AVASCULAR NECROSIS—AN ANTINEPOLASTIC TREATMENT RELATED TOXICITY: The Experiences of Two Institutions

Avascular necrosis (avn) is a complication of treatment for malignancies in children and adolescents. The authors present a two-center retrospective of experiences with avn in children treated for acute lymphoblastic leukaemia or non-Hodgkin lymphoma (8 from 191 patients with newly diagnosed disease in total of 19 sites). The median age at diagnosis was 16.6 years. Avn was observed in 4.1% of the group, higher among males than females (7/1), both during and after therapy. Early diagnosis of the process has enabled 7 patients to avoid surgical intervention. The increased incidence of avn, the multimodal character of symptoms, but unknown late consequences of avn showed that prospective studies of early recognition and proper therapy are needed.     

Congenital chloride diarrhoea in Kuwaiti children

Congenital chloride diarrhoea was diagnosed in 16 Kuwaiti children over a 7 year period (1980–1986) with an estimated incidence of 7.6 per 100,000 live births. The mean age at diagnosis was 3.2 months (range 1 week to 5 months). There were 9 boys and 7 girls with a mean age of 3 years 10 months (range 10 months to 7 years). All children had a shortened gestational period, abdominal distension and chronic diarrhoea. The serum electrolytes in all patients prior to treatment showed hyponatraemia, hypokalaemia, hypochloraemia and metabolic alkalosis. The diagnosis was confirmed by a stool chloride content that exceeded the sum of faecal sodium and potassium. Fifteen patients survived and showed catch-up growth with adequate replacement therapy and 1 died with renal failure.Abbreviations CCD congenital chloride diarrhoea - FCL Faecal choride     

Incidental neuroblastoma

The diagnosis of neuroblastoma in its early stage, especially in asymptomatic children, with the so-called incidentally diagnosed disease, may be associated with a good prognosis. The aim of this study is an attempt at analyzing this problem. Between 1 January 1993 and 30 April 1998, 40 children with newly diagnosed neuroblastoma started therapy at the authors' department. The disease was diagnosed incidentally in 5 (12.5%) patients. In no incidentally diagnosed child was stage IV disease detected, while in the remaining patients its incidence was 71%. All the children (median age 2 months) with incidental diagnosis have remained alive (median 39 months) in continuos remission without treatment. Among 35 children (median age 2 years and 7 months) with overt neuroblastoma, 18 died (median survival time 14.5 months). Seventeen patients have remained alive (median 45 months). The results show that children with incidentally diagnosed neuroblastoma are characterized by a more favorable prognosis than children with clinical disease.     

Diagnosis and treatment of hepatic amebic abscess in children

From 1 January 1976 to 31 December 1985, 11 children under the age of 12 years (range 11 months to 11 years) were treated for hepatic amebic abscess at the UCLA-affiliated hospitals with no mortality. There were 7 girls and 4 boys, and all were of Mexican or Mexican-American descent. In only 3 instances (27%) was the correct diagnosis considered on admission. In 3 patients the diagnosis was made when symptoms persisted following a negative laparotomy for appendicitis, but all 3 made a complete recovery on medical therapy. A delay in diagnosis in 2 other patients contributed to intrahospital rupture of the abscess and resultant urgent surgical drainage. In the remaining 6 patients, amebicidal therapy alone proved effective and no surgery was required. The complex of fever, abdominal pain, anemia, leukocytosis, and elevated erythrocyte sedimentation rate in a child without a definite diagnosis should prompt the clinician to entertain an early diagnosis of amebic liver abscess and to begin immediate therapy with a safe and efficacious drug.     

