伴副肿瘤综合征儿童神经母细胞瘤临床特征分析

目的 探讨伴有副肿瘤综合征儿童神经母细胞瘤的临床特点、治疗策略及预后. 方法 回顾性分析湖南省儿童医院2010年1月至2019年12月收治的9例伴副肿瘤综合征神经母细胞瘤患者的临床资料,包括一般资料、副肿瘤综合征症状、肿瘤情况、治疗策略及预后.随访截至2020年6月1日. 结果 9例中男5例,女4例;起病年龄为19.0...     

Prognosis of prune belly syndrome]

The Prune Belly syndrome (PBS) is unfrequent. Fourteen cases have been followed in our unit during the last 20 years. Four infants (29%) died during the first months of life, because of neonatal sepsis (2 cases) or end-stage renal failure (2 cases). Among the other 10 cases, 6 (43%) had normal glomerular filtration rate at a mean age of 10 years 6 months (6 months to 15 years), 4 had chronic renal failure, including 3 cases who developed end-stage renal failure at 8, 8 years 8 months and 17 years respectively. Resection of an urethral obstruction was performed in 2 cases. This surgical indication remains widely accepted, while the current tendency is to limit ureteral surgery in PBS. Orchidopexy was performed in 4 children, 3 of them less than 6 years 6 months of age. Fertility of these early operated children remains to be established, as all adults reported in the literature remain sterile when orchidopexy was not performed or was performed after age 6.     

Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study

In some children with bilateral Wilms' tumor, reduction of tumor burden cannot be accomplished without total nephrectomy. In Denys-Drash syndrome, nephrectomy is required for associated Wilms' tumor or after progression to end stage renal disease secondary to diffuse mesangial sclerosis because of risk of development of Wilms' tumor. Current recommendation is to wait at least 1-2 yr after completion of chemotherapy for Wilms' tumor before renal transplantation. The North American Pediatric Renal Transplant Cooperative Study dialysis (1992-2001) and transplant registries (1987-2002) were analyzed, comparing children 0-18 yr old with Wilms' tumor and Denys-Drash syndrome to other primary diagnoses. There were 37 children with Wilms' tumor and 33 with Denys-Drash syndrome in the dialysis registry. Of these, 10 children with Wilms' tumor and three with Denys-Drash syndrome did not receive a renal transplant and all died. The cause of death was Wilms' tumor in eight children with Wilms' tumor and in one with Denys-Drash syndrome. The transplant registry included 43 children with Wilms' tumor, 43 children with Denys-Drash syndrome, and 7469 patients with other diagnoses. Acute rejection, graft and patient survival profiles from all three groups at 6 months, 1 and 3 yr post-transplant were comparable. There were no graft failures or deaths because of recurrent Wilms' tumor in the Drash group. There was one death with Wilms' tumor in the Wilms' group - a 2.5-yr-old child transplanted after 6 months of dialysis who died of Wilms' <6 months after renal transplantation. In conclusion, most children dialyzed because of Wilms' tumor and Denys-Drash syndrome who did not receive a renal transplant died of Wilms' tumor. However, the outcomes of children with Wilms' tumor and Denys-Drash syndrome who proceeded to renal transplantation are comparable with children with other diagnoses, with no graft failures because of recurrence and only one death from Wilms' tumor in a Wilms' patient who received only a short course of dialysis prior to transplantation. Current practices in children with Wilms' tumor and Denys-Drash syndrome appear to be on target to portend good outcome following renal transplantation.     

Urine microalbumin/creatinine ratios in Singapore children.

The random urine albumin:creatinine (Ua:Uc) ratio was measured in 139 healthy children from newborn to age 4 years using the immunonephelometric method. This was shown to vary with age, the mean for neonates being 5.24mg/mmol (2SD range: 0.54-14.95mg/mmol) decreasing to 1.34mg/mmol (2SD range: 0.55-3.29mg/mmol) for the 2-4 years age range. The values for newborn to 6 months was significantly higher than the older age group (p less than 0.000001). 14 children with structural renal disease were then studied to determine the value of the random Ua:Uc ratio in detecting glomerular injury. This was found to be abnormal in children with glomerular filtration rate (GFR) less than 80ml/min/1.73m2 as well as in some children with complex bilateral renal structural abnormalities. Further longitudinal studies are required to determine the usefulness of this ratio in predicting progressive glomerular injury in this group of patients.     

