Comparison of Clinico-Radiological Features between Congenital Cystic Neuroblastoma and Neonatal Adrenal Hemorrhagic Pseudocyst

어홍,김지혜,장경미,유소영,임계연,김명준,김옥화 대한영상의학회 2011 Korean Journal of Radiology Vol.12 No.1

Objective: To evaluate the radiological and clinical fi ndings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. Materials and Methods: We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcifi cation, turbidity, vascular fl ow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer’s exact test. Results: All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ signifi cantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifi cations (n = 3) and vascular fl ow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifi cations only. Conclusion: Although the imaging fi ndings of two groups of cystic lesions were similar, prenatal detection, the presence of calcifi cation on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas. Objective: To evaluate the radiological and clinical fi ndings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. Materials and Methods: We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcifi cation, turbidity, vascular fl ow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer’s exact test. Results: All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ signifi cantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifi cations (n = 3) and vascular fl ow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifi cations only. Conclusion: Although the imaging fi ndings of two groups of cystic lesions were similar, prenatal detection, the presence of calcifi cation on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas.

고위험군 신경모세포종에서 Anti-GD2 Monoclonal Antibody (Dinutuximab)와 GM-CSF, Interleukin 2, Cis-retinoic Acid의 병합요법

전인상 대한소아혈액종양학회 2016 Clinical Pediatric Hematology-Oncology Vol.23 No.2

Neuroblastoma, one of the most common solid tumors in early childhood, exhibits aberrant cell-surface glycosylation patterns. In neuroblastoma, disialoganglioside (GD2) is expressed homogeneously and abundantly on 100% of neuroblastoma cells. GD2 is a good tumor marker for developing an anti-tumor-monoclonal antibody (mAb) to neuroblastoma. Immunotherapy, using anti-GD2-mAb, has been tried since last 20 years to improve the prognosis of high risk neuroblastoma patients who show a 5-year survival rate of less than 30% regardless of an intense multimodal therapy. Since the first clinical trial of murine anti-GD2-mAb 3F8 had been performed, multiple clinical studies showed that anti-GD2-mAb might improve the prognosis of high risk neuroblastoma patients. Anti-GD2-mAb removes the neuroblastoma cells via apoptosis by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. To elicit a stronger ADCC response to antibody therapy, cytokines such as, GM-CSF and interleukin-2 are concomitantly administered, which stimulate the natural anti-tumor activity of the immune system. Children’s Oncology Group performed a study of chimeric anti-GD2-mAb (ch14.18) administration with GM-CSF, IL-2 for high risk neuroblastoma patients and showed the improvement of overall survival rate. Based on this study US FDA approved the chimeric anti-GD2-mAb (commercially manufactured dinutuximab) for the treatment of high risk neuroblastoma. Dinutuximab is the the first mAb for use in combination of cytokines for the maintenance treatment of pediatric patients with high risk neuroblastoma who achieve at least a partial response to intensified multimodal therapy. The first anti-tumor-mAb used for children, dinutuximab, could be the base of further development of mAb against the cancers in childhood.

miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells

Gao, Shun-Li,Wang, Li-Zhong,Liu, Hai-Ying,Liu, Dan-Li,Xie, Li-Ming,Zhang, Zhi-Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Background: MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours but little is known about its role in neuroblastoma. Our aim was to investigate the potential role and mechanism of miR-200a in neuroblastomas. Materials and Methods: Expression levels of miR-200a in tissues were determined using RT-PCR. The effect of miR-200a and shAP-$2{\gamma}$ on cell viability was evaluated using MTS assays, and target protein expression was determined using Western blotting and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean${\pm}$S.E.M and differences were tested for significance using the 2-tailed Students t-test. Results: We determined that miR-200a expression was significantly lower in neuroblastoma tumors than the adjacent non-cancer tissue. Over-expression of miR-200 are reduced cell viability in neuroblastoma cells and inhibited tumor growth in mouse xenografts. We identified AP-$2{\gamma}$ as a novel target for miR-200a in neuroblastoma cells. Thus miR-200a targets the 3'UTR of AP-$2{\gamma}$ and inhibits its mRNA and protein expression. Furthermore, our result showed that shRNA knockdown of AP-$2{\gamma}$ in neuroblastoma cells results in significant inhibit of cell proliferation and tumor growth in vitro, supporting an oncogenic role of AP-$2{\gamma}$ in neuroblastoma. Conclusions: Our study revealed that miR-200a is a candidate tumor suppressor in neuroblastoma, through direct targeting of AP-$2{\gamma}$. These findings re-enforce the proposal of AP-$2{\gamma}$ as a therapeutic target in neuroblastoma.

