罕见抗-Di^(b)致严重胎儿新生儿溶血病的实验室检测与相关研究

目的对1例高频抗体导致的胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)进行检测、鉴定及配血。方法对患儿进行新生儿溶血试验,对母亲进行血清学意外抗体鉴定,并对母亲红细胞进行常见高频抗原鉴定;对检出抗体进行IgG分型检测,并用流式细胞术进行单核细胞体外吞噬致敏红细胞试验,以检测抗体相关的吞噬率;对患儿母亲、父亲及舅舅进行相关红细胞血型基因测序;利用稀释的母亲血浆和抗人球卡法,在献血者中进行大规模相合血液的筛选。结果产妇鉴定为Di(b-)稀有血型,产生了抗-Di b(效价512)并导致了严重的HDFN;抗-Di b亚型分型为IgG1和IgG2型,单核细胞体外吞噬效率为88.83%(74.7/84.09);产妇亲属中没有相合献血者,后续从5520名献血者中筛选到2例Di(b-)相合血液,患儿接收输血治疗后康复出院。后续在51334名献血者中筛查到17名Di(b-)献血者,该数据表明Di(b-)在广州地区献血者中的分布频率约为三千分之一(0.033%,17/51334)。结论综合利用血型血清学及分子生物学方法诊断了抗-Di b所致的严重HDFN,建立了1种有效大规模筛查Di(b-)稀有血型的方法并找到相合血液,为建立Di(b-)稀有血型库奠定了基础。

Refractory diarrhea: A paraneoplastic syndrome of neuroblastoma

Neuroblastoma(NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide(VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage Ⅰ-Ⅱ, and one was at stage Ⅲ. Four patients survived(followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment

Introduction: Brain metastasis is common in relapsed neuroblastoma patients, but the characteristics of brain metastasis remain largely unknown. This study aimed to investigate the status of brain metastasis with neuroblastoma in South China.Methods: In this retrospective case?based study, 106 patients with stage 4 neuroblastoma from the Department of Pediatric Oncology in Sun Yat?sen University Cancer Center between January 2004 and May 2013 were included. The incidence, risk factors, and survival status of these patients were reviewed and analyzed.Results: Of the 106 patients, 11(10.4%) developed brain metastasis, accounting for 20.0% of 55 patients with relapse or progression. The age at initial diagnosis of the 11 patients ranged from 2 to 10 years(median 4 years), which was younger than that of the patients without brain metastasis(median 5 years, range 1–10 years, P = 0.073). The male to female ratio of the 11 patients was 8:3, which was not signiicantly diferent from that of the patients with?out brain metastasis(P = 0.86). Patients with brain metastasis had higher lactate dehydrogenase levels than those without brain metastasis, but the diferences were not signiicant(P initial diagnosis to the develo= 0.076). Eight patients died, and 3 patients survived. The median interval from thepment of brain metastasis was 18 months(range 6–32 months). The median survival was 4 months(range 1 day to 29 months) after the diagnosis of brain metastasis. The median interval from the manifestation of brain metastasis to death was 3 months(range 1 day to 11 months).Conclusions: High?risk factors for brain metastasis in cases of neuroblastoma include bone marrow involvement and a younger age at initial diagnosis. Nevertheless, multiple treatment modalities can improve disease?free survival.

4DI110型空压机的技术改造与操作优化

文章通过介绍新引进的4DI110型离心式空压机(以下简称“空压机”)试运行阶段开始以来的运行情况和气温变化对空压机出口流量造成的影响,分析空压机出口流量随气温变化而变化的规律,指出空压机防喘阀V3004阀不能自动调节出口压力,影响空分装置工况的稳定。为实现空压机出口压力的稳定,对其防喘阀V3004阀采取增设自动旁路阀V3008阀的技术改造,同时优化和完善相关逻辑控制并阐述了空压机经技术改造后的操作优化和取得的实际效果。

FLUORESCENCE IN SITU HYBRIDIZATION COMBINED WITH IMMUNOFLUORESCENT STAINING FOR RAPID DETECTION OF Nmyc AMPLIFICATION IN NEUROBLASTOMA

