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  1. Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

    2014-01-01

    The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

  2. The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT

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    Alzahrani, M; El-Galaly, T C; Hutchings, M

    2016-01-01

    BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly d...

  3. Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

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    Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian; Liu, Yue-Ping; Wang, Wei-Hu; Jin, Jing; Song, Yong-Wen; Ren, Hua; Fang, Hui [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Chen, Bo; Lu, Ning-Ning; Li, Ning; Tang, Yuan; Tang, Yu; Dai, Jian-Rong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Ye-Xiong, E-mail: yexiong12@163.com [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2016-10-01

    Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.

  4. Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation

    International Nuclear Information System (INIS)

    Fuller, Lillian M.; Krasin, Matthew J.; Velasquez, William S.; Allen, Pamela K.; McLaughlin, Peter; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Swan, Forrest; Cabanillas, Fernando; Palmer, Judy L.; Cox, James D.

    1995-01-01

    Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

  5. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

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    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  6. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

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    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  7. Additional survival benefit of involved-lesion radiation therapy after R-CHOP chemotherapy in limited stage diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kwon, Jeanny; Kim, Il Han; Kim, Byoung Hyuck; Kim, Tae Min; Heo, Dae Seog

    2015-05-01

    The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥ 7 cm); and 75.3% underwent ≥ 6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥ 6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level. Copyright © 2015. Published by Elsevier Inc.

  8. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    International Nuclear Information System (INIS)

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

    2015-01-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

  9. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

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    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Ren, Hua; Jin, Jing [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China)

    2016-06-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  10. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    International Nuclear Information System (INIS)

    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping; He, Xiao-Hui; Dong, Mei; Ren, Hua; Jin, Jing; Li, Ye-Xiong

    2016-01-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  11. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09).

    Science.gov (United States)

    Yoon, Dok Hyun; Sohn, Byeong Seok; Oh, Sung Yong; Lee, Won-Sik; Lee, Sang Min; Yang, Deok-Hwan; Huh, Jooryung; Suh, Cheolwon

    2017-02-21

    The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine (n = 15), cervical lymph nodes (n = 4), stomach (n = 1), tonsil (n = 1), and spleen (n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9-47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9-104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia (n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

  12. INNOVATION DIFFUSION THEORY MAIN DEVELOPMENT STAGES

    Directory of Open Access Journals (Sweden)

    S. V. Lisafiev

    2011-01-01

    Full Text Available Abstract: Main innovation diffusion development theory stages are: Rogers model of moving new products to the market including characteristics of its segments; mathematic substantiation of this model by Bass; Moor model taking into account gaps between adjacent market segments; Goldenberg model making it possible to predict sales drops at new product life cycle initial stages. It is reasonable to use this theory while moving innovative products to the market.

  13. Atmospheric diffusion of large clouds

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, T. V. [Univ. of California, Lawrence Radiation Lab., Livermore, California (United States)

    1967-07-01

    Clouds of pollutants travel within a coordinate system that is fixed to the earth's surface, and they diffuse and grow within a coordinate system fixed to the cloud's center. This paper discusses an approach to predicting the cloud's properties, within the latter coordinate system, on space scales of a few hundred meters to a few hundred kilometers and for time periods of a few days. A numerical cloud diffusion model is presented which starts with a cloud placed arbitrarily within the troposphere. Similarity theories of atmospheric turbulence are used to predict the horizontal diffusivity as a function of initial cloud size, turbulent atmospheric dissipation, and time. Vertical diffusivity is input as a function of time and height. Therefore, diurnal variations of turbulent diffusion in the boundary layer and effects of temperature inversions, etc. can be modeled. Nondiffusive cloud depletion mechanisms, such as dry deposition, washout, and radioactive decay, are also a part of this numerical model. An effluent cloud, produced by a reactor run at the Nuclear Rocket Development Station, Nevada, is discussed in this paper. Measurements on this cloud, for a period of two days, are compared to calculations with the above numerical cloud diffusion model. In general, there is agreement. within a factor of two, for airborne concentrations, cloud horizontal area, surface air concentrations, and dry deposition as airborne concentration decreased by seven orders of magnitude during the two-day period. (author)

  14. Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced-stage Hodgkin's lymphoma and diffuse large B-cell lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Terasawa, T.; Lau, J.; Bardet, S.

    2009-01-01

    . RESULTS: Thirteen studies involving 360 advanced-stage HL patients and 311 DLBCL patients met our inclusion criteria. Advanced-stage HL studies included few unfavorable-risk patients. DLBCL studies were heterogeneous. FDG-PET had an overall sensitivity of 0.81 (95% CI, 0.72 to 0.89) and a specificity of 0.......97 (95% CI, 0.94 to 0.99) for advanced-stage HL, and a sensitivity of 0.78 (95% CI, 0.64 to 0.87) and a specificity of 0.87 (95% CI, 0.75 to 0.93) for DLBCL. Meta-regression and subgroup analyses did not identify factors that affect prognostic accuracy. CONCLUSION: For low- to intermediate-risk advanced...

  15. Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

    Science.gov (United States)

    Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

    2015-08-15

    Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

  16. Evaluation of diffuse large B-cell lymphoma patients with 64-slice multidetector computed tomography versus 18FDG positron emission tomography/computed tomography in initial staging and restaging after treatment.

    Science.gov (United States)

    Gómez León, Nieves; Vega, Gema; Rodríguez-Vigil Junco, Beatriz; Suevos Ballesteros, Carlos

    2018-04-25

    To prospectively compare the accuracy in initial staging and end-of-treatment restaging of diffuse large B-cell lymphoma (DLBCL) between 64-slice multidetector computed tomography (64MDCT) and 18FDG positron emission tomography/computed tomography (18FGD PET/CT) with intravenous contrast injection. Randomised and blind controlled clinical multicentric trial that included biopsy-proven DLBCL patients. Seventy-two patients from five different hospitals in the region of Madrid, Spain, were enrolled in the study between January 2012 and June 2015. Thirty-six were randomly allocated to 18FDG PET/TC and the other 36 to 64MDCT for initial staging and end-of-treatment restaging. A nuclear medicine physician and a radiologist independently analysed 18FDG PET/TC images and reached an agreement post-hoc. 64MDCT images were separately evaluated by a different radiologist. Every set of images was compared to the reference standard that included clinical data, complementary tests and follow-up. The study was approved by participating centres' ethics committees and written informed consent was obtained from all the participants. A good agreement was observed between both diagnostic techniques and the reference standard in initial staging [18FDG PET/CT (k=0.5) and 64MDCT (k=0.6)], although only the 18FDG PET/TC showed a good agreement with the reference standard for the end-of-treatment restaging (k=0.7). In DLBCL, both 18FDG PET/TC and 64MDCT have shown good agreement with the reference standard in initial staging. Nevertheless, 18FDG PET/CT has shown to be superior to 64MDCT in end-of-treatment response assessment. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  17. Transition Process from Diffuser Stall to Stage Stall in a Centrifugal Compressor with a Vaned Diffuser

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    Nobumichi Fujisawa

    2017-01-01

    Full Text Available The transition process from a diffuser rotating stall to a stage stall in a centrifugal compressor with a vaned diffuser was investigated by experimental and numerical analyses. From the velocity measurements, it was found that the rotating stall existed on the shroud side of the diffuser passage in the off-design flow condition. The numerical results revealed the typical vortical structure of the diffuser stall. The diffuser stall cell was caused by the systematic vortical structure which consisted of the tornado-type vortex, the longitudinal vortex at the shroud/suction surface corner (i.e., leading edge vortex (LEV, and the vortex in the throat area of the diffuser passages. Furthermore, the stage stall, which rotated within both the impeller and diffuser passages, occurred instead of the diffuser stall as the mass flow rate was decreased. According to the velocity measurements at the diffuser inlet, the diffuser stall which rotated on the shroud side was shifted to the hub side. Then, the diffuser stall moved into the impeller passages and formed the stage stall. Therefore, the stage stall was caused by the development of the diffuser stall, which transferred from the shroud side to the hub side in the vaneless space and expanded to the impeller passages.

  18. Investigation of the Stage Performance and Flow Fields in a Centrifugal Compressor with a Vaneless Diffuser

    Directory of Open Access Journals (Sweden)

    Ahti Jaatinen-Värri

    2014-01-01

    Full Text Available The effect of the width of the vaneless diffuser on the stage performance and flow fields of a centrifugal compressor is studied numerically and experimentally. The diffuser width is varied by reducing the diffuser flow area from the shroud side (i.e., pinching the diffuser. Seven different diffuser widths are studied with numerical simulation. In the modeling, the diffuser width b/b2 is varied within the range 1.00 to 0.50. The numerical results are compared with results obtained in previous studies. In addition, two of the diffusers are further investigated with experimental measurement. The main finding of the work is that the pinch reduces losses in the impeller associated with the tip-clearance flow. Furthermore, it is shown that a too large width reduction causes the flow to accelerate excessively, resulting in a highly nonuniform flow field and flow separation near the shroud.

  19. Prognosis of localized diffuse large B-cell lymphoma in younger patients

    DEFF Research Database (Denmark)

    Møller, Michael B; Christensen, Bjarne E; Pedersen, Niels T

    2003-01-01

    BACKGROUND: The International Prognostic Index (IPI) is widely used as a predictive model in diffuse large B-cell lymphoma (DLBCL) patients of all ages and stages. To determine the optimal IPI-based prognostic system at the time of diagnosis in younger patients with limited-stage DLBCL, the authors...

  20. Knowledge diffusion within a large conservation organization and beyond

    Science.gov (United States)

    Montambault, Jensen; Burford, Kyle P.; Gopalakrishna, Trisha; Masuda, Yuta J.; Reddy, Sheila M. W.; Torphy, Kaitlin; Salcedo, Andrea I.

    2018-01-01

    The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit–The Nature Conservancy–and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting “evidence” practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with

  1. Knowledge diffusion within a large conservation organization and beyond.

    Science.gov (United States)

    Fisher, Jonathan R B; Montambault, Jensen; Burford, Kyle P; Gopalakrishna, Trisha; Masuda, Yuta J; Reddy, Sheila M W; Torphy, Kaitlin; Salcedo, Andrea I

    2018-01-01

    The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit-The Nature Conservancy-and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting "evidence" practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with knowledge

  2. Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

    Science.gov (United States)

    Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

    2013-11-01

    Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

  3. Method of independently operating a group of stages within a diffusion cascade

    International Nuclear Information System (INIS)

    Benedict, M.; Allen, J.F.; Levey, H.B.

    1976-01-01

    A method of operating a group of the diffusion stages of a productive diffusion cascade with counter-current flow is described. The group consists of a top and a bottom stage which isolates the group from the cascade. The diffused gas produced in the top stage is circulated to the feed of the bottom stage, while at the same time undiffused gas from the bottom stage is circulated to the feed of the top stage whereby major changes in inventory distribution within the group of stages are prevented

  4. Diffuse reflectance relations based on diffusion dipole theory for large absorption and reduced scattering

    NARCIS (Netherlands)

    Bremmer, Rolf H.; van Gemert, Martin J. C.; Faber, Dirk J.; van Leeuwen, Ton G.; Aalders, Maurice C. G.

    2013-01-01

    Diffuse reflectance spectra are used to determine the optical properties of biological samples. In medicine and forensic science, the turbid objects under study often possess large absorption and/or scattering properties. However, data analysis is frequently based on the diffusion approximation to

  5. Diffusion Experiments in Opalinus Clay: Laboratory, Large-Scale Diffusion Experiments and Microscale Analysis by RBS.

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Gutierrez, M.; Alonso de los Rios, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2008-08-06

    The Opalinus Clay (OPA) formation in the Zurcher Weiland (Switzerland) is a potential host rock for a repository for high-level radioactive waste. Samples collected in the Mont Terri Underground Rock Laboratory (URL), where the OPA formation is located at a depth between -200 and -300 m below the surface, were used to study the radionuclide diffusion in clay materials. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), to understand the transport properties of the OPA and to enhance the methodologies used for in situ diffusion experiments. Through-Diffusion and In-Diffusion conventional laboratory diffusion experiments were carried out with HTO, 36{sup C}l-, I-, 22{sup N}a, 75{sup S}e, 85{sup S}r, 233{sup U}, 137{sup C}s, 60{sup C}o and 152{sup E}u. Large-scale diffusion experiments were performed with HTO, 36{sup C}l, and 85{sup S}r, and new experiments with 60{sup C}o, 137{sup C}s and 152{sup E}u are ongoing. Diffusion experiments with RBS technique were done with Sr, Re, U and Eu. (Author) 38 refs.

  6. Diffuse reflectance relations based on diffusion dipole theory for large absorption and reduced scattering.

    Science.gov (United States)

    Bremmer, Rolf H; van Gemert, Martin J C; Faber, Dirk J; van Leeuwen, Ton G; Aalders, Maurice C G

    2013-08-01

    Diffuse reflectance spectra are used to determine the optical properties of biological samples. In medicine and forensic science, the turbid objects under study often possess large absorption and/or scattering properties. However, data analysis is frequently based on the diffusion approximation to the radiative transfer equation, implying that it is limited to tissues where the reduced scattering coefficient dominates over the absorption coefficient. Nevertheless, up to absorption coefficients of 20  mm-1 at reduced scattering coefficients of 1 and 11.5  mm-1, we observed excellent agreement (r2=0.994) between reflectance measurements of phantoms and the diffuse reflectance equation proposed by Zonios et al. [Appl. Opt.38, 6628-6637 (1999)], derived as an approximation to one of the diffusion dipole equations of Farrell et al. [Med. Phys.19, 879-888 (1992)]. However, two parameters were fitted to all phantom experiments, including strongly absorbing samples, implying that the reflectance equation differs from diffusion theory. Yet, the exact diffusion dipole approximation at high reduced scattering and absorption also showed agreement with the phantom measurements. The mathematical structure of the diffuse reflectance relation used, derived by Zonios et al. [Appl. Opt.38, 6628-6637 (1999)], explains this observation. In conclusion, diffuse reflectance relations derived as an approximation to the diffusion dipole theory of Farrell et al. can analyze reflectance ratios accurately, even for much larger absorption than reduced scattering coefficients. This allows calibration of fiber-probe set-ups so that the object's diffuse reflectance can be related to its absorption even when large. These findings will greatly expand the application of diffuse reflection spectroscopy. In medicine, it may allow the use of blue/green wavelengths and measurements on whole blood, and in forensic science, it may allow inclusion of objects such as blood stains and cloth at crime

  7. Interleukin 10 gene promoter polymorphism and risk of diffuse large ...

    African Journals Online (AJOL)

    Purpose: Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma (NHL), this work was designed to study the impact of IL-10 (1082 G/A; rs1800896 and 819 C/T; rs1800871) gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell ...

