上海儿童医学中心WT-99方案诊治儿童肾母细胞瘤临床报告

目的：改善儿童肾母细胞瘤预后。方法：对1998年10月-2001年10月住院明确诊断为肾母细胞瘤及肾肉瘤的20例病人采用外科手术、内科化疗、选择性放疗,病理科、影像学科协作诊断综合治疗（即上海儿童医学中心WT-99方案）。按方案中条件根据分期及其他危险因素进行分组,并按分组给予不同药物组合和强度的化疗。Ⅰ期及Ⅱ期病理分型预后良好型的不放疗,估计手术不能完全切除时给予2个疗程术前化疗。结果：全组20例,年龄7个月至12岁。病理分类预后良好型14例,预后不良型3例;透明细胞肉瘤2例,横纹肌肉瘤样1例。临床结合病理分期为Ⅰ期5例,Ⅱ期5例,Ⅲ期6例,Ⅳ期3例,Ⅴ期1例。全组20例中获完全缓解18例（90％）,2例初治失败,缓解后复发1例。无病生存时间平均27个月17例（11-45个月）,占85％,目前均已停药。结论：所采用多专业联合诊断治疗工作模式及上海儿童医学中心WT-99诊治方案对儿童肾母细胞瘤有效。     

单中心儿童肾肿瘤SCMCWT-99方案临床报告

目的 改善儿童肾母细胞瘤预后。方法 对1998年10月至2007年12月住院明确诊断为肾母细胞瘤及肾肉瘤患儿,采用外科手术。内科化疗。选择性放疗,病理科。影像学科协作诊断综合治疗的上海儿中心WT-99方案。按方案中条件根据分期及其他危险因素进行分组,并按分组给予不同药物组合和强度的化疗。Ⅰ期及Ⅱ期病理分型预后良好型不放疗。估计手术不能完全切除时给予2个疗程术前化疗。结果 全组54例,年龄3个月至13岁。病理分类预后良好型39例,预后不良型4例,透明细胞肉瘤5例,横纹肌肉瘤样1例,分型困难或未分化型5例。临床结合病理分期为Ⅰ期19例,Ⅱ期7例,Ⅲ期19例,Ⅳ7例,Ⅴ期2例。54例中获完全缓解51例（94.4%）,3例初治失败。缓解后复发9例。随访1-104个月,中位31.5个月,估计5年无病生存率（EFS）和总生存率（SR）分别为75.7%和83.9%。结论 多专业联合诊断治疗工作模式及儿中心WT-99方案对儿童肾母细胞瘤有效。     

单中心儿童肾肿瘤SCMC WT-99方案临床报告

目的改善儿童肾母细胞瘤预后。方法对1998年10月至2007年12月住院明确诊断为肾母细胞瘤及肾肉瘤患儿,采用外科手术、内科化疗、选择性放疗,病理科、影像学科协作诊断综合治疗的上海儿中心WT-99方案。按方案中条件根据分期及其他危险因素进行分组,并按分组给予不同药物组合和强度的化疗。Ⅰ期及Ⅱ期病理分型预后良好型不放疗。估计手术不能完全切除时给予2个疗程术前化疗。结果全组54例,年龄3个月至13岁。病理分类预后良好型39例,预后不良型4例,透明细胞肉瘤5例,横纹肌肉瘤样1例,分型困难或未分化型5例。临床结合病理分期为Ⅰ期19例,Ⅱ期7例,Ⅲ期19例,Ⅳ7例,Ⅴ期2例。54例中获完全缓解51例(94.4%),3例初治失败。缓解后复发9例。随访1～104个月,中位31.5个月,估计5年无病生存率(EFS)和总生存率(SR)分别为75.7%和83.9%。结论多专业联合诊断治疗工作模式及儿中心WT-99方案对儿童肾母细胞瘤有效。     

肾母细胞瘤WT2003方案中放疗策略:附18例回顾性分析

目的 改善肾母细胞瘤放疗方案。方法 对1998年10月-2006年10月明确诊断肾母细胞瘤及肾透明细胞肉瘤、肾横纹肌样肉瘤术后18例患儿,按WT99和WT2003方案,FHⅢ期及以上,UFH各期进行全腹或瘤床放疗,放疗剂量10.8 Gy至21.6 Gy,肺转移全肺为12 Gy。结果 18例中年龄17个月-10岁。病理分型为预后良好型9例,预后不良型4例（局灶型1例,弥漫型1例,未分型2例）,透明细胞肉瘤2例,横纹肌肉瘤样1例,其他2例（化疗后不能分型）;分期结果为Ⅱ期4例,Ⅲ期10例,Ⅳ期2例,Ⅴ期2例。18例中获完全缓解16例（88.9%）,缓解后复发1例。结论 多学科多中心协作模式对儿童肾母细胞瘤有效,WT2003方案中放疗策略需随着放疗技术的发展而作修正。     

