RESUMO
Cisplatin is a broad-spectrum and highly effective chemotherapeutic agent, with a dose-dependent therapeutic effect.Unfortunately, high-does therapy is limited by ototoxicity, nephrotoxicity and neurotoxicity.Ototoxicity is a common and serious complication after cisplatin chemotherapy, which has greatly debilitating effect on patients′ quality of life.Currently, there are no FDA-approved drugs available to prevent cisplatin-induced hearing loss.In recent years, domestic and international studies on cisplatin-induced ototoxicity have revealed many new mechanisms and therapeutic targets.Many candidate agents have shown good hearing protection.Moreover, local drug delivery methods are being optimized, promising for further translations to clinical applications.
RESUMO
Neuroblastoma(NB)is the most common extracranial solid tumor in children.It is notable for highly heterogeneous and associated with tumor histologic classification and differentiation status, with ganglioneuroma representing fully mature and differentiated NB.Differentiation therapy reduces the adverse reactions caused by treatment without affecting normal cells and tissues by inducing the redifferentiation of NB cells, and has a good development prospect in the maintenance treatment of high-risk NB patients.Therefore, studying the key molecules and signaling pathways affecting NB differentiation is significant to further clarify the pathogenesis and improve the prognosis of neuroblastoma.This article reviews the important molecules related to NB cell differentiation, signaling pathways and the research progress of differentiation induction therapy.
RESUMO
Post transplant lymphoproliferative disease(PTLD)is one of the most serious malignant complication in children after solid organ transplantation.Immunosuppression after transplantation and Epstein-Barr virus infection are the two main reasons for the onset of PTLD.The diagnosis of the disease depends on pathology, which includes early lesions, monomorphic PTLD, polymorphic PTLD and Hodgkin′s lymphoma PTLD.The treatment includes reduction in immunosuppression, rituximab, chemotherapy, radiotherapy and surgery, etc.The selection of chemotherapy mainly depends on pathology.The advance in the management of PTLD will be reviewed in the manuscript.
RESUMO
Objective:To assess the impact of integrated curriculum (vertically integrated curriculum system) and traditional curriculum system on the perceptions of post competency of undergraduate medical students.Methods:Bibliographic retrieval method and expert consultation were used to compile the questionnaire of perceptions on the post competency of undergraduate medical students. The questionnaire was conducted online to survey the undergraduate medical students from Shanghai Jiao Tong University School of Medicine during March to April, 2019. SPSS 20.0 software was applied for data analysis, chi-square test was used to analyze the classroom teaching forms of medical undergraduates who received different curriculum systems, and their cognition of the doctor post competency and cognitive pathways, and finally the top 10 important competencies were compared.Results:A total of 200 questionnaires were distributed and 167 were recovered, with a recovery rate of 83.5%. Workshop learning was more common in the vertically integrated undergraduate curriculum. Compared with Chinese traditional curriculum, the medical students taught by the vertically integrated undergraduate curriculum were much better informed about competency ( P<0.05). The access to knowledge of competency was also statistically different between two groups of students ( P<0.05). Conclusion:The vertically integrated curriculum is more efficient in helping undergraduate medical students to acquire knowledge about competency.
RESUMO
Children who recovered from hematological malignancies have different degrees of secondary immunodeficiency.They are prone to acquire various infectious diseases, thus affecting their health and even endangering their life and may become the source of infection that affects the health of the surrounding people and residents of co-mmunities.Preventive vaccination is the easiest and most effective measure to prevent infectious diseases.However, in addition to the limited qualification of vaccination, due to the lack of the understanding to the safety, effectiveness and contraindications in the vaccination for this type of patients, there still exists blankness in the preventive vaccination work for this group in China.This paper summarizes some consensus on the vaccination for discharged patients of hematological malignancies in light of providing reference for the implementation of this clinical work in China.
RESUMO
Primary central nervous system lymphoma (PCNSL) is a form of extranodal non-Hodgkin lymphoma (NHL) and it is typically confined to brain, spinal cord, cranial nerves, eyes, and meninges without evidence of system spread.It is a rare subtype of NHL in childhood and adolescence, with an increased risk among patients with immunodeficiency.In the absence of prospective pediatric clinical trials, data from recent pediatric series and adult prospective trials was summarized, so as to help audience better understand the role of surgery, whole brain radiation therapy, and chemotherapy in the treatment as well.