24例儿童高危神经母细胞瘤调强适形放疗的近期疗效分析

目的 总结分析高危神经母细胞瘤患儿调强适形放疗（intensity-modulated radiotherapy,IMRT）疗效、安全性及相关经验。方法 回顾性选取2018年4月至2020年12月于湖南省人民医院儿童血液肿瘤科进行诊治并完成IMRT的高危组神经母细胞瘤患儿24例,收集相关资料,包括年龄、放疗剂量、放疗次数、实验室检查结果、不良反应、生存情况,分别进行归纳总结。结果 24例患儿均接受IMRT,其中男14例、女10例;平均年龄（65±23）个月,中位年龄59个月;原发瘤灶23例位于腹部,1例位于纵隔。放疗时患儿中位年龄41.5个月。放疗辐射剂量范围为14.4~36.0 Gy,平均剂量为（22±3）Gy,每日剂量为1.8~2.0 Gy,总次数8~20次,平均次数11.9次。其中6例接受了残留灶或转移灶放疗。放疗过程中3例出现咳嗽,2例出现腹泻,1例出现呕吐。放疗后2周,血肌酐范围值2.3~70.1 μmol/L,丙氨酸氨基转移酶范围值9.1~65.3 U/L,放疗开始后1~2周出现骨髓抑制Ⅲ度10例,Ⅳ度2例;放疗开始后3~4周出现骨髓抑制Ⅲ度4例,Ⅳ度1例。随访中位时间为13.5个月,其中23例（96%）疾病稳定,1例死亡,截至随访日期,未发现第2次恶性肿瘤及脏器功能异常。结论 IMRT能有效提高神经母细胞瘤局部控制率。IMRT治疗神经母细胞瘤患儿,短期内无明显不良反应,安全性高。     

Cyclosporine in steroid dependent and resistant childhood nephrotic syndrome

OBJECTIVE: To evaluate the efficacy of cyclosporine (CyA) monotherapy in steroid resistant (SRNS) and steroid dependent (SDNS) nephrotic syndrome in children. DESIGN: A retrospective study. SETTING: Tertiary kidney care center for children at Bangalore. METHODS: Forty-one children with SDNS and SRNS with normal renal functions were treated with CyA at a dose of 6 mg/kg/day initially and maintained at 3 to 4 mg/kg/day if remission was sustained. The dosage was adjusted according to the CyA blood levels in non-responders. RESULTS: The median age of patients was 93 months (range 48-936) months. Thirteen children had minimal change disease (MCNS), 10 had mesangial proliferative glomerulonephritis (GN). Ten had membrano-proliferative (GN) (MPGN) and 8 had focal segmental glomerulosclerosis (FSGS). Median age at onset of disease and median time for CyA usage from disease onset was 22 months and 16 months respectively. Median duration of CyA therapy was 24 months (range 6-72) months. The data was analyzed to determine significance of variables on the outcome. Median follow up was 71 months (range 20-205) months. Eleven children were CyA resistant. Of the remaining 30 who were CyA responders, 22 (73.33%) were CyA dependent. Seven children developed chronic renal failure (CRF). CONCLUSIONS: The predictors for CyA non-responsiveness were steroid resistance, non MCNS on biopsy and longer duration between onset of nephrotic syndrome and CyA usage, irrespective of the age of onset of the disease. There was a higher incidence of CyA dependence among young responders. Patients with CyA resistance are at high risk for significant infections and CRF.     

