Granulocyte colony-stimulating factor corrects the neutropenia associated with glycogen storage disease type Ib.

A young woman with glycogen storage disease, type Ib, and chronic neutropenia had severe recurrent infections. In a life-threatening situation, treatment with granulocyte colony-stimulating factor (G-CSF) resulted in the prompt correction of neutropenia. Subsequently, daily G-CSF therapy has allowed the maintenance of a normal neutrophil count and marked clinical improvement over a period of 18 months. The spectrum of neutropenic conditions which are responsive to G-CSF should include this inherited metabolic disorder.     

COVID-19疑似病例合并肝母细胞瘤多学科临床讨论

目的:探讨疫情期间新型冠状病毒感染(corona virus disease 2019,COVID-19)疑似病例合并肝母细胞瘤(hepatoblastoma,HB)患儿的诊治流程和管理体会。方法:2020年2月浙江大学医学院附属儿童医院收治1例疑似严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染合并HB患儿,通过多学科协作体系(multidisciplinary team,MDT)的诊治过程。经MDT讨论后,对患儿进行SARS-CoV-2核酸及抗体、血常规、肿瘤标记物、胸腹部CT以及超声等必要的辅助检查;化疗采用顺铂+5-氟尿嘧啶+长春新碱(C5V)方案,同时予头孢噻肟抗感染以及对症支持治疗。结果:患儿确诊为HB低危组,排除COVID-19,并顺利完成HB的第一阶段化疗疗程。住院1周后患儿体温恢复正常,精神食欲好转,各项指标达到出院标准,继续完成14天隔离治疗后出院。结论:疫情期间,对于疑似SARS-CoV-2感染的新发HB患儿,医务人员在尽可能快速地诊断和治疗肿瘤的同时,一定要...     

Hodgkin's disease in siblings: a family study.

Hodgkin's disease may sporadically occur in more than one member of a family. A family in which two siblings were documented to have the nodular sclerosing form of the disease was studied for immunological competency, distribution of HL-A antigens, and Epstein-Barr virus (EBV) antibody titers. All family members examined, except the living individual with HD, had no significant abnormality in humoral and cellular immunity. HL-A antigens previously reported to appear in Hodgkin's disease with increased frequency were not found. Antibody titers to the viral capsid antigen of EBV were normal. Therefore, none of the genetically associated laboratory tests related to cancer (particularly Hodgkin's disease) were found in this family. The evidence from this family thus supports the probable importance of environmental factors in the etiology of Hodgkin's disease, particularly in the nodular sclerosis group.     

MR imaging of the liver and complicating hepatic tumors in type Ia glycogen storage disease

Background A study to determine the usefulness of magnetic resonance imaging (MRI) of the liver in patients with type Ia glycogen storage disease was performed. Methods T1-weighted images and T2-weighted images were obtained with spin echo technique in 4 patients with type Ia glycogen storage disease. The T2 values for the liver parenchyma of these 4 patients, and for the complicating liver tumors in 2 of these patients, were measured. One patient underwent hepatic angiography. For each patient with liver tumors, the number, size, and MRI findings of the tumors and their signal intensity were compared to that for the liver parenchyma on both T1-weighted and T2-weighted images. Results There was a slight reduction of T2 relaxation time in the liver parenchyma. Complicating liver tumors were depicted as high-intensity areas on T2-weighted images. The mean T2 value for diseased liver parenchyma was 34.5 milliseconds, and for liver tumors, 41.5 milliseconds. The former was less than the value for normal liver parenchyma. Reduction of T2 relaxation time for diseased liver parenchyma was probably due to the regulation of proton movement by macromolecular glycogen granules. All complicating liver tumors were depicted as high-intensity areas, compared to the diseased liver parenchyma. Conclusion These findings suggest that MRI can be useful for the observation of type Ia glycogen storage disease and complicating liver tumors.     