儿童腹膜后肿瘤累及血管的外科治疗

目的探讨儿童腹膜后肿瘤累及血管的外科手术处理。方法回顾总结手术治疗腹膜后肿瘤94例，其中肾母细胞瘤40例，肾透明细胞肉瘤、恶性肾上腺皮质癌各1例，Ⅲ～Ⅳ期神经母细胞瘤52例，并对这些患儿的临床资料和诊疗经过进行分析。结果肾母细胞瘤5例瘤栓累及下腔静脉，3例切开血管壁取出瘤栓，2例化疗瘤栓缩小后再手术。肾透明细胞肉瘤1例，穿刺活检明确病理诊断后化疗、手术、放疗。恶性肾上腺皮质癌1例，放弃治疗。Ⅲ～Ⅳ期神经母细胞瘤52例，均化疗后延迟手术。无血管损伤大出血、重要脏器受损切除等并发症的发生。结论儿童腹膜后肿瘤累及血管时手术难度大，需化疗、手术和放疗综合治疗，才能提高手术的切除率和安全性。     

儿童肾肿瘤多中心协作组288例诊治报告

目的:总结中国小儿肿瘤专业委员会(CCCG)肾母细胞瘤(WT)-2015方案的疗效。方法:前瞻性研究,在CCCG-WT-2009方案基础上修正建立WT-2015方案。总结2015年9月至2018年12月在14家协作组成员单位明确诊断的288例初发肾肿瘤患儿的临床资料。分析儿童肾肿瘤的发病年龄、病理亚型分布、分期、疗效及预后因素。生存曲线应用Kaplan-Meier法,单因素分析应用Log-Rank法。结果:288例肾肿瘤中WT 261例,其中良好组织学型(FH)WT 254例,占97.3%,间变型(UFH)WT 7例,占2.7%。FHWT、UFHWT 3年无事件生存率(EFS)分别为(88.9±2.1)%、(80.0±17.9)%,优于WT-2009方案的81.2%、71.7%。Ⅲ、Ⅳ期FHWT有放疗指征者96例,其中76例实施放疗,20例因未放疗升至M方案化疗(环磷酰胺、依托泊苷、更生霉素、长春新碱、阿霉素),放疗与未放疗患儿3年EFS分别为(84.7±4.3)%及(84.7±8.1)%,预后差异无统计学意义(χ2=0.015,P=0.902)。肾肉瘤包括肾透明细胞肉瘤22例和肾横纹肌样瘤5例。3年EFS分别为(94.4±5.4)%及(20.0±17.9)%。将年龄、性别、病理类型、分期、手术中破溃否、治疗结束是否达到完全缓解(CR)、放疗否进行预后单因素分析,结果发现病理类型(χ2=44.329,P<0.01)和治疗结束时是否达到CR(χ2=49.459,P<0.01)是独立预后影响因素。结论:CCCG-WT-2015方案与WT-2009方案相比,预后改善,可扩大协作组对象应用本方案。     

多学科协作在儿童实体瘤诊断治疗整体方案中作用探讨

目的 有效实施儿童实体瘤的诊断治疗计划，提高儿童实体瘤的疗效。方法 建立由外科、肿瘤内科、放疗科、病理科、影像学科为基本组成的多学科协作小组，前瞻性设计诊断治疗方案，小组成员既分工又充分合作，对65例儿童实体瘤病人按方案及时实施合理的诊断和治疗步骤。结果 肾母细胞瘤26例，神经母细胞瘤21例，Ⅲ～Ⅳ期其他实体瘤18例，共65例病儿均得到明确的病理诊断与分型，并得到明确的分期或临床分组。65例中63例按时按期进人相应的治疗方案。26例。肾母细胞瘤中获完全缓解24例(92．30％)，其中延迟手术肿瘤完全切除1例；缓解24月复发获再次缓解1例；平均无病生存30个月(10～53个月)24例，占92．30％。神经母细胞瘤21例，获完全缓解15例，缓解率为71．42％，其中10例为化疗后延迟手术肿瘤完全切除；获随访18例，无病生存11～52个月11例(61．11％)，平均32个月。其他Ⅲ～Ⅳ期实体瘤(横纹肌肉瘤、尤文氏肉瘤和生殖细胞性恶性肿瘤)共18例，获完全缓解15例(83．33％)；无病生存13～53个月11例，占61．11％，平均29个月。结论 多学科协作的工作方式及所采用的诊断治疗方案对儿童实体瘤有效，值得推广。     