神经母细胞瘤并骨转移患儿临床特征及预后相关因素的单中心分析CSCD

目的分析伴骨转移神经母细胞瘤(neuroblastoma,NB)患儿的临床特征及预后相关因素,总结临床诊疗经验,以提高伴骨转移NB患儿的生存率。方法以2013年12月至2020年12月重庆医科大学附属儿童医院肿瘤外科收治的伴骨转移NB患儿为研究对象,收集并总结患儿临床资料及预后情况。随访时间截至2021年3月31日。结果共收集97例NB患儿,男68例,女29例,男女比例为2.4∶1;中位年龄为49.4个月。首发症状:发热47例(48.5%),骨痛38例(39.2%),腹痛或腹胀29例(29.9%),咳嗽15例(15.5%);伴骨转移的NB患儿存在多类骨转移(62.9%),且合并骨髓转移(73.2%),整体预后差,1年生存率为93.6%,5年生存率仅20.2%。经生存分析发现,女性、伴多类骨转移、肿瘤位于腹部、首诊时LDH测定值大于660 U/L以及术中肿瘤残留是预后不佳的影响因素,其中手术切除范围是独立预后影响因素。结论伴骨转移的NB患儿临床表现多样,其预后受诸多因素影响,肿瘤复发或进展是主要的致死原因。对于此类患儿,建议术中尽可能完全切除肿瘤,以改善预后。     

神经母细胞瘤并骨转移患儿临床特征及预后相关因素的单中心分析

目的 分析伴骨转移神经母细胞瘤(neuroblastoma,NB)患儿的临床特征及预后相关因素,总结临床诊疗经验,以提高伴骨转移NB患儿的生存率.方法 以2013年12月至2020年12月重庆医科大学附属儿童医院肿瘤外科收治的伴骨转移NB患儿为研究对象,收集并总结患儿临床资料及预后情况.随访时间截至2021年3月31日...     

利妥昔单抗治疗难治性激素耐药型肾病综合征的疗效和安全性

目的:探讨利妥昔单抗(RTX)治疗儿童难治性激素耐药型肾病综合征(SRNS)的疗效和安全性。方法:回顾性分析2013年9月至2018年3月东部战区总医院儿科收治并接受RTX治疗的10例难治性SRNS患儿的临床资料。结果:10例患儿发病年龄(4.47±2.75)岁,男女各5例;5例(50%)肾活检为局灶节段性肾小球肾炎,...     

Nephrotic syndrome in Saudi infants in the first year of life

Sixteen Saudi children with onset of nephrotic syndrome in infancy were seen at King Khalid University Hospital, Riyadh over a 5-year period. This figure represented 17% of the 92 cases of childhood nephrotic syndrome seen during the period. Onset of the nephrotic syndrome was less than or equal to 3 months of age in four patients. Ten of the patients developed renal failure. Eight patients died, seven of them by 1 year of age. Two patients given renal transplants have functioning grafts without recurrence of the disease. Renal biopsy in 12 patients showed congenital nephrotic syndrome of the Finnish type (4 cases), 2 each of congenital glomerulosclerosis, mesangioproliferative glomerulonephritis and minimal change disease, and 1 each of focal segmental glomerulosclerosis and tubular amyloidosis. Prognosis of infancy-onset nephrotic syndrome in Saudi children was poor. A significant prognostic factor appeared to be the age of onset of the disease rather than the histological lesion.     

A 23-year experience with malignant renal tumors in infancy and childhood.