  8. Profiling of diffuse large B-cell lymphoma by immunohistochemistry

    DEFF Research Database (Denmark)

    Sjö, Lene Dissing; Poulsen, Christian Bjørn; Hansen, Mads

    2007-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed...

  9. Large scale laboratory diffusion experiments in clay rocks

    International Nuclear Information System (INIS)

    Garcia-Gutierrez, M.; Missana, T.; Mingarro, M.; Martin, P.L.; Cormenzana, J.L.

    2005-01-01

    Full text of publication follows: Clay formations are potential host rocks for high-level radioactive waste repositories. In clay materials the radionuclide diffusion is the main transport mechanism. Thus, the understanding of the diffusion processes and the determination of diffusion parameters in conditions as similar as possible to the real ones, are critical for the performance assessment of deep geological repository. Diffusion coefficients are mainly measured in the laboratory using small samples, after a preparation to fit into the diffusion cell. In addition, a few field tests are usually performed for confirming laboratory results, and analyse scale effects. In field or 'in situ' tests the experimental set-up usually includes the injection of a tracer diluted in reconstituted formation water into a packed off section of a borehole. Both experimental systems may produce artefacts in the determination of diffusion coefficients. In laboratory the preparation of the sample can generate structural change mainly if the consolidated clay have a layered fabric, and in field test the introduction of water could modify the properties of the saturated clay in the first few centimeters, just where radionuclide diffusion is expected to take place. In this work, a large scale laboratory diffusion experiment is proposed, using a large cylindrical sample of consolidated clay that can overcome the above mentioned problems. The tracers used were mixed with clay obtained by drilling a central hole, re-compacted into the hole at approximately the same density as the consolidated block and finally sealed. Neither additional treatment of the sample nor external monitoring are needed. After the experimental time needed for diffusion to take place (estimated by scoping calculations) the block was sampled to obtain a 3D distribution of the tracer concentration and the results were modelled. An additional advantage of the proposed configuration is that it could be used in 'in situ

  10. Large Deviations for Two-Time-Scale Diffusions, with Delays

    International Nuclear Information System (INIS)

    Kushner, Harold J.

    2010-01-01

    We consider the problem of large deviations for a two-time-scale reflected diffusion process, possibly with delays in the dynamical terms. The Dupuis-Ellis weak convergence approach is used. It is perhaps the most intuitive and simplest for the problems of concern. The results have applications to the problem of approximating optimal controls for two-time-scale systems via use of the averaged equation.

  11. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    Carlos Bortoluzzi, Marcelo

    2010-01-01

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  12. Performance improvement of a centrifugal compressor stage by using different vaned diffusers

    International Nuclear Information System (INIS)

    Zhang, Y C; Kong, X Z; Li, F; Sun, W; Chen, Q G

    2013-01-01

    The vaneless diffuser (VLD) is usually adopted in the traditional design of the multi-stage centrifugal compressor because of the stage's match problem. The drawback of the stage with vaneless diffusers is low efficiency. In order to increase the efficiency and at the same time, induce no significant decline in the operating range of the stage, three different types of vaned diffusers are designed and numerically investigated: the traditional vaned diffuser (TVD), the low-solidity cascade diffuser (LSD) and the partial-height vane diffuser (PVD). These three types of vaned diffusers have different influences on the performance of the centrifugal compressor. In the present investigation, the first part investigates the performance of a centrifugal compressor stage with three different vaned diffusers. The second part studies the influences of the height and the position of partial height vanes on the stage performance, and discusses the matching problem between the PVD and the downstream return channel. The stage investigated in this paper includes the impeller, the diffuser, the bend and the return channel. In the process of numerical investigation, the flow is assumed to be steady, and this process includes calculation and simulation. The calculation of 3-D turbulent flow in the stage uses the commercial CFD code NUMECA together with the Spalart-Allmaras turbulence model. The simulation of the computational region includes the impeller passages, the diffuser passages and return channel passages. The structure and surrounding region are assumed to have a perfect cyclic symmetry, so the single channel model and periodic boundary condition are applied at the middle of the passage, that is to reduce the calculation region to only one region. The investigation showed that the low-solidity cascade diffuser would be a better choice as a middle course for the first stage of the multistage centrifugal compressor. Besides, the influences of the height and the position

  13. Validation of a Computational Model for the SLS Core Stage Oxygen Tank Diffuser Concept and the Low Profile Diffuser - An Advanced Development Design for the SLS

    Science.gov (United States)

    Brodnick, Jacob; Richardson, Brian; Ramachandran, Narayanan

    2015-01-01

    The Low Profile Diffuser (LPD) project originated as an award from the Marshall Space Flight Center (MSFC) Advanced Development (ADO) office to the Main Propulsion Systems Branch (ER22). The task was created to develop and test an LPD concept that could produce comparable performance to a larger, traditionally designed, ullage gas diffuser while occupying a smaller volume envelope. Historically, ullage gas diffusers have been large, bulky devices that occupy a significant portion of the propellant tank, decreasing the tank volume available for propellant. Ullage pressurization of spacecraft propellant tanks is required to prevent boil-off of cryogenic propellants and to provide a positive pressure for propellant extraction. To achieve this, ullage gas diffusers must slow hot, high-pressure gas entering a propellant tank from supersonic speeds to only a few meters per second. Decreasing the incoming gas velocity is typically accomplished through expansion to larger areas within the diffuser which has traditionally led to large diffuser lengths. The Fluid Dynamics Branch (ER42) developed and applied advanced Computational Fluid Dynamics (CFD) analysis methods in order to mature the LPD design from and initial concept to an optimized test prototype and to provide extremely accurate pre-test predictions of diffuser performance. Additionally, the diffuser concept for the Core Stage of the Space Launch System (SLS) was analyzed in a short amount of time to guide test data collection efforts of the qualification of the device. CFD analysis of the SLS diffuser design provided new insights into the functioning of the device and was qualitatively validated against hot wire anemometry of the exterior flow field. Rigorous data analysis of the measurements was performed on static and dynamic pressure data, data from two microphones, accelerometers and hot wire anemometry with automated traverse. Feasibility of the LPD concept and validation of the computational model were

  14. The ESO Diffuse Interstellar Band Large Exploration Survey (EDIBLES)

    Science.gov (United States)

    Cami, J.; Cox, N. L.; Farhang, A.; Smoker, J.; Elyajouri, M.; Lallement, R.; Bacalla, X.; Bhatt, N. H.; Bron, E.; Cordiner, M. A.; de Koter, A..; Ehrenfreund, P.; Evans, C.; Foing, B. H.; Javadi, A.; Joblin, C.; Kaper, L.; Khosroshahi, H. G.; Laverick, M.; Le Petit, F..; Linnartz, H.; Marshall, C. C.; Monreal-Ibero, A.; Mulas, G.; Roueff, E.; Royer, P.; Salama, F.; Sarre, P. J.; Smith, K. T.; Spaans, M.; van Loon, J. T..; Wade, G.

    2018-03-01

    The ESO Diffuse Interstellar Band Large Exploration Survey (EDIBLES) is a Large Programme that is collecting high-signal-to-noise (S/N) spectra with UVES of a large sample of O and B-type stars covering a large spectral range. The goal of the programme is to extract a unique sample of high-quality interstellar spectra from these data, representing different physical and chemical environments, and to characterise these environments in great detail. An important component of interstellar spectra is the diffuse interstellar bands (DIBs), a set of hundreds of unidentified interstellar absorption lines. With the detailed line-of-sight information and the high-quality spectra, EDIBLES will derive strong constraints on the potential DIB carrier molecules. EDIBLES will thus guide the laboratory experiments necessary to identify these interstellar “mystery molecules”, and turn DIBs into powerful diagnostics of their environments in our Milky Way Galaxy and beyond. We present some preliminary results showing the unique capabilities of the EDIBLES programme.

  15. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  16. Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen Juul; Nielsen, Anne Lerberg; Pedersen, Lars Møller

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially curable type of lymphoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is part of clinical routine for DLBCL in most hospitals and also recommended for staging and end-of-therapy evaluation. FDG......-PET/computed tomography (CT) is able to identify nodal and extranodal sites with greater accuracy than CT alone. Little evidence supports the use of surveillance FDG-PET imaging in the follow-up setting because of high rates of false-positive scans and because most studies are retrospective. This article discusses FDG...

  17. Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Wasif Saif; Sapna Khubchandani; Marek Walczak

    2007-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

  18. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  19. Diffusion-weighted MRI of epithelial ovarian cancers: Correlation of apparent diffusion coefficient values with histologic grade and surgical stage

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ji-Won, E-mail: fromentin@naver.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Rha, Sung Eun, E-mail: serha@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Oh, Soon Nam, E-mail: hiohsn@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Park, Michael Yong, E-mail: digirave@kmle.com [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Byun, Jae Young, E-mail: jybyun@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of); Lee, Ahwon, E-mail: klee@catholic.ac.kr [Department of Hospital Pathology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137-701 (Korea, Republic of)

    2015-04-15

    Highlights: •The solid component of all invasive epithelial cancers showed high b{sub 1000} signal intensity. •ADCs can predict the histologic grade of epithelial ovarian cancer. •ADCs correlate negatively to the surgical stage of epithelial ovarian cancer. •ADCs may be useful imaging biomarkers to assess epithelial ovarian cancer. -- Abstract: Objective: The purpose of this article is to correlate the apparent diffusion coefficient (ADC) values of epithelial ovarian cancers with histologic grade and surgical stage. Materials and methods: We enrolled 43 patients with pathologically proven epithelial ovarian cancers for this retrospective study. All patients underwent preoperative pelvic magnetic resonance imaging (MRI) including diffusion-weighted images with b value of 0 and 1000 s/mm{sup 2} at 3.0-T unit. The mean ADC values of the solid portion of the tumor were measured and compared among different histologic grades and surgical stages. Results: The mean ADC values of epithelial ovarian cancers differed significantly between grade 1 (well-differentiated) and grade 2 (moderately-differentiated) (P = 0.013) as well as between grade 1 and grade 3 (poorly-differentiated) (P = 0.01); however, no statistically significant difference existed between grade 2 and grade 3 (P = 0.737). The receiver-operating characteristic analysis indicated that a cutoff ADC value of less than or equal to 1.09 × 10{sup −3} mm{sup 2}/s was associated with 94.4% sensitivity and 85.7% specificity in distinguishing grade 1 and grade 2/3 cancer. The difference in mean ADC values was statistically significant for early stage (FIGO stage I) and advanced stage (FIGO stage II-IV) cancer (P = 0.011). The interobserver agreement for the mean ADC values of epithelial ovarian cancers was excellent. Conclusion: The mean ADC values of the solid portion of epithelial ovarian cancers negatively correlated to histologic grade and surgical stage. The mean ADC values may be useful imaging

  20. One-stage reconstruction technique for large congenital eyelid coloboma.

    Science.gov (United States)

    Hashish, Aiman; Awara, Amr Mahmoud

    2011-08-01

    To determine the functional and cosmetic outcome of using skin graft from prepuce (after circumcision) to reconstruct eyelids in congenital lid coloboma. Four male infants with large eyelid coloboma and marked exposure keratopathy were included. All the patients were selected from the outpatient clinic of Tanta University Eye Hospital, Egypt from March 2006 till August 2009. One-stage reconstruction was used to repair the defect. For upper eyelid coloboma, sliding tarsoconjunctival flap with a free skin graft from of skin of prepuce (after circumcision) was done.For lower lid coloboma, conjunctival dissection with reflection over the cornea with use of a free skin graft from prepuce. All infants had large unilateral defect, 3 upper lids and 1 lower lid. The cosmetic and functional outcome of using skin of the prepuce was satisfactory with good color match in all cases. Also functional and cosmetic results of tarsoconjunctival sliding flap was excellent. All the cases were followed up for a period ranged from 7 to 36 months. Tarsoconjunctival rotational flap and the use of skin of prepuce are very helpful and seems to be an adequate method of reconstruction of large eyelid defect in male patients when the usual donor sites for skin grafts are not available as in infants.

  1. Design Study for a Staged Very Large Hadron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Alex W.

    2002-02-27

    Particle physics makes its greatest advances with experiments at the highest energy. The only sure way to advance to a higher-energy regime is through hadron colliders--the Tevatron, the LHC, and then, beyond that, a Very Large Hadron Collider. At Snowmass-1996 [1], investigators explored the best way to build a VLHC, which they defined as a 100 TeV collider. The goals in this study are different. The current study seeks to identify the best and cheapest way to arrive at frontier-energy physics, while simultaneously starting down a path that will eventually lead to the highest-energy collisions technologically possible in any accelerator using presently conceivable technology. This study takes the first steps toward understanding the accelerator physics issues, the technological possibilities and the approximate cost of a particular model of the VLHC. It describes a staged approach that offers exciting physics at each stage for the least cost, and finally reaches an energy one-hundred times the highest energy currently achievable.

  2. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

    International Nuclear Information System (INIS)

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance

  3. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

    2018-04-12

    Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

  4. Logical analysis of diffuse large B-cell lymphomas.

    Science.gov (United States)

    Alexe, G; Alexe, S; Axelrod, D E; Hammer, P L; Weissmann, D

    2005-07-01

    The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical

  5. Histogram analysis of diffusion kurtosis imaging of nasopharyngeal carcinoma: Correlation between quantitative parameters and clinical stage.