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

Ji Hwan Jo,Seung Do Ahn,Minji Koh,Jong Hoon Kim,Sang-wook Lee,Si Yeol Song,Sang Min Yoon,Young Seok Kim,Su Ssan Kim,Jin-hong Park,Jinhong Jung,Eun Kyung Choi 대한방사선종양학회 2019 Radiation Oncology Journal Vol.37 No.3

Purpose: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site. Materials and Methods: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14–36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival. Results: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%. Conclusion: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

신경아세포종 : 전산화단층촬영소경

윤춘식 대한영상의학회 1994 대한영상의학회지 Vol.30 No.1

목 적: 소아에서 가장 많은 복부악성종양중의 하나인 신경아세포종의 진단에 도움을 주고자 전산화단층촬영소견의 특징을 분석하였다. 대상 및 방법: 1983년부터 1990년 9월 사이에 조직병리학적으로 확진된 51예의 신경아세포종중 전산화단층촬영소견분석이 가능하였던 25예를 대상으로 하였다. 결 과: 가장 많이 발생한 부위는 부신(40%)였고, 후복막(32%), 후종격동(16%) 순이었다. 특징적인 CT소견은 석회화는 복부종양의 경우 86%, 종격동 종양의 경우50%에서 보였고 종양내 괴사나 출혈성 괴사는 복부종양(86%), 종격동 종양(25%)에서 보였다. 조영증강후에는 종괴내 연부조직의 조영증강뿐아니라 작은 격막상의 조영증강 소견들이 빈번해 보였다. 복부 종양의 90%에서 종괴나 전이된 림프절에의해 주요 혈관들인 하대정맥이나 대동맥 등의 encasement가 있었고 림프절의 전이소견은 복부종양의 95%, 종격동종양의 경우 25%에서 보였다. 가장 흔히 침습을 보인 장기는 신장으로 6예에서 있었다. 결 론: 신경아세포종의 진단은 이상의 전산화단층촬영의 특징적인 소견들을 보이는 종양에서 비교적 쉽게 얻을 수 있을 것으로 생각된다. Purpose : To evaluate the characteristic CT findings of neuroblastoma, we studied neurobalstomas.Materials and Methods : We analysed CT findings of available 25 cases among pathologically proved 51 neurobalstomas from Jan. 1983 to Sept. 1990.Results : The most frequent site of origin is adrenl gland (40%) and the second is retroperitoneurn (32%) and the third ismediastinum (16%). Characteristic CT findings are as follows : Calcifications within the tumor is detected in 86% of abdominal neuroblastomas and 50% of mediastinal origin. Hemorrhagic and necrotic changes within the tumor is noted at 86% in the tumor of abdominal origin and 25% in mediastinal neuroblastomas. Contrast enhanced study showed frequently septated enhanced appearance with/without solid contrast enhancement. Encasements of major great vessels such as aorta and IVC with/without displacement by metastatic lymphnodes or tumor are frequently seen in 90% of abdominal neuroblastomas. Multiple lymphadenopathy are detected in 95% of abdominal neurobalstomas and 25% of mediastinal neuroblastomas. The most common organ of contiguous direct invasion is kidney in 6 cases and the next one is liver but intraspinal canal invasion is also noted in 2 cases.Concusion : We concluded that diagnosis of neuroblastoma would be easily obtained in masses of pediatric group from recognition of above characteristic findings.

소아 신경모세포종의 치료 후 조직소견의 변화와 예후와의 관계

서연경,정유진,김준식,김흥식,박우현,최순옥,이병육,권건영,Seo, Yeon Kyong,Jung, Yu Jin,Kim, Joon Sik,Kim, Heung Sik,Park, Woo Hyun,Choi, Soon Ok,Lee, Byung Yook,Kwon, Kun Young 대한소아청소년과학회 2003 Clinical and Experimental Pediatrics (CEP) Vol.46 No.11