Myeloproliferative disease in two young siblings

Two siblings developed a myeloproliferative disease. One of them was a 9-year-old girl with a short history of bleeding, whose initial clinical and hematologic features were concordant with idiopathic myelofibrosis. Shortly afterwards this disorder evolved to a leukemic phase which subsequently resulted in the death of the patient. Four years later, at the age of 16, her brother was diagnosed as having acute myelofibrosis, and some months afterwards he died from fulminant pneumonia coincidently with pancytopenia and presence of scarce blast cells in peripheral blood. From the pathogenetic point of view, neither exposure to bone marrow toxins nor bone marrow chromosome abnormalities could be detected. HLA-typing disclosed the same haplotype (A2, A9, B5, B21, C5) in both patients.     

Loss of heterozygosity on chromosome 1 in human hepatoblastoma

In previous studies we have found loss of heterozygosity (LOH) on chromosome arm 11p in 33% of hepatoblastomas (HBs). In addition, cytogenetic studies have revealed aberrations of chromosome arm 1p in single cases. Therefore, we have used the PCR to amplify 10 microsatellites on the short arm and 7 microsatellites on the long arm of chromosome 1 to assess allelic loss in 32 cases of HB. LOH on chromosome 1 was found in 11 cases. Seven HBs showed LOH on chromosome 1p, 7 cases had LOH on 1q, and 3 tumors had LOH on both 1p and 1q. Six HBs with LOH on 1p had LOH at DIS243 (1p36.3), and one tumor had a loss at DIS80 maintaining heterozygosity at DIS243. A common region of overlap was present at the telomeric chromosomal portion of 1p between DIS80 and DIS243. Of the HBs with LOH on 1q, 4 showed a common region of overlap at 1q31-q32.1, and the other 3 at DIS1609 located more telomerically. The parental origin of the lost allele was of random distribution for chromosome arm 1p and of paternal origin for chromosome arm 1q. Our data suggest that tumor suppressor genes located at the telomeric region of chromosome arm 1p and different regions of chromosome arm 1q may be involved in the pathogenesis of HB. © 1996 Wiley-Liss, Inc.     

Von Hippel-Lindau disease and rapidly progressing pheochromocytomas in siblings

Familial Cancer - Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited condition with a predisposition to the development of a variety of tumors including pheochromocytomas. A number...     

Two novel in vitro human hepatoblastoma models,HepU1 and HepU2, are highly characteristic of fetal-embryonal differentiation in hepatoblastoma

Using comparative genomic hybridization (CGH), we present a genome‐wide screening of a mixed mesenchymal–epithelial hepatoblastoma, its recurrence and 2 novel hepatoblastoma cell lines raised from the ascites, 18 (HepU1) and 23 (HepU2) months after diagnosis of a hepatoblastoma in a 35‐month‐old boy. Both cell lines were also characterized by GTG‐banding, multicolor‐fluorescence in situ hybridization (M‐FISH) and multicolor banding (M‐Band). On the basis of CGH, we compared the cytogenetics of histologically different tumor areas of the parental tumor and its recurrence with the hepatoblastoma cell lines. We found different CGH profiles in the parental tumor rev ish enh(1q31–q32,8p,12,17,20,X), dim(4q34–q35,18q23)[cp] and its recurrence rev ish enh(8q24,17,Xq26–q28), dim(7q11.2–q21,13q34)[cp]. Although both epithelial cell lines were obtained at different times and the clonal ancestor of HepU2 had been exposed to a higher cumulative dose of chemotherapy, HepU1 and HepU2 have an identical karyotype: 48‐56,XY,+Y,dup(2)(q32–q34),t(3;4)(q21;q34),+8,+12,+13, +17,+t(18;19)(q21;q?),+20[cp] and identical CGH profiles: rev ish enh(2q24–q33,8,12,13q,17,20), dim(4q34–q35,18q22–q23). In common with previously described hepatoblastoma cell lines, HepU1 and HepU2 demonstrate a gain of chromosome 20. The in situ aberrations most closely resembling that of HepU1 and HepU2 were found in areas of fetal–embryonal differentiation of the primary tumor. Interestingly, both cell lines mimic this histology in their three‐dimensional growth pattern in vitro. HepU1 and HepU2 are thus cytogenetically and phenotypically highly characteristic of fetal–embryonal hepatoblastoma. © 2003 Wiley‐Liss, Inc.     