    Science.gov (United States)

    Xu, Xiao-Quan; Ma, Gao; Wang, Yan-Jun; Hu, Hao; Su, Guo-Yi; Shi, Hai-Bin; Wu, Fei-Yun

    2017-07-18

    To evaluate the correlation between histogram parameters derived from diffusion-kurtosis (DK) imaging and the clinical stage of nasopharyngeal carcinoma (NPC). High T-stage (T3/4) NPC showed significantly higher Kapp-mean (P = 0.018), Kapp-median (P = 0.029) and Kapp-90th (P = 0.003) than low T-stage (T1/2) NPC. High N-stage NPC (N2/3) showed significantly lower Dapp-mean (P = 0.002), Dapp-median (P = 0.002) and Dapp-10th (P Histogram parameters, including mean, median, 10th, 90th percentiles, skewness and kurtosis of Dapp and Kapp were calculated. Patients were divided into low and high T, N and clinical stage based on American Joint Committee on Cancer (AJCC) staging system. Differences of histogram parameters between low and high T, N and AJCC stages were compared using t test. Multiple receiver operating characteristic (ROC) curves were used to determine and compare the value of significant parameters in predicting high T, N and AJCC stage, respectively. DK imaging-derived parameters correlated well with clinical stage of NPC, therefore could serve as an adjunctive imaging technique for evaluating NPC.

  6. Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City (Japan); Iehara, Tomoko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Paediatrics, Graduate School of Medical Science, Kyoto City (Japan)

    2010-05-15

    We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

  7. Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

    International Nuclear Information System (INIS)

    Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko; Iehara, Tomoko; Hosoi, Hajime

    2010-01-01

    We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

  8. Insights into cadmium diffusion mechanisms in two-stage diffusion profiles in solar-grade Cu(In,Ga)Se{sub 2} thin films

    Energy Technology Data Exchange (ETDEWEB)

    Biderman, N. J.; Sundaramoorthy, R.; Haldar, Pradeep [Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203 (United States); U.S. Photovoltaic Manufacturing Consortium, Albany, New York 12203 (United States); Novak, Steven W.; Lloyd, J. R. [Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203 (United States)

    2015-12-07

    Cadmium diffusion experiments were performed on polished copper indium gallium diselenide (Cu(In,Ga)Se{sub 2} or CIGS) samples with resulting cadmium diffusion profiles measured by time-of-flight secondary ion mass spectroscopy. Experiments done in the annealing temperature range between 275 °C and 425 °C reveal two-stage cadmium diffusion profiles which may be indicative of multiple diffusion mechanisms. Each stage can be described by the standard solutions of Fick's second law. The slower cadmium diffusion in the first stage can be described by the Arrhenius equation D{sub 1} = 3 × 10{sup −4} exp (− 1.53 eV/k{sub B}T) cm{sup 2} s{sup −1}, possibly representing vacancy-meditated diffusion. The faster second-stage diffusion coefficients determined in these experiments match the previously reported cadmium diffusion Arrhenius equation of D{sub 2} = 4.8 × 10{sup −4} exp (−1.04 eV/k{sub B}T) cm{sup 2} s{sup −1}, suggesting an interstitial-based mechanism.

  9. Insights into cadmium diffusion mechanisms in two-stage diffusion profiles in solar-grade Cu(In,Ga)Se2 thin films

    International Nuclear Information System (INIS)

    Biderman, N. J.; Sundaramoorthy, R.; Haldar, Pradeep; Novak, Steven W.; Lloyd, J. R.

    2015-01-01

    Cadmium diffusion experiments were performed on polished copper indium gallium diselenide (Cu(In,Ga)Se 2 or CIGS) samples with resulting cadmium diffusion profiles measured by time-of-flight secondary ion mass spectroscopy. Experiments done in the annealing temperature range between 275 °C and 425 °C reveal two-stage cadmium diffusion profiles which may be indicative of multiple diffusion mechanisms. Each stage can be described by the standard solutions of Fick's second law. The slower cadmium diffusion in the first stage can be described by the Arrhenius equation D 1  = 3 × 10 −4  exp (− 1.53 eV/k B T) cm 2  s −1 , possibly representing vacancy-meditated diffusion. The faster second-stage diffusion coefficients determined in these experiments match the previously reported cadmium diffusion Arrhenius equation of D 2  = 4.8 × 10 −4  exp (−1.04 eV/k B T) cm 2  s −1 , suggesting an interstitial-based mechanism

  10. Diffuse large B-cell lymphoma in the era of precision oncology: How imaging is helpful

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Hina J.; Keraliya, Abhishek R.; Lele, Vikram R.; Tirumani, Sree Harsha; DiPiro, Pamela J.; Jagannathan, Jyothi P. [Dept. of Imaging, Dana Farber Cancer Institute, Harvard Medical School, Boston (United States)

    2017-01-15

    Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL.

  11. Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

    Science.gov (United States)

    Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

    2018-02-01

    Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

  12. Survival in patients with oral and maxillofacial diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Janet Ofelia Guevara-Canales

    2013-11-01

    Full Text Available The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A overall survival (OS at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables, and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor; (B prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox, and multivariate analysis with Cox's regression model (all the variables together. The data were considered significant at p ≤ 0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3% occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p = 0.042, clinical stage (p = 0.007 and performance status (p = 0.031. These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status.

  13. Hierarchical optimization in isotope separation-gaseous diffusion: plant, cascade, stage, principles, and applications

    Energy Technology Data Exchange (ETDEWEB)

    Guais, J. C.

    1975-09-01

    The large scale system represented by a gaseous diffusion plant model, and its hierarchical mathematical structure are the reasons for a decomposition method, minimizing the total cost of enrichment. This procedure has been used for years in the optimization problems of the french projects.

  14. Hierarchical optimization in isotope separation. Gaseous diffusion: plant, cascade, stage. Principles and applications

    International Nuclear Information System (INIS)

    Guais, J.C.

    1975-01-01

    The large scale system represented by a gaseous diffusion plant model, and its hierarchical mathematical structure are the reasons for a decomposition method, minimizing the total cost of enrichment. This procedure has been used for years in the optimization problems of the french projects [fr

  15. Management of severe subarachnoid hemorrhage (SAH) with diffusion-weighted imaging in acute stage

    International Nuclear Information System (INIS)

    Shamoto, Hiroshi; Shimizu, Hiroaki; Matsumoto, Yasushi; Fujiwara, Satoru; Tominaga, Teiji

    2007-01-01

    Determining the treatment strategy of severe subarachnoid hemorrhage (SAH) (Hunt and Kosnik Grade 4 and 5) requires objective evaluation to represent severity. In the present study, we investigated the role of diffusion-weighted imaging (DWI) in the acute stage as an objective tool. DWI was performed within 48 hours after the onset and preoperatively in 36 patients who fulfilled following the inclusion criteria: admission Hunt and Kosnik Grade 4 or 5, and Fischer Group 3. Twelve of 14 patients without abnormal findings in DWI underwent surgery in the acute stage. Although 2 of 14 patients with high age were supposed to undergo surgery in the chronic stage, 1 patient died in aneurysmal re-rupture. Glasgow outcome scales (GOS) were good recovery (GR) in 5, moderate disability (MD) in 6, standard deviation (SD) in 1 and D in 2 patients. Thirteen of 22 patients with DWI abnormality had small lesions less than 10 mm in diameter. Twelve of 13 patients underwent surgery in the acute stage, and 1 died of aneurysmal re-rupture while waiting for surgery in the chronic stage. GOS were GR in 3, MD in 4, SD in 3 and D in 3 patients. Although 5 patients with diffuse DWI lesions underwent surgery in the acute stage, 2 were SD and 3 were D. Four patients were supposed to undergo delayed surgery. However, 2 of them died of recurrent hemorrhage while waiting. GOS were SD in 2 and D in 2 patients. The present study indicates that DWI may provide objective evaluation of brain damage in severe SAH. However, since there were varieties of DWI findings and clinical courses, careful decisions must be taken in management of severe SAH patients. (author)

  16. An homeopathic cure to pure Xenon large diffusion

    CERN Document Server

    Azevedo, C.D.R.; Freitas, E.D.C.; Gonzalez-Diaz, D.; Monrabal, F.; Monteiro, C.M.B.; dos Santos, J. M. F.; Veloso, J.F.C.A.; Gomez-Cadenas, J. J

    2016-02-03

    The NEXT neutrinoless double beta decay experiment will use a high- pressure gas electroluminescence-based TPC to search for the decay of Xe-136. One of the main advantages of this technology is the possibility to reconstruct the topology of events with energies close to Qbb. The rejection potential associated to the topology reconstruction is limited by our capacity to prop- erly reconstruct the original path of the electrons in the gas. This reconstruction is limited by different factors that include the geometry of the detector, the density of the sensors in the tracking plane and the separation among them, etc. Ultimately, the resolution is limited by the physics of electron diffusion in the gas. In this paper we present a series of molecular additives that can be used in Xenon gas at very low partial pressure to reduce both longitudinal and transverse diffusion. We will show the results of different Monte-Carlo simulations of electron transport in the gas mixtures from wich we have extracted the value of...

  17. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2017-01-01

    Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

  18. Large-time behavior of solutions to a reaction-diffusion system with distributed microstructure

    NARCIS (Netherlands)

    Muntean, A.

    2009-01-01

    Abstract We study the large-time behavior of a class of reaction-diffusion systems with constant distributed microstructure arising when modeling diffusion and reaction in structured porous media. The main result of this Note is the following: As t ¿ 8 the macroscopic concentration vanishes, while

  19. Flow structures in large-angle conical diffusers measured by PIV

    DEFF Research Database (Denmark)

    Meyer, Knud Erik; Nielsen, L.; Nielsen, N.F.

    2004-01-01

    Flow in two different conical diffusers with large opening angles (30° and 18°) have been measured with stereoscopic Particle Image Velocimetry (PIV). The measurements were done in a cross section just after the exit of the diffuser. The Reynolds number was 100000 based on upstream diameter...

  20. Very large polycystic kidneys presenting with end stage renal failure ...

    African Journals Online (AJOL)

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited cause of renal impairment and End Stage Renal Disease (ESRD). Apart from cysts in the kidneys and other organs such as the liver, pancreas and other organs, patients also develop abdominal hernia thought to be as a result of ...

  1. Travelling wave and convergence in stage-structured reaction-diffusion competitive models with nonlocal delays

    International Nuclear Information System (INIS)

    Xu Rui; Chaplain, M.A.J.; Davidson, F.A.

    2006-01-01

    In this paper, we first investigate a stage-structured competitive model with time delays, harvesting, and nonlocal spatial effect. By using an iterative technique recently developed by Wu and Zou (Wu J, Zou X. Travelling wave fronts of reaction-diffusion systems with delay. J Dynam Differen Equat 2001;13:651-87), sufficient conditions are established for the existence of travelling front solution connecting the two boundary equilibria in the case when there is no positive equilibrium. The travelling wave front corresponds to an invasion by a stronger species which drives the weaker species to extinction. Secondly, we consider a stage-structured competitive model with time delays and nonlocal spatial effect when the domain is finite. We prove the global stability of each of the nonnegative equilibria and demonstrate that the more complex model studied here admits three possible long term behaviors: coexistence, bistability and dominance as is the case for the standard Lotka-Voltera competitive model

  2. Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Talita Maira Bueno da Silveira da Rocha

    2013-01-01

    Full Text Available OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7% patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5% patients of this cohort received rituximab as first-line treatment and nine (7.1% received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7% had parenchymal central nervous system involvement; seven (77.7% had stage III or IV disease; one (11.1% had bone marrow involvement; two (22.2% had received intrathecal chemoprophylaxis; and 3 (33.3% had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration

  3. Diffusion MRI for rectal cancer staging: ADC measurements before and after ultrasonographic gel lumen distension

    Energy Technology Data Exchange (ETDEWEB)

    Palmucci, S., E-mail: spalmucci@sirm.org; Piccoli, M.; Piana, S.; Foti, P.V.; Siverino, R.O.A.; Mauro, L.A.; Milone, P.; Ettorre, G.C.

    2017-01-15

    Objectives: To compare Apparent Diffusion Coefficient (ADC) measurements in rectal neoplastic lesions before and after lumen distension obtained with sonography transmission gel. Methods: From January 2014 to July 2016, 25 patients (average age 63.7, range 41–85, 18 males) were studied for pre-treatment rectal cancer staging using a 1.5 T MRI. Diffusion MRI was obtained using echo-planar imaging with b = 800 value; all patients were studied acquiring diffusion sequences with and without rectal lumen distension obtained using sonography transmission gel. In both diffusion sequences, two blinded readers calculated border ADC values and small ADC values, drawing regions of interest respectively along tumour borders and far from tumour borders. Mean ADC values among readers − for each type of ADC measurement − were compared using Wilcoxon matched pairs signed rank test. Correlation was assessed using Pearson analysis. Results: Border ADC mean value for diffusion MR sequences without endorectal contrast was 1.122 mm{sup 2}/sec, with 95% Confidence Interval (CI) = 1.02–1.22; using gel lumen distension, higher border ADC mean value of 1.269 mm{sup 2}/s (95% CI = 1.16–1.38) was obtained. Wilcoxon matched pairs signed rank test revealed statistical difference (p < 0.01); a strong Pearson correlation was reported, with r value of 0.69. Small-ADC mean value was 1.038 mm{sup 2}/s (95% CI = 0.91–1.16) for diffusion sequences acquired without endorectal distension and 1.127 mm{sup 2}/s (95% CI = 0.98–1.27) for diffusion sequences obtained after endorectal gel lumen distension. Wilcoxon analysis did not show statistical difference (p = 0.13). A very strong positive correlation was observed, with r value of 0.81. Conclusions: ADC measurements are slightly higher using endorectal sonographic transmission gel; ROI should be traced far from tumour borders, to minimize gel filled-pixel along the interface between lumen and lesion. Further studies are needed to

  4. Diffusion MRI for rectal cancer staging: ADC measurements before and after ultrasonographic gel lumen distension

    International Nuclear Information System (INIS)

    Palmucci, S.; Piccoli, M.; Piana, S.; Foti, P.V.; Siverino, R.O.A.; Mauro, L.A.; Milone, P.; Ettorre, G.C.