Ⅲ、Ⅳ期肾母细胞瘤综合治疗15年经验

目的总结近15年来对Ⅲ、Ⅳ期。肾母细胞瘤患儿的多模式综合治疗经验。方法1995年5月至2010年12月浙江大学医学院附属儿童医院共对26例单侧Ⅲ、Ⅳ期肾母细胞瘤患儿采用多模式的综合治疗。诊断标准：肾门、主动脉旁淋巴结转移;弥漫性腹腔播散或术时散落;腹膜有肿瘤种植;镜检或肉眼有肿瘤残留;局部浸润至重要脏器;肿瘤远处转移。全部病例按年限和治疗方式分为两组：①术前单纯介入治疗组（TACE组）11例,为1995年至2002年收治病例,采用术前肾动脉化疗栓塞（TACE）,1周后手术切除瘤肾,术后化疗或加放疗的综合治疗;②术前介入治疗加短期全身化疗组（T＋S组）15例,为2003年至2010年收治病例,采用术前TACE加2～3周静脉化疗,然后手术切除瘤肾,术后化疗或加放疗的综合治疗。TACE采用吡柔比星40mg／m。,长春地辛3mg／m2,超液碘油5～10mL。术前短期静脉化疗采用长春地辛3mg／（m2·周）,共2次;放线菌素D10we／（kg·d）,共5次。术后化疗和放疗按照北京儿童医院肾母细胞瘤治疗方案。TACE组与T＋s组分别有3例和9例接受术后放疗。结果两组患儿术后分期为：TACE组Ⅲ期10例,Ⅳ期1例;T＋S组Ⅲ期11例,Ⅳ期4例。两组各有弥漫问变型2例。两组肿瘤完整切除率分别为63．6％（7／11）和80．0％（12／15）,P=0．407。随访至2010年12月,两组平均随访时间分别为118（102—186）个月和43．5（1～92）个月,无瘤生存率分别为72．7％和100．0％,Kaplan-Meier生存分析显示两组差异有统计学意义（P=0．040）。结论本研究表明,术前动脉栓塞化疗加短期静脉化疗,手术切除瘤肾,术后继续化疗和放疗的多模式综合治疗是对Ⅲ、Ⅳ期肾母细胞瘤患儿的合理治疗方案。     

儿童恶性肾横纹肌样瘤3例临床分析及文献回顾

目的通过总结3例原发于肾脏的儿童恶性横纹肌样瘤的临床资料,探讨儿童肾横纹肌样瘤的诊断、治疗及预后。方法收集我院近8年来收治的3例病理明确诊断的原发于肾脏的恶性横纹肌样瘤（男2例,女1例）,对其发病特点、病理特点、治疗及随访等临床资料进行总结分析,并复习相关文献。结果根据国际儿童肿瘤组织肾横纹肌样瘤的临床分期诊断,3例患儿均为Ⅲ期。均行手术、化疗及放疗治疗。化疗以ICE与VDC交替方案为主,化疗周期分别为6、6、15周期,放疗采用外放疗。随访至2012年7月（3例随访时间分别是8、14、8个月）。2例获完全缓解（CR）,1例复发后经手术、化疗及放疗后病情部分缓解（PR）。结论恶性肾横纹肌样瘤是一种少见、病理形态独特的肿瘤。治疗应在明确诊断和确切分期的基础上,行手术、化疗和选择性放疗的综合性治疗。     

儿童非肾母细胞瘤肾脏肿瘤的临床治疗探讨

目的总结和探讨儿童非。肾母细胞瘤肾脏肿瘤的治疗方法。方法1998年7月至2010年7月我们共收治非肾母细胞瘤肾脏肿瘤患儿18例,其中男性14例,女性4例,年龄最大9岁,最小2个月,平均年龄（40．17±34．04）个月,术后病理诊断包括肾透明细胞肉瘤9例（9／18,50％）,肾横纹肌样瘤2例（2／18,11．1％）,肾癌2例（2／18,10．1％）,肾中胚层。肾瘤1例（1／18,5．56％）,后。肾间质瘤1例（1／18,5．56％）,后肾腺瘤1例（1／18,5．56％）,肾血管平滑肌脂肪瘤1例（1／18,5．56％）,肾原始神经外胚叶瘤1例（1／18,5．56％）。结果随访9例肾透明细胞肉瘤,8（8／9）例无瘤生存,最长随访时间5年,最短2个月,平均随访时间（24．56±17．27）个月,1例手术化疗后下腔静脉瘤栓残留水平至右心房入口,放弃治疗1．5年后死亡。2例肾横纹肌样瘤经手术、放疗及化疗,随访3年和4年均无瘤存活。2例。肾癌单纯手术切除,密切随访25个月、13个月无复发及转移。1例。肾原始神经外胚叶瘤经手术及化疗,随访16个月无瘤存活。1例肾中胚层肾瘤、1例后。肾间质瘤、1例后。肾腺瘤、1例肾血管平滑肌脂肪瘤均完整切除,现最长随访时间4年,最短1年,无一例复发。结论儿童非肾母细胞瘤肾脏肿瘤所占比例虽小,但临床鉴别诊断困难,病理诊断非常重要,手术、化疗及放疗综合治疗是诊治的首要选择。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

Understanding infant formula

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.