Malignant schwannoma in siblings with neurofibromatosis

Three brothers with neurofibromatosis (NF) died of sarcoma. The proband tumor had malignant schwannoma. The histologic nature of the sarcoma in the other two brothers was not known, but it seemed likely to be similar to that of the proband. However, the sarcomatous lesions in these two siblings developed in the patients' right lower limbs which showed clinical and radiological evidence of anterior bowing of the tibia. Their mother and two other siblings have neurofibromatosis, but have not developed malignant tumors. The unaffected father died at age 61 of carcinoma of the common bile duct. An unaffected sister developed adenocarcinoma of both colon and lung. Although it is known that patients with NF are at a high risk of developing malignant sarcoma and second primary malignancies, it is not clear whether this association is genetically determined. The family we report has some of the features of a "cancer family" and suggests that sarcomatous transformation in patients with NF may be genetically influenced. This report raises the possibility that the presence of congenital malformation and exposure to irradiation may predispose patients with neurofibromatosis to develop malignant schwannoma.     

Early-Onset Breast Cancer in a Family with Neurofibromatosis Type 1 Associated with a Germline Mutation in BRCA1

Neurofibromatosis type 1 (NF1), which may occur as an autosom-al dominant disorder, is caused by the absence of neurofibromin protein due to somatic mutations in the NF1 gene, and it has been associated with an increased risk of breast cancer. Herein we describe a family with two women affected by both NF1 and early-onset breast cancer. We evaluated whether the concomitance of NF1 and early-onset breast cancer could be due to disease-causing mutations in both NF1 and BRCA1 gene in a Korean family with clinical features of both NF1 and hereditary breast cancer. Mutation analyses identified nonsense mutations in NF1 and BRCA1 genes. Our findings indicate that an awareness of the possible concomitance of NF1 and BRCA1 gene mutations is important for identifying the genetic origin of early-onset breast cancer in patients with NF1 to achieve early detection of cancers and decrease breast cancer-associated morbidity and mortality in these patients.     

Establishment and characterization of a hepatoblastoma cell-line from a patient with secondary acute myeloid-leukemia

A girl who had been treated, apparently successfully, with surgery and chemotherapy for a hepatoblastoma, fell ill two years later with what was diagnosed as an AMF M(4). A cell line was established from her peripheral blood. This cell line had epithelial morphology and grew both in suspension culture and as a monolayer. The cells were positive for epithelial surface markers, including the liver-specific alpha-fetoprotein, but not for leukocyte markers. The cell-line's karyotype was markedly abnormal. It did not have any specific aneuploidies or any other aberrations characteristic of leukemias; instead it had gains of 2q and chromosome 20, the most common cytogenetic changes in hepatoblastoma. It is most likely that the patient had a relapse of hepatoblastoma with massive seeding of the blood leading to a leukemia-like picture without, of course, excluding other possibilities.     

Chromosomal aberrations and CD38 expression in two siblings with B-cell chronic lymphocytic leukemia: a report of two siblings

In this study our purpose was to define chromosomal aberrations and CD38 expression in male siblings 69 and 66-years-old with B-cell chronic lymphocytic leukemia (B-CLL). Cells from peripheral blood were analysed by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The alteration detectable by CGH was the over-representation of the Y chromosome in both samples. Interphase FISH were performed using locus (13q14 and 17p53) and centromere (chromosome 12, 17 and Y) specific DNA probes. One brother (patient 1, 69 years of age) showed deletion of the 13q14 region, this alteration was associated with low CD38 expression, both predicting a favourable prognosis. However, the younger patient's (patient 2, 66 years of age) cells expressed CD38 in high percent, which is considered as an indicator of poor prognosis, and deletion of the 13q14 was not seen. Other, relatively frequent chromosomal alterations including trisomy 12 and deletion of 17p53 were not present in any of the samples. The cytogenetic findings and the CD38 expression are in concordance with the clinico-pathological data of the siblings. Thus, we found the variability of these parameters described in B-CLL even in the familial form of the disease.     

