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Objective:To explore the clinical features, risks of recurrence and prognosis of neuroblastoma (NB) with intraspinal extension in children, and to perform a long-term follow-up to monitor their health problems.Methods:Clinical data of 22 children with NB with intraspinal extension treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2007 to December 2019 were retrospectively analyzed, including gender, age at diagnosis, clinical stage, and risks of recurrence.They were divided into non-recurrent group and recurrent group, and the survival was analyzed by Kaplan-Meier method.Results:(1)Fifteen(68.2%) children had motor nervous symptoms as the initial symptoms, including lower limb pain, weakness, and limited mobility, and 10(45.5%) showed moderate-to-severe nervous compression.(2)Neuronal enolase(NSE) (<200 μg/L), lactate dehydrogenase(LDH) (≤500 U/L) and vanillylmandelic acid(VMA) were in the normal range in most of children in the non-recurrence group, and a single site was involved.(3)Tumor lesions were not completely resected in the majority of children in the recurrent group, and their NSE (≥200 μg/L), LDH (>500 U/L) and VMA (more than 3 times higher) were abnormally higher, or suffered multisite pyramidal metastasis.(4)The median survival time (MST) was 119.4 months for children in the non-recurrent group, while it was only 25.3 months for those in the recurrent group.The 3-year overall survival (OS) rate was (95.5±6.4)% for the non-recurrent group, compared to only (20.0±17.9)% for children in the recurrent group ( χ2=9.387, P=0.002). Likewise, the 3-year event-free survival (EFS) rate for children in the non-recurrent group was (94.1±5.7)%, whereas it was only (20.0±17.9)% for children in the recurrent group( χ2=29.700, P<0.001). (5)Eleven of 22 children had long-term health problems, especially motor nerve function defects and scoliosis. Conclusions:Motor neurological, and moderate-to-severe neurological compression predominates are the main symptoms of NB children with intraspinal extension at the initial diagnosis.Patients who exhibit intradural tumor remnants, higher NSE, LDH, or VMA levels, and intradural extension with multiple sites of cone metastases are prone to recurrence.Once relapsed, the prognosis is extremely poor.The prognosis of NB with intraspinal extension in children is related to the severity of the initial neurological impairment, the duration of tumor compression, and the treatment regimen.Early diagnosis and intervention may reduce the risk of long-term health problems in children.
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Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.
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Objective:To investigate the clinical value of individualized therapy based on the molecular target detection to improve the prognosis of children with refractory or relapsed malignant solid tumor.Methods:The clinical data of children who were diagnosed with malignant solid tumors between September 1 st 2012 and March 31 th 2019 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled.The chemosensitivity of commonly used antitumor drugs was investigated and analyzed by detecting the target gene or protein with immunohistochemistry, real time fluorescence quantitative polymerase chain reaction and next generation sequencing.The tumor response rates and survival rates of patients with refractory or relapsed malignant solid tumors in individualized therapy group were compared with that in palliative therapy group. Results:The chemosensitivity of commonly used antitumor drugs was investigated in 172 patients.When other tissues were collected after neoadjuvant chemotherapy in 159 cases, the tumor tissues were collected before primary chemotherapy in 13 cases.The results of chemosensitivity in whole patients suggested the natural resistance of tumor cells to commonly used antitumor drugs except Methotrexate.The resis-tance rate of anthracyclines increased from 41.9% to 78.3% after chemotherapy ( P<0.05). Both the median survival time [(6.0±4.6) months] and the expected 2-year survival rate [(39.2±22.6)%] of individualized therapy group were higher than the median survival time [(1.5±1.4) months] and the expected 2-year survival rate (0) of palliative therapy group in 29 children developing primary and refractory disease (all P<0.05). The median survival time [(6.0±2.3) months] of the individualized therapy group was higher than that [(1.0±0.5) months] of palliative therapy group in 29 children suffering from relapsed disease ( P<0.05). However, there was no significant diffe-rence of expected 2-year survival rate between the 2 groups ( P=0.292). Conclusions:An attempt may be made to expand the application scope of Methotrexate in therapy of children suffering from malignant solid tumors.Individualized therapy based on the target detection of chemosensitivity can increase the overall survival rate of patients with refractory malignant solid tumors.However, treatment methods for children with recurrence disease still need further researches.