    2017-01-01

    Objectives: To compare Apparent Diffusion Coefficient (ADC) measurements in rectal neoplastic lesions before and after lumen distension obtained with sonography transmission gel. Methods: From January 2014 to July 2016, 25 patients (average age 63.7, range 41–85, 18 males) were studied for pre-treatment rectal cancer staging using a 1.5 T MRI. Diffusion MRI was obtained using echo-planar imaging with b = 800 value; all patients were studied acquiring diffusion sequences with and without rectal lumen distension obtained using sonography transmission gel. In both diffusion sequences, two blinded readers calculated border ADC values and small ADC values, drawing regions of interest respectively along tumour borders and far from tumour borders. Mean ADC values among readers − for each type of ADC measurement − were compared using Wilcoxon matched pairs signed rank test. Correlation was assessed using Pearson analysis. Results: Border ADC mean value for diffusion MR sequences without endorectal contrast was 1.122 mm 2 /sec, with 95% Confidence Interval (CI) = 1.02–1.22; using gel lumen distension, higher border ADC mean value of 1.269 mm 2 /s (95% CI = 1.16–1.38) was obtained. Wilcoxon matched pairs signed rank test revealed statistical difference (p < 0.01); a strong Pearson correlation was reported, with r value of 0.69. Small-ADC mean value was 1.038 mm 2 /s (95% CI = 0.91–1.16) for diffusion sequences acquired without endorectal distension and 1.127 mm 2 /s (95% CI = 0.98–1.27) for diffusion sequences obtained after endorectal gel lumen distension. Wilcoxon analysis did not show statistical difference (p = 0.13). A very strong positive correlation was observed, with r value of 0.81. Conclusions: ADC measurements are slightly higher using endorectal sonographic transmission gel; ROI should be traced far from tumour borders, to minimize gel filled-pixel along the interface between lumen and lesion. Further studies are needed to investigate better

  5. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    OpenAIRE

    Mansour Ansari; Hamid Nasrollahi; Majdaddin Rajaei; Maral Mokhtari; Seyed Hasan Hamedi; Mohammad Mohammadianpanah; Shapour Omidvari; Ahmad Mosalaei; Niloofar Ahmadloo

    2017-01-01

    Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymp...

  6. Diffusion

    International Nuclear Information System (INIS)

    Kubaschewski, O.

    1983-01-01

    The diffusion rate values of titanium, its compounds and alloys are summarized and tabulated. The individual chemical diffusion coefficients and self-diffusion coefficients of certain isotopes are given. Experimental methods are listed which were used for the determination of diffusion coefficients. Some values have been taken over from other studies. Also given are graphs showing the temperature dependences of diffusion and changes in the diffusion coefficient with concentration changes

  7. A case of primary diffuse large B-cell non-Hodgkin's lymphoma misdiagnosed as chronic periapical periodontitis.

    Science.gov (United States)

    Jessri, M; AbdulMajeed, A A; Matias, M A; Farah, C S

    2013-06-01

    Lymphoma is a malignant neoplasm of component cells of the lymphoid system which is very rare in the jaws. Here we report a case of primary diffuse large B-cell lymphoma located in the periapical region of a mandibular molar which was misdiagnosed as chronic periapical periodontitis. The present case was diagnosed at an early stage and effectively managed by chemotherapy. Although lymphoma of the mandible is rare, it must be considered in the differential diagnosis of radiolucent lesions in this region. Lack of knowledge of this rare presentation may lead to delays in diagnosis and poor prognosis. © 2013 Australian Dental Association.

  8. COPD, stage and treatment in a large outpatient clinic

    DEFF Research Database (Denmark)

    Holm, Claire Præst; Holm, Jakob; Nørgaard, Annette

    2017-01-01

    of exacerbations. Our aim was to describe COPD patient characteristics and compare roflumilast treatment eligible to non-eligible patients. An observational cross-section study was conducted. Patients were included from a large COPD outpatient clinic. Information regarding COPD patient characteristics...... was registered on a standardized form and lung function was measured. Patients were categorized according to the GOLD classification. Eligibility for roflumilast treatment was assessed and patient characteristics compared between groups. 547 patients were included. Most patients (54%) were in GOLD group D. 62...

  9. Large Time Asymptotics for a Continuous Coagulation-Fragmentation Model with Degenerate Size-Dependent Diffusion

    KAUST Repository

    Desvillettes, Laurent

    2010-01-01

    We study a continuous coagulation-fragmentation model with constant kernels for reacting polymers (see [M. Aizenman and T. Bak, Comm. Math. Phys., 65 (1979), pp. 203-230]). The polymers are set to diffuse within a smooth bounded one-dimensional domain with no-flux boundary conditions. In particular, we consider size-dependent diffusion coefficients, which may degenerate for small and large cluster-sizes. We prove that the entropy-entropy dissipation method applies directly in this inhomogeneous setting. We first show the necessary basic a priori estimates in dimension one, and second we show faster-than-polynomial convergence toward global equilibria for diffusion coefficients which vanish not faster than linearly for large sizes. This extends the previous results of [J.A. Carrillo, L. Desvillettes, and K. Fellner, Comm. Math. Phys., 278 (2008), pp. 433-451], which assumes that the diffusion coefficients are bounded below. © 2009 Society for Industrial and Applied Mathematics.

  10. Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma

    Science.gov (United States)

    de Jong, Antoinette; Kwee, Thomas C; de Klerk, John MH; Adam, Judit A; de Keizer, Bart; Fijnheer, Rob; Kersten, Marie José; Ludwig, Inge; Jauw, Yvonne WS; Zijlstra, Josée M; den Bos, Indra C Pieters - Van; Stoker, Jaap; Hoekstra, Otto S; Nievelstein, Rutger AJ

    2014-01-01

    The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL. PMID:24795837

  11. Clinical usefulness of diffusion-weighted MRI in various stages of ischemic stroke

    International Nuclear Information System (INIS)

    Song, So Youne; Cho, Woo Ho; Kim, Soung Hee; Kim, Jung Sook; Kim, Young Hoon; Kim, Myung Gyu; Hur, Gham

    2002-01-01

    Diffusion-weighted MRI (DWI) is well known to be sensitive in the detection of hyperacute infarct, but has not been systematically investigated in patients with acute or subacute infarct. We evaluated the usefulness of diffusion-weighted MRI in assessing the various stages of brain infarct. Fifty-five consecutive patients with symptoms of brain infarct underwent fast spinecho T2-weighted MRI (T2WI) and DWI. Using only a brief clinical history, two radiologists first attempted to detect the lesion using T2W1, which was then compared with DWI. The usefulness of the latter was then evaluated in terms of the following criteria: 1) Its abilility to detect a lesion not seen at T2WI(detection); 2) localization of the responsible ischemic focus among multiple high-signal intensities seen at T2WI (localization); 3) conspicuity of a lesion which was subtle at T2WI (conspicuity); 4) detection of multiple lesions (multiplicity). DWI was useful in 44 of 55 patients (80%), including 9 of 9 (100%) with hyperacute infarct (<6 hours), 20 of 27 (74%) with acute infarct (<48 hours), and 15 of 19 (79%) with subacute infarct (<2 weeks). Among the nine patients at the hyperacute stage, DWI was useful for detection of the lesion in six (67%), for localization, 4 (44%) in one (11%), for conspicuity in four (44%), and for multiplicity in five (56%); at the acute stage (20 patients), for detection in three (15%), for localization in ten (50%), for conspicuity in eight (40%), and for moltiplicity in five (25%); and at the subacute stage (15 patients), for detection in three (20%), for localization in nine (60%), for conspicuity in two (13%), and for multiplicity in three (20%). DWI is very sensitive for the diagnosis of hyperacute infarct. In the assessment of this, it is useful during the acute or subacute period for the detection of small lesions, the localization of ongoing lesions among multiple high signal intensities seen at T2WI, and the determination of lesion conspicuity

  12. MR diffusion weighted imaging experimental study on early stages of articular cartilage degeneration of knee

    International Nuclear Information System (INIS)

    Dai Jingru; Dai Shipeng; Pang Jun; Xu Xiaokun; Wang Yuexin; Zhang Zhigang

    2008-01-01

    Objective: To study the appearance of MR diffusion weighted imaging in early stages of cartilage degeneration and to detect its values. Methods: In 20 goat left knees, intra- articular injection of 5 units of papain was performed causing a loss of cartilage proteoglycan. Twenty right knees were used as control group. MR diffusion weighted imaging was performed at 24 hours after intra-articular injection of papain. ADC of each part of articular cartilage was measured and compared with each other. The proteoglycan content was measured biochemically and histochemically. Routine MRI and DWI were performed in 100 patients with osteoarthritis and 20 healthy people. The ADC of each interested part of articular cartilage was measured and compared with each other. Results: In experimental control group, the ADCav of articular cartilage was (14.2±2.3) x 10 -4 mm 2 /s. In early stages of cartilage degeneration group, the ADCav of articular cartilage was (17.5±4.2) x 10 -4 mm 2 /s. The ADCav of the control group was lower than that of the early stages of cartilage degeneration group (t=2.709; P=0.016). The proteloglycan content of articular cartilage was 4.22 x 10 6 μg/kg in control group, and 0.82 x 10 6 μg/kg in experimental group at 24 hours after injection of papain. The difference between control group and experimental group was significant (t=2.705, P=0.018). In healthy people, the ADCav of articular cartilage was (7.6±2.2) x 10 -4 mm 2 /s. In osteoarthritis group, the ADCav of articular cartilage was (10.3±4.2) x 10 -4 mm 2 /s. The ADCav in the healthy group was significantly lower than that in the osteoarthritis group (t=2.609,P=0.014). Conclusion: DWI is an useful method in detecting early stages of cartilage degeneration which can not be showed on routine sequences. (authors)

  13. EBV-positive diffuse large B-cell lymphoma of the elderly

    NARCIS (Netherlands)

    C.Y. Ok (Chi Young); T.G. Papathomas (Thomas); L.J. Medeiros (L. Jeffrey); K.H. Young (Ken)

    2013-01-01

    textabstractEpstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in

  14. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-15

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

  15. Modeling of electromagnetic and thermal diffusion in a large pure aluminum stabilized superconductor under quench

    CERN Document Server

    Gavrilin, A V

    2001-01-01

    Low temperature composite superconductors stabilized with extra large cross-section pure aluminum are currently in use for the Large Helical Device in Japan, modern big detectors such as ATLAS at CERN, and other large magnets. In these types of magnet systems, the rated average current density is not high and the peak field in a region of interest is about 2-4 T. Aluminum stabilized superconductors result in high stability margins and relatively long quench times. Appropriate quench analyses, both for longitudinal and transverse propagation, have to take into account a rather slow diffusion of current from the superconductor into the thick aluminum stabilizer. An exact approach to modeling of the current diffusion would be based on directly solving the Maxwell's equations in parallel with thermal diffusion and conduction relations. However, from a practical point of view, such an approach should be extremely time consuming due to obvious restrictions of computation capacity. At the same time, there exist cert...

  16. Nasopharyngeal carcinoma: comparison of diffusion and perfusion characteristics between different tumour stages using intravoxel incoherent motion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Vincent; Li, Xiao; Huang, Bingsheng; Khong, Pek Lan [University of Hong Kong, Queen Mary Hospital, Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, Hong Kong (China); Lee, Victor Ho Fun; Lam, Ka On [University of Hong Kong, Queen Mary Hospital, Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Hong Kong (China); Fong, Daniel Yee Tak [University of Hong Kong, School of Nursing, Li Ka Shing Faculty of Medicine, Hong Kong (China); Chan, Queenie [Philips Healthcare, Hong Kong, New Territories (China)

    2014-01-15

    To explore intravoxel incoherent motion (IVIM) characteristics of nasopharyngeal carcinoma (NPC) and relationships with different tumour stages. We prospectively recruited 80 patients with newly diagnosed undifferentiated NPC. Diffusion-weighted MR imaging was performed and IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated. Patients were stratified into low and high tumour stage groups based on American Joint Committee on Cancer (AJCC) and TNM staging for determination of the predictive powers of IVIM parameters using t test, multiple logistic regression and ROC curve analyses. D, f and D* were all statistically significantly lower in high-stage groups in AJCC, T and N staging. D, f and D* were all independent predictors of AJCC staging, f and D* were independent predictors of T staging, and D was an independent predictor of N staging. D was most powerful for AJCC and N staging, whereas f was most powerful for T staging. Optimal cut-off values (area under the curve, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) were as follows: AJCC stage, D = 0.782 x 10{sup -3} mm{sup 2}/s (0.915, 93.3 %, 76.2 %, 3.92, 0.09); T staging, f = 0.133 (0.905, 80.5 %, 92.5 %, 10.73, 0.21); N staging, D = 0.761 x 10{sup -3} mm{sup 2}/s (0.848, 87.5 %, 66.7 %, 2.62, 0.19). Multivariate analysis showed no diagnostic improvement. Nasopharyngeal carcinoma has distinctive intravoxel incoherent motion characteristics parameters in different tumour staging, potentially helping pretreatment staging. (orig.)

  17. Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study

    Science.gov (United States)

    Kim, Junghoon; Avants, Brian; Patel, Sunil; Whyte, John; Coslett, H. Branch; Pluta, John; Detre, John A.; Gee, James C.

    2008-01-01

    Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume> 1.5 cm 3). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain-behavior relationships in the TBI population. PMID:17999940

  18. Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2018-06-13

    CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  19. Continuous and discreet methods in the aggregation and des fuzzy stages of a diffuse controller of neutron power

    International Nuclear Information System (INIS)

    Najera H, M.C.; Benitez R, J.S.

    2003-01-01

    The results of a comparative study are presented of: to) A denominated diffuse controller 'exact', designed by means of an innovative method that determines analytically so much the group of exit resultant in the aggregation stage like the de fuzzy process, and b) a diffuse controller denominated 'discreet' based on the discretization of the variable of having left as much for the aggregation as for the de fuzzy. These stages incorporated to the control algorithms whose objective is the ascent and regulation of the neutron power, carrying out an analysis of its performance. (Author)

  20. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  1. Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju

    2014-01-01

    PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of...