Objective: To establish a method to improve the detection of disseminated tumor cells in bone marrow and peripheral blood samples of neuroblastoma patients and analysis of cytogenetic aberration. Methods: Immunofluorescent staining was performed using a cocktail of primary monoclonal neuroblastoma antibodies (14.G2a, 5.1H11). Fluorescence in situ hybridization was applied with fluorescent probes specific for Nmyc genes afterwards. A novel computer assisted scanning system for automatic search, image analysis and repositioning of these positive cells was developed. Fifty-six bone marrow and peripheral blood samples from 7 patients were evaluated by this method. Results: Fluorescence in situ hybridization can be combined with immunofluorescent staining in detecting Nmyc amplification in neuroblastoma patients. Fluorescence in situ hybridization results correlated well with data obtained by conventional cytogenetic procedures. Conclusion: The technique described allows search of tumor cells in the bone marrow as well as detection of Nmyc amplification in interphase nuclei.

Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression

Objective:AlkB homolog 5(ALKBH5)has been proven to be closely related to tumors.However,the role and molecular mechanism of ALKBH5 in neuroblastomas have rarely been reported.Methods:The potential functional single-nucleotide polymorphisms(SNPs)in ALKBH5 were identified by National Center for Biotechnology Information(NCBI)dbSNP screening and SNPinfo software.TaqMan probes were used for genotyping.A multiple logistic regression model was used to evaluate the effects of different SNP loci on the risk of neuroblastoma.The expression of ALKBH5 in neuroblastoma was evaluated by Western blotting and immunohistochemistry(IHC).Cell counting kit-8(CCK-8),plate colony formation and 5-ethynyl-2'-deoxyuridine(EdU)incorporation assays were used to evaluate cell proliferation.Wound healing and Transwell assays were used to compare cell migration and invasion.Thermodynamic modelling was performed to predict the ability of miRNAs to bind to ALKBH5 with the rs8400 G/A polymorphism.RNA sequencing,N6-methyladenosine(mA)sequencing,mA methylated RNA immunoprecipitation(MeRIP)and a luciferase assay were used to identify the targeting effect of ALKBH5 on SPP1.Results:ALKBH5 was highly expressed in neuroblastoma.Knocking down ALKBH5 inhibited the proliferation,migration and invasion of cancer cells.miR-186-3p negatively regulates the expression of ALKBH5,and this ability is affected by the rs8400 polymorphism.When the G nucleotide was mutated to A,the ability of miR-186-3p to bind to the 3'-UTR of ALKBH5 decreased,resulting in upregulation of ALKBH5.SPPI is the downstream target gene of the ALKBH5 oncogene.Knocking down SPP1 partially restored the inhibitory effect of ALKBH5 downregulation on neuroblastoma.Downregulation of ALKBH5 can improve the therapeutic efficacy of carboplatin and etoposide in neuroblastoma.Conclusions:We first found that the rs8400 G>A polymorphism in the m6A demethylase-encoding gene ALKBH5 increases neuroblastoma susceptibility and determines the related mechanisms.The aberrant regulation of ALKBH5 by miR-186-3p caused by this genetic variation in ALKBH5 promotes the occurrence and development of neuroblastoma through the ALKBH5-SPP1 axis.

Neuroblastoma in Saudi Children: A Single Center Experience (2006-2014)

Introduction: Neuroblastoma is the most common extracranial solid tumor in childhood and survival rate has improved during the last few decades. Only a few studies, related to Neuroblastoma in Saudi Arabian children, have been performed. We report epidemiologic data and our clinical experience from the department of Pediatric Hematology Oncology (PHO), King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Method: A retrospective observational study of all patients, with diagnosis of Neuroblastoma, who attended PHO-KFMC from July 2006 to June 2014 was performed. The survival periods (overall survival and disease-free survival) and the final outcomes for patients treated and followed at KFMC were recorded. The survival data were statistically correlated with the clinical, pathological and biological features of patients and tumors and compared to national and international cohorts. Results: Eight-year data were available for the 42 patients of which 22 (52.4%) were male and 20 (47.6%) were females. Age at diagnosis ranged 0 - 91 months with a mean and median of 26.3 and 18.5 months respectively. 16 (38.1%) patients were under one year and 26 (61.9%) above 1 year of age. The event-free survival (EFS) and overall survival (OS) rates were 66.5% and 71.5% respectively. EFS and OS among those who were <1 year age at presentation was 75% and 82%, whereas ≥1 yr age group had 59% and 62% survival rates respectively. Patients with tumors in the adrenal had considerably lower EFS (59%) and OS (63%);in comparison to patients with tumors sites other than the adrenal who had EFS and OS of 85% and 89% respectively. Both EFS and OS survival rates at the end of follow-up interval were 100.0%, in the low and intermediate risk groups. In contrast, patients in the high risk group had EFS and OS rates of 44% and 48% respectively. This difference was statistically significant (p < 0.05). Conclusion: Our results are very encouraging and comparable with known published international cohorts, and reveal an excellent outcome for stage 1, 2, 3 & 4 s. The prognosis for advanced (stage 4) disease remains rather poor. A collaborative Saudi-wide effort, with an emphasis on research in detecting clinical and biologic characteristics of aggressive disease and tailoring therapy, is needed.

