儿童初治肝母细胞瘤83例临床特征及预后分析

目的探讨肝母细胞瘤(HB)患儿的临床特征、生存情况及预后危险因素。方法回顾性分析2012年1月至2019年10月郑州大学第一附属医院儿童医院血液肿瘤科收治的83例初治HB患儿的临床资料, 记录患儿的性别、年龄、首发临床表现、治疗前病变范围(PRETEXT)分期、病理类型、病初甲胎蛋白(AFP)、治疗方法及治疗结果。2018年之前确诊的患儿采用"武汉方案"治疗, 2018年之后确诊的患儿采用"儿童肝母细胞瘤多学科诊疗专家共识(CCCG-HB-2016)"方案治疗。Kaplan-Meier生存分析法计算生存率, 单因素分析采用Log-Rank检验, 多因素预后分析采用Cox回归模型。结果 83例患儿中男51例、女32例;发病年龄25.2(9.0, 34.0)月龄, <3岁64例(77%)。最常见的首发临床表现为腹部包块(45例, 54%)。PRETEXT Ⅰ期8例, Ⅱ期43例, Ⅲ期20例, Ⅳ期12例。随访时间40(17, 63)个月, 全组HB患儿1年总体生存率(OS)和无事件生存率(EFS)分别为(84±4)%和(79±5)%, 5年OS和EFS分别为(78±5)%和(76±...     

小儿肝母细胞瘤24例的临床特点及预后因素分析

目的探讨小儿肝母细胞瘤的临床特点和生存状况,明确其预后影响因素。方法 2009年1月-2013年6月上海市儿童医院初诊并接受治疗的肝母细胞瘤共24例,采用国际儿童肿瘤协会的PRETEXT分期法进行疾病分期,采用手术和化疗相结合的治疗方法,评估其生存率与疾病分期、治疗策略的相关性。结果 24例患者中男15例,女9例,平均年龄(19±12.4)个月。随访至2014年6月30日,平均随访时间(25.6±19.5)个月。Ⅱ期3例(12.5%),Ⅲ期12例(50%),Ⅳ期9例(37.5%),5年总体生存率(OS)和无病生存率(EFS)分别为65.63%±9.83%和43.93%±12.04%。Ⅱ期、Ⅲ期、Ⅳ期的5年OS分别为:100%、91.67%±8.33%和22.22%±14.7%(P=0.001);5年EFS分别为100%、48.89%±13.06%和12.5%±16.67%(P=0.0003)。治疗策略上先行肿瘤根治术3例,均痊愈;余21例行肿瘤穿刺/活检,化疗,手术,再化疗,至今生存13例,复发死亡4例,放弃/失访4例。结论小儿肝母细胞瘤发病年龄小,治疗倾向于手术完整切除为主,辅以术前和术后化疗。疾病分期和肿瘤的完整切除是影响肝母细胞瘤的危险因素。     

14例肝母细胞瘤患儿的临床疗效观察

目的：通过对儿童肝母细胞瘤患儿的临床治疗结果的回顾总结,对ICE化疗方案的有效性和安全性进行评估。方法：自2000年6月至2008年6月,14例初发患儿入选,男7例,女7例,中位年龄：1.33岁（范围0.25～8.25岁）。临床分期：Ⅰ期6例,Ⅱ期1例,Ⅲ期5例,Ⅳ期2例。诊断时血甲胎蛋白（AFP）水平显著升高13例,1例AFP正常。采用多科室协作模式进行治疗,其中一期手术8例,3例进行了二期手术。化疗方案采用ICE方案,14例患儿共接受了73个疗程化疗,其中术前化疗25个疗程。结果：14例患儿治疗后有效12例（85.7%）,其中完全缓解10例（71.4%）,部分缓解2例,2例无效。随访至2008年7月31日,疾病处于长期完全缓解者9例（64.3%）,中位随访时间为35个月（范围：16～96个月）。5年总生存率（OS）为：（70.71±12.37）%,5年无事件生存率（EFS）为：（64.29±12.81）%。1例患儿复发,2例失访。结论：ICE化疗方案联合手术治疗能有效并且安全地治疗儿童肝母细胞瘤,Ⅳ期患儿的治疗有待于进一步研究。［中国当代儿科杂志,2009,11（8）：659-662］     