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As an important part of childhood tumors, infantile malignant solid tumor is relatively rare, which has some common characteristics of childhood cancer as well as its own particularity.Most infantile tumors are embryo-derived tumors, whose pathogenesis is related to developmental biology, genetics and environmental factors.The distribution of constituent ratio of infantile malignant tumors is different from that of older children, and the epidemiological data statistics can be influenced by the imperfect children tumor registration system, population migration, birth defects and perinatal factors, environmental exposure, gender, race and other factors.Heterogeneity is one of the prominent features of malignant solid tumor in infants. The experience gained from treatment of older children cannot be directly extrapolated to infants.The principle of treating infantile malignant solid tumors should take into account both the effectiveness and the long-term impact on infant growth.Early diagnosis and appropriate treatment mean that the prognosis of most infants with malignant solid tumor to be better than that of older children.Therefore, it is necessary to manage these tumors as a separate entity.The advance of epidemiology and prognostic factors of infantile malignant solid tumors at home and abroad was reviewed in this paper.
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Objective To investigate the diagnostic value and the impact on treatment decision of 18F-FDG PET/CT in differentiated thyroid carcinoma (DTC) patients with elevated serum thyroglobulin (Tg) levels and negative radioiodine 131I post-therapy whole body scan (131I-RxWBS).Methods Totally 72 patients with DTC who had elevated serum Tg levels and negative 131I-RxWBS were enrolled,and 18F-FDG PET/CT was performed.The imaging results of 18F-FDG PET/CT were compared with the clinical results of surgical pathology or 6 to 36 months follow up.The diagnostic efficacy of 18F-FDG PET/CT in detection of recurrence and/or metastasis of DTC with elevated Tg levels and negative 131I-RxWBS was evaluated.Results The accuracy,sensitivity,specificity,positive prediction value and negative prediction value of 18F-FDG PET/CT in diagnosis of DTC with elevated Tg levels and negative 131I-RxWBS was 83.33％ (60/72),89.47％ (34/38),76.47％ (26/34),80.95％ (34/42) and 86.67％ (26/30),respectively.18F-FDG PET/CT changed the treatment strategies of 35 patients (35/72,48.61 ％) among 72 patients,while recurrence or metastasis of DTC was not found during clinical follow-up in 23 of these 35 patients (23/35,65.71％) who underwent reoperation,but was detected in the other 12 patients (12/35,34.29％).Conclusion 18F-FDG PET/CT is a valuable method for detection of recurrence and/or metastasis of DTC with elevated Tg levels and negative 131I-RxWBS,also for guiding the follow-up treatment strategy.
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Objective@#To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study.@*Methods@#Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses.@*Results@#The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%.@*Conclusions@#In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.
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Objective · To investigate the clinical characteristics and multidisciplinary treatment of children with clear cell sarcoma of kidney (CCSK). Methods · Data of seven children with CCSK treated at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between Jan 2011 and Jan 2016 were collected. The retrospective analysis of clinical manifestations, features of imaging and pathology, treatment, and follow-up was performed. Results · Of 7 children with CCSK, 6 were male and 1 was female with the median age of 28 months (4-59 months), and 3 were at stageⅠ, 2 at stage Ⅲ, and 2 at stage Ⅳ. All cases were discussed and evaluated by multidisciplinary teams, including pediatric hematology/oncology, pediatric surgery, pathology, radiology and radiotherapy. CCCG-WT-2009 protocol was adopted to treat these patients. The median follow-up period was 22 months (8-56 months). Six children survived and one died. Conclusion · The multidisciplinary treatment mode can effectively improve the prognosis of CCSK. CCCG-WT-2009 protocol has good therapeutic effect and high cure rate for children with early stage CCSK, but the treatment of advanced stage CCSK needs to be further explored and perfected.