  2. Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

    2018-01-01

    Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

  3. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Kania, P W; Ino, Y

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  4. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

    DEFF Research Database (Denmark)

    Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed...

  5. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  6. Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Biccler, Jorne Lionel; Eloranta, Sandra; Brown, Peter de Nully

    2018-01-01

    The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B-cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we co...

  7. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  8. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Bernatsky, Sasha; Velásquez García, Héctor A; Spinelli, John; Gaffney, Patrick; Smedby, Karin E; Ramsey-Goldman, Rosalind; Wang, Sophia S.; Adami, Hans-Olov; Albanes, Demetrius; Angelucci, Emanuele; Ansell, Stephen M.; Asmann, Yan W.; Becker, Nikolaus; Benavente, Yolanda; Berndt, Sonja I.; Bertrand, Kimberly A.; Birmann, Brenda M.; Boeing, Heiner; Boffetta, Paolo; Bracci, Paige M.; Brennan, Paul; Brooks-Wilson, Angela R.; Cerhan, James R.; Chanock, Stephen J.; Clavel, Jacqueline; Conde, Lucia; Cotenbader, Karen H; Cox, David G; Cozen, Wendy; Crouch, Simon; De Roos, Anneclaire J.; De Sanjose, Silvia; Di Lollo, Simonetta; Diver, W. Ryan; Dogan, Ahmet; Foretova, Lenka; Ghesquières, Hervé; Giles, Graham G.; Glimelius, Bengt; Habermann, Thomas M.; Haioun, Corinne; Hartge, Patricia; Hjalgrim, Henrik; Holford, Theodore R.; Holly, Elizabeth A.; Jackson, Rebecca D.; Kaaks, Rudolph; Kane, Eleanor; Kelly, Rachel S.; Klein, Robert J.; Kraft, Peter; Kricker, Anne; Lan, Qing; Lawrence, Charles; Liebow, Mark; Lightfoot, Tracy; Link, Brian K.; Maynadie, Marc; McKay, James; Melbye, Mads; Molina, Thierry Jo; Monnereau, Alain; Morton, Lindsay M.; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Offit, Kenneth; Purdue, Mark P.; Rais, Marco; Riby, Jacques; Roman, Eve; Rothman, Nathaniel; Salles, Gilles; Severi, Gianluca; Severson, Richard K.; Skibola, Christine F.; Slager, Susan L.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Staines, Anthony; Teras, Lauren R.; Thompson, Carrie A.; Tilly, Hervé; Tinker, Lesley F.; Tjonneland, Anne; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C H; Vijai, Joseph; Vineis, Paolo; Virtamo, Jarmo; Wang, Zhaoming; Weinstein, Stephanie; Witzig, Thomas E.; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Yawei; Zheng, Tongzhang; Zucca, Mariagrazia; Clarke, Ann E

    2017-01-01

    Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

  9. Large-eddy simulation with accurate implicit subgrid-scale diffusion

    NARCIS (Netherlands)

    B. Koren (Barry); C. Beets

    1996-01-01

    textabstractA method for large-eddy simulation is presented that does not use an explicit subgrid-scale diffusion term. Subgrid-scale effects are modelled implicitly through an appropriate monotone (in the sense of Spekreijse 1987) discretization method for the advective terms. Special attention is

  10. Production of a large area diffuse arc plasma with multiple cathode

    International Nuclear Information System (INIS)

    Wang Cheng; Cui Hai-Chao; Li Wan-Wan; Liao Meng-Ran; Xia Wei-Dong; Xia Wei-Luo

    2017-01-01

    An arc channel at atmospheric pressure tends to shrink generally. In this paper, a non-transferred DC arc plasma device with multiple cathode is introduced to produce a large area arc plasma at atmospheric pressure. This device is comprised of a 42-mm diameter tubular chamber, multiple cathode which is radially inserted into the chamber, and a tungsten anode with a nozzle in its center. In argon/helium atmosphere, a large area and circumferential homogenous diffuse arc plasma, which fills the entire cross section surrounded by the cathode tips, is observed. Results show that the uniformity and stability of diffuse arc plasma are strongly related to the plasma forming gas. Based on these experimental results, an explanation to the arc diffusion is suggested. Moreover, the electron excitation temperature and electron density measured in diffuse helium plasma are much lower than those of constricted arc column, which indicates the diffuse helium plasma probably deviates from the local thermodynamic equilibrium state. Unlike the common non-transferred arc plasma devices, this device can provide a condition for axial-fed feedstock particles. The plasma device is attempted to spheroidize alumina powders by using the central axis to send the powder. Results show that the powder produced is usually a typical hollow sphere. (paper)

  11. THEMIS Observations of the Magnetopause Electron Diffusion Region: Large Amplitude Waves and Heated Electrons

    Science.gov (United States)

    Tang, Xiangwei; Cattell, Cynthia; Dombeck, John; Dai, Lei; Wilson, Lynn B. III; Breneman, Aaron; Hupack, Adam

    2013-01-01

    We present the first observations of large amplitude waves in a well-defined electron diffusion region based on the criteria described by Scudder et al at the subsolar magnetopause using data from one Time History of Events and Macroscale Interactions during Substorms (THEMIS) satellite. These waves identified as whistler mode waves, electrostatic solitary waves, lower hybrid waves, and electrostatic electron cyclotron waves, are observed in the same 12 s waveform capture and in association with signatures of active magnetic reconnection. The large amplitude waves in the electron diffusion region are coincident with abrupt increases in electron parallel temperature suggesting strong wave heating. The whistler mode waves, which are at the electron scale and which enable us to probe electron dynamics in the diffusion region were analyzed in detail. The energetic electrons (approx. 30 keV) within the electron diffusion region have anisotropic distributions with T(sub e(right angle))/T(sub e(parallel)) > 1 that may provide the free energy for the whistler mode waves. The energetic anisotropic electrons may be produced during the reconnection process. The whistler mode waves propagate away from the center of the "X-line" along magnetic field lines, suggesting that the electron diffusion region is a possible source region of the whistler mode waves.

  12. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  13. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  14. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-01-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

  15. A Characterization of the Diffuse Galactic Emissions at Large Angular Scales Using the Tenerife Data

    Directory of Open Access Journals (Sweden)

    J. F. Macías-Pérez

    2013-01-01

    diffuse emission in the range from 20 to 60 GHz. To discriminate between different models of AME, low frequency microwave data from 10 to 20 GHz are needed. We present here a reanalysis of published and unpublished Tenerife data from 10 to 33 GHz at large angular scales (from 5 to 15 degrees. We cross-correlate the Tenerife data to templates of the main galactic diffuse emissions: synchrotron, free-free, and thermal dust. We find evidence of dust-correlated emission in the Tenerife data that could be explained as spinning dust grain emission.

  16. Jump rates for surface diffusion of large molecules from first principles

    Energy Technology Data Exchange (ETDEWEB)

    Shea, Patrick, E-mail: patrick.shea@dal.ca; Kreuzer, Hans Jürgen [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 3J5 (Canada)

    2015-04-21

    We apply a recently developed stochastic model for the surface diffusion of large molecules to calculate jump rates for 9,10-dithioanthracene on a Cu(111) surface. The necessary input parameters for the stochastic model are calculated from first principles using density functional theory (DFT). We find that the inclusion of van der Waals corrections to the DFT energies is critical to obtain good agreement with experimental results for the adsorption geometry and energy barrier for diffusion. The predictions for jump rates in our model are in excellent agreement with measured values and show a marked improvement over transition state theory (TST). We find that the jump rate prefactor is reduced by an order of magnitude from the TST estimate due to frictional damping resulting from energy exchange with surface phonons, as well as a rotational mode of the diffusing molecule.

  17. [Characteristics of high resolution diffusion weighted imaging apparent diffusion coefficient histogram and its correlations with cancer stages in patients with nasopharyngeal carcinoma].

    Science.gov (United States)

    Wang, G J; Wang, Y; Ye, Y; Chen, F; Lu, Y T; Li, S L

    2017-11-07

    Objective: To investigate the features of apparent diffusion coefficient (ADC) histogram parameters based on entire tumor volume data in high resolution diffusion weighted imaging of nasopharyngeal carcinoma (NPC) and to evaluate its correlations with cancer stages. Methods: This retrospective study included 154 cases of NPC patients[102 males and 52 females, mean age (48±11) years]who had received readout segmentation of long variable echo trains of MRI scan before radiation therapy. The area of tumor was delineated on each section of axial ADC maps to generate ADC histogram by using Image J. ADC histogram of entire tumor along with the histogram parameters-the tumor voxels, ADC(mean), ADC(25%), ADC(50%), ADC(75%), skewness and kurtosis were obtained by merging all sections with SPSS 22.0 software. Intra-observer repeatability was assessed by using intra-class correlation coefficients (ICC). The patients were subdivided into two groups according to cancer volume: small cancer group (histogram parameters and cancer stages was evaluated with Spearman test. Results: The ICC of measuring ADC histogram parameters of tumor voxels, ADC(mean), ADC(25%), ADC(50%), ADC(75%), skewness, kurtosis was 0.938, 0.861, 0.885, 0.838, 0.836, 0.358 and 0.456, respectively. The tumor voxels was positively correlated with T staging ( r =0.368, P histogram (ADC(mean), ADC(25%), ADC(50%)) increases with T staging in NPC smaller than 2 cm(3).

  18. Stage design

    International Nuclear Information System (INIS)

    Shacter, J.

    1975-01-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage

  19. White matter abnormalities in treatment-naive adolescents at the earliest stages of Anorexia Nervosa: A diffusion tensor imaging study.

    Science.gov (United States)

    Gaudio, Santino; Quattrocchi, Carlo Cosimo; Piervincenzi, Claudia; Zobel, Bruno Beomonte; Montecchi, Francesca Romana; Dakanalis, Antonios; Riva, Giuseppe; Carducci, Filippo

    2017-08-30

    Few studies have examined white matter (WM) integrity in long-lasting Anorexia Nervosa (AN) patients using Diffusion Tensor Imaging (DTI). In this paper, we investigated WM integrity at the earliest stages of AN (i.e. less than 6 months duration). Fourteen treatment-naive female adolescents with AN restrictive type (AN-r) in its earliest stages and 15 age-matched healthy females received brain MRI. Fractional Anisotropy (FA), Axial Diffusivity (AD), Radial diffusivity (RD), and Mean Diffusivity (MD) maps were computed from DTI data using Tract-Based Spatial Statistics analysis. AN-r patients showed FA decreases compared to controls (p FWE < 0.05) mainly in left anterior and superior corona radiata and left superior longitudinal fasciculus. AN-r patients also showed decreased AD in superior longitudinal fasciculus bilaterally and left superior and anterior corona radiata, (p FWE < 0.05). No significant differences were found in RD and MD values between the two groups. FA and AD integrity appears to be specifically affected at the earliest stages of AN. Alterations in the microstructural properties of the above mentioned tracts, also involved in cognitive control and visual perception and processing, may be early mechanisms of vulnerability/resilience of WM in AN and sustain the key symptoms of AN, such as impaired cognitive flexibility and body image distortion. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mandrup, Charlotte; Petersen, Anders; Højfeldt, Anne Dirks

    MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma   C. Mandrup1, A. Petersen1, A. D. Hoejfeldt1, H. F. Thomsen1, J. Madsen1, J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1 and H. E Johnsen1. 1Department of Hematology, 2Pathological Institute, Aalborg Hospital, Aarhus...... University Hospital, Aalborg, Denmark Introduction: The aim of this project was to analyse microRNA (miRNA) expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at diagnosis may be nodal and/or extranodal. At present, there are no known determinants for none...... of the manifestations, and no way to predict the potential progression from nodal to extranodal disease. miRNA are small regulatory RNA molecules with core function to repress/cleave sequence complementary mRNA targets. Abnormalities in miRNA genetics and expression are known to affect initiation and development...

  1. Large-eddy simulation of a turbulent piloted methane/air diffusion flame (Sandia flame D)

    International Nuclear Information System (INIS)

    Pitsch, H.; Steiner, H.

    2000-01-01

    The Lagrangian Flamelet Model is formulated as a combustion model for large-eddy simulations of turbulent jet diffusion flames. The model is applied in a large-eddy simulation of a piloted partially premixed methane/air diffusion flame (Sandia flame D). The results of the simulation are compared to experimental data of the mean and RMS of the axial velocity and the mixture fraction and the unconditional and conditional averages of temperature and various species mass fractions, including CO and NO. All quantities are in good agreement with the experiments. The results indicate in accordance with experimental findings that regions of high strain appear in layer like structures, which are directed inwards and tend to align with the reaction zone, where the turbulence is fully developed. The analysis of the conditional temperature and mass fractions reveals a strong influence of the partial premixing of the fuel. (c) 2000 American Institute of Physics

  2. Large diffusion anisotropy and orientation sorting of phosphorene nanoflakes under a temperature gradient.

    Science.gov (United States)

    Cheng, Yuan; Zhang, Gang; Zhang, Yingyan; Chang, Tienchong; Pei, Qing-Xiang; Cai, Yongqing; Zhang, Yong-Wei

    2018-01-25

    We perform molecular dynamics simulations to investigate the motion of phosphorene nanoflakes on a large graphene substrate under a thermal gradient. It is found that the atomic interaction between the graphene substrate and the phosphorene nanoflake generates distinct rates of motion for phosphorene nanoflakes with different orientations. Remarkably, for square phosphorene nanoflakes, the motion of zigzag-oriented nanoflakes is 2-fold faster than those of armchair-oriented and randomly-oriented nanoflakes. This large diffusion anisotropy suggests that sorting of phosphorene nanoflakes into specific orientations can be realized by a temperature gradient. The findings here provide interesting insights into strong molecular diffusion anisotropy and offer a novel route for manipulating two-dimensional materials.

  3. Capgras syndrome associated with limbic encephalitis in a patient with diffuse large B-cell lymphoma

    OpenAIRE

    Soares Neto, Herval Ribeiro; Cavalcante, Wagner Cid Palmeira; Martins Filho, Sebastião Nunes; Smid, Jerusa; Nitrini, Ricardo

    2016-01-01

    We report the case of a patient with insidious onset and slowly progressive cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional thoughts typical of delusional misidentification syndromes. Clinical presentation along with extensive diagnostic work-up revealed limbic encephalitis secondary to diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose corticosteroid but no significant improvement was observed. No specific treatment for lymphoma...