DOWN－REGULATION OF C－MYC ONCOGENE DURING NGF－INDUCED DIFFERENTIATION OF NEUROBLASTOMA CELL LINES

There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probe were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c-myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and overexpression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma.

Targeted molecular therapy (modified RIST regimen) in relapsed high risk stage Ⅳ neuroblastoma: two cases report

The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan.We treated two children with recurrent neuroblastoma with this so called RIST protocol.Both patients,off therapy for 15 and 31 months,respectively are well,and developing normally,without any complications.These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.

Application of Monoclonal Antibody in the Differential Diagnosis of Neuroblastoma and Leukemia in Children

Thirty-six cases of neuroblastoma and two hundredand twenty-nine cases with various kinds of leukemia inchildren were observed systematically. The applicationof monoclonal antibody in the differential diagnosis ofmetastasis of neuroblastoma cells in bone marrow and leu-kemia cells was studied and some precautions should betaken for a rapid and accurate diagnosis. The accordantrate between clinical diagnoses and the results of thisstudy was 91%.

The inhibitory effect of dihydroartemisinin on the growth of neuroblastoma cells

Objective:To evaluate the inhibitory effect of dihydroartemisinin on neuroblastoma cell line SH-SY5 Y,explore the possible mechanism of dihydroartemisinin against neuroblastoma cells.Methods:The cell viability of dihydroartemisinin treated SH-SY5 Y cells was examined by MTT assay and morphology of cells was observed by using inverted microscope.Cell cycle was examined with flowcytometry assay,then cyclin D1 and caspase-3 proteins expression was detected by ELISA and western blotting assay.Results:MTT analysis results showed that cell viability significantly decreased after exposure to 0.05,0.50,5.00 and 50.00 mmol/L dihydroartemisinin in a dose-dependent manner,and the lower density of cells was observed in treated groups.The number of cells in sub-G1 phase was increased after treatment with different doses of dihydroartemisinin compared with the control group.The expression of cyclin D1 protein was decreased,while the expression of caspase-3 protein was increased in treated group.Conclusions:Dihydroartemisinin could inhibit the proliferation through stopping the cell cycle and inducing the apoptosis in neuroblastoma SH-SY5 Y cells.

Removal of pediatric stage Ⅳ neuroblastoma by robot-assisted laparoscopy: A case report and literature review

