ABSTRACT
OBJECTIVE: Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. METHODS: We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. RESULTS: From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. CONCLUSION: Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT.
Subject(s)
Body Mass Index , CA-125 Antigen , Fibrin Fibrinogen Degradation Products , Fibrinogen , Hemoglobins , Ovarian Neoplasms , Venous Thrombosis , Humans , Female , Venous Thrombosis/etiology , Venous Thrombosis/blood , Retrospective Studies , Middle Aged , Ovarian Neoplasms/blood , Ovarian Neoplasms/complications , CA-125 Antigen/blood , Aged , Fibrin Fibrinogen Degradation Products/analysis , Hemoglobins/analysis , Fibrinogen/analysis , Adult , Partial Thromboplastin Time , Blood Glucose/analysis , Leukocyte Count , Prothrombin Time , Republic of Korea/epidemiology , Monocytes , Preoperative Period , Platelet Count , Aged, 80 and over , Risk Factors , Membrane ProteinsABSTRACT
Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.
Subject(s)
Ovarian Neoplasms , Thrombosis , Humans , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/metabolism , Thrombosis/etiology , Ovarian Neoplasms/complications , Ovarian Neoplasms/surgery , Plasminogen , Biomarkers , HomocysteineABSTRACT
PURPOSE: Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. MATERIALS AND METHODS: Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. RESULTS: We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. CONCLUSION: Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.
Subject(s)
Breast Neoplasms , Pancreatic Neoplasms , Peritoneal Neoplasms , Humans , Female , Ascites , Precision Medicine , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Peritoneal Neoplasms/pathology , Organoids/pathology , Pancreatic NeoplasmsABSTRACT
PURPOSE: The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. MATERIALS AND METHODS: Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. RESULTS: PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). CONCLUSION: Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Prevalence , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/epidemiology , Carcinoma, Pancreatic Ductal/genetics , Risk Factors , Trypsin Inhibitor, Kazal Pancreatic , Pancreatic NeoplasmsABSTRACT
Background: Circulating tumor DNA (ctDNA) is a non-invasive biomarker for evaluating cancer prognosis. The aim of this study was to analyze the genomic profile of circulating tumor DNA (ctDNA) in breast cancer patients, and evaluate its clinical implications. Methods: Targeted sequencing of ctDNA was performed in 38 patients using commercially available Oncomine Breast cfDNA panel. Whole exome sequencing was performed on matched tumor DNA (n=20). Survival analysis and response to chemotherapy in the study population were evaluated. The detected genomic variants were validated and serially monitored with droplet digital polymerase chain reaction (ddPCR) in 5 patients. Results: At least one variant or copy number alteration was detected in the ctDNA of 31 of 38 (82%) breast cancer patients, with the most common variants being in TP53 (50%), PIK3CA (15%) and ESR1 (14%). When comparing genomic profiles of ctDNA and those of matched tumor DNA in 20 patients, the concordance rate was 9.7% among positives. The patients with variants in TP53 showed significantly poorer overall survival than those without [hazard ratio (HR) =3.90, 95% confidence interval (CI): 1.10-13.84, P=0.035] and its impact was also statistically significant in multivariate analysis with breast cancer subtype included. In serially monitored results, changes in the allele frequency of somatic variants (PI3KCA, TP53) of ctDNA were found to be reflective of response to chemotherapy. Conclusions: The genomic profile of ctDNA reflects and provides additional information to the tumor DNA genome profile. Follow-up monitoring of mutations detected in ctDNA is useful in the clinical management of breast cancer patients.
ABSTRACT
Sarcopenia and adipopenia have prognostic significance in cancer. Analysis of a single abdominal computed tomography (CT) section at the third lumbar vertebra has been widely adopted for this purpose. The approach using a single section at the first lumbar vertebra level (L1) may extend clinical viability. We evaluated the prognostic value of sarcopenia and adipopenia assessed using a CT section at L1 in acute myeloid leukemia (AML). Data from 96 patients with available imaging were retrospectively reviewed. Patients with sarcopenia (37.5%) had significantly worse overall survival (OS) (median 17.8 months vs. not reached, p = 0.038) and treatment-related mortality (TRM) (22.2% vs. 3.0%, p = 0.0019) than those without. Subcutaneous adipopenia (51.0%) was significantly associated with inferior OS (median 17.9 months vs. not reached, p = 0.0011), progression-free survival (PFS) (median 6.2 months vs. not reached, p = 0.004), and TRM (16.3% vs. 4%, p = 0.024). Visceral adipopenia (30.2%) was associated with poor OS (12.7 vs. 31.7 months, p = 0.0055) and PFS (3.7 vs. 31.7 months, p = 0.003). Multivariable analyses found sarcopenia, subcutaneous adipopenia and visceral adipopenia were significant negative prognostic factors for OS. Sarcopenia and adipopenia assessed using a single CT section at the L1 level are useful in predicting the prognosis of AML.