INCIDENTAL NEUROBLASTOMA

The diagnosis of neuroblastoma in its early stage, especially in asymptomatic children, with the so-called incidentally diagnosed disease, may be associated with a good prognosis. The aim of this study is an attempt at analyzing this problem. Between 1 January 1993 and 30 April 1998, 40 children with newly diagnosed neuroblastoma started therapy at the authors' department. The disease was diagnosed incidentally in 5 (12.5%) patients. In no incidentally diagnosed child was stage IV disease detected, while in the remaining patients its incidence was 71%. All the children (median age 2 months) with incidental diagnosis have remained alive (median 39 months) in continuos remission without treatment. Among 35 children (median age 2 years and 7 months) with overt neuroblastoma, 18 died (median survival time 14.5 months). Seventeen patients have remained alive (median 45 months). The results show that children with incidentally diagnosed neuroblastoma are characterized by a more favorable prognosis than children with clinical disease.     

Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia

BACKGROUND: Essential Thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by excessive production of platelets. The disorder is usually affecting adults and is rarely diagnosed in children. PATIENTS UND METHODS: In this retrospective study we describe 12 children aged 5-16 years in whom ET was presumed. RESULTS: Median follow-up was 59 months (range 10-72). At diagnosis 7 patients had clinical symptoms (syncope, poor concentration, fatigue, abdominal pain and mild bleeding), 5 patients were diagnosed accidentally (operation, allergy, enuresis, pneumonia, routine examination). Median platelet count at diagnosis was 1 325 x 10 (9)/L (range 600-3 050). In 11 cases bone marrow morphology was consistent with ET, one patient had chronic idiopathic myelofibrosis. Cytogenetics were normal in all studied cases. Within 6 months after the initial presentation one patient who was diagnosed accidentally developed thrombosis, another patient had mild bleeding. 8 patients were treated with acetylsalicylic acid (in addition, 1 patient received hydroxyurea, 2 patients received anagrelide). On last follow-up all patients were alive, none had developed leukemia. 5 patients experienced hematological remission. 2 of these children had not received any therapy. CONCLUSIONS: Many patients had symptoms attributable to ET. The clinical course is heterogeneous with complete normalization of platelets in the absence of cytoreductive therapy in some children. Due to the low incidence of ET in children indications for therapy are unclear and can only be deduced from findings obtained from studies in adults.     

Reduced lung diffusion capacity after Mycoplasma pneumoniae pneumonia

BACKGROUND: Mycoplasma pneumoniae is a frequent but underdiagnosed cause of community-acquired pneumonia (CAP) in children, and appropriate macrolide treatment is often given late. The aim of this work was to estimate the frequency of pulmonary involvement in children 6 months after a clinical episode of Mycoplasma CAP. METHODS: We measured carbon monoxide diffusion capacity (TLCO) and conducted spirometric tests in 35 children without asthma or chronic lung disease (ages 4.5 to 15 years), 6 months and 1 year after acute CAP caused by M. pneumoniae (23 children), pneumococci (5 children) or viruses (7 children). Only 11 of 23 patients with M. pneumoniae CAP required hospitalization, whereas all the patients with pneumococcal or viral pneumonia were admitted to hospital. RESULTS: Lung volumes and spirometric tests were normal for all children. TLCO was normal 6 months after pneumococcal or viral pneumonia (87 to 112% of expected values for height and sex). After acute M. pneumoniae CAP, 11 of 23 patients (48%) had TLCO values <80% of the expected value. The extent of change in lung diffusion capacity was correlated with the delay to diagnosis and treatment: TLCO was low in 8 of 11 patients given macrolide treatment 10 days or more after the onset of acute symptoms vs. only 3 of 10 patients given appropriate treatment in the first 10 days. TLCO was low in 7 of 7 who received macrolide therapy for <2 weeks. TLCO had increased slightly after 1 year in the 5 patients retested after a new course of macrolide treatment. TLCO reached the lower normal range in 2 patients controlled after 3 years. CONCLUSIONS: The abnormal TLCO values suggest that some children with Mycoplasma pneumonia have reduced pulmonary gas diffusion after recovery from the illness. The reduction is related to delay and short macrolide therapy.     

