained stable. The most common etiologies of RF were: bilateral nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts), progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts), and other causes (5 pts). The etiology of renal failure was not reported in three children. Children with unilateral WT and a normal contralateral kidney have a very low incidence of RF, and this review does not support a recommendation for parenchymal sparing procedures in these patients. Children with bilateral WT are at risk for the development of RF, and parenchymal sparing procedures are warranted. © 1996 Wiley-Liss, Inc.     

High survival rate in childhood non-Hodgkin lymphoma without CNS involvement: results of BFM 95 study in Kuwait

Non-Hodgkin lymphomas (NHL) in children are the second most common malignant tumors in Kuwait. Until 1995 the patients (pts) received institutional protocols. From October 1995 to September 2000 21 children with NHL were treated. Five children were treated by NHL BFM 90 protocol, 7 pts received NHL BFM 95 scheme, and 9 children underwent therapy abroad or according to different types of protocols. The results of a retrospective analysis of NHL BFM 95 protocol in Kuwait are reported. Seven patients diagnosed with NHL--group B: 3 children with Burkitt lymphoma (B-cell NHL) and group A: 4 children with lymphoblastic lymphoma (T-cell NHL)--were treated from October 1995 to September 2000 in the Kuwait Cancer Control Centre according to NHL BFM 95 protocol. Group B consisted of 2 girls and 1 boy; median age at diagnosis was 4 years 8 months, 2 pts classified as stage II and 1 pt as stage III. All patients were assigned to risk group R2. Median follow-up is 2 years 8 months. Group A included 1 girl and 3 boys; median age at diagnosis was 5 years 8 months, 1 pt classified as stage III and 3 pts as stage IV. All patients were assigned to IR group. Median follow-up is 3 years 6 months. In group B all 3 pts are in 1st CR; in group A 3 pts are in 1st CR and 1 pt having Li-Fraumani syndrome died after the 3rd relapse of disease during therapy. In both groups there was no toxic death, myelotoxicity WHO grade III-IV, hepatotoxicity WHO grade II-III. Treatment results of NHL BFM 95 study in our small group of patients are very optimistic. Six patients are in 1st CR and one died due to progression of disease. Despite the small group of patients, the results suggest that NHL BFM 95 protocol is highly effective and safe with regular supportive care.     

High Survival Rate in Childhood Non-Hodgkin Lymphoma without CNS Involvement: Results of BFM 95 Study in Kuwait

Non-Hodgkin lymphomas (NHL) in children are the second most common malignant tumors in Kuwait. Until 1995 the patients (pts) received institutional protocols. From October 1995 to September 2000 21 children with NHL were treated. Five children were treated by NHL BFM 90 protocol, 7 pts received NHL BFM 95 scheme, and 9 children underwent therapy abroad or according to different types of protocols. The results of a retrospective analysis of NHL BFM 95 protocol in Kuwait are reported. Seven patients diagnosed with NHL--group B: 3 children with Burkitt lymphoma (B-cell NHL) and group A: 4 children with lymphoblastic lymphoma (T-cell NHL)--were treated from October 1995 to September 2000 in the Kuwait Cancer Control Centre according to NHL BFM 95 protocol. Group B consisted of 2 girls and 1 boy; median age at diagnosis was 4 years 8 months, 2 pts classified as stage II and 1 pt as stage III. All patients were assigned to risk group R2. Median follow-up is 2 years 8 months. Group A included 1 girl and 3 boys; median age at diagnosis was 5 years 8 months, 1 pt classified as stage III and 3 pts as stage IV. All patients were assigned to IR group. Median follow-up is 3 years 6 months. In group B all 3 pts are in 1st CR; in group A 3 pts are in 1st CR and 1 pt having Li-Fraumani syndrome died after the 3rd relapse of disease during therapy. In both groups there was no toxic death, myelotoxicity WHO grade III-IV, hepatotoxicity WHO grade II-III. Treatment results of NHL BFM 95 study in our small group of patients are very optimistic. Six patients are in 1st CR and one died due to progression of disease. Despite the small group of patients, the results suggest that NHL BFM 95 protocol is highly effective and safe with regular supportive care.     

