BACKGROUND: Lymphocytes seen during the chemotherapy of childhood ALL are not fully understood regarding their clinical significance. The lymphoid aggregates found during the complete remission period are more confusing. We investigated the characteristics of lymphoid aggregates and the clinial course of children with these in the marrow during the chemotherapy of childhood ALL. This is the first study about this subject. METHODS: From January 1996 to April 1998, 210 bone marrow specimens were diagnosed as complete remission status of ALL and among them, ten patients (4.8%) showed lymphoid aggreagates on the marrow clot sections at the time of complete remission. We reviewed bone marrow specimens, performed immunohistochemical stains for CD3, CD 10 and CD79a and investigated the clinical course. RESULTS: The ten cases were composed of nine ALL, L1 and one ALL, L2. All of them were treated under guidance of the CCG (children's cancer group) protocol. Fourteen lymphoid aggregates from ten cases were found. They showed mean number of 1.4 per clot section, mean diameter of 132 micrometer, regular (36%) or irregular (64%) margin and composition of mature lymphocytes (21%), immature lymphocytes (29%) or mixed pattern (50%). The mean interval between the diagnosis and the emergence of lymphoid agregates was 29 months (2~55 months). One patient in the course of consolidation chemotherapy expired due to upper gastrointestinal bleeding and other nine cases are still in the continuous complete remission state. The lymphoid cells consisting of lymphoid aggregates showed positive reaction only for CD79a and negative reactions for CD3 and CD10. CONCLUSION: Lymphpoid aggregates found at the time of complete remission are collections of regenerating B-lymphocytes and they are not residual leukemic blasts, and show no effect on the complete remission state.
B-Lymphocytes ; Bone Marrow* ; Child ; Coloring Agents ; Consolidation Chemotherapy ; Diagnosis ; Drug Therapy ; Hemorrhage ; Humans ; Lymphocytes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hepatoid adenocarcinoma is a rare variant of adenocarcinoma that can occur in the stomach. This neoplasm has a poor prognosis and it frequently presents at an advanced stage of disease; it is clinically characterized by increased serum levels of alpha-fetoprotein (AFP) in most cases. We experienced a case of hepatoid adenocarcinoma of the stomach with multiple liver metastases that mimicked germ cell tumor in a 43-year-old man. He had incidentally detected gastric adenocarcinoma via gastrofibroscopy and he underwent subtotal gastrectomy. The postoperative pathologic stage was II (T2N1M0). He complained of epigastric pain. The serum AFP was markedly increased (227,325 IU/mL) and abdominal CT revealed multiple liver masses. We considered these as extragonadal germ cell tumors that occurred in the liver because of the markedly elevated AFP, the short duration of follow-up and early stage of stomach cancer at the that time. To confirm the diagnosis, biopsy of liver mass was done and he was diagnosed with hepatoid adenocarcinoma.
Adenocarcinoma* ; Adult ; alpha-Fetoproteins ; Biopsy ; Diagnosis ; Follow-Up Studies ; Gastrectomy ; Germ Cells* ; Humans ; Liver ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal* ; Prognosis ; Stomach ; Stomach Neoplasms ; Tomography, X-Ray Computed

The human genome has evolved as a consequence of evolutionary forces, such as natural selection. In this study, we investigated natural selection on the human genes by comparing the numbers of nonsynonymous(NS) and synonymous (S) mutations in individual genes. We initially collected all coding SNP data of all human genes from the public dbSNP. Among the human genes, we selected 3 different selection groups of genes: positively selected genes (NS/S > or = 3), negatively selected genes (NS/S < or = 1/3) and neutral selection genes (0.9 < NS/S < 1.1). We characterized human genes targeted by natural selection. Negatively selected human genes were markedly associated with disease occurrence, but not positively selected genes. Interestingly, positively selected genes displayed an increase in potentially deleterious nonsynonymous SNPs with an increased frequency of tryptophan and tyrosine residues, suggesting a correlation with protective effects against human disease. Furthermore, our nonsynonymous/synonymous ratio data imply that specific human genes, such as ALMS1 and SPTBN5 genes, are differentially selected among distinct populations. We confirmed that inferences of natural selection using the NS/S ratio can be used extensively to identify functional genes selected during the evolutionary adaptation process.
Clinical Coding ; Genome, Human ; Humans ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Tryptophan ; Tyrosine