Results of an endocrinological follow-up of patients with childhood-or adolescent-onset malignancies

BACKGROUND: Established reports about endocrine follow-ups in children and adolescents with cancer were rare. PATIENTS: 53 children were included in the clinical trial. The mean age was 9.6 years (0.5; 17.2 years), 10 patients died within the study period. The mean body length was normal with -0.14 SDS (-2.3; 2.5 SDS), as well as the body weight with 0.01 SDS and BMI with a mean of -0.03 SDS. Children and adolescents with different types of malignant tumors were included. According to the therapy protocol or tumor entity we divided this population in 5 subgroups (group 1 leukemia with 17 patients, group 2 lymphoma with 11 patients, group 3 tumor of CNS with 10 patients, group 4 bone and soft tissue tumors with 8 patients, group 5 different tumors with 7 patients). METHOD: Anthropometrical and laboratory parameters were analyzed in intervals of 6 months over 2 years from the time point of diagnosis. RESULTS: We found differences in body height in children affected by cerebral tumors at the time of diagnosis and therefore before any therapy was started. These patients were significantly shorter (-0.6 SDS) than the other children. The body weight increased within the first year of therapy and was still higher than normal in the second year (comparison at the time point; from start to the first year+0.5 SDS, to second year+0.4 SDS) independently from the cortisone administration. Moreover, significant differences in the growth factor concentrations between the groups and time points were identified. Interestingly, children who survived their malignant disease tended to have higher levels of IGF-I and IGFBP-3 concentration than the patients who died within the study period. Additionally, the thyroid function was affected, shown as an increase of TSH with a concomitant decrease of the free thyroxin in 91% of all patients independent from the diagnosis (start TSH 1.8, fT4 15.6, after first year TSH 2.8, fT4 15.0). Thyroid function was monitored in 12 children, in 5 patients a short- or long-term substitution with thyroid hormone was indicated. Endocrine testing was initiated in 4 children, in 2 patients affection of the adrenal gland could be excluded, a suspected pituitary dysfunction after radiation was confirmed in 2 patients. CONCLUSION: We could represent that children and adolescents with malignant diseases showed affection of the endocrine system due to the tumour and the intensive therapy. The dysregulations in the endocrine system can be diagnosed through closely spaced monitoring and interdisciplinary cooperation.     

Lymphocyte-predominant Hodgkin disease in children

PURPOSE: To describe the clinicobiological features, treatment, treatment outcome, and sequelae of children with lymphocyte-predominant Hodgkin disease. PATIENTS AND METHODS: The authors performed a retrospective chart review of 754 patients with Hodgkin disease diagnoses at New York Medical College and St. Jude Children's Research Hospital from 1962 to 2000 to identify those with lymphocyte-predominant histology. Hematopathologists at the treating institutions reviewed stored tissue specimens and reconfirmed the histopathology of each case. RESULTS: Fifty-one children (44 boys, 7 girls) were identified. The median age was 10.5 years (range 3.2-18.5); five children were younger than age 60 months. The median duration of lymphadenopathy before diagnosis was 4 months (range 0.5-30). Thirty-six children had stage 1 disease, eight had stage 2 disease, four had stage 3 disease, and three had stage 4 disease. Fifteen children underwent staging laparotomy, and four of these were upstaged. Treatment comprised combined modality therapy (n = 27), radiation therapy alone (n = 17), and chemotherapy alone (n = 7). Four children had a Hodgkin disease recurrence. Forty-eight (94%) patients were alive and disease-free at a median follow-up of 8 years (range 0.4-32.6). Eleven patients had long-term, therapy-related adverse effects (cardiac, infertility, pulmonary, and second malignant neoplasms). Three patients died. Two died of complications of second malignant neoplasms and one died of infectious complications after Hodgkin disease recurrence. CONCLUSIONS: Children with lymphocyte-predominant Hodgkin disease respond favorably to a variety of treatment modalities and are ideal candidates for less toxic therapy.     