  4. [Diffuse large B-cell lymphoma complicated with drug-induced vasculitis during administration of pegfilgrastim].

    Science.gov (United States)

    Ito, Yuta; Noda, Kentaro; Aiba, Keisuke; Yano, Shingo; Fujii, Tsunehiro

    A 59-year-old female with diffuse large B-cell lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen. In addition, we administered pegfilgrastim for treating chemotherapy-induced febrile neutropenia. She complained of fever and neck and chest pain a few days after pegfilgrastim administration during the third and fourth courses of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis observed in this case was caused by pegfilgrastim administration because similar symptoms appeared with both injections of pegfilgrastim.

  5. Nuclear criticality safety evaluation of large cylinder cleaning operations in X-705, Portsmouth Gaseous diffusion Plant

    International Nuclear Information System (INIS)

    Sheaffer, M.K.; Keeton, S.C.; Lutz, H.F.

    1995-06-01

    This report evaluates nuclear criticality safety for large cylinder cleaning operations in the Decontamination and Recovery Facility, X-705, at the Portsmouth Gaseous Diffusion Plant. A general description of current cleaning procedures and required hardware/equipment is presented, and documentation for large cylinder cleaning operations is identified and described. Control parameters, design features, administrative controls, and safety systems relevant to nuclear criticality are discussed individually, followed by an overall assessment based on the Double Contingency Principle. Recommendations for enhanced safety are suggested, and issues for increased efficiency are presented

  6. Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers.

    Science.gov (United States)

    Liu, Song; Zhang, Yujuan; Chen, Ling; Guan, Wenxian; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang

    2017-10-02

    Whole-lesion apparent diffusion coefficient (ADC) histogram analysis has been introduced and proved effective in assessment of multiple tumors. However, the application of whole-volume ADC histogram analysis in gastrointestinal tumors has just started and never been reported in T and N staging of gastric cancers. Eighty patients with pathologically confirmed gastric carcinomas underwent diffusion weighted (DW) magnetic resonance imaging before surgery prospectively. Whole-lesion ADC histogram analysis was performed by two radiologists independently. The differences of ADC histogram parameters among different T and N stages were compared with independent-samples Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of ADC histogram parameters in differentiating particular T or N stages of gastric cancers. There were significant differences of all the ADC histogram parameters for gastric cancers at different T (except ADC min and ADC max ) and N (except ADC max ) stages. Most ADC histogram parameters differed significantly between T1 vs T3, T1 vs T4, T2 vs T4, N0 vs N1, N0 vs N3, and some parameters (ADC 5% , ADC 10% , ADC min ) differed significantly between N0 vs N2, N2 vs N3 (all P histogram parameters held great potential in differentiating different T and N stages of gastric cancers preoperatively.

  7. Off-axis multipass amplifier as a large aperture driver stage for fusion lasers

    International Nuclear Information System (INIS)

    Murray, J.E.; Downs, D.C.; Junt, J.T.; Hermes, G.L.; Warren, W.E.

    1981-01-01

    A multipass amplifier configuration is described which has potential as a large aperture, high gain driver stage for fusion laser systems. We avoid the present limitations of large aperture switches by using an off-angle geometry that does not require an optical switch. The saturated gain characteristics of this multipass amplifier are optimized numerically. Three potential problems are investigated experimentally, self-lasing, output beam quality, and amplified spontaneous emission output. The results indicate comparable cost for comparable performance to a linear chain, with some operational advantage for the multipass driver stage

  8. MAGNETIC FIELD STRUCTURE OF THE LARGE MAGELLANIC CLOUD FROM FARADAY ROTATION MEASURES OF DIFFUSE POLARIZED EMISSION

    Energy Technology Data Exchange (ETDEWEB)

    Mao, S. A. [National Radio Astronomy Observatory, P.O. Box O, Socorro, NM 87801 (United States); McClure-Griffiths, N. M.; McConnell, D. [Australia Telescope National Facility, CSIRO Astronomy and Space Science, Epping, NSW 1710 (Australia); Gaensler, B. M. [Sydney Institute for Astronomy, School of Physics, University of Sydney, Sydney, NSW 2006 (Australia); Haverkorn, M. [Department of Astrophysics, Radboud University, P.O. Box 9010, 6500-GL Nijmegen (Netherlands); Beck, R. [Max-Planck-Institut fuer Radioastronomie, D-53121 Bonn (Germany); Wolleben, M. [Square Kilometre Array South Africa, The Park, Pinelands 7405 (South Africa); Stanimirovic, S. [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); Dickey, J. M. [Physics Department, University of Tasmania, Hobart, TAS 7001 (Australia); Staveley-Smith, L., E-mail: mao@astro.wisc.edu [International Centre for Radio Astronomy Research (ICRAR), The University of Western Australia, Crawley, WA 6009 (Australia)

    2012-11-01

    We present a study of the magnetic field of the Large Magellanic Cloud (LMC), carried out using diffuse polarized synchrotron emission data at 1.4 GHz acquired at the Parkes Radio Telescope and the Australia Telescope Compact Array. The observed diffuse polarized emission is likely to originate above the LMC disk on the near side of the galaxy. Consistent negative rotation measures (RMs) derived from the diffuse emission indicate that the line-of-sight magnetic field in the LMC's near-side halo is directed coherently away from us. In combination with RMs of extragalactic sources that lie behind the galaxy, we show that the LMC's large-scale magnetic field is likely to be of quadrupolar geometry, consistent with the prediction of dynamo theory. On smaller scales, we identify two brightly polarized filaments southeast of the LMC, associated with neutral hydrogen arms. The filaments' magnetic field potentially aligns with the direction toward the Small Magellanic Cloud (SMC). We suggest that tidal interactions between the SMC and the LMC in the past 10{sup 9} years are likely to have shaped the magnetic field in these filaments.

  9. EFFECT OF FORCED ROTATING VANELESS DIFFUSERS ON CENTRIFUGAL COMPRESSOR STAGE PERFORMANCE

    Directory of Open Access Journals (Sweden)

    S. SERALATHAN

    2011-10-01

    Full Text Available Non-uniform flow at the exit of the centrifugal impeller mixes in the vaneless space of the diffuser causing a rise in static pressure as well as significant loss of total pressure. These mixing losses are usually an important source of inefficiency. Forced rotating vaneless diffusers is one such concept which reduces the energy losses associated with diffusion. Forced rotating vaneless diffuser involves the concept of blade cutback and shroud extension. In the present computational investigations, the effects of blade cutback of 5%, 10% and 20% of vane length, shroud extension of 10%, 20%, 30% and 40% of impeller tip diameter and impeller without shroud extension on flow diffusion and performance are analyzed, while all the other dimensions remaining same. The performance characteristics of various blade cutback configurations are less in terms of efficiency, energy coefficient as well as static pressure rise. The objective of obtaining higher static pressure rise with wide operating range and reduced losses over stationary vaned diffuser is achieved by shroud extension of 30%, followed by shroud extension of 20%.

  10. Chaotic dynamics of large-scale double-diffusive convection in a porous medium

    Science.gov (United States)

    Kondo, Shutaro; Gotoda, Hiroshi; Miyano, Takaya; Tokuda, Isao T.

    2018-02-01

    We have studied chaotic dynamics of large-scale double-diffusive convection of a viscoelastic fluid in a porous medium from the viewpoint of dynamical systems theory. A fifth-order nonlinear dynamical system modeling the double-diffusive convection is theoretically obtained by incorporating the Darcy-Brinkman equation into transport equations through a physical dimensionless parameter representing porosity. We clearly show that the chaotic convective motion becomes much more complicated with increasing porosity. The degree of dynamic instability during chaotic convective motion is quantified by two important measures: the network entropy of the degree distribution in the horizontal visibility graph and the Kaplan-Yorke dimension in terms of Lyapunov exponents. We also present an interesting on-off intermittent phenomenon in the probability distribution of time intervals exhibiting nearly complete synchronization.

  11. Corticospinal tract damage in patients with severe diffuse axonal injury in a chronic stage on diffusion tensor magnetic resonance imaging and motor evoked potential

    International Nuclear Information System (INIS)

    Yasokawa, Yu-to; Nakayama, Noriyuki; Iwama, Toru; Okumura, Ayumi; Shinoda, Jun; Miwa, Kazuhiro

    2005-01-01

    The aim of this study is to evaluate the disturbed motor function of the corticospinal tract (CST) of diffuse axonal injury (DAI) using diffusion tensor magnetic resonance (DTMR) imaging and motor evoked potential (MEP) examination, and to analyze these comparatively. Forty-three patients (86 sides of the CST) with severe DAI in a chronic stage underwent DTMR imaging and MEP examination using transcranial magnetic stimulation. Fractional anisotrophy (FA) values of 6 regions of interests (ROIs) in the CST were measured on FA map obtained from DTMR imaging. The lowest FA value among the FA values of the 6 ROIs in each of the CSTs was defined as the minimum FA value. And the lowest magnetic stimulation strength that could derive MEP was defined as the minimum threshold of MEP. The mean minimum FA value of the CSTs in which MEP could not be obtained even by the maximum strength of magnetic stimulation (the MEP (-) group) was significantly lower than that of the CSTs in which MEP could be obtained (the MEP (+) group). In the MEP (+) group, the minimum FA value decreased with the increase of the minimum threshold of MEP with a significant correlation. These results demonstrate that physiological motor dysfunction disclosed on MEP is significantly correlated with morphological damage of the CST observed on DTMR imaging in patients with DAI in a chronic stage. DTMR imaging is strongly suggested to be helpful to evaluate disturbed motor function and to infer its severity in DAI. (author)

  12. Performance improvement of centrifugal compressor stage with pinched geometry or vaned diffuser

    Energy Technology Data Exchange (ETDEWEB)

    Jaatinen, A.

    2009-07-01

    Centrifugal compressors are widely used for example in refrigeration processes, the oil and gas industry, superchargers, and waste water treatment. In this work, five different vaneless diffusers and six different vaned diffusers are investigated numerically. The vaneless diffusers vary only by their diffuser width, so that four of the geometries have pinch implemented to them. Pinch means a decrease in the diffuser width. Four of the vaned diffusers have the same vane turning angle and a different number of vanes, and two have different vane turning angles. The flow solver used to solve the flow fields is Finfo, which is a Navier-Stokes solver. All the cases are modeled Chien's k-epsilon turbulence model. All five vaneless diffusers and three vaned diffusers are investigated also experimentally. For each construction, the compressor operating map is measured according to relevant standards. In addition to this, the flow fields before and after the diffuser are measured with static and total pressure, flow angle and total temperature measurements k-omega SST turbulence model. The simulation results indicate that it is possible to improve the efficiency with the pinch, and according to the numerical results, the two best geometries are the ones with most pinch at the shroud. These geometries have approximately 4 percentage points higher effciency than the unpinched vaneless diffusers. The hub pinch does not seem to have any major benefits. In general, the pinches make the flow fields before and after the diffuser more uniform. The pinch also seems to improve the impeller effciency. This is down to two reasons. The major reason is that the pinch decreases the size of slow flow and possible backflow region located near the shroud after the impeller. Secondly, the pinches decrease the flow velocity in the tip clearance, leading to a smaller tip leakage flow and therefore slightly better impeller efficiency. Also some of the vaned diffusers improve the efficiency

  13. Successful three stage repair of a large congenital abdominal region defect

    Directory of Open Access Journals (Sweden)

    Vaidehi Agrawal

    2015-06-01

    Full Text Available We present two infants born with large, right upper quadrant defects which cannot be categorized as either a gastroschisis or omphalocele. We successfully managed one infant with a three stage repair using polytetrafluoroethylene (PTFE patch, porcine urinary bladder matrix (UBM and delayed surgical closure. The second infant passed away due to parental consent care withdrawal.

  14. Titanium zoning and diffusion chronometry reveal dynamic and late-stage quartz growth in the Youngest Toba Tuff, Indonesia

    Science.gov (United States)

    Tierney, C. R.; Reid, M. R.; Burns, D. H.; Costa Rodriguez, F.; Chesner, C. A.