RESUMO
Objective:To investigate the safety of Rituximab combined with intensive chemotherapy in the treatment of aggressive mature B-cell lymphoma/leukemia in children.Methods:The clinical data of 77 patients with primary pediatric aggressive mature B-cell lymphoma/leukemia who were treated according to the Chinese Children Cancer Group(CCCG)-mature B-cell lymphoma(BNHL)-2015 protocol at Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiaotong University School from November 1, 2014 to July 31, 2018 were collected.A comparison was drawn on the adverse reactions and recovery of immune function indexes between patients in the Rituximab combined with intensive chemotherapy group (R4 group) and the chemotherapy alone group (R3 group).Results:Rituximab combined with AA was associated with a significantly lower platelet count [79.5%(35/44 cases) vs.54.5%(24/44 cases), χ2=6.223, P=0.011] and a higher incidence of infection [70.5%(31/44 cases) vs.36.4%(16/44 cases), χ2=10.275, P=0.001] compared with AA alone; Rituximab combined BB was associated with a higher incidence of mucositis and infection compared with BB alone [40.8%(20/49 cases) vs.29.3%(22/75 cases) and 85.7%(42/49 cases) vs. 72.0%(54/75 cases), respectively], but the differences were not statistically significant.A greater proportion of patients in the R4 group had a decrease in peripheral blood CD 19 positive cells (no statistically significant difference, P>0.05) and a greater proportion had a decrease in serum IgG ( P<0.05) compared to the R3 group, but there was no significant difference in treatment-related mortality between both groups.For patients in the R4 group, the average recovery time of IgG and IgM level was 13.1 months, and the longest recovery time was 31 months after the end of treatment. Conclusions:Rituximab combined with intensive chemotherapy is generally safe in the treatment of aggressive mature B-cell lymphoma/leukemia in children.However, it is often accompanied with prolonged immunoglo-bulin deficiency and the potential risk of secondary infection.Therefore, the strict control over the indications for its application is required, and the gamma globulin replacement therapy deserves to be investigated in the future.
RESUMO
Objective:To analyze the clinical characteristics, therapeutic modalities and prognosis of desmoplastic small round cell tumor (DSRCT) in children, and to summarize the international research progress.Methods:A total of 8 children with DSRCT admitted to Shanghai Children′s Medical Center, Shanghai Jiaotong University, School of Medicine, from January 1999 to August 2019 were retrospectively studied.The clinical characteristics, consultation process and follow-up results were summarized, and the Kaplan-Meier survival analysis method was used to calculate the survival rate.Results:Among these 8 cases, there were 6 male children and 2 female children.Seven cases originated in the abdomen and pelvis, and 1 case originated in the sacral region.All cases had infiltrate surrounding tissues or viscera, and 4 cases(50%) had extra-peritoneal metastasis, including distant lymph node metastasis, liver, lung and bone metastasis.All patients received chemotherapy, among which 3 patients received radiotherapy, and 2 patients received autologous hematopoietic stem cell transplantation.The medical follow-up was continued to February 15, 2020, with the median follow-up period being 59 months.Three cases died and 5 cases survived (2 cases in complete remission, 1 case in recurrent relapse, 2 cases in partial remission still under treatment). The median relapse time was 14.5 months, the 3-year relapse-free survival rate was (30.0±17.5)%, and 3-year overall survival was (51.4±20.4)%.Conclusions:Half of DSRCT had distant metastasis; the prognosis was poor despite the aggressive multimodality therapeutic approaches, such as chemotherapy, cytoreductive surgery, and whole abdominopelvic radiotherapy and stem cell transplantation.
RESUMO
Neuroblastoma(NB)is one of the most common malignant tumors in children.The prognosis of patients with high-risk NB remains poor despite intensive multimodal treatments including surgery, chemotherapy, radiation therapy and autologous hematopoietic stem cell transplantation.Recently, with good therapy results in hematological malignant tumors, more attention has been paid to immunotherapy for solid tumors such as NB.However, the efficacy of immunotherapy for NB is not as good as that for other hematological malignancies, which may be related to the complex tumor microenvironment(TME)of solid tumors.In order to better understand the direction and future application of immunotherapy in NB, we review TME and current immunotherapy for NB.
RESUMO
Neuroblastoma(NB)has the highest incidence in pediatric extracranial solid tumors, so its pathogenesis is urgently needed to figure out and guide the targeted therapies.Both heterogeneous pathological characteristics and various clinical phenotypes show that NB has cryptic biological and genetic features.This paper reviews the evidence of gene mutations and epigenetic changes in NB to prospect for new therapeutic targets.