Inhaled corticosteroids for maintenance treatment in childhood pulmonary sarcoidosis

We present our experience with sequential oral and inhaled corticosteroid therapy in childhood pulmonary sarcoidosis. Fifteen children were followed-up for a mean of 7y. Treatment consisted of oral prednisolone 2mg/kg/d on initial diagnosis. After remission was reached, alternate day therapy with 1 mg/kg was continued. The dose was tapered to a maintenance dose which controlled the activity of the disease. When patients were free of symptoms and had no clinical and laboratory findings, inhaled corticosteriod treatment was started. Relapse treatment consisted of cessation of inhaled corticosteroids and start of oral corticosteroids at a dosage of 2 mg/kg/d and then a tapered dose. Five patients were given oral corticosteroids only. Nine patients were given inhaled steroids after oral corticosteroid therapy had been discontinued. Clinical and radiological remissions were achieved in every patient.
Conclusion : Sequential oral and inhaled corticosteroid therapy may be an alternative treatment regimen for sarcoidosis in children.     

儿童系统性红斑狼疮合并脑后部可逆性脑病综合征4例并文献复习

目的 分析儿童系统性红斑狼疮（SLE）合并脑后部可逆性脑病综合征（PRES）的临床特征,提高对本病的认识。方法 报告北京协和医院诊断的4例儿童SLE合并PRES的临床资料,在PubMed数据库检索相关病例行文献复习,分析儿童SLE合并PRES的临床表现、影像学检查、治疗及预后情况。结果 ①4例SLE患儿均伴有狼疮性肾炎,从确诊SLE至出现PRES的时间1~63个月,出现PRES时1例正在接受甲泼尼龙及环磷酰胺(CTX)冲击治疗。PRES均以惊厥、头痛起病,并伴血压升高。②PubMed数据库检索到11例SLE合并PRES的儿童病例,结合本文报道的4例,15例进入分析。女性14例。年龄最小8岁。从确诊SLE至出现PRES的间隔中位时间为6个月（1个月至8年）。15例出现PRES时均有惊厥发作,10例伴头痛,7例呕吐,9例意识丧失,7例视力障碍。15例均有血压升高。12例有狼疮性肾炎。治疗SLE予甲泼尼龙或CTX冲击治疗分别为4和3例,予羟氯喹2例,予环孢素和利妥昔单抗各1例,PRES分别发生在免疫抑制剂治疗后的2 d至4年。15例行头颅MRI检查示大脑后循环皮质下白质受累为主。12例予降血压治疗,10例予抗惊厥药物短期治疗。9例SLE处于活动期,继予糖皮质激素和免疫抑制剂治疗;6例非活动期的SLE患儿减停糖皮质激素及免疫抑制剂。15例神经系统症状均恢复,随访均未遗留神经系统后遗症。9例复查头颅MRI示颅内病变完全或基本消失。结论 儿童SLE合并PRES主要表现为惊厥、头痛、意识障碍和视觉障碍。对于有狼疮性肾炎的SLE患儿血压升高时,尤其同时予大剂量糖皮质激素或CTX等免疫抑制剂治疗时,应警惕PRES的发生。早期诊断和治疗PRES预后较好。     

Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes

Sumpter KM, Adhikari S, Grishman EK, White PC. Preliminary studies related to anti‐interleukin‐1β therapy in children with newly diagnosed type 1 diabetes. Background: Interleukin‐1β (IL‐1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL‐1β in patients with this disorder. We characterized the effects of IL‐1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL‐1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL‐1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed‐meal tolerance testing (MMTT) at 3–4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL‐1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra‐treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin‐dose‐adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.     

婴幼儿原发性心脏肿瘤的诊断与治疗

目的:总结婴幼儿原发性心脏肿瘤的诊断和治疗经验。方法:回顾性分析2013年8月至2019年2月大连医科大学附属大连市儿童医院心脏中心收治的7例疑似原发性心脏肿瘤婴幼儿的诊治过程,患儿均行超声心动图等检查明确诊断,根据肿瘤的大小和位置选择治疗方案。出院后行随访观察。结果:7例患儿均经超声心动图诊断为原发性心脏肿瘤,其中2...     