Gastric carcinoma in siblings with Friedreich's ataxia

Friedreich's ataxia is a hereditary neurological condition characterized by severe ataxia. We report the cases of two siblings with thiscondition, both of whom developed signet ring cell adenocarcinoma of the stomach at a young age. This association has not been previously described and it suggests the presence of an unidentified aberrant gene.     

Type of acetylation in children with Hodgkin's disease

Examination of a healthy European population showed 60% to be "slow" acetylators and 40% "rapid" ones. A similar distribution was established in pediatric controls. Among children with Hodgkin's disease, there were 4.1 times more slow acetylators. N-acetyltransferase activity was found to increase with tumor advancement. Conversion of acetylation pattern was observed in pediatric patients with Hodgkin's disease.     

Therapeutic drug monitoring and dose adaptation of cisplatin in a newborn with hepatoblastoma: a case report

Cancer Chemotherapy and Pharmacology - Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In...     

100例肝母细胞瘤基于新危险分层的治疗结果分析

目的提出适合中国肝母细胞瘤(HB)患者的危险分层方法,探讨高危HB患者的新治疗方法。方法2014年9月至2018年9月,中山大学肿瘤防治中心和中山大学附属第一医院收治的年龄≤18岁的100例初治HB患者,根据临床分期、甲胎蛋白水平、病理分型等因素,分为极低危、低危、中危和高危4个危险层级。极低危患者手术后不行化疗,随访观察;低危患者术后用C5V方案(顺铂+氟尿嘧啶+长春新碱)化疗共4个周期;中危患者术前和术后行C5VD方案(顺铂+氟尿嘧啶+长春新碱+阿霉素)化疗,共6~8个周期;高危患者术前和术后行C5VD方案与IIV方案(异环磷酰胺+伊立替康+长春新碱)交替化疗,共8个周期。结果100例患者分为极低危2例,低危10例,中危51例,高危37例。化疗前有可评价病灶者83例,化疗后部分缓解65例,疾病稳定10例,疾病进展8例,一线化疗客观有效率为78.3%。中位随访20个月,复发和进展30例,死亡27例。全组患者2年无进展生存率为69.2%,2年总生存率为72.0%。其中极低危、低危、中危、高危的2年无进展生存率分别为100%、88.9%、75.3%和43.2%,2年总生存率分别为100%、100%、81.0%和44.8%。结论新的HB危险分层方法简便可行。根据新危险分层方法分层后,对患者采取不同的治疗策略,极低危、低危和中危HB可获得较好的预后,高危HB患者的生存率仍有待提高,需要探讨新的治疗策略。     

Success in Treating Hepatoblastoma by Transcatheter Arterial Infusion Combined with Radical Resection： a Case Report

Hepatoblastoma is the most common malignant hepatic tumor in children. About 50% of the cases occur before the age of 18 months and almost all before the age of 2 years. We present an extremely rare case of hepatoblastoma in an 11-year-old girl, which was pathologically verified and treated twice with transcatheter arterial infusion combined with radical resection. To date she has been followed-up for 15 years and has shown normal development after the operation. She has received no chemotherapy or radiation and has displayed no evidence of metastatic or recurrent disease.     

Multiple neoplasms in two siblings with a variant form of Fanconi's anemia.

Two siblings with a variant form of Fanconi's anemia developed multiple neoplasms after prolonged survival and treatment with androgens. One of the siblings developed two separate oral squamous cell carcinomata, and the other developed acute leukemia and hepatoma. Androgens may have had a carcinogenic role in the appearance of the hepatic neoplasm. There is an increased incidence of neoplasm associated with Fanconi's anemia. This may be related to frequent spontaneous chromosomal abberations and/or to increased cellular susceptibility to viral transformation.