A retrospective analysis of 77 children treated between 1974 and 1996 was undertaken to evaluate morbidity and the evolution of therapy. A Wilms' tumor (WT) was present in 73 children. 74% of patients (pats.) with WT survived (54 of 73 pats.). Histological specimens of 67 patients were re-evaluated, including 4 children with non-WT histology. Among patients with Wilms' tumors (WT), nephroblastoma (NB) of intermediate risk predominated (73%; 46 of 63 pats.). Low-risk tumors occurred in 5 of 63 children (8%; mesoblastic nephroma 3, cystic partially diff. NB 1, completely necrotic NB 1). High-risk WT were diagnosed in 12 of 63 patients (19%) (NB with anaplasia 10, clear cell sarcoma 1, malignant rhabdoid tumor 1). Nephrogenic rests were present in 14 cases. We observed 3 children of school age with renal carcinoma and one patient with an intrarenal neuroblastoma. WT histology was the most important factor determining prognosis (p = 0.018). The risk for relapses was 2.6-fold higher in patients with high-risk WT compared to the standard risk group. Stages were re-evaluated according to SIOP 93-01. Comparing relapse-free survival of stages I, II and III, respectively, there was a reduced survival rate for stage III (p=0.019). According to the SIOP/GPOH protocol in 1989, the regimen was switched from primary surgery to preoperative chemotherapy without biopsy in 1989 (11 pats.). Compared to earlier years, survival improved (n.s.). In 3 patients preoperative diagnosis by means of imaging failed. During preoperative chemotherapy a venous occlusive disease of the liver occurred in 2 patients. Preoperative chemotherapy led to an impressive tumor shrinkage in the majority of patients. 2 patients of the preoperative group died (focal anaplastic NB). Long-term morbidity was analysed in 49 patients and included radiation-induced scoliosis (35), chest-wall deformity (3), congestive cardiomyopathy after relapse (1) and arterial hypertension (2). Over the years there was a trend to reduce frequency and dose of irradiation. Prognosis of WT is excellent but unfavorable histology (high risk) predicts a poor prognosis. In our experience, reduction of tumor volume due to preoperative chemotherapy facilitates tumor removal by surgery and may prevent tumor spillage and the deleterious effects of radiation in young children. Surgery without delay is necessary if the diagnosis is unclear or the tumor fails to respond to preoperative chemotherapy.     

Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study

BACKGROUND: A secondary end point of the NBL90 protocol (Rubie H et al. Pediatr Oncol 2001;36:247-250) was the concern in this infant population for possible carboplatin-(CBDCA) induced late side effects including impaired renal and hearing functions. PROCEDURE: Glomerular filtration rate (GFR), tubular function (TF), pure tone audiometry (PTA), high-frequency, and transient evoked-otoacoustic emission were prospectively assessed in 30 children alive and disease-free 6 years after the end of the treatment. RESULTS: Median age at diagnosis and at assessment was 4.7 months and 7 years, respectively. Blood pressure was < or =97.5 centile in all children. The mean estimated GFR was 114 +/- 13 ml/min/1.73 m(2) by Schwartz formula [range 87-145]. TF assessment failed to demonstrate any impairment. 29/30 children had grade 0 ototoxicity and all transient evoked otoacoustic emission were normal. CONCLUSIONS: With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90.     

Congenital or childhood nephrotic syndrome with diffuse mesangial sclerosis

Diffuse mesangial sclerosis (DMS) has been described as a distinct morphological pattern observed in patients presenting with a congenital or infantile nephrotic syndrome (NS) leading to end stage renal failure (ESRF) before the age of 3 years (Habib & Bois: Helv. Peadiat. Acta 28: 91-107, 1973). In recent years, we diagnosed this entity in 36 infants and we wish to report our findings which extend our previous observations. The nephropathy was discovered before 1 year of age in 26 patients. In one of these the onset was neonatal. Five additional children were between 1 and 2 years of age at onset of the disease and the remaining 5 were between 24 and 42 months old. Thirty-three patients presented with a NS often preceded by a proteinuria and associated with renal failure in 6 of them. The 3 remaining patients presented with renal failure. Thirty-one patients reached ESRF before the age of 4 years. Progression was slower in 5 patients who were respectively 5, 5, 6, 8 and 11 years old at ESRF. Thirteen patients were transplanted and none recurred their original disease. Seven patients in 4 families had similarly affected siblings. In 16 patients (6 boys and 10 girls) the nephropathy was isolated. In the remaining 20 several associated findings were noted. In 14 infants a diagnosis of Drash syndrome was made on the basis of the association of a male pseudo-hermaphroditism (PsH) and Wilms tumour (WT) in 5, of a male PsH in 5 additional infants and of a WT in 4 female patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