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Objective · To investigate the changes of neutrophils and lymphocytes during chemotherapy courses in children with high-risk neuroblastoma, as well as severe infection rate and its relationship with combination chemotherapy regimens in order to provide guidance to prevent infection in these children. Methods · A total of 45 cases of children with high-risk neuroblastoma, who were hospitalized in Xinhua Hospital from July 2012 to September 2015 were recruited. Reactions after chemotherapy and the results of routine blood tests on every 5 days during the whole chemotherapy circles were recorded. Follow-up visits were carried out to learn the infection occurrence. Results · The counts of neutrophils and lymphocytes dropped to the minimum at the 10th day or so during chemotherapy, then rised near the 15th day. Infections were negatively correlated with the numbers of neutrophils (r =-0.245) and lymphocytes (r=-0.227) at the 10th day. Persistent lymphopenia occured after the forth course of chemotherapy. Rate of grade Ⅳ bone marrow suppression after chemotherapy was 90%, and severe infection rate was 15.5%. There were significant differences in the rates of grade Ⅲ bone marrow suppression (P=0.008), grade Ⅳ bone marrow suppression (P=0.001) and severe infection (P=0.010) among the 3 combination chemotherapy regimens used in high-risk neuroblastoma children. Conclusion · Children with high-risk neuroblastoma had obviously high rates of bone marrow suppression and severe infection after chemotherapy, especially after cyclophosphamide+doxorubicin+vincristine regimens. More attention should be paid to this group of children and preventive measures were worthy of taking into account.
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Hepatoblastoma (HB)is the most common malignant liver tumor in children.Surgical resection was the major treatment approach to HB,whereas more than 60% patients had unresectable mass at diagnosis,even though complete resection,there were about 30% patients recurrent.With the introduction of adjuvant chemotherapy,the treat-ment of HB has been developed to multidisciplinary cooperation from single surgical resection,such strategy greatly im-proved the prognosis of children with HB,but there still be a great challenge in the treatment of high -risk patients.All famous children′s HB study groups have begun to focus on the optimization of chemotherapy,surgery opportunity,strate-gy based on risk -stratification,looking for new potential therapeutic targets and prognosis -related risk factors.
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Objectives To investigate the clinical profile and prognosis of hemophagocytic syndrome (HPS). Methods A retrospective study was carried out to analyze the clinical features and laboratory findings in 28 children with HPS. Fisher's exact probability method and Logistic multivariate regression were used to explore the prognostic risk factors.. Results HPS was clinically characterized by prolonged fever (100%), hepatomegaly (64.29%),and other minor features including respiratory symptoms (53.57%), splenomegaly (50%), hydrops of multiple serous cavity (42.86%), lymphadenectasis (32.14%), jaundice (17.85%), skin rash (14.29%), central nervous system involvement (14.29%), and alimentary tract hemorrhage (10.71%). Labo-ratory data showed that 1iver dysfunction, pancytopenia, coagulation abnormalities, disseminated intravascular coagulation, hy-pertriglyceridemia, decreased number of natural killer cells and hyponatremia were prominent. The etiological analysis indicated that infection associated hemophagocytic syndrome was most common (60.71%), in which EB virus associated HPS was pre-dominant, accounting for 64.71%. Significant difference was observed in the difference of albumin,blood urea nitrogen and acti-vated partial thromboplastin time between death and survival cases (P<0.05). The Logistic regression multivariate analysis showed that hypoalbuminemia was an independent prognostic factor. Conclusions There are various underlying diseases and clinical manifestations for HPS. The lower level of serum albumin is an independent prognostic factor. A prompt diagnosis and treatment is very important for HPS prognosis due to the rapid progression and high mortality.