中国儿童白血病协作组2018方案治疗儿童急性T淋巴细胞白血病的多中心中期结果总结

目的总结中国儿童白血病协作组2018(CCLG-ALL 2018)方案对急性T淋巴细胞白血病(T-ALL)的治疗效果, 并探讨影响预后的相关因素。方法前瞻性多中心队列研究。纳入国内21家三甲医院的新诊断T-ALL患儿共299例患儿为研究对象, 接受CCLG-ALL 2018方案的治疗, 收集临床资料, 评估治疗效果, 通过Lasso回归进行变量筛选, 利用筛选的变量进行模型构建, 评估与无事件生存率(EFS)、总生存率(OS)及累积复发率相关的预后指标。结果纳入299例新诊断T-ALL患儿, 占全部急性淋巴细胞白血病患儿的9.9%(299/3 026), 其中男224例、女75例, 发病年龄7.0(4.7, 10.6)岁。经过规范CCLG-ALL 2018方案治疗, 随访31.1(17.3, 43.8)个月, 患儿3年OS为(91.3±1.8)%, 3年EFS为(83.2±2.7)%, 累积复发率为(7.9±1.7)%。诱导治疗第15天微小残留病(MRD)>10.00%为EFS(HR=1.89, 95%CI 1.04～3.44)、OS(HR=2.82, 95%CI 1.35～5....     

儿童多系统受累朗格罕细胞组织细胞增生症53例临床分析

目的分析多系统受累朗格罕细胞组织细胞增生症(MS-LCH)患儿的临床特征及远期预后,评价改良DAL-HX83/90方案对MS-LCH患儿的疗效。方法回顾性病例分析。研究对象为2011年1月至2019年5月郑州大学第一附属医院儿童医院血液肿瘤科收治的53例MS-LCH患儿,初始化疗采用改良DAL-HX83/90方案,按是否累及危险器官分为无危险器官受累(RO-)组和累及危险器官(RO+)组,RO+组再分为Ⅰ组(仅肺受累)、Ⅱ组(肺外,伴或不伴肺受累),总结临床特征和随访结果,Kaplan-Meier生存分析法计算生存率,Log-Rank检验及Cox比例风险回归模型对年龄、性别、危险器官受累、6周诱导化疗反应进行单因素及多因素预后分析。结果53例MS-LCH患儿中男34例、女19例,发病年龄21月龄(3月龄至13岁),RO-组31例,RO+组22例,其中Ⅰ组12例、Ⅱ组10例。随访时间51(12~144)个月,6周诱导化疗有效率89%(47/53),进展复发率30%(16/53),5年无事件生存率(EFS)为(67±6)%,5年总生存率(OS)为(83±5)%。单因素分析发现6周诱导化疗有效者5年EFS、OS明显高于无效者[(76±6)%比0,(88±4)%比(41±22)%],差异均有统计学意义(χ²=34.743、10.608,均P<0.05)。RO-组5年EFS、OS明显高于RO+组[(80±7)%比(49±10)%,(93±4)%比(70±10)%],差异均有统计学意义(χ²=6.022、4.793,均P<0.05)。Ⅰ组5年EFS明显高于Ⅱ组[(83±10)%比(10±9)%],差异有统计学意义(χ²=9.501,P=0.002),年龄、性别与EFS、OS无明显相关性(均P>0.05)。Cox比例风险回归模型分析发现6周诱导化疗反应是影响EFS(HR=13.114,95%CI 3.759~45.742,P<0.01)、OS(HR=7.748,95%CI 1.542~38.920,P=0.013)的独立危险因素。结论采用改良DAL-HX83/90方案治疗无危险器官受累MS-LCH,患儿多数可获长期生存。但累及肝、脾或造血系统的MS-LCH患儿疾病进展和复发率较高。     

儿童肝母细胞瘤临床病理特征分析

目的探讨儿童肝母细胞瘤的临床病理特征。方法回顾分析经病理检查证实的68例肝母细胞瘤患儿的临床病理资料。结果 68例肝母细胞瘤患儿中男44例、女24例,3岁55例、≥3岁13例,初发时单发59例,甲胎蛋白(AFP)均明显升高。高危患儿27例,出现转移和/或肝外临近器官侵袭和/或门静脉及肝静脉三分支/下腔静脉受侵22例。术前影像分期PRETEXTⅣ期患儿13例。患儿年龄、AFP浓度、病理类型和PRETEXT分期有显著相关性(P均0.05);病理学类型和AFP浓度有显著相关性(P=0.002)。病理学类型在高危组、标危组之间的分布差异有统计学意义(P=0.043)。结论儿童肝母细胞瘤患儿临床病理特征差异性可能有助有指导临床治疗和预后评估。     

儿童肝母细胞瘤临床病理特征分析#br#

目的探讨儿童肝母细胞瘤的临床病理特征。方法回顾分析经病理检查证实的68例肝母细胞瘤患儿的临床病理资料。结果 68例肝母细胞瘤患儿中男44例、女24例,3岁55例、≥3岁13例,初发时单发59例,甲胎蛋白(AFP)均明显升高。高危患儿27例,出现转移和/或肝外临近器官侵袭和/或门静脉及肝静脉三分支/下腔静脉受侵22例。术前影像分期PRETEXTⅣ期患儿13例。患儿年龄、AFP浓度、病理类型和PRETEXT分期有显著相关性(P均0.05);病理学类型和AFP浓度有显著相关性(P=0.002)。病理学类型在高危组、标危组之间的分布差异有统计学意义(P=0.043)。结论儿童肝母细胞瘤患儿临床病理特征差异性可能有助有指导临床治疗和预后评估。     