Subject(s)
Adipose Tissue/diagnostic imaging , Fats/analysis , Leukemia, Myeloid, Acute/complications , Muscle, Skeletal/diagnostic imaging , Sarcopenia/complications , Adult , Aged , Aged, 80 and over , Female , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Prognosis , Retrospective Studies , Sarcopenia/diagnostic imaging , Tomography, X-Ray Computed , Young AdultABSTRACT
INTRODUCTION: Autologous peripheral blood stem cell (PBSC) transplantation has become a standard treatment option for many oncology patients. The aim of this study was to evaluate the performance of two cell separators, Spectra Optia (Terumo BCT, Japan) and Amicus (Fresenius-Kabi) for autologous PBSC collection. METHODS: We retrospectively evaluated 56 apheresis by Spectra Optia with Continuous Mononuclear Cell Collection (cMNC) from 20 patients, and 50 apheresis by Amicus from 27 patients between December 2018 and December 2019. CD34+ collection efficiency (CE2) and platelet (PLT) loss were evaluated. RESULTS: There was no significant difference in CD34+ CE2 between Spectra Optia with cMNC (median, 28.8%) and Amicus (median, 33.1%; P = 0.537). PLT loss was significantly lower in Amicus (median, 28.6%) than in Spectra Optia with cMNC (median, 37.8%; P = 0.009). CONCLUSION: CD34+ CE2 was comparable between Spectra Optia and Amicus, and PLT loss was significantly lower in Amicus. To the best of our knowledge, this is the first report comparing autologous PBSC collection of the Spectra Optia and Amicus. These results may provide general guidance with regard to device selection to apheresis clinics that use both separators for optimal outcomes depending on each patient's characteristics.
Subject(s)
Blood Component Removal/methods , Hematopoietic Stem Cell Mobilization/methods , Peripheral Blood Stem Cells/cytology , Adult , Blood Component Removal/instrumentation , Female , Hematopoietic Stem Cell Mobilization/instrumentation , Humans , Male , Middle Aged , Transplantation, Autologous , Young AdultABSTRACT
BACKGROUND: Peripheral blood stem cell (PBSC) collection is important for successful hematopoietic stem cell transplantation. This study aimed to investigate the laboratory parameters associated with the optimal timing of autologous PBSC collection from lymphoma and multiple myeloma patients. METHODS: We retrospectively evaluated data from 1105 PBSC apheresis procedures performed on 379 adult patients at the National Cancer Center between June 2005 and December 2019. Laboratory parameters, including cutoff values for the number of hematopoietic progenitor cells (HPCs) and circulating CD34+ cells, were analyzed to determine their association with CD34+ cell yield. RESULTS: The pre-apheresis HPC and CD34+ cell count were statistically significant variables associated with harvested CD34+ cell in lymphoma and MM patients. The optimal cutoff values were 18 × 106 /L for pre-HPC count (66.8% sensitivity, 66.4% specificity) and 11/µL for pre-CD34+ cell count (85.8% sensitivity, 87.2% specificity), to achieve CD34+ cell yields ≥ 1.0 × 106 /kg for each apheresis procedure. Moreover, the optimal cutoff values were 23 × 106 /L for pre-HPC count (71.0% sensitivity, 69.0% specificity) and 18/µL for pre-CD34+ cell count (87.5% sensitivity, 86.3% specificity) to achieve CD34+ cell yields ≥ 2.0 × 106 /kg for each apheresis procedure. CONCLUSION: HPC count is a potential surrogate marker for monitoring the starting time for PBSC collection. Applying cutoff values for the number of HPC and CD34+ cells may be clinically useful for optimizing the timing of PBSC collection.