RESUMO
Objective@#To assess the efficacy of stratified treatment of pediatric non-distant metastatic rhabdomyosarcoma (RMS).@*Methods@#A retrospective review was conducted in 129 pediatric patients with non-distant metastatic RMS between January 2005 and December 2016 at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.According to their pathological types, TNM stages and postoperative pathologic staging, the 129 patients were grouped a low-risk group, an intermediate-risk group and a high-risk group.Multimodality therapies were applied to all patients including chemotherapy, surgery and radiotherapy.The overall survival (OS) and event-free survival (EFS) rates were analyzed by using the Kaplan-Meier method.@*Results@#Of 129 patients, 119 cases were included in this study.In 119 patients, the age of onset for the RMS ranged from 7 to 191 months, with the median onset age of 48 months.The median follow-up time was 40 months for event-free patients with RMS, and 36 months for all the 119 patients.The 5-year OS and EFS for all patients were (92.1±2.9)% and (76.5±4.4)%, respectively.While the 5-year EFS for patients in the low-risk group, intermediate-risk group and high-risk group were all above 70%, and the difference among the three groups was not statistically significant (χ2=2.679, P=0.262). A subsequent univariate analysis revealed that the onset age for RMS (≤1 year old or≥10 years old), TNM stage and postoperative pathologic stage were important predictors of EFS with statistical significance (all P<0.05), while gender, pathological type and primary site of RMS did not exhibit any significant impact on 5-EFS (all P>0.05). The 5-year EFS of RMS patients with Forkhead Box Protein O1(FOXO1)-positive was significantly lower than that of FOXO1-negative patients [(56.3%±14.8)% vs.(83.3±15.2)%], and the difference was statistically significant (χ2=4.588, P=0.028).@*Conclusions@#It is important that the stratification treatment should be strictly implemented on RMS patients.First, further improvement is necessary for the treatment of patients in the low-risk group due to their poorer prognosis compared to that of their intermediate-risk counterparts, for whom one feasible option is to reduce the dose of chemotherapy drug.Furthermore, FOXO1 can be used as an indicator for poor prognosis, where stratified treatment is necessary for pediatric patients with RMS.
RESUMO
Objective To assess the efficacy of stratified treatment of pediatric non-distant metastatic rhabdomyosarcoma (RMS).Methods A retrospective review was conducted in 129 pediatric patients with non-distant metastatic RMS between January 2005 and December 2016 at Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.According to their pathological types,TNM stages and postoperative pathologic staging,the 129 patients were grouped a low-risk group,an intermediate-risk group and a high-risk group.Multimodality therapies were applied to all patients including chemotherapy,surgery and radiotherapy.The overall survival (OS) and event-free survival (EFS) rates were analyzed by using the Kaplan-Meier method.Results Of 129 patients,119 cases were included in this study.In 119 patients,the age of onset for the RMS ranged from 7 to 191 months,with the median onset age of 48 months.The median follow-up time was 40 months for event-free patients with RMS,and 36 months for all the 119 patients.The 5-year OS and EFS for all patients were (92.1 ±2.9) ％ and (76.5 ± 4.4) ％,respectively.While the 5-year EFS for patients in the low-risk group,intermediate-risk group and high-risk group were all above 70％,and the difference among the three groups was not statistically significant (x2 =2.679,P =0.262).A subsequent univariate analysis revealed that the onset age for RMS (≤ 1 year old or ≥ 10 years old),TNM stage and postoperative pathologic stage were important predictors of EFS with statistical significance (all P ＜ 0.05),while gender,pathological type and primary site of RMS did not exhibit any significant impact on 5-EFS (all P ＞ 0.05).The 5-year EFS of RMS patients with Forkhead Box Protein O1 (FOXO1)-positive was significantly lower than that of FOXO1-negative patients [(56.3 ％ ± 14.8) ％ vs.(83.3 ± 15.2) ％],and the difference was statistically significant (x2 =4.588,P =0.028).Conclusions It is important that the stratification treatment should be strictly implemented on RMS patients.First,further improvement is necessary for the treatment of patients in the low-risk group due to their poorer prognosis compared to that of their intermediate-risk counterparts,for whom one feasible option is to reduce the dose of chemotherapy drug.Furthermore,FOXO1 can be used as an indicator for poor prognosis,where stratified treatment is necessary for pediatric patients with RMS.