Large cell anaplastic lymphoma in children--clinical experiences with a newly defined histologic entity

The clinical characteristics of 31 patients (pts.) (17 boys, 14 girls, median age 12 11/12 years) with large cell anaplastic lymphoma (LCAL) have been evaluated. 17 of these pts. had originally been diagnosed as suffering from "malignant histiocytosis" ("MH") and were therefore included in the DAL-Histiocytosis X 83 study. Another 14 pts. with Ki-1 lymphomas were enrolled in the BFM-NHL therapy studies. According to Murphyclassification 24 pts. (77%) had stage III or IV disease and in general presented in a severe condition. The lymphatic system was involved in 28 pts., 8 pts. (26%) had skin infiltration. With regard to lymphoma involvement of lung, bones and bone-marrow were unexpectedly frequent. CNS involvement was seen in just one pt. Despite rather heterogeneous therapy approaches (ALL-schedules, DAL-HX 83 protocol for treatment of "MH", combination of B-NHL-BFM and AML-BFM schedules, CHOP, BFM protocols for B-NHL) 30 out of 31 pts. achieved clinical remission (CR). The only nonresponder died during bone marrow transplantation of septicemia. 4 pts. relapsed during therapy. 3 of them died, 1 during a BMT. 1 pt. achieved 2nd CR with a BFM-B-NHL protocol. 3 pts. experienced a late relapse, 1 died, 1 2nd CR was achieved, the third pt. is still alive after 2 further relapses disease-free for 3 years. 23 pts. (74%, 13 out of 14 of BFM-NHL therapy study, 10 out of 17 of DAL-HX 83 study, 1 pt. after BMT) are in 1st CR with a median observation time of 2 9/12 years (range 5/12 to 17 9/12 years).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thirty-year population-based review of childhood renal tumours with an assessment of prognostic features including tumour DNA characteristics

We have reviewed all paediatric kidney tumours seen in the West Midlands Health Authority Region over a 30-year period. There were 205 cases confirmed after a review of the pathology by three paediatric pathologists. Seven were cases of bone metastasising renal tumour (clear cell sarcoma), 5 were rhabdoid tumours, 2 were renal cell carcinomas, and 13 were mesoblastic nephromas. In 3 cases, it was not possible to define further the histological diagnosis. The remaining 175 cases were considered to be Wilms' tumour (86%), which is equivalent to an incidence of 5.7/10⁶/year. In the cases of Wilms' tumour, there were 91 boys and 84 girls (1.1:1). The majority of patients were Caucasian with only 7% of non-Caucasian origin. At presentation, 78% of the patients were less than 5 years old. All of these patients except 9 had surgery as part of their treatment, 154 children had total nephrectomy, 3 had partial nephrectomy, and 9 had other surgical procedures. The majority also received chemotherapy and radiotherapy. Sex, chemotherapy, and stage all had prognostic significance in univariate analysis. The actuarial survival at 10 years increased from 17% for patients treated in the first decade of the study to 78% for patients treated in the third. DNA characteristics were investigated using flow cytometry in paraffin-embedded material and adequate information was obtained in 73 cases of Wilms' tumour. Only 7 had aneuploid tumours. Univariate survival analysis of these 73 results showed that stage, sex, the percentage of cells in the synthetic phase and the proliferative index from the DNA investigations had predictive value. © 1993 Wiley-Liss, Inc.     

儿童肾癌的临床及CT和病理特点分析

目的 探讨儿童肾癌的临床、CT及病理特点,积累其临床诊治经验.方法 回顾性分析2014年至2016年单中心收治的7例儿童肾癌患儿的临床、CT、病理资料,并随访其生存情况.就诊时年龄5～12岁,女4例,男3例,左侧5例,右侧2例.临床表现多为血尿(4/7)、腹部包块(3/7)、腰痛(1/7).CT平扫肿瘤呈低密度,多位于上下极,可见钙化(6/7)及坏死区,增强特点多为“快进快出”(4/7),部分为“快进慢出”(2/7).结果 7例患儿全部获得随访,随访时间8～35个月.1例肿瘤位于左腹膜后,确诊时已发生腹膜后及颈部淋巴结转移,行肿瘤部分切除活检,术后5个月死亡.1例为复发性肾癌,行肾窝肿瘤切除加腹膜后淋巴结清扫,术后5个月出现淋巴结转移,予放化疗后带瘤生存.余5例患儿均行根治性肾切除加淋巴结清扫,术后均无瘤生存.病理多为肾透明细胞(5/7)及乳头状肾细胞癌(2/7),癌细胞呈巢团状、乳头状、腺管样结构分布,可见砂粒体(6/7),核级多为3～4级.4例患儿淋巴结转移,共清扫出60枚淋巴结,淋巴结阳性率为16.7％.5例加做免疫组化,TFE3 (4/5)、CD10 (5/5)、Kb67 (4/5)、E-cardherin (4/5)、Vinentin (3/5)、CK(3/5)阳性率较高,4例确诊为MiT家族异位性肾癌.结论 儿童肾癌多发生于年长患儿,有其特有的临床、CT及病理特点,MiT家族异位性肾癌常见,病理及免疫组化是确诊和分型的主要手段.     