BACKGROUND Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of approximately 1/10000. Surgical resection is an effective treatment for children with NB. Robot-assisted laparoscopic surgery is a new method and is superior to conventional laparoscopic surgery, since it has been preliminarily applied in clinical practice with a significant curative effect. This paper discusses significance and feasibility of complete resection of stage IV NB using robot-assisted laparoscopic surgery, while comparing its safety and effectiveness with conventional laparoscopic surgery. CASE SUMMARY In June 2018, a girl with stage IV retroperitoneal NB, aged 3 years and 5 mo, was admitted. Her weight was 15 kg, and her height was 100 cm. Robot-assisted, fiveport laparoscopic resection of NB was performed. Starting from the middle point between the navel and the anterior superior iliac spine to the left lower abdomen, the pneumoperitoneum and observation hole (10 mm) were established using the Hasson technique. Operation arm #1 was located between the left anterior axillary line, the navel, and the costal margin (8 mm);operation arm #2 was located at the intersection of the right anterior axillary line and Pfannenstiel line (8 mm);one auxiliary hole was located between arm #2 (on the Pfannenstiel line) and the observation hole (12 mm);and another auxiliary hole (5 mm) was located slightly below the left side of the xiphoid. Along the right line of Toldt and the hepatic flexure of the transverse colon, the colon was turned to the left and below with a hook electrode. Through Kocher's incision, the duodenum and the pancreatic head were turned to the left to expose the inferior vena cava and the abdominal aorta. The vein was separated along the right external iliac, and the inferior vena cava was then lifted to expose the right renal vein from the bottom to the top. The tumor was transected horizontally below the renal vein, and it was first cut into pieces and then resected. The right renal artery and the left renal vein were also exposed, and the retrohepatic inferior vena cava was isolated. The tumor was resected along the surface of the psoas muscle, the back of the inferior vena cava, and the right side of the abdominal aorta. Finally, the lymph node metas-tases in front of the abdominal aorta and left renal vein were completely removed. The specimens were loaded into a disposable specimen retrieval bag and removed from the enlarged auxiliary hole. T-tube drainage was placed and brought out through a hole in the right lower quadrant of the abdomen. The operative time was 389 min, the time of pneumoperitoneum was 360 min, the intraoperative blood loss was approximately 200 mL, and the postoperative recovery was smooth. There were no complications, such as lymphatic fistula, diarrhea, bleeding, and paralytic ileus. Two months after discharge, there were no other complications. The literature on the application of robot-assisted laparoscopic surgery in the treatment of NB in children was reviewed CONCLUSION The robot has the advantages of a three-dimensional view and flexible operation, and it can operate finely along blood vessels. The successful experience of this case confirmed that robot-assisted laparoscopic surgery can skeletonize the abdominal blood vessels in the tumor and cut the tumor into pieces, indicating that robot-assisted laparoscopic surgery is feasible.

Comparison of Diagnosing and Staging Accuracy of PET(CT) and MIBG on Patients with Neuroblastoma: Systemic Review and Meta-analysis

To perform a systemic review and meta-analysis of the diagnostic accuracy of PET（CT） and metaiodobenzylguanidine（MIBG） for diagnosing neuroblastoma（NB）, electronic databases were searched as well as relevant references and conference proceedings. The diagnostic accuracy of MIBG and PET（CT） was calculated for NB, primary NB, and relapse/metastasis of NB based on their sensitivity, specificity, and area under the summary receiver operating characteristic curve（AUSROC） in terms of per-lesion and per-patient data. A total of 40 eligible studies comprising 1134 patients with 939 NB lesions were considered for the meta-analysis. For the staging of NB, the per-lesion AUSROC value of MIBG was lower than that of PET（CT） [0.8064±0.0414 vs. 0.9366±0.0166（P〈0.05）]. The per-patient AUSROC value of MIBG and PET（CT） for the diagnosis of NB was 0.8771±0.0230 and 0.6851±0.2111, respectively. The summary sensitivity for MIBG and PET（CT） was 0.79 and 0.89, respectively. The summary specificity for MIBG and PET（CT） was 0.84 and 0.71, respectively. PET（CT） showed higher per-lesion accuracy than MIBG and might be the preferred modality for the staging of NB. On the other hand, MIBG has a comparable diagnosing performance with PET（CT） in per-patient analysis but shows a better specificity.

Inhibition of Neuroblastoma Cell Growth by Difluoromethylornithine (DFMO) and Bortezomib through Suppression of LIN28 and MYCN

Neuroblastoma (NB) is the most common childhood cancer arising from the nervous system. Many high-risk neuroblastoma (HRNB) patients develop relapse after initial response to induction treatment and overall long term survival remains poor (less than 60%), emphasizing the need for new therapeutic approaches and more effective treatments. Combination therapies present a favorable approach to improve efficacy, decrease toxicity, and reduce development of drug resistance. Difluoromethylornithine (DFMO) has shown promise in recent clinical trials as a therapeutic agent in treating HRNB. Proteasomes are known to play an important role in tumor cell growth. Bortezomib was the first proteasome inhibitor shown to have anticancer activity clinically. In this study we explore the mechanistic and therapeutic effects of the novel drug combination of DFMO and bortezomib in NB. Cell proliferation studies demonstrated synergistic inhibition of NB cell growth. Bortezomib induced cleaved caspase-3 apoptotic pathway whereas DFMO induced a cytostatic effect on NB cells. Western blot analyses demonstrated down regulation of MYCN, LIN28 and NF-kB in response to DFMO and bortezomib, pathways that are important in cancer stem cells. A decrease in ATP-per-cell when treated with combination therapy suggests inhibition of glycolytic metabolism in NB cells. DFMO as a single agent or in combination with bortezomib significantly reduced tumor growth in xenograft mice. Given the lack of effective treatments, DFMO coupled with bortezomib offers a potential new therapeutic treatment for children with NB.