RESUMO
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.
RESUMO
Currently,the undergraduate teaching of pediatrics in China is still the science-based curriculum,having a big gap with international medical teaching idea and mode.Medical colleges of the University of Ottawa and Shanghai Jiao Tong University co-established the 0ttawa-Shanghai Joint School of Medicine (OSJSM) in October 2014.By enriching the curriculum content (including theory,skill and professionalism),adding "active" teaching,introducing clinical pediatricians to the students-management group,and applying formative evaluation method,the OSJSM started transforming to the competency-based cultivation,improving the teaching quality.
RESUMO
Objective@#To assess the clinical features and long-term outcomes of neuroblastoma (NB) in children less than 18 months of age, so as to provide evidence for further improvement of treatment.@*Method@#Clinical data(sex, age, stage, risk group, treatment response, follow-up, etc.) of 155 NB patients under age of 18 months from June 2000 to December 2015 in Shanghai Children′s Medical Center were analyzed retrospectively. The clinical features were summarized and the long-term follow-up results were evaluated. The overall survival (OS) and event-free survival (EFS) were analyzed by using Kaplan-Meier method. Factors including age, stage, risk group, bone marrow and bone metastasis, N-MYC status and dehydrogenase(LDH) level were analyzed by Log-Rank test.@*Result@#Totally 155 eligible patients (96 males, 59 females) were included. The median age of disease onset was 7 months (11 days to 18 months). There were 31 cases of stage 1, 19 cases of stage 2, 45 cases of stage 3, 38 cases of stage 4 and 21 cases of stage 4S. The median follow-up time was 36 months (range 4 to 189 months), the 3-year and 5-year EFS rate were 89.6% and 85.2% respectively and the 3-year and 5-year OS rate were 96.2% and 94.1%, respectively. A total of 15 recurrent or progressed cases were observed. The median time to first recurrence was 11 months (range 3 to 39 months), 6 cases eventually died. Second malignancy occurred in one patient. The patients who had relapsed disease within 12 months from initial diagnosis have much lower 3-year OS rate than those in whom the disease recurred 12 months later (25.7% vs. 83.3%, P=0.020). Although the number of chemotherapy courses in median-high risk group reduced from 8.6 courses to 7.5 courses after the revision in 2008, the survival rate showed no significant difference between before and after (5-year EFS 74.4% vs. 84.3%, 5-year OS 89.0% vs. 92.9%, both P>0.05). In patients with stage 1 and stage 2, the 3-year EFS of 34 cases with surgery alone and 16 cases accepted chemotherapy were both 100%. Age at diagnosis, stage, risk group, MYCN status, LDH level, bone marrow involvement and bone infiltration had significant impacts on prognosis(all P<0.05).@*Conclusion@#Satisfactory outcomes could be achieved in neuroblastoma in children aged within 18 months; the prognosis was better in children at age less than 12 months compared with 12-18 months. MYCN amplification, LDH more than 5 times upper limit of normal range, bone marrow and bone infiltration were associated with worse prognosis.Excellent survival rates could be achieved in children with stage 1 and 2 disease within 18 month′s old accepted surgery alone, chemotherapy or radiotherapy could be avoided in these patients so as to reduce long-term adverse reactions.