5岁以上神经母细胞瘤患者的临床特点及疗效分析

目的 总结5岁以上神经母细胞瘤（NB）患儿的临床特点及疗效,为改善其预后提供理论基础。方法 回顾性分析54例初治NB患儿临床资料,进行临床特点、疗效总结以及Kaplan-Meier生存分析。结果 54例患儿中男36例、女18例,均为3、4期。以腹膜后占位最多见（76%,41/54）,其次为纵隔占位（18%,10/54）、椎管内占位（4%,2/54）和盆腔占位（2%,1/54）。截止至随访日期,54例患儿中存活30例（56%）：无病生存23例（77%,其中9例为复发再度化疗后完全缓解）、肿瘤部分缓解6例（20%,均为复发再度化疗患儿）、进展1例（3%,为复发再度化疗后进展）;死亡24例（44%）,其中22例为复发再度化疗后死亡、2例为初治期间多脏器衰竭死亡;治疗、随访期间共38例复发。Kaplan-Meier生存分析提示：54例患儿平均生存时间53.8个月;3期患儿总生存率（OS）为80%,高于4期患儿（53%）,差异具有统计学意义（P < 0.01）;复发患儿平均生存时间（51.68个月）低于无复发病例（62.57个月）,差异有统计学意义（P < 0.01）。结论 年长儿NB临床分期多属晚期,但规律治疗仍可提高疗效,应增加患儿信心,坚持规范治疗。     

肾脏疾病患儿急性肾损伤的临床分析

目的 了解儿童肾脏疾病中是否存在急性肾损伤(AKI),儿童肾脏疾病基础上AKI的发生率和病因构成,探讨AKI与肾脏疾病患儿住院时间、住院费用和短期预后的关系.方法 对我科住院的部分肾脏疾病患儿进行前瞻性的临床研究.病例入选标准:①确诊(原发性)肾病综合征(NS)、紫癜性肾炎(HSPN)和狼疮性肾炎(LN)的2～18岁住院患儿;②发病或复发≤3个月.AKI的诊断采用成人的AKI诊断标准.结果 共有95例患儿入选本研究,包括原发性NS 65例、HSPN 15例和LN 15例,其中33例(34.7%)符合AKI的诊断标准.LN、HSPN患儿伴发的AKI,100%表现为血肌酐升高;NS伴发的AKI中,65.4%的患儿表现为尿量减少,其中只有19.2%的患儿同时伴有血肌酐升高.AKI的病因:①NS基础上发生的AKI中,只有少数存在明确病因(26.9%),且多由肾外因素导致(15.4%),包括环孢素A的副作用、低血容量和肾小管间质损害;②LN和HSPN基础上发生的AKI,均由基础肾小球疾病导致.AKI组的住院时间和住院费用显著高于非AKI组[住院时间分别为28(6～94)、21(7～100)d;Z=-1.971,P=0.049;住院费用分别为12 035.7(1561.7～94 783.1)、8594.3(1390.1～98 876.5)元;Z=-1.993,P=0.046];随访6个月和12个月时,AKI组和非AKI组的血肌酐水平差异无统计学意义[随访6个月时分别为(60.4±91.8)、(42.8±12.2)μmol/L,t=0.937,P=0.358;随访12个月时分别为(48.7±18.1)、(47.7±14.2)μ,mol/L,t=0.197,P=0.845].结论 在儿童肾脏病急性期,34.7%的病例发生AKI;原发性NS中,非肾性因素是导致AKI发生的主要原因,而在LN和HSPN中,AKI的常见病因为基础肾小球疾病.AKI组的住院时间和住院费用高于非AKI组,但6个月和12个月随访时的血肌酐水平与非AKI组的患儿相比无显著差异.