No abstract available.
Adult ; Autoantigens/*genetics ; Cell Cycle Proteins/*genetics ; Chromosomes, Human, Pair 8 ; Chromosomes, Human, Pair 9 ; Humans ; Janus Kinase 2/*genetics ; Male ; Myeloproliferative Disorders/complications/*genetics ; Sarcoma, Myeloid/complications/*genetics ; Translocation, Genetic

Purpose: This study evaluated thyroid cancer risk in a lung cancer screening population according to the presence of an incidental thyroid nodule (ITN) detected on low-dose chest computed tomography (LDCT). Methods: Of 47,837 subjects who underwent LDCT, a lung cancer screening population according to the National Lung Screening Trial results was retrospectively enrolled. The prevalence of ITN on LDCT was calculated, and the ultrasonography (US)/fine-needle aspiration (FNA)–based risk of thyroid cancer according to the presence of ITN on LDCT was compared using the Fisher exact or Student t-test as appropriate. Results: Of the 2,329 subjects (female:male=44:2,285; mean age, 60.9±4.9 years), the prevalence of ITN on LDCT was 4.8% (111/2,329). The incidence of thyroid cancer was 0.8% (18/2,329, papillary thyroid microcarcinomas [PTMCs]) and was higher in the ITN-positive group than in the ITN-negative group (3.6% [4/111] vs. 0.6% [14/2,218], P=0.009). Among the 2,011 subjects who underwent both LDCT and thyroid US, all risks were higher (P<0.001) in the ITNpositive group than in the ITN-negative group: presence of thyroid nodule on US, 94.1% (95/101) vs. 48.6% (928/1,910); recommendation of FNA according to the American Thyroid Association guideline and Korean Thyroid Imaging Reporting and Data System guideline, 41.2% (42/101) vs. 2.4% (46/1,910) and 39.6% (40/101) vs. 1.9% (37/1,910), respectively. Conclusion Despite a higher risk of thyroid cancer in the LDCT ITN-positive group than in the ITN-negative group in a lung cancer screening population, all cancers were PTMCs. A heavy smoking history may not necessitate thorough screening US for thyroid incidentalomas.

Essential thrombocythemia (ET) is a clonalmyeloproliferative disorder that can rarely transform into acute leukemia in 1~5% of cases. A recent study has found that a significant proportion of leukemic cases from ET were associated with a cytogenetic abnormality (17p deletion). Herein, we report two cases of acute myeloid leukemic transformations harboring a 17p abnormality from a series of 119 ET patients. The first case, a 48-year-old female, developed acute myeloid leukemia with maturation (AML-M2) accompanying myelodysplasia was diagnosed 6.1 years after the initial diagnosis of ET. She was treated with hydroxyurea. Her karyotype showed a monosomy 17. The second case, a 61-year-old male, developed acute megakaryoblastic leukemia (AML-M7) with a very complex hyperdiploidy including addition of 17p13 that developed 6.5 years after the initial diagnosis. He was treated with hydroxyurea and anagrelide. The immunohistochemistry showed p53 overexpression in both cases. Our cases support the specificity of chromosome 17 abnormality and p53 overexpression in acute leukemic transformation from ET.
Chromosome Aberrations ; Chromosomes, Human, Pair 17* ; Diagnosis ; Female ; Humans ; Hydroxyurea ; Immunohistochemistry ; Karyotype ; Leukemia ; Leukemia, Megakaryoblastic, Acute ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Monosomy ; Sensitivity and Specificity ; Thrombocythemia, Essential*