Subject(s)
Blood Component Removal/methods , Hematopoietic Stem Cell Mobilization/methods , Lymphoma/therapy , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Neutrophils , Retrospective Studies , Transplantation, Autologous , Young AdultABSTRACT
OBJECTIVE: We investigated the proportions of and reclassified BRCA1/2 variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers. METHODS: Data from 805 patients who underwent genetic testing for BRCA1/2 from January 1, 2006 to August 31, 2018 were included. The VUS in BRCA1/2 were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines. RESULTS: A BRCA1 pathogenic variant was found in 17.0% (137/805) of the patients, and BRCA1 VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a BRCA2 pathogenic variant and 18.4% (148/805) of the patients possessed BRCA2 VUS. Fifty-three specific BRCA1 VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For BRCA2, 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants. CONCLUSIONS: Approximately 33.3% (36/108) of the specific BRCA1/2 variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Fallopian Tube Neoplasms , Ovarian Neoplasms , Peritoneal Neoplasms , Fallopian Tube Neoplasms/genetics , Fallopian Tubes , Female , Genetic Predisposition to Disease , Genetic Variation , Humans , Ovarian Neoplasms/genetics , Peritoneal Neoplasms/geneticsABSTRACT
Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and an increase in MVD can be used as a marker of poor prognosis in MM patients. We developed an automated image analyzer to assess MVD from images of BM biopsies stained with anti-CD34 antibodies using two color models. MVD was calculated by merging images from the red and hue channels after eliminating non-microvessels. The analyzer results were compared with those obtained by two experienced hematopathologists in a blinded manner using the 84 BM samples of MM patients. Manual assessment of the MVD by two hematopathologists yielded mean±SD values of 19.4±11.8 and 20.0±11.8. The analyzer generated a mean±SD of 19.5±11.2. The intraclass correlation coefficient (ICC) and Bland-Altman plot of the MVD results demonstrated very good agreement between the automated image analyzer and both hematopathologists (ICC=0.893 [0.840-0.929] and ICC=0.906 [0.859-0.938]). This automated analyzer can provide time- and labor-saving benefits with more objective results in hematology laboratories.
Subject(s)
Bone Marrow/pathology , Image Processing, Computer-Assisted/methods , Microvascular Density/physiology , Antibodies/immunology , Antigens, CD34/immunology , Antigens, CD34/metabolism , Automation , Bone Marrow/metabolism , Humans , Multiple Myeloma/diagnosis , PrognosisABSTRACT
BACKGROUND AND OBJECTIVES: ABO isoagglutinin titre is important for evaluating and monitoring ABO-incompatible (ABOi) stem cells or solid organ transplantations. There are several methods to measure the titre level, including the tube haemagglutination method, micro-column agglutination and erythrocyte-magnetized technology (EMT). However, few studies have reported isoagglutinin measured by EMT. Here, we compared the isoagglutinin titre of normal individuals obtained by an automated instrument with that obtained by conventional manual methods to evaluate the feasibility of replacing the manual method with the automated instrument. MATERIALS AND METHODS: The ABO isoagglutinin titre was measured on residual samples of healthy individuals who visited the health promotion centre of the National Cancer Center, Korea, from April to October 2015. Samples from 120 patients were collected, which included 20 males and 20 females for each blood group (A, B and O). IgM and IgG ABO isoagglutinin titres of each blood group were measured by the tube haemagglutination, micro-column agglutination and EMT techniques. The median (minimum-maximum) titres were compared, and the concordance between two methods was evaluated with the rate of results showing within one titre difference. RESULTS: The median ABO IgM and IgG titres of all blood groups obtained by the EMT method were higher than that obtained by the conventional tube haemagglutination and micro-column agglutination. CONCLUSION: The agreement between the two methods was comparable in case of IgM but low in IgG.
Subject(s)
ABO Blood-Group System/blood , Hemagglutination , Immunologic Tests/methods , Female , Hemagglutination Tests/methods , Humans , Male , Republic of KoreaABSTRACT
BACKGROUND: The collection of a sufficient number of stem cells is important for success of allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the factors associated with successful allogeneic peripheral stem cell (PBSC) collection in healthy donors. METHODS: We retrospectively reviewed clinical data of allogeneic PBSC collection in 175 donors from 2007 to 2017 at the National Cancer Center, Korea. This study analyzed factors associated with the CD34+ cell yield such as the characteristics of donors, including age, laboratory results before apheresis, and data of procedures on the first day. The CD34+ cell dose of ≥ 4.0â¯×â¯106/kg have recently been the accepted minimum recommended dose in allogeneic HSCT settings, and this was the target dose in our study. RESULTS: The factors associated with the CD34+ cell yield were age (pâ¯=â¯0.007), baseline platelet (PLT) (pâ¯=â¯0.014), and pre-collection hematopoietic progenitor cells (HPCs) (pâ¯=â¯0.001) by multivariate analysis. This study represented that age, baseline platelet count, and pre-collection HPC count are important predictive factors as shown in other previous studies. CONCLUSION: Our data suggest that young age, high baseline platelet counts and high HPC counts before collection might be useful for identifying successful mobilizers.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Adolescent , Adult , Aged , Female , Healthy Volunteers , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors , Young AdultABSTRACT
POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.