Investigation of TT virus in the etiology of pediatric acute lymphoblastic leukemia

Infectious agents have been implicated in the pathogenesis of pediatric acute lymphoblastic leukemia (ALL). A novel human DNA virus, TT virus (TTV), has been identified in children possessing characteristics as an etiologic agent, making the virus a potential candidate. Analysis of specimens from children with ALL was performed to determine if an association exists. Archived specimens (79 peripheral blood mononuclear cells, PBMC/bone marrow cells, BMC, and 125 cerebrospinal fluid, CSF) obtained at diagnosis and during therapy from 28 pediatric patients were tested for TTV. All of the diagnostic BMC/PBMC were negative for TTV, but 7 patients had follow-up specimens that converted to TTV positivity. TTV was not detected in any CSF. The absence of TTV at diagnosis suggests TTV is unlikely to be causally associated with ALL in the cases analyzed. However, the data support TTV transmission through blood products and suggest that the CNS is not a sanctuary site for TTV.     

OFF-LABEL USE OF GRANULOCYTE COLONY-STIMULATING FACTOR IN NONCONGENITAL NEUTROPENIA: Retrospective Data from the Italian Neutropenia Registry

This paper reviews a series of 70 consecutive children with rhabdomyosarcoma (RMS) diagnosed during 1971-1978 and treated in five Italian institutions. Thirteen were classified as group I, 12 as group II, 37 as group III, and 8 as group IV according to the Intergroup RMS Study staging system. Survival was influenced by tumor extension at diagnosis, primary site, and response to therapy. The 5-year-survival rate was 92% for group I patients, 67% for group II, 44% for group HI, and 0% for group IV. Thirty-four children had all therapy stopped after 12-32 months of complete remission, 7 had late recurrences, and 3 died from disease. Musculoskeletal sequelae were diagnosed in 11 children, short stature in 3, corneal opacity in 2, and cardiac failure in 1.     

Euthyroid sick syndrome in children with Hodgkin disease

Euthyroid sick syndrome is related to profound changes in thyroid metabolism induced by nonthyroidal diseases. To determine whether children with newly diagnosed Hodgkin disease might present thyroid abnormalities and to establish their predictive value, the authors performed regular thyroid function testing. Seven children (5 M, 2 F) with a mean age of 10.4 years (range: 4.6-15 years) at diagnosis were studied for a period of 6.9 years (4.2-10.5 years). Five patients presented at diagnosis with euthyroid sick syndrome characterized by borderline low thyroxine circulating levels (T3 0.8-1.3 ng/mL, FT3 1.5-1.7 pg/mL) and mildly raised TSH (4.6-5 microU/mL). Thyroid function turned normal within 6 months of therapy. Subsequently, 3 children developed overt hypothyroidism (T4 35-40 ng/mL, FT4 2-7 pg/mL, TSH 5.5-11 microU/mL) requiring substitution therapy. Euthyroid sick syndrome was not associated with a poorer outcome in terms of survival or long-term thyroid consequences. Thyroid function testing should be performed routinely at diagnosis and thereafter in children with Hodgkin disease to detect subtle abnormalities.     

Long-Term Results in Childhood Rhabdomyosarcoma: A Retrospective Study in Italy

This paper reviews a series of 70 consecutive children with rhabdomyosarcoma (RMS) diagnosed during 1971-1978 and treated in five Italian institutions. Thirteen were classified as group I, 12 as group II, 37 as group III, and 8 as group IV according to the Intergroup RMS Study staging system. Survival was influenced by tumor extension at diagnosis, primary site, and response to therapy. The 5-year-survival rate was 92% for group I patients, 67% for group II, 44% for group HI, and 0% for group IV. Thirty-four children had all therapy stopped after 12-32 months of complete remission, 7 had late recurrences, and 3 died from disease. Musculoskeletal sequelae were diagnosed in 11 children, short stature in 3, corneal opacity in 2, and cardiac failure in 1.     

Diagnosis, misdiagnosis, and associated diseases of achalasia in children and adolescents: a twelve-year single center experience

Purpose

Although achalasia is a rare disorder in children, its symptom may mimic common childhood diseases. This study aimed to assess the diagnosis and management of achalasia in children and adolescents in a Brazilian single center during a 12-year period.