BACKGROUND: The lymphocytes including morphologically immature lymphoid cells are frequently increased in the marrow aspirates of children with neuroblastoma. We studied about the clonality of these lymphoid cells and its effects on the marrow involvement and prognosis of disease. METHODS: We evaluated 30 marrow aspirates of 23 children with neuroblastoma from 1990 to 1998. We tested the immunoglobulin heavy chain gene rearrangement PCR for B cell clonality and T cell receptor gamma gene rearrangement PCR for T cell clonality with bone marrow specimens. RESULTS: Younger children showed negative bone marrow involvement more than older children. In this group, the proportions of immature lymphoid cells and total lymphocytes were higher (3.4+/-3.2% vs. 0.8+/-1.9%, 31.3+/-17.0% vs. 14.7+/-12.0%). Immunoglobulin heavy chain gene rearrangements were present in 19/30 (64%) specimens and more frequently observed in negative marrow involvement cases. Seven cases with the proportions of total lymphocytes more than 30% showed significantly high long-term survival probability (P=0.05). Ten cases with B cell monoclonality showed the tendency of high long-term survival probability (P=0.13). CONCLUSION: The increase of lymphocytes including morphologically immature lymphoid cells in the marrow aspirates of children with neuroblastoma were frequently observed in the children without marrow involvement of malignancy and closely related to B cell clonality. The increase of total lymphocytes and related B cell monoclonality may be one of possible explanations of goodprognosis of children with neuroblastoma.
Bone Marrow* ; Child* ; Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains ; Lymphocytes* ; Neuroblastoma* ; Polymerase Chain Reaction ; Prognosis* ; Receptors, Antigen, T-Cell

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.
Asian Continental Ancestry Group/genetics ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Crohn Disease/*genetics ; *Exome ; Female ; Genetic Predisposition to Disease ; *Genetic Variation ; Humans ; Immunologic Deficiency Syndromes/genetics ; Infant ; Male ; Phenotype ; Receptors, Interleukin-17/genetics ; Republic of Korea ; Sequence Analysis, DNA/*methods ; X-Linked Inhibitor of Apoptosis Protein/genetics

BACKGROUND/AIMS: The palliative prognostic index (PPI) was designed to predict life expectancy based on clinical symptoms. In this study, a PPI was constructed and used with other biological parameters to predict 3-week survival in patients with advanced cancer. METHODS: The study included 222 patients. The PPI was constructed with five variables (performance status, oral intake, edema, dyspnea at rest, and delirium). PPI scores were grouped as follows: 4 (group 1); > 4 and < or = 6 (group 2); and > 6 (group 3). At admission, seven biological variables (white blood cell count, lymphocyte, C-reactive protein [CRP], bilirubin, albumin, creatinine, and lactate dehydrogenase) were measured. RESULTS: The overall survival duration was 50 days in group 1, 22 days in group 2, and 14 days in groups 3. Using the PPI, a survival of < 3 weeks in group 3 was predicted with a sensitivity of 76.5% and a specificity of 65.4%. The important factors significantly affecting the 3-week survival rate were a PPI score > 6 and increases in serum bilirubin and CRP levels. Furthermore, the 3-week survival rate in patients with hepatopancreatobiliary cancer was more accurately predicted using a combination of the PPI, CRP, and serum bilirubin levels. CONCLUSIONS: Although a PPI has limitations, it can be quickly applied to determine survival duration in patients admitted to hospice and accurately predicts 3-week survival. Furthermore, bilirubin and CRP are useful factors for predicting 3-week survival in patients with gastrointestinal cancer, including hepatopancreatobiliary cancer.
Bilirubin ; Blood Cell Count ; C-Reactive Protein ; Creatinine ; Dyspnea ; Edema ; Gastrointestinal Neoplasms ; Hospice Care ; Hospices ; Humans ; Lactic Acid ; Life Expectancy ; Lymphocytes ; Prospective Studies ; Sensitivity and Specificity ; Survival Analysis ; Survival Rate ; Terminally Ill

Habitual abortion or recurrent pregnancy loss has been defined as the occurrence of three or more clinically recognized pregnancy loss before 20 gestational weeks. A recognized cause of habitual abortion is a genetic abnormality, and karyotyping of couples will reveal that about 5% have some abnormality, most frequently a balanced translocation. However, it has been reported that duplication of chromosome is a rare condition associated with habitual abortion. We have experienced a case of chromosomal duplication 9q as polymorphism found in fetus of the patient with habitual abortion. Father of the fetus also has the same chromosomal duplication on 9q. This represents familial polymorphism and it is very rare variant. We presented with brief review of literatures.
Abortion, Habitual* ; Chromosome Duplication ; Family Characteristics ; Fathers ; Female ; Fetus* ; Humans ; Karyotyping ; Pregnancy