Clinicopathologic correlates of loss of heterozygosity in Wilms' tumor: A preliminary analysis

Wilms' tumor-specific loss of heterozygosity (LOH) for DNA markers located at chromosomes 11p13, 11p15, 16q, and 1p has been reported to occur in a minority of Wilms' tumors. We hypothesized that tumors classified by region of LOH would exhibit specific clinicopathologic patterns. We have therefore determined the constitutional and tumor genotypes for markers at 11p13, 11p15, 16q, and 1p in a large series of Wilms' tumor patients who were registered on a Pediatric Oncology Group study and on the National Wilms' Tumor Study, to determine whether tumor-specific LOH for any of these regions was associated with any specific phenotype. Of 286 cases, 27% had LOH at both 11p13 and p15 (BOTH), 3% at 11p13 only, 8% at 11p15 only, and 62% at neither. Significant associations were found between younger age at diagnosis and LOH for BOTH, but not for 11p15 only, and between the presence of intralobar nephrogenic rests and LOH for BOTH. The incidence of nephrogenic rests (all types combined) and of bilateral tumors was the same in tumors with or without LOH. There was a negative association between anaplastic histology and LOH for 11p. There was no association between LOH on 11p and outcome as assessed by relapse-free and overall survival. The associations between age at diagnosis and LOH are interpreted as suggesting the existence of a Wilms' tumor locus on 11p in addition to WT1 at 11p13 and the putative WT2 at 11p15. LOH for chromosome 16q was identified in 17% of 204 tumors and was associated with a significantly worse outcome. Outcome for patients with LOH for 1p was also worse but not significantly so. © 1996 Wiley-Liss, Inc.     

Laparoscopic treatment of renal cancer in children: A multicentric study and review of oncologic and surgical complications

ObjectiveThe aim was to report a multicentric study with a longer follow-up to evaluate the laparoscopic radical nephrectomy in children with renal cancer.Material and methodsThis was a retrospective multicentric study, from October 2005 to January 2012, of children who underwent a laparoscopic radical nephrectomy for small renal malignant tumors.ResultsSeventeen children were included in this study. Sixteen underwent chemotherapy before surgery according the SIOP (Société Internationale d'Oncologie Pédiatrique) protocol and one was treated by surgery only for a carcinoma. All except one could be treated by laparoscopy; the biggest tumoral size was 8 cm. The median hospital stay was 3 days (2–10). The pathologic examination showed 15 Wilms' tumors, one clear cell sarcoma and one TFE3 renal cell carcinoma. With a median follow-up of 42 months (range 12 and 77 months) after laparoscopic radical nephrectomy, 15 children had no oncological complications (port site or local recurrence, pulmonary metastasis) and one had a local recurrence without intraoperative tumoral rupture. The child with TFE3 renal cell carcinoma died 4 years after surgery from brain and lung metastases without local recurrence. No small bowel obstruction occurred.ConclusionsRadical nephrectomy in children for Wilms' tumor or other renal cancer can be safely performed laparoscopically and our indications can be summarized, for trained laparoscopic surgeons, by small tumors under about 8 cm diameter, especially without crossing the lateral edge of the vertebra on the CT scan at the time of surgery.     