목 적 : 진행된 신경모세포종 환아의 약물치료 후 수술한 예에서 조직변화를 관찰하여 예후와의 상관관계를 알아보고자 이 연구를 시행하였다. 방 법 : 1991년 1월부터 2000년 6월까지 계명대학교 동산병원 소아과에서 진단된 신경모세포종 환아 중 항암치료 후 종양절제를 시행한 6례를 대상으로 하였다. 진단 당시 침생검소견과 항암치료 후 조직소견에서 신경모세포의 분화정도와 핵 모양 및 간질조직의 기질화 양상과 석회와 유무 등을 비교하여 변형된 Shimada 분류에 따라 분류하였다 결 과 : 항암치료 전과 후에 조직소견의 변화를 관찰하였으며 변형된 Shimada 분류에 따라 2가지 예후군으로 분류하였으며, 좋은 예후군 3례 중 2명은 생존해 있으며, 1명은 추적되지 않고 사망한 것으로 추정하였으며, 나쁜 예후군의 3례는 각각 패혈증과 retinoic acid 복용 중 발생한 출혈성 췌장염으로 사망하였다. 결 론 : 항암치료 전과 후에 조직소견의 변화를 관찰하였으며 Shimada 분류에 따라 비교하고, 치료 후 종양세포의 성숙을 관찰하였으며, 좋은 예후군에서 생존수가 많은 것을 확인할 수 있었다. Purpose : Neuroblastoma is a malignant neoplasm which arises from primitive sympathetic neuroblasts, and occasionally can matured from a malignant neuroblastoma into a benign ganglioneuroma. It has the highest rate of spontaneous regression of any pediatric tumor. We performed a retrospective study of pathologic features after combination therapy in advanced neuroblastoma. Prognostic effects of the individual morphologic feature and prognostic groupings according to modified Shimada classification systems were analyzed. Methods : The treatment results for six patients with neuroblastoma seen at Keimyung University from Jan. 1991 to June 2000 were analyzed. Patients were treated with a combination of chemotherapy, radiation therapy, and surgery, and classified by two major prognostic criteria based on morphological features of neuroblastoma, such as modified Shimada classification and histologic grading. Results : Three cases were classified to a good histologic group; among them, two cases survived, but one case was lost in follow-up. There were three cases classified in a poor histologic group. All of these patients expired due to sepsis and hemorrhagic pancreatitis. Conclusion : Prognostic classification due to pathologic findings had significant value in evaluating the survival rate of neuroblastoma patients.

신경모세포종 -15년간 한 병원에서의 임상적 경험-

김대연,김성철,김인구,Kim, Dae-Yeon,Kim, Seong-Chul,Kim, In-Koo 대한소아외과학회 2005 소아외과 Vol.11 No.2

Neuroblastoma treatment remains challenging, but treatment has become more effective due to the establishment of clinical and biological variables that determine prognostic risks. Initially, stage and age were the prime determinants of survival used in clinical practice. Risk-based therapy currently is the hallmark of neuroblastoma treatment. This study reviews one center's experience with the management of neuroblastoma. Sixty-three patients with neuroblastoma were treated from 1989 to 2003. All patients were graded according to the International Neuroblastoma Staging System (INSS) at diagnosis. There were 37 boys and 26 girls. The median age was 2.14 years (range, 33 days-10.2years). The primary site was the adrenal gland in 47, dumbbell shape extending into spinal canal in 6, retroperitoneum in 5, mediastinum in 3, and other sites in 2. The probability of 5-year overall survival (OS) and event free survival (EFS) were 46.7 % and 44.2 % by Kaplan-Meier method. According to INSS, there were stage 1 in 2 cases, stage 2 in 5, stage 3 in 12, stage 4 in 42, and stage 4s in 2. There were statistically significant differences in the survival rates between patients with stage1, 2 and stage 3, 4(P<0.05). For the stage 3 and 4, the extents of surgical resection, determined from the operative records and pathologies, were complete resection in 17 cases, minimal residual in 15, and partial resection 11, and the 5-year OS rate was 57.8, 51.4, and 13.6 %, respectively. There is a trend toward higher OS with more complete resection (P<0.05). We conclude that age and stage at diagnosis are prognostic factors, and complete excision of the primary tumor can provide better prognosis for patients with stage 3 and 4 neuroblastoma.

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

조지환,안승도,고민지,김종훈,이상욱,송시열,윤상민,김영석,김수산,박진홍,정진홍,최은경 대한방사선종양학회 2019 Radiation Oncology Journal Vol.37 No.3

Purpose: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site. Materials and Methods: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14–36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival. Results: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%. Conclusion: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

Patterns of recurrence after radiation therapy for high-risk neuroblastoma

Jo, Ji Hwan,Ahn, Seung Do,Koh, Minji,Kim, Jong Hoon,Lee, Sang-wook,Song, Si Yeol,Yoon, Sang Min,Kim, Young Seok,Kim, Su Ssan,Park, Jin-hong,Jung, Jinhong,Choi, Eun Kyung The Korean Society for Radiation Oncology 2019 Radiation Oncology Journal Vol.37 No.3

Purpose: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site. Materials and Methods: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14-36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival. Results: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%. Conclusion: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.

신경모세포성종양의 조직학적 분화도에 따른 면역조직화학적 특성 및 배수성 분석

고재향,정우희,정순희,김태승,박찬일 대한병리학회 1995 Journal of Pathology and Translational Medicine Vol.29 No.1