Abstract：

Objective Acute kidney injury (AKI) was recently proposed for early recognition of renal function impairment and prompt interventions. Previous study revealed that AKI was highly associated with the prognosis. However, there was rare report of AKI in renal diseases, especially in children cohorts.Therefore, we performed the prospective clinical research in children with renal diseases in our hospital,aiming to study the prevalence, the clinical characteristics and the short-term prognosis of AKI. Method The study was designed as a prospective, single-center observational study. Inclusion criteria: ① the primary diagnosis was primary nephrotic syndrome (NS), Henoch-Schoenlein purpura nephritis (HSPN) or lupus nephritis ( LN), ② the duration from the onset of the renal diseases to the admission was less than 3 months. The serum creatinine and urine output of the subjects would be prospectively monitored. AKI was defined by the adult criteria and stratified by Acute Kidney Injury Network (AKIN) criteria. The patients were followed up at 6 months and 12 months after enrollment. Result Between October 2007 and April 2009, a total of 95 children were included, including 65 cases with NS, 15 HSPN and 15 LN. Mean age was (8. 9 ±3. 9) years (range 2-16 years). Thirty-three of the 95 patients (34. 7% ) fulfilled the AKI criteria,13 patients (13.7%) were diagnosed as acute renal failure (ARF). All the AKI in children with LN and HSPN presented with serum creatinine elevation. However, 65.4% of AKI in NS presented with decreasing urine output, only 19. 2% accompanied with increasing creatinine, with higher stages of urine output.Regarding the etiology, only 26.9% of AKI in NS had definite cause, most of which resulted from side-effect of cyclosporine, hypowlemia or tubule-interstitial damage, independent of glomerular diseases. In contrast,the AKI in LN and HSPN were exclusively caused by glomerular diseases. The length and costs of hospitalization of AKI group were significantly higher than non-AKI[length of hospitalization ( d), 28 (6 to 94) vs. 21 ( 7 to 100 ), Z = - 1. 971, P = 0. 049; cost of hospitalization ( yuan), 12 035.7 ( 1561.7 to 94 783.1) vs. 8594.3 (1390.1 to 98 876.5), Z= - 1.993, P=0.046]. There was no significant difference in the serum creatinine at 6-month and 12-month follow-up between AKI group and non-AKI[6-month, (60.4 ±91.8) μmol/L vs. (42. 8 ± 12. 2) μmol/L, t =0. 937, P =0. 358; 12-month, (48. 7 ±18.1) μmol/L vs. (47.7±14.2) μmoL/L, t=0.197, P=0.845]. Conclusion Theprevalence of AKI (34.7%) was higher than that of ARF ( 13.7% ) in children with renal diseases. Most of the AKI in NS resulted from non-glomerular diseases. In contraat, most AKI in LN and HSPN were caused by underlying glomerular diseases. The length and costs of hospitalization were significantly higher in AKI group.However, there was no significant difference in serum creatinine between AKI and non-AKI group in the follow-up at 6 months and 12 months. Further investigations on criteria for the diagnosis of AKI in children with renal diseases are still needed.     

Bilateral Wilms' tumor

During a 16-year period, 49 children were treated for Wilms' tumor (WT); 7 were bilateral, 5 synchronous and 2 metachronous. The age at primary diagnosis was 6 months to 5 years (mean 2.4 years). All but 1 child received preoperative chemotherapy with tumor reduction. Unilateral nephrectomy was performed in 2 metachronous cases. In 3 synchronous WTs, the tumor was enucleated in 5 kidneys and a heminephrectomy was performed in 1 kidney with a double pelvis. Two children were not operated upon. At relapse in the contralateral kidney the tumor was enucleated. Three patients died of WT, 1 is alive with disease, and 3 are without evidence of disease. Renal salvage procedures were technically feasible without complications and are advocated to preserve renal function. Accepted: 17 June 1998     

Management of Wilms tumors in Drash and Frasier syndromes

Background

Children with WT1 gene‐related disorders such as Denys–Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end‐stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron‐sparing surgery was beneficial.

Procedure

We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007.

Results

We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate‐risk tumors and one high‐risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron‐sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft‐tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end‐stage renal disease‐related complications. The median follow‐up time for the 18 survivors was 136 months (range, 17–224 months).

Conclusion

Most Wilms tumors in children with WT1‐related disorders were early‐stage and intermediate‐risk tumors, with a young age at diagnosis. In patients without end‐stage renal disease, nephron‐sparing surgery should be considered for delaying the onset of renal failure. Pediatr Blood Cancer 2009;52:55–59. © 2008 Wiley‐Liss, Inc.     