High-dosage chemotherapy in primary metastasized and relapsed Ewing's sarcoma. (EI)CESS]

BACKGROUND: Patients (pts) with primary metastatic Ewing tumours (ET) have a poor prognosis for event free survival (EFS) compared to pts with localised disease. Following relapse the prognosis is extremely poor. Therefore these primary metastatic and relapsed pts were piloted for high dose therapy (HDT) for the last years. PATIENTS AND METHODS: Between April 1984 and May 1997, 131 ET pts who underwent HDT were registered in the German CESS/EICESS office: 79 pts with primary metastases and 52 pts with relapsed tumours. After induction therapy, consisting of chemotherapy and local therapy, pts received high dose regimens, mainly based on melphalan and/or etoposide (92%). Stem cell rescue was applied from allogeneic bone marrow (n = 13), autologous bone marrow (n = 17), or peripheral blood stem cells (n = 95). The date of analysis was September 1st, 1998. Outcome was calculated by Kaplan-Meier-analyses. RESULTS: The median time under study since high dose therapy was 3.7 years. 35/131 pts (26.7%) were in continuous complete remission, 80/131 pts (61.1%) had relapsed or progressed, 11/131 pts (8.4%) died of complications and 5/131 pts (3.8%) presented with secondary malignancies. For the total group of primary metastatic pts, EFS five years after diagnosis was 19% for pts with HDT and 27% for those without (p = 0.9209). The subgroup of pts with primary lung and bone metastases seemed to benefit from HDT (EFS five years after diagnosis: 34% versus 5%, p = 0.0001). Outcome of pts with an early ET relapse (< 2 years) was also improved by HDT (EFS four years after relapse: 17% versus 2%, p = 0.0001). CONCLUSIONS: The total group of primary metastatic ET pts showed no obvious benefit from HDT, based on melphalan and/or etoposide. Pts with metastases to multiple organ systems, and early relapse seemed to benefit from HDT. The value of HDT should be assessed in prospective clinical trials.     

Cardiorespiratory status after treatment for acute lymphoblastic leukemia

The use of certain chemotherapeutic agents is associated with dose-related cardiotoxicity and, potentially, with restrictive lung disease. Therefore, we assessed the cardiopulmonary status and exercise capacity of 19 patients (pts; 9M:10F) 1.1 to 7.1 years (mean 4.6 ± 1.5 years) after successful treatment of acute lymphoblastic leukemia (ALL) with Dana Farber Cancer Institute protocols. As body mass and nutritional status may influence exercise capacity, we also evaluated their anthropometric status and the plasma levels of rapid turnover proteins. Seven pts designated as “standard risk for relapse” (SR) had received low cumulative doses of doxorubicin (50 ± 21 mg/m²), while twelve pts at “high or very high risk for relapse” (HR/VHR) had received higher doses (349 ± 16 mg/m²). The evaluations included a questionnaire, anthropometric assessments, echocardiography, pulmonary function studies, exercise testing, and nutritional assays. Patients' data were compared with published normative data or with control values from our laboratories. In addition, we compared SR pt data with HR/VHR pt data. No pt had overt symptoms or signs of cardiorespiratory compromise. The pts had a higher percent of body fat than age-matched healthy controls (29.7 ± 7.9% vs. 20 ± 6%; P < 0.001). On echocardiography, cardiac systolic function was within normal limits in all. However, HR/VHR pts had lower left ventricular (LV) shortening fractions than SR pts (P < 0.05). LV filling velocity, indicative of diastolic function (the E/A ratio), was normal in most pts. Pulmonary function studies were normal. Exercise capacity was below predicted in most cases but heart rates at peak exercise and leg muscle function were within normal limits, suggesting a deconditioned state. Plasma levels of rapid turnover proteins were also normal. Despite lack of overt morbidity in our pt population, subtle abnormalities persist in cardiac function while pulmonary function is normal. Longitudinal studies will identify if further abnormalities or overt morbidity develop. In later years, continuing obesity and a sedentary state may contribute to clinically relevant heart disease. © 1996 Wiley-Liss, Inc.     

Late recurrent metastasis in Wilms' tumour

Recurrence of Wilms' tumour after 5 years of disease-free survival is rare. We present the case of a 26-year-old man who had been diagnosed of Wilms' tumour at the age of 6 years treated by surgery, chemotherapy, and radiotherapy and who remained disease free for 8 years, after which lung metastases were detected. Second complete remission was attained with surgery and chemotherapy and 20 years after initial diagnosis he again presented with lung metastases, similarly achieving complete remission with surgery and secondline chemotherapy. The clinical and biological aspects of late metastasis in this neoplasm are discussed. © 1994 Wiley-Liss, Inc.     

Wilms's tumour and aniridia: clinical and cytogenetic features.