Methods

Patients with achalasia were identified from a database built during the period of January 2000?CJanuary 2012 from a Pediatric Gastroenterology reference center. Information regarding demographic data, clinical symptoms, diagnosis, treatment, and long-term follow-up were described.

Results

Thirteen patients were studied; median age was 7 (1?C14)?years. Most frequent symptoms were vomiting (84.6?%) and dysphagia (69.2?%). Weight loss occurred in 46.0?% of patients and chronic cough in 46.1?%. Associated disorders were Down??s syndrome, Allgrove syndrome, and congenital central hypoventilation syndrome. Achalasia was misdiagnosed with anorexia nervosa. Six patients were previously treated as having gastroesophageal reflux disease and asthma. Five patients had pneumatic balloon dilation as initial therapy whereas five had esophageal myotomy. Finally, 11 patients had surgical therapy with a favorable follow-up.

Conclusion

Achalasia symptoms may mimic common diseases in children, and therefore, may delay the diagnosis. This study emphasizes the importance of the clinical symptoms for the diagnosis of achalasia, mainly in those cases with associated disorders.     

Analysis of causes of death during intensive chemotherapy according to treatment protocol AML-BFM 93

BACKGROUND: During intensive chemotherapy for AML, more than 10% of patients die because of treatment complications but not because of progression of their underlying disease. In order to improve supportive care and to decrease mortality, we analysed the causes of death and their relationship to the cycles of chemotherapy in children undergoing treatment for AML according to the study AML-BFM 93. RESULTS: Thirty-five (7.4%) of a total of 471 patients treated according to protocol AML-BFM 93 died before or within the first 6 weeks after diagnosis (early death). Fourty-nine patients (10%) did not achieve remission, and 18 (4 %) died of therapy-related complications after having achieved remission. In comparison to earlier AML-BFM studies, early mortality was reduced from 13%, 12%, 9% (AML-BFM 78, 83, 87) to 7% (AML-BFM 93, p-trend = 0.03). In contrast, mortality of patients in complete continuous remission (CCR) did not change. Infectious complications, in particular due to bacterial and fungal pathogens, were the main cause of death. One patient died of arrhythmia associated with SIAD. After stem-cell transplantation in first remission, 7 of 51 patients died, mainly because of graft-versus-host-disease and/or infections. The incidence of infectious complications decreased with the number of chemotherapy cycles and was highest during induction therapy. Fatal complications occurred in one patient during maintenance therapy and in one patient thereafter; both patients were in CCR. Another 14 patients died during intensive therapy (before day 150) mostly with a low percentage of blasts, but no haematologic recovery. The cause of death in these children was mainly bacterial infection or invasive aspergillosis, but seldom progression of leukaemia. CONCLUSION: This analysis confirmed the high incidence of fatal infections in children with AML during chemotherapy-induced severe neutropenia. To increase overall survival in children undergoing therapy for AML, we propose (1) to improve the prophylactic and therapeutic measures for haemorrhage and infections, (2) to continue risk-adapted therapy and (3) to treat high-risk patients in specialised centres only.     

DIAGNOSIS OF CONGENITAL NEPHROTIC SYNDROME: A CLINICAL AND A PATHOLOGIC CHALLENGE

The diagnosis of congenital nephrotic syndrome (NS) is a challenge both for clinicians and for pathologists. We observed three cases in a series of 50 children with NS nonresponsive to therapy, corresponding to one case each of minimal change disease, Finnish-type glomerulopathy, and diffuse mesangial sclerosis--two histopathologic studies were performed in each case. The age at presentation did not predict the diagnosis nor the prognosis: The NS presented at 7 months of age in the patient with diffuse mesangial sclerosis, but it was present at birth in the patient with minimal change disease. In these 2 patients the final diagnosis was made with the first renal biopsy. Conversely, in the patient with Finnish-type glomerulopathy, the diagnosis was only possible in the repeat biopsy, as the early pathologic changes were nonspecific. This study shows the essential role of the renal biopsy in determining the etiologic diagnosis and prognosis in patients with congenital nephrotic syndrome.