    2017-12-01

    The enormous 74 ka Youngest Toba Tuff (YTT) ejected 2800 km3 of compositionally zoned (68-77 wt.% SiO2) ignimbrite and co-ignimbrite ash. Titanium zoning within YTT quartz records a dynamic growth history, and sometimes concludes with a final growth stage under different conditions. We investigated the timescales of quartz growth using diffusion chronometry, and determined whether the last stage of crystallization was the result of a discrete and chamber-wide magmatic event. This work offers insight into the dynamics and timescales of storage and remobilization of voluminous silicic magmas - an important consideration for hazards assessment. High-resolution (1 µm steps) hyperspectral CL was mapped from 5-20 quartz crystals from each of five pumices spanning the YTT compositional spectrum. CL intensity was calibrated to Ti concentration via EPMA, and numerically modeled time-dependent diffusional relaxation curves where fit to concentration profiles across zone boundaries. CL-bright/high-Ti rims are found in quartz from all samples, but become less common and have lower Ti concentrations with increasing host pumice silica content (e.g., 70 ppm vs 50 ppm). Some large crystals contain distinct CL-bright interior zones with similar Ti concentration to the rims. Onset of growth of CL-bright rims commenced between 15 and 100 years before eruption, and interior bands between 30 and 1500 years. Neither rim nor interior ages correlate significantly with host pumice silica. Rim growth on quartz evidently occurred closer to eruption than a previous estimate of several decades to centuries for quartz from a single YTT pumice (Matthews et al., 2012). The similar timing for the onset of high-Ti quartz rim growth across all samples suggests a marked and temporally discrete magmatic event in the years to decades prior to eruption and may be recording the chamber-wide influence of magmatic recharge or remobilization. High-Ti interior zones likely record older recharge events that

  15. Primary testicular diffuse large B-cell lymphoma: A case report

    Directory of Open Access Journals (Sweden)

    Muhammad Sadiq

    2017-12-01

    Full Text Available Primary testicular diffuse large-B cell lymphoma (DLBCL is an uncommon and aggressive disease with predominant manifestation in the older age. Herein, we report a case of 47-year-old male patient who presented with three months history of left testis swelling. The patient underwent unilateral (left radical orchiectomy. Histopathological examination revealed extensive involvement and replacement of testicular parenchyma by a tumor composed of large discohesive sheets of cells with pleomorphic, hyperchromatic nuclei and prominent nucleoli. Immunohistochemical (IHC staining showed reactivity for LCA & Pan B (CD20 and negativity for OCT 3/4, SALL4 and Inhibin. Moreover, Pan T (CD3 highlighted reactive T-cells. These features rendered the diagnosis of DLBCL of testis. The hybrid 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG positron emission tomography/computed tomography (PET/CT demonstrated two para-aortic FDG avid lymph nodes on the left side at the level of L2 vertebra. Presently, the patient has been planned for doxorubicin-based chemotherapy (i.e., cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP along with intrathecal Methroxate (MTX, which would presumably improve the prognosis. Our study would expand the pool of this uncommon tumor towards its better understanding. Keywords: Primary testicular lymphoma, Diffuse large-B cell lymphoma, Orchiectomy, Doxorubicin-based chemotherapy

  16. Grain Boundaries Act as Solid Walls for Charge Carrier Diffusion in Large Crystal MAPI Thin Films.

    Science.gov (United States)

    Ciesielski, Richard; Schäfer, Frank; Hartmann, Nicolai F; Giesbrecht, Nadja; Bein, Thomas; Docampo, Pablo; Hartschuh, Achim

    2018-03-07

    Micro- and nanocrystalline methylammonium lead iodide (MAPI)-based thin-film solar cells today reach power conversion efficiencies of over 20%. We investigate the impact of grain boundaries on charge carrier transport in large crystal MAPI thin films using time-resolved photoluminescence (PL) microscopy and numerical model calculations. Crystal sizes in the range of several tens of micrometers allow for the spatially and time resolved study of boundary effects. Whereas long-ranged diffusive charge carrier transport is observed within single crystals, no detectable diffusive transport occurs across grain boundaries. The observed PL transients are found to crucially depend on the microscopic geometry of the crystal and the point of observation. In particular, spatially restricted diffusion of charge carriers leads to slower PL decay near crystal edges as compared to the crystal center. In contrast to many reports in the literature, our experimental results show no quenching or additional loss channels due to grain boundaries for the studied material, which thus do not negatively affect the performance of the derived thin-film devices.

  17. Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Wedge, Eileen; Hansen, Jakob Werner; Garde, Christian

    2017-01-01

    Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure...... for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially...

  18. Modelling of the diffusion of pollutants in the atmosphere under varying conditions in large cultivated regions

    International Nuclear Information System (INIS)

    Wueneke, C.D.; Schultz, H.

    1975-01-01

    The most important routines of a numerical code based on the particle-in-cell-method for calculating the transport and the turbulent dispersion of inert and radio-active pollutants in the atmosphere have been programmed and have been tested successfully on the CDC computer CYBER 73/76 of the Regional Computer Centre for Niedersachsen in Hanover. Compared to the Gaussian plume model such a numerical code based on the particle-in-cell-method offers several advantages for the computation of the diffusion under varying conditions in large cultivated regions. (orig.) [de

  19. Non-destructive measurement methods for large scale gaseous diffusion process equipment

    International Nuclear Information System (INIS)

    Mayer, R.L.; Hagenauer, R.C.; McGinnis, B.R.

    1994-01-01

    Two measurement methods have been developed to measure non-destructively uranium hold-up in gaseous diffusion plants. These methods include passive neutron and passive γ ray measurements. An additional method, high resolution γ ray spectroscopy, provides supplementary information about additional γ ray emitting isotopes, γ ray correction factors, 235 U/ 234 U ratios and 235 U enrichment. Many of these methods can be used as a general purpose measurement technique for large containers of uranium. Measurement applications for these methods include uranium hold-up, waste measurements, criticality safety and nuclear accountability

  20. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Taskinen, M.; Louhimo, R.; Koivula, S.

    2014-01-01

    Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment...... tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein...

  1. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    Science.gov (United States)

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  2. Treatment of diffuse large B-cell lymphoma of the liver with yttrium-90 microsphere embolization.

    Science.gov (United States)

    Fenske, Timothy S; Benjamin, Heather; Kroft, Steven H; Hohenwalter, Eric J; Rilling, William S

    2008-11-01

    A 41-year-old male with a 4-year history of chronic hepatitis C presented with a 1-month history of abdominal pain, fatigue, weight loss, and night sweats. Laboratory examinations, chest, abdomen, and pelvic CT scans, PET-CT scans, ultrasound-guided needle biopsies of liver lesions, bone-marrow biopsy, flow cytometry, and immunohistochemical staining for B-cell markers including CD20. Chemoresistant diffuse large B-cell lymphoma, with gradual loss of CD20 antigen expression. Embolization of hepatic tumors using yttrium-90 microspheres (Therasphere, Theragenics Corporation, Buford, GA).

  3. A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

    2015-03-25

    Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3 months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinical stage IV in the Ann Arbor staging classification). The first course of chemotherapy improved anasarca remarkably and the patient's body weight returned to what it was 3 months before. We experienced a patient with remarkable anasarca caused by DLBCL infiltration of the pituitary gland. A pituitary gland lesion with central hypothyroidism should be considered as one of the differential diagnoses of edema. This case was very valuable because we could assess it by following the time course of symptoms (edema and delayed relaxation time of the Achilles tendon reflex), laboratory data, and imaging findings (swelling anterior pituitary lobe).

  4. Value of diffusion-weighted imaging in predicting parametrial invasion in stage IA2-IIA cervical cancer

    International Nuclear Information System (INIS)

    Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan; Kim, Bohyun

    2014-01-01

    To investigate the value of diffusion-weighted imaging (DWI) in evaluating parametrial invasion (PMI) in stage IA2-IIA cervical cancer. A total of 117 patients with stage IA2-IIA cervical cancer who underwent preoperative MRI and radical hysterectomy were included in this study. Preoperative clinical variables and MRI variables were analysed and compared between the groups with and without pathologically proven PMI. All variables except age were significantly different between patients with and without pathologic PMI (P < 0.05). All variables except squamous cell carcinoma (SCC) antigen were also significantly correlated with pathologic PMI on univariate analysis (P < 0.05). Multivariate analysis indicated that PMI on MRI (P < 0.001) and tumour apparent diffusion coefficient (ADC) (P = 0.029) were independent predictors of pathologic PMI. Area under the curve of PMI on MRI increased significantly from 0.793 to 0.872 when combined with tumour ADC (P = 0.002). When PMI on MRI was further stratified by tumour ADC, the false negative rate was 2.0 % (1/49). In stage IA2-IIA cervical cancer, tumour ADC and PMI on MRI seem to be independent predictors of pathologic PMI. Combining the two predictors improved the diagnostic performance of identifying patients at low risk of pathologic PMI. (orig.)

  5. Primary diffuse large B cell lymphoma arising from a leiomyoma of the uterine corpus.

    Science.gov (United States)

    Zhao, Lianhua; Ma, Qiang; Wang, Qiushi; Zeng, Ying; Luo, Qingya; Xiao, Hualiang

    2016-01-20

    Primary diffuse large B cell lymphoma (DLBCL) of the uterus is rare, and primary DLBCL arising from a uterine leiomyoma (collision tumor) has not been reported in the literature. We describe the clinical, histological, immunohistochemical, and molecular features of primary DLBCL arising from a leiomyoma in the uterine corpus. A 73-year-old female patient had a uterine mass for 23 years. An ultrasound scan revealed marked enlargement of the uterus, measuring 18.2 × 13 × 16.3 cm, with a 17.6 × 10.9 × 11.6 cm hypoechoic mass in the uterine corpus. The tumors consisted of medium- to large-sized cells exhibiting a diffuse pattern of growth with a well-circumscribed leiomyoma. The neoplastic cells strongly expressed CD79α, CD20 and PAX5. Molecular analyses indicated clonal B-cell receptor gene rearrangement. To the best of our knowledge, no previous cases of primary DLBCL arising from a leiomyoma have been reported. It is necessary to differentiate a diagnosis of primary DLBCL arising from a leiomyoma from that of leiomyoma with florid reactive lymphocytic infiltration (lymphoma-like lesion). Careful analysis of clinical, histological, immunophenotypic, and genetic features is required to establish the correct diagnosis.

  6. Orbital diffuse large B-cell lymphoma with combined variable immunodeficiency.

    Science.gov (United States)

    Parikh, Vishal S; Jagadeesh, Deepa; Fernandez, James M; Hsi, Eric D; Singh, Arun D

    2017-10-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.

  7. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  8. Patterns of failure of diffuse large B-cell lymphoma patients after involved-site radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Holzhaeuser, Eva; Berlin, Maximilian; Bezold, Thomas; Mayer, Arnulf; Schmidberger, Heinz [University Medical Center Mainz, Department of Radiation Oncology and Radiotherapy, Mainz (Germany); Wollschlaeger, Daniel [University Medical Center Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz (Germany); Hess, Georg [University Medical Center Mainz, Department of Internal Medicine, Mainz (Germany)

    2017-12-15

    Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B-cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). We identified 60 histologically confirmed stage I-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann-Whitney U-test. After initial chemoimmunotherapy (mostly R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a median follow-up of 44 months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed significantly improved PFS compared to stage III/IV (93% vs 65%; p ≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been associated with significantly increased PFS (100% vs 70%; p ≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p ≤ 0.004) and OS (100% vs 82%; p ≤ 0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade III or IV side effects have not been observed. These data suggest that a reduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because

  9. Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    2017-12-12

    Chidamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm by Histology; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Rituximab; Gemcitabine; Cisplatin; Dexamethasone; HDAC Inhibitor

  10. Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy

    OpenAIRE

    Nakashima, Yasuhiro; Shiratsuchi, Motoaki; Abe, Ichiro; Matsuda, Yayoi; Miyata, Noriyuki; Ohno, Hirofumi; Ikeda, Motohiko; Matsushima, Takamitsu; Nomura, Masatoshi; Takayanagi, Ryoichi

    2013-01-01

    Background Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of p...

  11. Whole-body MRI, dynamic contrast-enhanced MRI, and diffusion-weighted imaging for the staging of multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2017-06-15

    Magnetic resonance imaging (MRI) is the most sensitive imaging technique for the detection of bone marrow infiltration, and has therefore recently been included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. Nevertheless, conventional MRI only provides anatomical information and is therefore only of limited use in the response assessment of patients with multiple myeloma. The additional information from functional MRI techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced MRI, can improve the detection rate of bone marrow infiltration and the assessment of response. This can further enhance the sensitivity and specificity of MRI in the staging of multiple myeloma patients. This article provides an overview of the technical aspects of conventional and functional MRI techniques with practical recommendations. It reviews the diagnostic performance, prognostic value, and role in therapy assessment in multiple myeloma and its precursor stages. (orig.)

  12. Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström’s macroglobulinaemia

    Directory of Open Access Journals (Sweden)

    Radojković Milica

    2011-01-01

    Full Text Available Introduction. Waldenström’s macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström’s macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström’s macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. Case Outline. A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström’s macroglobulinaemia. Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström’s macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. Conclusion. The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenström’s macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

  13. Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

    Directory of Open Access Journals (Sweden)

    Milovanović Milena

    2017-06-01

    Full Text Available In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL, primary cutaneous follicle center lymphoma (PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT, and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O. The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP.

  14. Multi-staged robotic stereotactic radiosurgery for large cerebral arteriovenous malformations

    International Nuclear Information System (INIS)

    Ding, Chuxiong; Solberg, Timothy D.; Hrycushko, Brian; Medin, Paul; Whitworth, Louis; Timmerman, Robert D.

    2013-01-01

    Purpose: To investigate a multi-staged robotic stereotactic radiosurgery (SRS) delivery technique for the treatment of large cerebral arteriovenous malformations (AVMs). The treatment planning process and strategies to optimize both individual and composite dosimetry are discussed. Methods: Eleven patients with large (30.7 ± 19.2 cm 3 ) AVMs were selected for this study. A fiducial system was designed for fusion of targets between planar angiograms and simulation CT scans. AVMs were contoured based on single contrast CT, MRI and orthogonal angiogram images. AVMs were divided into 3–8 sub-target volumes (3–7 cm 3 ) for sequential treatment at 1–4 week intervals to a prescription dose of 16–20 Gy. Forward and inversely developed treatment plans were optimized for 95% coverage of the total AVM volume by dose summation from each sub-volume, while minimizing dose to surrounding tissues. Dose-volume analysis was used to evaluate the PTV coverage, dose conformality (CI), and R 50 and V 12Gy parameters. Results: The treatment workflow was commissioned and able to localize within 1 mm. Inverse optimization outperformed forward planning for most patients for each index considered. Dose conformality was shown comparable to staged Gamma Knife treatments. Conclusion: The CyberKnife system is shown to be a practical delivery platform for multi-staged treatments of large AVMs using forward or inverse planning techniques

  15. Evaluating neighborhood structures for modeling intercity diffusion of large-scale dengue epidemics.

    Science.gov (United States)

    Wen, Tzai-Hung; Hsu, Ching-Shun; Hu, Ming-Che

    2018-05-03

    Dengue fever is a vector-borne infectious disease that is transmitted by contact between vector mosquitoes and susceptible hosts. The literature has addressed the issue on quantifying the effect of individual mobility on dengue transmission. However, there are methodological concerns in the spatial regression model configuration for examining the effect of intercity-scale human mobility on dengue diffusion. The purposes of the study are to investigate the influence of neighborhood structures on intercity epidemic progression from pre-epidemic to epidemic periods and to compare definitions of different neighborhood structures for interpreting the spread of dengue epidemics. We proposed a framework for assessing the effect of model configurations on dengue incidence in 2014 and 2015, which were the most severe outbreaks in 70 years in Taiwan. Compared with the conventional model configuration in spatial regression analysis, our proposed model used a radiation model, which reflects population flow between townships, as a spatial weight to capture the structure of human mobility. The results of our model demonstrate better model fitting performance, indicating that the structure of human mobility has better explanatory power in dengue diffusion than the geometric structure of administration boundaries and geographic distance between centroids of cities. We also identified spatial-temporal hierarchy of dengue diffusion: dengue incidence would be influenced by its immediate neighboring townships during pre-epidemic and epidemic periods, and also with more distant neighbors (based on mobility) in pre-epidemic periods. Our findings suggest that the structure of population mobility could more reasonably capture urban-to-urban interactions, which implies that the hub cities could be a "bridge" for large-scale transmission and make townships that immediately connect to hub cities more vulnerable to dengue epidemics.