Subject(s)
Bone Marrow/metabolism , POEMS Syndrome/diagnosis , Adult , Aged , Aged, 80 and over , Antigens, CD19/metabolism , Bone Marrow/pathology , Female , Glycoproteins/analysis , Humans , Immunophenotyping , Lymphocytes/cytology , Lymphocytes/metabolism , Male , Middle Aged , Paraproteinemias/diagnosis , Republic of Korea , Retrospective Studies , Young AdultABSTRACT
Human leukocyte antigen (HLA) class II alleles have been previously associated with cervical cancer. However, these associations vary widely across racial and ethnic groups. Therefore, we evaluated the effect of HLA class II alleles on cervical cancer in a Korean population. HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles were analyzed in 457 cervical cancer patients and compared to those of 926 control subjects. The odds ratio (OR) of each allele between the patients and controls was calculated using the logistic regression model. Patients, had significantly lower frequencies of HLA-DRB1 and HLA-DQB1 alleles than control subjects: HLA-DRB1*13:02:01 (4.4% vs 8.8%; OR 0.48, 95% confidence interval (CI) 0.27-0.84; pâ¯=â¯0.001), HLA-DRB1*04:06 (2.1% vs 4.7%; OR 0.44, 95% CI 0.20-0.97; pâ¯=â¯0.033), and HLA-DQB1*06:04:01 (2.3% vs 5.0%; OR 0.46, 95% CI 0.22-0.94; pâ¯=â¯0.021). No significant association was observed for HLA-DQA1. Protective associations between HLA-DRB1*13:02, HLA-DRB1*04:06, and HLA-DQB1*06:04 alleles and cervical cancer were found in the Korean population.
Subject(s)
Genotype , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Uterine Cervical Neoplasms/genetics , Adult , Aged , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Histocompatibility Testing , Humans , Korea , Logistic Models , Middle Aged , Polymorphism, GeneticABSTRACT
Assessment of bone marrow (BM) involvement in peripheral T-cell lymphoma, not otherwise specified (PTCL) is straightforward in cases of extensive involvement but difficult in cases of minimal to partial involvement. We evaluated the usefulness of CD3 as an immunohistochemical marker for assessing BM involvement in PTCL patients. BM biopsies of 92 PTCL patients were immunohistochemically stained for CD3, CD4, CD8, CD20, and CD56, and evaluated by two hematopathologists. CD3 positivity was graded according to the proportion of CD3-positive cells and the number of CD3-positive cells in a cluster. These criteria were used to determine the cut-offs at which significant differences in progression-free survival (PFS) and overall survival (OS) were observed. Multivariate analysis controlling the International Prognostic Index (IPI) score and its individual factors revealed that >20 CD3-positive cells in a cluster adversely affected PFS (relative risk [RR], 2.1; 95% confidence interval [CI], 1.0-4.3; P=0.047) and OS (RR, 2.4; 95% CI, 1.1-5.1; P=0.028) independent of IPI score. A cluster with >20 CD3-positive cells is a candidate indicator for BM involvement in PTCL.
Subject(s)
Bone Marrow/pathology , CD3 Complex/metabolism , Lymphoma, T-Cell, Peripheral/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Lymphoma, T-Cell, Peripheral/mortality , Lymphoma, T-Cell, Peripheral/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Progression-Free Survival , Proportional Hazards Models , Retrospective Studies , Survival Rate , Young AdultABSTRACT
The prognostic significances of the germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB) types of diffuse large B-cell lymphoma (DLBCL) have been reported to be different. We analyzed the effect of the cell of origin (COO) of bone marrow (BM) involvement in patients with DLBCL who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in a single institute.The subtype of BM involvement was evaluated in 633 patients who were diagnosed with primary DLBCL and had been treated with R-CHOP. BM trephine biopsies were analyzed, and immunohistochemical staining of CD20, CD79a, and CD3 was performed. Additional staining of CD10, Bcl-6, and MUM1 was performed to determine the COO based on a previously reported algorithm.BM involvement was present in 81 patients (12.8%). Among them, 30 patients (37.0%) had GCB-type BM involvement and 51 (63.0%) showed non-GCB-type involvement. Kaplan-Meier survival analysis showed that the non-GCB type had the worst progression-free survival (PFS) and overall survival (OS) (Pâ<.001). In multivariate analysis controlled for the International Prognostic Index (IPI) score, non-GCB type was an independent predictor of PFS (Pâ<.004) and OS (Pâ=.042), whereas GCB type was not a prognostic factor independent of the IPI score.Further prognostication based on the COO of BM involvement is a useful indicator of PFS, independent of IPI score. Accurate staging based on the COO should be included in the examination of BM in DLBCL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Lymphocytes/pathology , Bone Marrow/pathology , Germinal Center/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prednisone/administration & dosage , Prognosis , Rituximab , Treatment Outcome , Vincristine/administration & dosage , Young AdultABSTRACT