Lethal effect of mononuclear cells derived from human umbilical cord blood differentiating into dendritic cells after in vitro induction of cytokines on neuroblastoma cells

BACKGROUND： Dendritic cell is the most major antigen presenting cell of organism. It is proved in recent studies that human umbilical cord blood mononuclear cells induced and cultured in vitro by recombinant human granulocyte-macrophage colony stimulating factor （rhG-MCSF） and recombinant human interleukin-4 （rhlL-4） can generate a great many dendritic cells and promote the lethal effect of T cells on human neuroblastoma, but it is unclear that whether the lethal effect is associated with the most proper concentration of dendritic cells. OBJEETIVE： To investigate the lethal effect of human umbilical cord blood mononuclear cells induced in vitro by cytokines differentiating into dendritic cells on human neuroblastoma, and its best concentration range. DESIGN ： Open experiment SEI-FING： Department of Pediatrics, the Medical School Hospital of Qingdao University MATERIALS ： The study was carried out in the Shandong Provincial Key Laboratory （Laboratory for the Department of Pediatrics of the Medical School Hospital of Qingdao University） during September 2005 to May 2006. Human umbilical cord blood samples were taken from the healthy newborn infants of full-term normal delivery during October to November 2005 in the Medical School Hospital of Qingdao University, and were voluntarily donated by the puerperas. Main instruments： type 3111 CO2 incubator （Forma Scientific, USA）, type 550 ELISA Reader （Bio-Rad, USA）. Main reagents： neuroblastoma cell line SK-N-SH （Shanghai Institute of Life Science, Chinese Academy of Sciences）, RPMI-1640 culture fluid and fetal bovine serum （Hyclone）, rhlL-4 （Promega, USA）, rhG-MCSF （Harbin Pharmaceutic Group Bioengineering Co.Ltd）, rat anti-human CDla monoclonal antibody and FITC-labeled rabbit anti-rat IgG （Xiehe Stem cell Gene Engineering Co.Ltd）. METHODS： ① Human umbilical cord blood mononuclear cells obtained with attachment methods differentiated into human umbilical cord blood dendritic cells, presenting typical morphology of dendritic cells after in vitro induction by rhG-MCSF and rhlL-4. ② Different concentrations of dendritic cells[ dendritic cells： neuroblastoma cells=20：1,50：1,100：1 （2×10^8 L^-1,5×10^8 L^-1,1×10^9 L^-1）], 1×10^9 L^-1 T cells and 1×10^7 L^-1 neuroblastoma cells were added in the experimental group. 1 ×10^9 L^-1 T cells and 1 ×10^7 L^-1 neuroblastoma cells were added in the control group. ③ Main surface marker CDla molecules of dendritic cells were detected with indirect immunofluorescence, and the percent rate of dendritic cells was counted with ultraviolet light and expressed as the expression rate of CD1a^＋ cells. ④Single effector cells and target cells were respectively set in the experimental group and control group to obtain the lethal effect. The lethal effect of dendritic cells on neuroblastoma cells was indirectly evaluated by detecting cellular survival with MTT assay. The lethal effect（%）= （1-A experimentat well-A effector cell /A target cell well）×100%.⑤The expenmental data were presented as Mean ±SD, and paired t test was used. MAIN OUTCOME MEASURES： ① Morphological characters of dendritic cells in the process of induction and differentiation. ②CD1a^＋ cellular expression rate. ③Lethal effect of dendntic cells on neuroblastoma cells. RESULTS： ①Morphological characters of dendritic cells in the process of induction and differentiation： On the 15^th day after human umbilical cord blood mononuclear cells were induced by rhG-MCSF and rhlL-4, typical morphology of dendritic cells could be seen under an inverted microscope. ②Expression rate of CD1a^＋ cells was （43.12±5.83）%. ③Lethal effect of dendritic cells on neuroblastoma cells： Lethal effect of dendritic cells stimulated T cells in each experimental group （ dendritic cells： neuroblastoma cells=100：1,50：1, 20：1 respectively） on neuroblastoma cells was significantly higher than that in control group[（31.00 ±4.41 ）%, （30.92±5.27）%,（33.57±5.35）%,（26.23±5.20）%, t=3.51,2.98,4.24, P〈 0.01 ）; But the lethal effect of dendntic cells on neuroblastoma was significantly lower when their ratio was 100：1 and 50：1 in comparison with 20：1 （t=2.01,2.36, P 〈 0.05）, and no significant difference in lethal effect existed between the ratio at 100：1 and 50：1 （t=0.06,P 〉 0.05）. CONCLUSION： Dendritic cells differentiated from human umbilical cord blood mononuclear cells after in vitro induction of cytokines can promote the lethal effect of T cells on neuroblastoma cells. The lethal effect is associated with the concentration of dendritic cells within some range.