A survey carried out to detect children with aniridia/Wilms''s tumour syndrome identified 8 living and 3 dead children. The incidence of aniridia was found to be 1 in 43 among Wilms''s tumour patients in the UK. The clinical features included complete bilaterial aniridia, cataracts, glaucoma, mental retardation, hyperkinesis, hypospadias, and undescended testes. A high incidence of bilateral tumours (36%), male sex, presentation at a young age, and advanced maternal age appeared to be associated with the syndrome. The 8 living children each had a deletion on the short arm of chromosome 11. In contrast, although 2 patients with sporadic aniridia without Wilms''s tumour had other malformations, neither had genitourinary anomalies, and the only additional problems in patients with familial aniridia were cataracts. Among 49 children with Wilms''s tumour without aniridia ony one had bilateral tumours. No chromosome abnormalities were detected in patients with familial aniridia, nor were they detected in patients with Wilms''s tumour without aniridia or in those with sporadic aniridia without Wilms''s tumour. While many infants with the Wilms''s tumour/aniridia syndrome are clinically diagnosable at birth, chromosome analysis using the elongated chromosome method is especially valuable to confirm the diagnosis in girls with sporadic aniridia and in boys who lack the genitourinary malformations. The presence of an 11p13 deletion confirms the diagnosis of the Wilms''s tumour/aniridia syndrome and indicates a very high risk for the development of Wilms''s tumour.     

Rathke's cleft cysts in children and adolescents: association with female puberty

There are few pediatric data regarding manifestations and outcomes of Rathke's cleft cysts (RCC). We retrospectively reviewed 13 cases treated at Massachusetts General Hospital over 10 years. Age at presentation was 12-17 years, except for one 7-year-old who presented with sexual precocity. There was a female preponderance [11 females, 2 males, p = 0.01], and all were pubertal at diagnosis. Common features at presentation were headaches (11/13), endocrine abnormalities (5/13) and visual disturbances (2/13). Four patients underwent transsphenoidal surgery. Symptoms improved in all but one, in whom headaches persisted. Recurrent growth in one patient was treated successfully by excision. For conservatively treated patients, cyst size was unchanged over follow-up (6 months-5 years). Female preponderance and pubertal presentation suggest a possible link between sex hormones and RCC pathogenesis. Although estrogen and progesterone receptor immunostaining was negative in the cyst lining, estrogen receptor immunostaining was positive in adjacent pituitary cells. Further investigations regarding this issue are warranted.     

Clinical aspects of the rhabdoid tumor of the kidney: A report of the national wilms' tumor study group

Rhabdoid tumor of the kidney (RTK), originally described as a monophasic sarcomatous variant of Wilms' tumor, is now recognized as a highly malignant, non-Wilms' tumor possibly of neuroectodermal origin. Twenty-one National Wilms' Tumor Study patients with this tumor were treated in the years 1969 through 1978. Mean patient age was 18 months with 16 of the 21 younger than 2 years at diagnosis. Two patients were Stage I, 10 Stage II, 5 Stage III, and 4 Stage IV. One patient only is continuously disease free and another is surviving disease free following excision of bilateral pulmonary metastases. One patient died of sepsis early during therapy. Thus 18 of the 19 patients who relapsed died, 15 within 1 year of diagnosis, all with progressive tumor growth. The rapid appearance of metastases (mean 4 months), often to multiple sites, and short subsequent survival signal a very malignant tumor resistant to current treatment stratagems.     

Der(16)t(1;16)(q21;q13) in Wilms' tumor: Friend or foe

The der(16)t(1;16)(q21;q13) chromosomal abnormality has been reported rarely in Wilms' tumor. This abnormality has also been found in several other pediatric and adult neoplasms, and may imply a poor prognosis in at least some of these solid tumors. To investigate its clinical significance in Wilms' tumor, we examined the records of 65 consecutive children with Wilms' tumor whose tumor cells were successfully karyotyped. The t(1;16) was present in seven patients (10%) whose ages ranged from 2.5 to 4.7 years (median 3.5 years) at diagnosis. Six of the seven patients were female. All four stages of Wilms' tumor were represented (two patients had stage IV disease). No patient had bilateral disease. All tumors were of “favorable histology.” All seven patients are alive and off therapy with a median follow-up of 3.2 years (range, 2 to 8.5 years). One patient with this abnormality developed brain metastases within 4 months of completion of therapy. Comparison of these patients with the remaining 58 Wilms' tumor patients revealed no significant differences with regard to disease stage, histology, survival, or relapse-free survival. Cytogenetic evidence of der(16)t(1;16)(q21;q13) in Wilms' tumor does not appear to portend an adverse clinical outcome, although only a larger study that includes molecular detection methods can provide more conclusive evidence. © 1996 Wiley-Liss, Inc.     