Clinical decision support (CDS) search is performed to retrieve key medical literature that can assist the practice of medical experts by offering appropriate medical information relevant to the medical case in hand. In this paper, we present a novel CDS search framework designed for passage retrieval from biomedical textbooks in order to support clinical decision-making using laboratory test results. The framework utilizes two unique characteristics of the textual reports derived from the test results, which are syntax variation and negation information. The proposed framework consists of three components: domain ontology, index repository, and query processing engine. We first created a domain ontology to resolve syntax variation by applying the ontology to detect medical concepts from the test results with language translation. We then preprocessed and performed indexing of biomedical textbooks recommended by clinicians for passage retrieval. We finally built the query-processing engine tailored for CDS, including translation, concept detection, query expansion, pseudo-relevance feedback at the local and global levels, and ranking with differential weighting of negation information. To evaluate the effectiveness of the proposed framework, we followed the standard information retrieval evaluation procedure. An evaluation dataset was created, including 28,581 textual reports for 30 laboratory test results and 56,228 passages from widely used biomedical textbooks, recommended by clinicians. Overall, our proposed passage retrieval framework, GPRF-NEG, outperforms the baseline by 36.2, 100.5, and 69.7 percent for MRR, R-precision, and Precision at 5, respectively. Our study results indicate that the proposed CDS search framework specifically designed for passage retrieval of biomedical literature represents a practically viable choice for clinicians as it supports their decision-making processes by providing relevant passages extracted from the sources that they prefer to refer to, with improved performances.
Subject(s)
Decision Support Systems, Clinical , Information Storage and Retrieval/methods , Medical Laboratory Science , Algorithms , Biological Ontologies , Humans , SemanticsABSTRACT
BACKGROUND: Reconstitution of the immune system after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in post-transplant outcomes. However, the clinical relevance of the lymphocyte subset (LST) counts to transplant-related complications and survival outcomes after allo-HSCT has not been fully elucidated. PATIENTS AND METHODS: A total of 70 patients who had undergone allo-HSCT from 2007 to 2013, with LST results both 7 days before conditioning and 30 or 90 days after allo-HSCT were included. The LST counts in the peripheral blood were determined using 6-color flow cytometry. Clinical information, including transplant-related events during the first 100 days after allo-HSCT, was reviewed, and any association between these events and LST was analyzed. RESULTS: At 30 days after allo-HSCT, the CD4+ T-cell (P = .009) and B-cell (P = .035) counts were lower and the natural killer (NK) cell count was greater (P < .001) than before conditioning. The CD8+ T-cell (P = .001) and NK cell (P < .001) counts were high 90 days after transplantation. The hazard ratios for a low NK cell count on days 30 and 90 for acute graft-versus-host disease were 6.22 and 14.67, respectively. Patients with low NK cell counts at 30 and 90 days after allo-HSCT had poorer overall survival (P = .043 and P = .028, respectively) and greater nonrelapse mortality (P = .036 and P = .033, respectively). A low NK cell count on day 30 was still prognostic for overall survival (P = .039) on multivariable analysis. CONCLUSION: NK cell counts after allo-HSCT, especially on day 30, were predictive of acute graft-versus-host disease, nonrelapse mortality, and survival. Serial lymphocyte subset analysis can be used to identify and treat patients at risk during the early period after allo-HSCT.
Subject(s)
Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Lymphocyte Count , Adult , Biomarkers , Female , Follow-Up Studies , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Immunophenotyping , Kaplan-Meier Estimate , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Male , Middle Aged , Mortality , Odds Ratio , Patient Outcome Assessment , Postoperative Period , Prognosis , Proportional Hazards Models , ROC Curve , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous , Young AdultABSTRACT
An erratum is presented to correct a typographical error on Fig. 1 in [Opt. Express 22(9), 10398 (2014)].
ABSTRACT
Due to its strong correlation with the pathophysiology of many diseases, information about human red blood cells (RBCs) has a crucial function in hematology. Therefore, measuring and understanding the morphological, chemical, and mechanical properties of individual RBCs is a key to understanding the pathophysiology of a number of diseases in hematology, as well as to opening up new possibilities for diagnosing diseases in their early stages. In this study, we present the simultaneous and quantitative measurement of the morphological, chemical, and mechanical parameters of individual RBCs employing optical holographic microtomography. In addition, it is demonstrated that the correlation analyses of these RBC parameters provide unique information for distinguishing and understanding diseases.