CT对儿童原发肝脏卵黄囊瘤和肝母细胞瘤的鉴别诊断

目的 探讨儿童原发肝脏卵黄囊瘤的影像学表现,并寻找可能与肝母细胞瘤相鉴别的影像学特征。方法 回顾性分析北京大学第一医院收治的1例原发肝脏卵黄囊瘤患儿的临床表现,尤其是其影像学资料,与22例肝母细胞瘤资料进行对比分析,并复习相关文献。结果 原发肝脏卵黄囊瘤患儿为1岁11个月男童,甲胎蛋白(AFP)明显升高,腹部增强CT及B超均提示肝脏右叶巨大单发占位,未见明显钙化,肿物内可见出血、坏死,有包膜下积液等肿瘤破裂迹象。肝母细胞瘤患儿AFP亦明显升高,腹部增强CT提示多为单发肝脏巨大肿物,结节状多见,无包膜,多见点状或片状钙化,肿物周边有明显血流信号,未见有肿瘤破裂迹象。复习文献8例原发肝脏卵黄囊瘤患儿的影像学资料显示多有出血和坏死表现,1例有明显肿瘤破裂表现,无钙化。结论 原发肝脏卵黄囊瘤和肝母细胞瘤都表现为肝脏巨大占位伴AFP明显升高,前者影像学特征是肿物更容易出现出血、坏死和肿瘤破裂迹象,有包膜,无钙化,对二者有一定的临床鉴别价值。     

MicroRNAs在肝母细胞瘤诊断、鉴别诊断及预后评估中的研究进展

肝母细胞瘤(hepatoblastoma,HB)在儿童恶性肿瘤中较为罕见,多见于5岁以下儿童,男性较多见,约占儿童原发性肝脏恶性肿瘤的80%。其中仅95%的肝母细胞瘤存在甲胎蛋白(α-fetoprotein,AFP)异常升高,而且与病理类型、肿瘤分期等相关性不大。仅通过异常升高的AFP水平进行肝母细胞瘤诊断、鉴别诊断及预后评估存在一定的局限性。目前已有诸多研究发现mi RNAs在HB的发生、发展中起重要作用,且具有高度组织特异性、保守性和时序性,在不同病理类型的HB中m RNAs呈特异性表达。因此,有望联合AFP与micro RNAs进行HB的分子分型,组成HB的分子指纹,用于肝母细胞瘤诊断、鉴别诊断及预后评估,具有重要的参考意义。     

儿童肝母细胞瘤精准肝切除手术效果评价

目的对儿童肝母细胞瘤精准肝切除的手术效果进行评价,探讨肝母细胞瘤手术治疗方式。方法选取自2014年6月至2019年5月于首都医科大学附属北京儿童医院进行精准肝切除治疗的肝母细胞瘤患儿作为研究对象(为精准肝切除组)。回顾性收集患儿肿瘤分期、危险度分级、肿瘤生长部位、肿瘤体积大小、术前化疗情况、手术时间、术中失血量、术后血清谷丙转氨酶(alanine aminotransferase,ALT)水平、谷草转氨酶(aspartate aminotransferase,AST)水平、术后并发症、腹腔引流管留置时间、术后住院时间、远期生存状况等指标,并与同期收治的行标准肝叶切除手术的肝母细胞瘤患儿(为标准肝叶切除组)进行对比,对其手术疗效进行评估。结果本次研究共纳入134例患儿,其中88例行精准肝切除术(65.7%),46例行标准肝叶切除术(34.3%)。对比采用不同手术方式进行肿瘤切除手术的患儿,发现精准肝切除组术中失血量、ALT及AST水平低于标准肝叶切除组,术后引流管留置天数少于标准肝叶切除组。远期预后方面,两组2年无事件生存(events free survival,EFS)率和2年总体生存(overall survival,OS)率差异无统计学意义(P>0.05);应用PRETEXT分期(pretreatment extension stage)进行分层后发现,精准肝切除组中PRETEXTⅢ期患儿的2年OS率高于标准肝叶切除组。结论对于儿童肝母细胞瘤患者,在进行个体化评估后,采用精准肝切除手术可以达到完整去除肿瘤病灶、减轻手术打击、减少术后并发症的目的,预后良好。     

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     

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.     

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.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

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.     

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.     

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.