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Objective To analyze the outcome of childhood B-cell acute lymphoblastic leukemia treated (ALL) with SCMC-ALL-2005 protocol. Methods Newly diagnosed B-cell ALL from May 1, 2005 to April 30, 2009 in ifve hospitals were treated and followed up according to SCMC-ALL-2005 protocol. Results A total of 601 cases with newly diagnosed B-cell ALL were enrolled. Among them, 539 cases (89.68%) were followed up until September 30, 2011. In 601 patients, there were 284 low-risk cases (LR group), 231 moderate-risk cases (MR group) and 86 high-risk cases (HR group) which were treated with SCMC-ALL-2005 protocol. The total complete remission rate during the period of induction was 98.84%and 7 cases did not achieve complete remission. The median time of the ifrst event occurring was 35 months (2.94 years). Among 539 cases completing follow-up, 403 cases (74.77%) completed treatment including 223 cases (86.43%) in LR group, 150 cases (73.17%) in MR group and 30 cases (39.47%) in HR group. The rate of cases completing treatment was signiifcantly different among three groups (P=0.001). The completion rate was highest in LR group and lowest in HR group. The 3-year overall survival (OS) rate was (83.3±1.8)%, and the 3-year EFS (event-free survival) rate was (79.2±1.9)%using a Kaplan-Meier method. The 5-year OS rate was (79.5±3.3)%, and the 5-year EFS rate was (70.9±3.7)%. There were signiifcant differences in 3-year EFS rate and 5-year EFS rate among three groups (P<0.05). Conclusions Childhood B-ALL treated with SCMC-ALL-2005 protocol achieved a better therapeutic effect and prognosis. The multi-center collaborative research is useful for the standard treatment of ALL.
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Objective To apply 3C3R model in problem design of PBL for pediatrics teaching.Methods The 3C3R model comprises two classes of components:core components and processing components.Core components of the model are 3C,which are content,context and connection while processing components are 3R,which are researching,reasoning and reflecting.3C3R model was used in the problem design for the PBL case of ‘ Why the mouth of Baobao became purple when he was crying?' Totally 76 eight-year program medical students and 7 tutors were enrolled as teaching object.The anonymous questionnaires from the students were collected for assessment of PBL teaching.Results The percentage of students with scores ≥4 for content in PLB problem design was 90.8％,for context was 80.3％,for connection was 64.5％,for researching was 81.6％,for reasoning was 69.7％ and for reflecting was 40.8％.The percentage of tutors with scores ≥4 for content in PLB problem design was 100％,for context was 71.4％,for connection was 28.6％,for researching was 71.4％,for reasoning was100％,for reflecting was57.1％.Both students and tutors held a positive attitude towards the component of content,context,researching and reasoning in problem design model.But the components of connection and reflection needed to be improved.Conclusion The 3C3R model is helpful for problem design of PBL in pediatric teaching.
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BACKGROUND: Similar to other prosthesis, metal-metal prosthesis would produce plenty of wear particles and metal ions, mainly presented as cobalt (Co~(2+)) and chromium (Cr~(3+)), which can lead to osteolysis, eventually, result in aseptic loosening. OBJECTIVE: To observe the effect of Co~(2+) and Cr~(3+) ions on the cells viability and expression of RANK in rats m0nocyte-macrophage cells (RAW264.7) in vitro. METHODS: Monocyte-macrophage cells (RAW264.7) were cultured in vitro, and then the cells were exposed to Co~(2+) and Cr~(3+) ions. The cell viability was assured by MTT test and the level of RANK Mrna was detected by semi-quantitative RT-PCR at different times. RESULTS AND CONCLUSION: Compared to the control group, MTT test demonstrated that Co~(2+) and Cr~(3+)ions could decrease the cell activity of monocyte-macrophage cells obviously. When the cells were exposed to Co~(2+) Cr~(3+) ions, compared to the control group, the Mrna expression of RANK of the metal ions group was increased at 12 hours (P < 0.05), reached its peak level at 24 hours (P < 0.05), and decreased at 48 hours than that of 24 hours (P < 0.05). The results revealed that metal ions have a cytotoxic effect on monocyte-macrophage cells, stimulate the expression of RANK, and have the potential of facilitating monocyte-macrophages cells transform into osteoclast-like cells.