ABO-mismatched renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the Midwest Organ Bank (MOB)

Successful ABO-mismatched renal transplantation (RT) (blood group A2 donor to blood group B or O recipient) has occurred in adults in the setting of a low titer (< or =4) natural isoagglutinin (anti-A) level in the recipient of the mismatched organ. Similar experiences have rarely occurred in children. Between 1986-1996, 11 pediatric patients (6 male and 5 female) received 11 ABO-mismatched kidneys [7 cadaveric (CAD) and 4 living related donor (LRD)]. There were 8 O recipients/A2 donor pairs, 2 B recipients/A2 donor pairs and 1 B recipient/A2B donor pair. Recipient age at the time of RT was 14.7+/-3.0 yr (mean +/- SD). Prior to RT, 2 recipients underwent splenectomy and none received donor-specific transfusions. Induction and early maintenance immunosuppression consisted of corticosteroids (11 pts), ALG/ATG (6 pts), OKT3 (3 pts), azathioprine (11 pts) and cyclosporine (8 pts). The mean 30-d cyclosporine dosage was 10.6+/-4.0 mg/kg/d. Eight patients suffered > or =1 acute rejection episodes, the initial episode occurring within the first 31 d post-transplant in 7 of them. Five grafts (45.4%) failed secondary to vascular thrombosis (1), acute rejection (2) and chronic rejection (2). The remaining grafts (54.5%) all functioned for >1000 d (range: 1023-3746 d). The pre-transplant anti-A titer was determined in 6 pts; in 4 it was low (2) and in 2 it was high (8). Graft survival in all but one of these patients (whose titer was 8 and who suffered a non-rejection-related vascular thrombosis) was > or =2 yr. In summary, ABO-mismatched RT in pediatric patients is an uncommon practice. However, the adult experience and our preliminary pediatric experience suggests that evaluation of recipient isoagglutinin levels in this setting may be helpful in the selection of donor/recipient pairs in whom mismatched transplantation can be successful.     

Pediatric renal transplantation: anesthesia and perioperative complications

The appropriate choice of anesthesia for patients (pts) undergoing renal transplantation (Ktx) requires minimal toxicity and accurate monitoring for pts at high risk for metabolic, cardiovascular, and respiratory perioperative complications. We evaluated the anesthetic management and postoperative follow-up in pediatric Ktx performed in the last 12 years in our institution. From 1988 to 1999, 75 ASA class II-III pts (45 males, 22 females) younger than 18 years scheduled for Ktx were studied: 49 received a graft from a cadaveric donor (CD) and 26 from a living donor (LD). All pts were treated with dialysis within 24 h before the procedure. Standard monitoring consisted of an electrocardiogram, central venous pressure, non-invasive arterial pressure, pulse oximetry, and inspiratory and expiratory gas analysis. If necessary, an arterial cannula and pediatric pulmonary catheter were introduced. Anesthesia was induced with sodium thiopental, propofol, halothane, or sevoflurane and maintained with isoflurane and/or fentanyl and droperidol in O2:N2O (FiO2 0.4%). As muscle relaxants atracurium or cisatracurium besilate were used, except in allergic pts, in whom vecuronium or rocuronium bromide was administered. Dopamine, 20% mannitol, and furosemide were used to increase diuresis. Continuous morphine and ketoralac infusions were used for postoperative pain relief. The surgical technique was the same in all cases. Complications and renal-function (RF) recovery were evaluated relating to CD and LD using the chi-square test; differences in mean anesthesia and surgical time were evaluated by Student's t-test; survival curves were calculated from the day of Ktx to death or last follow-up and estimated by the Kaplan-Meier method. Values of P below 0.05 were considered significant. Postoperative immunosuppressive therapy was based on cyclosporine together with other conventional drugs. Mean anesthesia time was 228 +/- 65 min. Mean kidney ischemia time for CD was 16.5 +/- 4 h. Four pts (3 CD, 1 LD) died within 72 h postoperatively: 3 due to cardiac failure and 1 to metabolic coma. Six pts showed cardiovascular and 3 had infective complications, all successfully treated. Three pts (2 CD, 1 LD) died within 2 to 12 months after, surgery; 10 (6 CD, 4 LD) had graft failure and are still alive on dialysis; 58 (38 CD, 20 LD) are alive in good health after a mean follow-up of 57.6 +/- 36.6 months (range 12-120 months). Fifteen of 26 pts younger than 12 years (21 CD and 5 LD) recovered RF intraoperatively (10 CD, 5 LD); 1 with CD and 1 with LD showed postoperative graft failure and 2 with CD died within 72 h postoperatively, 22 (18 CD and 4 LD) are alive in good health. This group showed no statistical difference compared to pts older than 12 years. Of 16 pts (15 CD and 1 LD) with body weight (BW) less than 25 kg, 6 showed intraoperative (5 CD, 1 LD) recovery of RF. The 3 deaths were all in CD pts, 2 within 72 h and one 2 months after surgery; only 1 LD had postoperative graft failure. Twelve pts (75%) (12 CD, 80%) are alive in good health. Compared to pts with BW of 25 kg or more, this group showed lower intraoperative recovery of RF (P < or = 0.05). No peri- and postoperative complications occurred in all 26 LD pts (100%). Recent advances in surgery, anesthesia, immunosuppression, and antimicrobial prophylaxis have made Ktx a more predictable procedure even in pediatric pts. For high-risk pts, mortality and morbidity can be controlled by accurate surgical, anesthetic, and postoperative management. Pts younger than 12 years and with BW less than 25 kg are more likely to develop peri- and postoperative complications.     

Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood - a phase-II-study

BACKGROUND: The topoisomerase-I-inhibitor Topotecan (TPT) has shown a broad activity in the therapy of adult malignant diseases. In pediatric oncology TPT has been rarely used. METHODS: From 1/98 to 8/99 we conducted a multicenter phase-II-study of TPT (1.5 mg/m (2)/d in 30 min i. v. for 5 days every 21 days) in pediatric patients (pts) with malignant tumors refractory to conventional therapy (either second line or any relapse). PATIENTS: A total of 20 pts received 81 cycles. The 7 female and 13 male pts had a median age of 10.2 years at the beginning of the TPT therapy. RESULTS: The median number of administered TPT cycles was 4 with an interval of 23.5 days. The median administered TPT dose was 1.48 mg/m (2)/d. No complete responses, but 2 partial responses and 9 stable diseases were observed. In 9 pts the disease progressed. The mean duration until progression for SD was 130 and not different from PR with 131 days. The median cumulative TPT dose until progression in responders was 30 mg/m (2). For all study-pts the median overall survival time was 235 days with 1 pt. still alive. The main toxicity was hematological with anemia grade III/IV (10/42 % of all evaluable TPT cycles), neutropenia grade III/IV (49/18 %) and thrombopenia grade III/IV (35/36 %). Non-hematologic toxicity was mild with the exception of 4 cycles with infection grade III and 1 grade IV. No patient died of therapy-related complications. CONCLUSIONS: TPT as monotherapy has shown an antitumor activity in pediatric pts with various malignancies. Toxicity was mainly hematological and manageable. Further evaluation of TPT treatment is planned using combinations with other cytostatic drugs.     

保留肾单位手术治疗儿童肾细胞癌

目的 探讨保留肾单位手术治疗儿童肾细胞癌的安全性和可行性.方法 对我院1973年1月至2016年12月收治的11例行保留肾单位手术治疗儿童肾细胞癌的临床资料进行回顾性分析.男8例,女3例;年龄4.5～13.5岁,平均7.5岁;左侧5例,右侧6例.临床表现:无痛肉眼血尿4例,腹部包块1例,行B型超声检查偶然发现6例,血尿病史1～7个月,平均3个月.结果 11例患儿均行开放性经腹膜保留肾单位手术,肿瘤直径2.2～6.9 cm,平均3.3 cm.肿瘤位于肾上极4例,肾中极背侧1例、肾中极腹侧1例、肾下极5例.手术时间88～175min,平均107 min,术中阻断肾蒂时间19～25min,平均20.4 min,出血量10～100ml,平均35ml.本组手术均安全进行,无继发出血、漏尿等并发症.术后病理提示9例为Xp 11.2易位/TFE3基因融合相关性肾癌,1例为透明细胞癌,1例为嫌色细胞癌.11例均获随访,随访时间25～129个月,平均53.2个月,无复发及死亡病例.结论 儿童肾癌应用保留肾单位手术的指征应十分严格,在此前提下,保留肾单位手术治疗儿童肾癌安全、可行.