Olfactory Neuroblastoma Treated by Minimally Invasive Endoscopic Resection and Postoperative Adjuvant Radiotherapy: A Representative Case and an Updated Review of the Literature

This paper presents a case of an olfactory neuroblastoma, treated with minimally invasive endoscopic resection, followed by adjuvant radiotherapy and critically reviews the current literature with regard to diagnosis and management of such malignancies. Olfactory neuroblastoma is considered to be an uncommon malignancy of the nasal cavity. The tumor arises from the specialized sensory epithelial olfactory cells, normally situated at the upper part of the nasal cavity, including the superior nasal concha, the roof of the nose and the cribriform plate. The imaging modality of choice is computed tomography and magnetic resonance imaging. Combination of surgery and radiotherapy is considered to be the standard of care for primary site disease by the majority of researchers. Combined transfacial and neurosurgical conventional approaches are adopted in most cases, mainly due to the endocranial extension and the close anatomic relationship of esthesioneuroblastomas with the ethmoid roof and cribriform plate. However, recent literature supports that endoscopic resection correlates with similar oncologic control rates, compared with open surgery, when basic oncologic surgical principles are maintained.

Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells

Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma （NB）, the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes （CTLs） and natural killer （NK） cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.

THE RELATIONSHIP BETWEEN EXPRESSIONS OF N-myc AND c-myc ONCOGENES IN NEUROBLASTOMA:AN IN SITU HYBRIDIZATION AND IMMUNOCYTOCHEMICAL STUDY

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Safety and Efficacy of Intrathecal Morphine in Children Undergoing Surgery for Abdominal Neuroblastoma. Dose Finding, Randomized, Clinical Study

Background: Pediatric patients have remained undertreated for postoperative pain because of the difficulty of pain assessment and apprehension. Intrathecal opioids—including morphine—have become a popular method for providing post-operative analgesia in children. Objectives: To compare different doses of morphine via intrathecal route (2 μg/kg, 5 μg/kg, and 10 μg/kg) for post-operative analgesia in pediatric patients following for abdominal neuroblastoma surgery. Methods: This randomized, double-blinded, study was approved by local ethics committee of South Egypt Cancer Institute, Assiut University, Assiut—Egypt, and registered at https://www.clinicaltrials.gov/ at no.: “NCT03158584”. Forty-five patients scheduled for surgical excision of abdominal neuroblastoma were divided into 3 groups (15 patients each);group (I): received intrathecal morphine 2 μg/kg added to normal saline (3 mL volume). Group (II): received intrathecal morphine 5 μg/kg. Group (III): received intrathecal morphine 10 μg/kg. Intra-, and post-operative hemodynamics, FLACC score, time to first request of rescue analgesia, total analgesic consumption, and side effects were recorded for 24 hours. Results: there was a significant reduction in FLACC score in groups II and III starting immediately till 24 hours postoperatively compared to group I (P 0.05). No significant difference was observed between groups in side effects. Conclusions: 5 μg/kg of IT morphine achieved a reasonable balance between postoperative analgesia, and the incidence of side effects in pediatric patients following major abdominal cancer surgeries.

Vancomycin-related convulsion in a pediatric patient with neuroblastoma:A case report and review of the literature

BACKGROUND Vancomycin is often used as an anti-infective drug in patients receiving antitumor chemotherapy.There are concerns about its adverse drug reactions during treatment,such as nephrotoxicity,ototoxicity,hypersensitivity reactions,etc.However,potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been reported.CASE SUMMARY A 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected convulsion.No other potential disease conditions could explain the occurrence of the convulsion.The subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this convulsion.The peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L,respectively,which were much higher than the safe range.Simulation with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg·h/L.Therefore,vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment strategy.CONCLUSION Unexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of vancomycin.Overall evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.