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Objective To investigate the effects of all trans-retinoic acid (ATRA) on the expressions of iron metabolism-related genes and their products in K562 cells and the possible relationship. Methods (1) The characteristics of K562 leukemic cell differentiation induced by ATRA was evaluated by Benzidine, Wright's, NSE and NBT staining.(2) The expression levels of cellular surface antigens (CD71 and CD 13) in K562 cells cultured with ATRA were measured by flow cytometry. (3) IRP/IRE binding activity was assessed by RNA/protein band-shift assay.(4) Ferritin was determined by radioimmunoassay.(5) The mRNA expression levels of H-Fn, TfR and IRP2 in K562 cells cultured with different concentrations of ATRA were delineated by RT-PCR method, confirmed by sequencing of RT-PCR products. Results K562 cells could be induced to differentiate into neutrophils by ATRA, confirmed by cytochemical staining. The expression of CD71 decreased while CD13 increased. The mRNA expression levels of TfR and IRP2 were decreased while mRNA expression level of H-Fn was increased in K562 cells cultured with ATRA, compared to that in control cells. Concomitantly,IRP binding activity was significantly decreased but the level of ferritin was significantly increased in K562 cells cultured with ATRA. Conclusions During the course of K562 cells induction and differentiation to myelocytes by ATRA, the expression level of iron metabolism-related genes and products were changed but the upstream-regulation mechanism still remains unclear.
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Objective To determine the plasma concentration of cytarabine(Ara-C) in children with leukemia and obtain dynamics parameters, and investigate the relationship between the parameters and clinical effect in order to provide the basis for optimization of Ara-C application. Methods Using highperformance liquid chromatogram (HPLC) to determine the plasma concentration of Ara-C, its metabolite Ara-U and infusion rate in 37 children with acute leukemia, their therapeutic reaction, remission, treatment-related infection, side-effect and long-term treatment effect were analyzed in statistic. Results Ara-C by 1～2 g/m2 intravenous drop infusion for 2 hours, the peak plasma concentration time was 2 h and peak concentration were (14.37-84.44)μmol/L, and the median was (41.42±22.80)μmol/L. The median infusion rate was 869.57at 30 minutes after Ara-C drip completion, its average level was (253.40±81.49) μmol/L, over six-times than Ara-C peak concentration. The median continuous complete remission time in 37 children was 29.8 months (5.0～53.1 months), 3y-DFS was (90.63±5.15)%. The therapy-related infection rate was 56.8 %(21/37),including three children (8.1 %) suffered from severe infection, but there was no therapy-related death and no children were off the protocol due to poor tolerance. Conclusion As post-remission treatment, high-dose Ara-C would not cause cumulation in vivo in children with acute leukemia and side-effect were slight. Ara-C could improve the long-term continuous complete remission rate and clinical cure rate for children with leukemia. Therefore, it was worth to apply in clinical.
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[Objective]To investigate the cytotoxicity of cobalt(Co2+) and chromium(Cr3+)ions on mice osteoblast(MC3T3E1)and the effects on the secretion of RANKL/OPG from osteoblast because of the stimulation of Co2+ and Cr3+ ions. [Methods]The osteoblast in vitri was cultured.The cell viability was assured by MTT test.ELISA method was applied to detect RANKL(receptor activator of nuclear factor-kB ligand),OPG(osteoprotegerin) content in serum supernatant.[Results]Compared to the control,MTT test demonstrated that Co2+ and Cr3+ ions can obviously decrease the cell viability of osteoblast.When osteoblast were exposed to Co2+ and Cr3+ ions for 24 and 48 hours,the releasion of OPG increased by 32.1% and 17.8% as compared with the control(P