TRPC6基因变异致儿童激素耐药型肾病综合征四例并文献复习

目的:探讨TRPC6基因变异致儿童激素耐药型肾病综合征(SRNS)的特征、治疗及预后。方法:回顾性分析2017年1月至2019年12月在上海市儿童医院肾脏风湿科住院的4例(SRNS)且经基因检测为TRPC6变异患儿的临床资料。以“肾病综合征”“TRPC6”“儿童”“nephrotic syndrome”“TRPC6 variation”“child”为检索词,检索建库至2020年8月中国知网数据库、万方数据库、维普数据库及PubMed数据库并进行文献复习。结果:4例SRNS患儿中,男1例、女3例,起病年龄4岁1月龄至12岁2月龄。临床均以浮肿、大量蛋白尿、低蛋白血症起病,4例出现贫血,2例出现继发性甲状旁腺功能亢进,1例肾萎缩。肾脏病理结果示1例为免疫复合物相关性肾炎,3例为局灶节段肾小球硬化。4例患儿病初予足量糖皮质激素治疗4周以上,均为激素耐药,后予糖皮质激素联合免疫抑制剂(如环磷酰胺、钙调神经磷酸酶抑制剂、霉酚酸酯)治疗,症状没有改善。4例患儿2~6个月进展为终末期肾病。全外显子测序显示4例患儿TRPC6基因变异类型分别为c.2684G>T、c.523C>T、c.2678G>A、c.2683C>T,均为新发变异。文献检索纳入中文文献1篇,外文文献9篇,共27例。汇总分析31例(包括本组)病例资料,其中18例错义变异,移码变异、同义变异、剪切变异各1例。起病年龄4月龄至14岁,18例患儿临床表现为大量蛋白尿、低蛋白血症,6例仅表现为蛋白尿,19例患儿病理类型为局灶节段肾小球硬化,IgA肾病、微小病变各2例,塌陷性肾小球病、C1q肾病、免疫复合物相关性肾小球肾炎各1例。18例患儿激素治疗无效,11例钙调神经磷酸酶抑制剂类药物无效。该疾病预后不佳,12例患儿出现肾衰竭,进展至终末期肾病时间为4个月至13.8年。结论:TRPC6基因变异致SRNS的患儿起病年龄较小,病理特征多为局灶节段肾小球硬化,激素及免疫抑制剂治疗多无效,进展迅速预后差。     

Plasminogen activator inhibitor type-1 and interleukin-6 in haemolytic uraemic syndrome

OBJECTIVE: Because haemolytic uraemic syndrome (HUS) is an important cause of renal dysfunction in children, the availability of prognostic markers of disease severity could assist in identifying those at risk of developing long-term sequelae. The aim of this study was to test the hypothesis that plasma levels of plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in children at the time of diagnosis of HUS would predict renal function outcome in terms of glomerular filtration rate (GFR). METHODOLOGY: Fourteen children suffering from diarrhoeal HUS were studied. Plasma samples were assayed for PAI-1 and IL-6, and GFR was measured at intervals after discharge from hospital. Twelve months following their recovery from HUS, the children were allocated to one of two outcome groups depending on whether GFR was above (Good Outcome, n = 9), or below (Poor Outcome, n = 5) 80 mL/min per 1.73 m2. RESULTS: Elevated concentrations of PAI-1 were found in 4 of 5 Poor Outcome and 4 of 9 Good Outcome children. At the same time, increased concentrations of IL-6 were observed in 3 of 5 Poor Outcome and 3 of 9 Good Outcome children. Renal function continued to be compromised in four Poor Outcome children 36 months after diagnosis. CONCLUSIONS: Our data show that PAI-1 and IL-6 are elevated in the plasma of some children at the time of diagnosis of HUS, but that neither is a definitive prognostic marker of poor outcome 3 years later.     

Late presentation of opsoclonus-myoclonus-ataxia syndrome in a child with stage 4S neuroblastoma

Opsoclonus-myoclonus-ataxia syndrome (OMA) in children is most commonly associated with occult neuroblastoma (NB). Although children with OMA and NB have decreased mortality, they suffer from increased neurologic morbidity. The pathogenesis of OMA in NB is not well understood, but current research and treatments support an immune-mediated process. The authors describe an unusual presentation of OMA occurring following 6 months of chemotherapy in a child with stage 4S NB who presented with partial Horner syndrome. Histopathologic examination of his primary cervical tumor showed NB maturation, which may have played a role in precipitating OMA syndrome. Further study of unusual cases of OMA in NB may provide better understanding of the syndrome and additional treatment options for these children.