RESUMO
Objective@#To investigate the long-term efficacy and prognostic factors of pediatric relapsed Wilms tumor (WT) after retreatment.@*Method@#Sixteen children in Shanghai Children′s Medical Center with relapsed Wilms tumor were enrolled consecutively in this study between April 2006 and June 2016. All patients were diagnosed according to pathology, imaging and medical and surgical oncologist′s assistance. Relapse treatment included surgical excision, chemotherapy and selective radiation therapy. The clinical features, long-term outcomes and prognostic factors of patients were analyzed retrospectively.Survival data were analyzed by Kaplan-Meier.Log-Rank analysis was used for univariate analysis.@*Result@#One case was excluded because of giving up the therapy even though no disease progress was identified. A total of 15 cases (5 males and 10 females) were included in this study. The median age at diagnosis was 3.8 years (range 0.5-9.1 years). The tumor staging at diagnosis included one case of stageⅠ, 7 cases of stageⅡand 7 cases of stage Ⅲ. Among cases of stage Ⅲ, 6 cases had radiation therapy history. The pathology of all patients′ recurrent tumor was favorable histology (FH). The median follow-up time was 34.6 months (range 12.5-132.7 months) until March 21, 2017. The time from initial diagnosis to relapse was 7.9 months (range 3.1-17.9 months). Four cases experienced local recurrence, 9 cases relapsed with metastases (6 cases in lungs, 2 in livers, 1 in mediastinum) and 2 cases relapsed in both local site and with metastases. Except to 2 cases received irregular retreatment, 13 cases received regimen I (doxorubicin, vincristine, epoposide and cyclophosphamide for 25 weeks) as relapsed chemotherapy. Five cases received autologous bone marrow transplantation (ABMT). Until the last follow-up, 8 cases achieved continuous complete remission (range 6.7-104.3 months), 3 cases had relapse again or progressing and 4 cases died. The estimated 5-year overall survival (OS) rate and event free survival (EFS) rate were (70±15)% and (52±15)%. According to whether received ABMT or not, the 5-year EFS rate were 51% and 53%. According to whether relapsed within 6 months after diagnosis or not, the 5-year EFS rate were 38% and 56% respectively.@*Conclusion@#The 5-year EFS rate of pediatric relapsed FH WT have reached above 50% by multi-disciplinary treatment in our experience and we encourage patients and doctors to receive retreatment.
RESUMO
Objective To improve understanding of the clinical manifestations, diagnosis and treatment of childhood Kasabach-Merritt phenomenon (KMP). Methods The clinical data of 13 patients admitted for KMP to XXX from January 2010 to January 2016 was retrospectively analyzed, with a review of relevant literature. Results The patients were 10 males and 3 females. The age of presentation varied from newborn to 5 months. 12 patients had cutaneous manifestations, like petechiae, ecchymosis, jaundice, skin masses, etc, 1 patient had pleural effusion. The location of lesions varied. The laboratory hallmark consists of profound thrombocytopenia and hypofibrinogenemia with elevated D-dimers. The median time from initial presentation to diagnosis was 60 days. After approaches like surgery, corticosteroids, propranolol, interferon, sirolimus, etc, 10 patients got remission while 3 patients died. 6 patients treated with sirolimushad complete response. Conclusions KMP is characterized with vascular tumor, severe thrombocytopenia and consumptive coagulopathy. Clinically, KMP often presents with early-onset and delay in diagnosis. Surgery is an effective approach for KMP. Sirolimus appears to be a promising treatment for KMP.
RESUMO
Objective To evaluate the outcomes of children with stage Ⅳ malignant extracranial germ cell tumors. Methods Twenty-five patients were enrolled in the retrospective analysis. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method with SPSS 13.0. Results Of the 25 children, there were 13 males and 12 females. The mean age at diagnosis was 2 years old (ranged 1 to 11). Five patients receiving chemotherapy in another hospital before (n=1), or giving up treatment after confirmed diagnosis (n=1), or giving up effective treatment after received less than 2 cycles (n=3) were excluded from this analysis. Of the 20 patients, 90.0% (18/20) achieved complete remission and 5.0% (1/20) achieved partial remission after treatment. The 5-year EFS rate and 5-year OS rate were 70.0%±10.2% and 82.4%±9.2% respectively. There was no death occurred due to complications. Conclusions The effect of this treatment program is positive. The cumulative dose of the drugs is not high, compared with other schemes such as PEB, but there are more drugs involved. Whether these drugs may cause long-term adverse reactions needs further research.
RESUMO
Pediatric inherited cancer predisposition syndromes are a group of diseases caused by germ-line mutation of cancer related genes. The patients are susceptible to cancers. TP53 germ-line mutation is the most commonly seen mutant gene in cancers that accounts for 20%-30%of all germ-line mutations of inherited cancers. TP53 gene mutation screening could help clinicians to better manage the patients and their family members.
RESUMO
Current 5 -year overall survival rates (OS)for children and adolescents treated for Hodgkin lym-phoma (HL)exceed 90%.However,this early success is negatively impacted by late mortality due to adverse health -related squeal of therapy.This challenge has resulted in the development of various strategies aimed at identifying the optimal balance between maintaining OS and avoidance of long -term morbidity of therapy.With new imaging tech-niques,the success of reducing therapy in a subset of rapid early responders is demonstrated.Treatment strategy is not only a risk -adjusted but also response -based combined -modality therapy.