  16. Prognostic value of defining the systemic tumor volume with FDG-PET in diffuse large b cell lymphoma

    International Nuclear Information System (INIS)

    Byun, Byung Hyun; Lim, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Kang, Hye Jin; Na, Im Il; Ryoo, Baek Yeol; Yang, Sung Hyun

    2007-01-01

    We measured the systemic tumor volume using FDG-PET in patients with diffuse large B cell lymphoma (DLBL). We also investigated its prognostic role, and compared it with that of other prognostic factors. FDG PET was performed in 38 newly diagnosed DLBL patients (20 men, 18 women, age 55.715.1 years) at pre-treatment of chemotherapy. Clinical staging of lymphoma was evaluated by Ann Arbor system. On each FDG PET scan, we acquired volume of interest (VOl) at the cut-off value of SUV=2.5 in every measurable tumor by the automatic edge detection software. According to the VOI, we measured the metabolic volume and mean SUV, and estimated volume-activity indexes (SUV Vol) as mean SUV times metabolic volume. And then, we calculated the summed metabolic volume (VOLsum) and summed SUV Vol (SUV Volsum) in every FDG PET scan. Maximum SUV of involved lesion (SUVmax) was also acquired on each FDG PET scan. Time to treatment failure (TTF) was compared among VOLsum (median), SUV Volsum (median), SUVmax (median), clinical stage, gender, age, LDH, and performance status-assigned response designations by Kaplan-Meier survival analysis. Initial stages of DLBL patients were stage I in 4, II in 14, III in 15, and IV in 4 by Ann Arbor system. Median follow up period was 15.5months, and estimated mean TTF was 22.3 months. Univariate analysis demonstrated that TTF is statistically significantly reduced in those with high VOLsum (>215.1cm2, p=0.004), high SUV Volsum (>1577.5, p=0.003), and increased LDH (p=0.036). TTF did not correlate with SUVmax (p=0.571), clinical stage (p=0.194), gender (p=0.549), and age (p=0.128), and performance status =2 (p=0.074). Multivariate analysis using VOLsum, SUV Volsum, LDH, and performance status demonstrated no statistically significant predictor of TTF (p>0.05). Systemic tumor volume measurement using FDG-PET is suggestive to be the significant prognostic factor in patients with DLBL

  17. Diffusion mechanisms taking place at the early stages of cobalt deposition on Au(111)

    International Nuclear Information System (INIS)

    Oviedo, O A; Leiva, E P M; Mariscal, M M

    2008-01-01

    In the present work a detailed atomic-level analysis of some of the main diffusion mechanisms which take place during cobalt adatom deposition are studied within atom dynamics (AD) and the nudged elastic band (NEB) method. Our computer simulations reveal a very fast exchange between Co and Au atoms when the deposit is a single cobalt adatom. However, when the nucleus size increases, a decrease in the exchange probability is observed. Activation energies for different transitions are obtained using AD in combination with the NEB method

  18. Quantitative diffusion and swelling kinetic measurements using large-angle interferometric refractometry.

    Science.gov (United States)

    Saunders, John E; Chen, Hao; Brauer, Chris; Clayton, McGregor; Chen, Weijian; Barnes, Jack A; Loock, Hans-Peter

    2015-12-07

    The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

  19. Numerical insights into the early stages of nanoscale electrodeposition: nanocluster surface diffusion and aggregative growth

    DEFF Research Database (Denmark)

    Mamme, Mesfin Haile; Kohn, Christoph; Deconinck, Johan

    2018-01-01

    Fundamental understanding of the early stages of electrodeposition at the nanoscale is key to address the challenges in a wide range of applications. Despite having been studied for decades, a comprehensive understanding of the whole process is still out of reach. In this work, we introduce a nov...

  20. Numb Chin Syndrome as First Symptom of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Mario Carbone

    2014-01-01

    Full Text Available Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes, especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma, and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney, prostate, and nasopharynx. Haematological malignancies like acute lymphocytic leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this neuropathy. The authors report a case of a 71-year-old woman in which the numb chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which caused infiltration and reabsorption of the alveolar ridge and lower mandibular cortex. A biopsy of the mass was performed on fragments of tissue collected from the mandibular periosteum, medullary and cortical mandibular bone, and inferior alveolar nerve.

  1. A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

    Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

  2. Microarray-based classification of diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius

    2005-01-01

    on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used......OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation...... for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1...

  3. High density high performance plasma with internal diffusion barrier in Large Helical Device

    International Nuclear Information System (INIS)

    Sakamoto, R.; Kobayashi, M.; Miyazawa, J.

    2008-10-01

    A attractive high density plasma operational regime, namely an internal diffusion barrier (IDB), has been discovered in the intrinsic helical divertor configuration on the Large Helical Device (LHD). The IDB which enables core plasma to access a high density/high pressure regime has been developed. It is revealed that the IDB is reproducibly formed by pellet fueling in the magnetic configurations shifted outward in major radius. Attainable central plasma density exceeds 1x10 21 m -3 . Central pressure reaches 1.5 times atmospheric pressure and the central β value becomes fairly high even at high magnetic field, i.e. β(0)=5.5% at B t =2.57 T. (author)

  4. Conditional survival of patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Pedersen, Niels Tinggaard; Christensen, Bjarne E

    2006-01-01

    BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survive...... survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...... a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...

  5. Strong motion modeling at the Paducah Diffusion Facility for a large New Madrid earthquake

    International Nuclear Information System (INIS)

    Herrmann, R.B.

    1991-01-01

    The Paducah Diffusion Facility is within 80 kilometers of the location of the very large New Madrid earthquakes which occurred during the winter of 1811-1812. Because of their size, seismic moment of 2.0 x 10 27 dyne-cm or moment magnitude M w = 7.5, the possible recurrence of these earthquakes is a major element in the assessment of seismic hazard at the facility. Probabilistic hazard analysis can provide uniform hazard response spectra estimates for structure evaluation, but a deterministic modeling of a such a large earthquake can provide strong constraints on the expected duration of motion. The large earthquake is modeled by specifying the earthquake fault and its orientation with respect to the site, and by specifying the rupture process. Synthetic time histories, based on forward modeling of the wavefield, from each subelement are combined to yield a three component time history at the site. Various simulations are performed to sufficiently exercise possible spatial and temporal distributions of energy release on the fault. Preliminary results demonstrate the sensitivity of the method to various assumptions, and also indicate strongly that the total duration of ground motion at the site is controlled primarily by the length of the rupture process on the fault

  6. Diffusion Experiments with Opalinus and Callovo-Oxfordian Clays: Laboratory, Large-Scale Experiments and Microscale Analysis by RBS

    International Nuclear Information System (INIS)

    Garcia-Gutierrez, M.; Alonso, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2009-01-01

    Consolidated clays are potential host rocks for deep geological repositories for high-level radioactive waste. Diffusion is the main transport process for radionuclides (RN) in these clays. Radionuclide (RN) diffusion coefficients are the most important parameters for Performance Assessment (PA) calculations of clay barriers. Different diffusion methodologies were applied at a laboratory scale to analyse the diffusion behaviour of a wide range of RN. Main aims were to understand the transport properties of different RNs in two different clays and to contribute with feasible methodologies to improve in-situ diffusion experiments, using samples of larger scale. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed, together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), for diffusion analyses at the micrometer scale. The main experimental and theoretical characteristics of the different methodologies, and their advantages and limitations are here discussed. Experiments were performed with the Opalinus and the Callovo-Oxfordian clays. Both clays are studied as potential host rock for a repository. Effective diffusion coefficients ranged between 1.10 - 10 to 1.10 - 12 m 2 /s for neutral, low sorbing cations (as Na and Sr) and anions. Apparent diffusion coefficients for strongly sorbing elements, as Cs and Co, are in the order of 1.10-13 m 2 /s; europium present the lowest diffusion coefficient (5.10 - 15 m 2 /s). The results obtained by the different approaches gave a comprehensive database of diffusion coefficients for RN with different transport behaviour within both clays. (Author) 42 refs

  7. Diffusion Experiments with Opalinus and Callovo-Oxfordian Clays: Laboratory, Large-Scale Experiments and Microscale Analysis by RBS

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Gutierrez, M.; Alonso, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2009-09-25

    Consolidated clays are potential host rocks for deep geological repositories for high-level radioactive waste. Diffusion is the main transport process for radionuclides (RN) in these clays. Radionuclide (RN) diffusion coefficients are the most important parameters for Performance Assessment (PA) calculations of clay barriers. Different diffusion methodologies were applied at a laboratory scale to analyse the diffusion behaviour of a wide range of RN. Main aims were to understand the transport properties of different RNs in two different clays and to contribute with feasible methodologies to improve in-situ diffusion experiments, using samples of larger scale. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed, together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), for diffusion analyses at the micrometer scale. The main experimental and theoretical characteristics of the different methodologies, and their advantages and limitations are here discussed. Experiments were performed with the Opalinus and the Callovo-Oxfordian clays. Both clays are studied as potential host rock for a repository. Effective diffusion coefficients ranged between 1.10{sup -}10 to 1.10{sup -}12 m{sup 2}/s for neutral, low sorbing cations (as Na and Sr) and anions. Apparent diffusion coefficients for strongly sorbing elements, as Cs and Co, are in the order of 1.10-13 m{sup 2}/s; europium present the lowest diffusion coefficient (5.10{sup -}15 m{sup 2}/s). The results obtained by the different approaches gave a comprehensive database of diffusion coefficients for RN with different transport behaviour within both clays. (Author) 42 refs.

  8. Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Caramuta, S; Lee, L; Özata, D M; Akçakaya, P; Georgii-Hemming, P; Xie, H; Amini, R-M; Lawrie, C H; Enblad, G; Larsson, C; Berglund, M; Lui, W-O

    2013-01-01

    Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL

  9. [Early diffuse hypertrophic osteitis recurrence. Unexpected and consternating development after a large évidement cavity. Apropos of 15 cases].

    Science.gov (United States)

    Fleury, P; Basset, J M; Candau, P; Bré, M; Despreaux, G; Fabre, A; Saliba, N

    1985-01-01

    The authors report 15 cases collected over a period of 13 years (1972 - 1984) of a particularly serious eventuality affecting certain evacuation cavities: Early recurrence of diffuse hypertrophic osteitis (E.R.D.H.O.). This is a rare complication, occurring in 1.5% of cases of chronic otitis. However, the fact of having operated upon 7 cases in 1984 alone, whilst during the previous 12 years, only 8 had been seen, raised the alarm. The classical pattern of this complication occurs in 3 stages, each involving surgical operation: at the outset, chronic otitis with cholesteatoma or osteitis, most often mixed, for which an "inadequate" surgical procedure is performed. then, after a variable period which may exceed 10 years, a very large evacuation cavity was created by the authors. finally, 3rd and final stage: within 6 months, this cavity filled progressively and, at operation, the authors discovered a cavity virtually completely filled with a "fantastic" "moist sugar" osteitis, requiring a new evacuation cavity, even larger than that created before. In all cases, a successful result was obtained within a varying period, sometimes accompanied by spectacular improvement in general condition. The most plausible etiopathogenic hypothesis advanced to attempt to explain this phenomenon is that of secondary infection by a varied microbial flora, including, on the one hand, aerobic organisms usually discovered in such cases (pseudomonas pyocyaneus, proteus mirabilis) and, secondly, this being of essential importance, "anaerobic" bacteria, the bacteriological diagnosis of which requires application of a strict protocol. The authors have taken three decisions following their bibliographic investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

    2017-06-01

    The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

    Science.gov (United States)

    Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

    2018-03-11

    Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

  12. Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

    2015-05-01

    Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Diffuse stenotic change in large intracranial arteries following irradiation therapy for medulloblastoma

    International Nuclear Information System (INIS)

    Yamakami, Iwao; Sugaya, Yuichi; Sato, Masanori; Osato, Katunobu; Yamaura, Akira; Makino, Hiroyasu.

    1990-01-01

    We reported a case of a patient who developed a diffuse stenotic change in the large intracranial arteries and repeated episodes of cerebral infarction after irradiation therapy for medulloblastoma. A three-year-old girl underwent the subtotal removal of cerebellar medulloblastoma and the subsequent irradiation therapy in the whole brain and spine (30 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). Two years later, she again underwent surgery and irradiation therapy because a recurrence of medulloblastoma had manifested itself in the frontal lobe; (40 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). One and half years after the second irradiation, she started suffering from frequent and refractory cerebral ischemic attacks. Cerebral angiography revealed a diffuse narrowing, and multifocal stenoses in the bilateral anterior and middle cerebral arteries. Computerized tomography demonstrated multiple cerebral infarctions. Her neurological condition deteriorated because of recurring strokes and she died at ten years of age. Most of the reported cases of patients who developed stenotic arteriopathy were children in the first decade of their life, and who were irradiated for parasellar brain tumor of low malignancy. Stenotic arteriopathy after irradiation has rarely been recognized in patients with malignant brain tumor. However, life expectancy is increasing even for those with malignant brain tumor, and it may make stenotic arteriopathy after irradiation recognized more commonly in patients with malignant brain tumor. Careful irradiation and subsequent angiographical examination should be required even in patients with malignant brain tumor. (author)

  14. Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup of early stage parkinsonism

    International Nuclear Information System (INIS)

    Meijer, Frederick J.A.; Rumund, Anouke van; Tuladhar, Anil M.; Aerts, Marjolein B.; Titulaer, Imke; Esselink, Rianne A.J.; Bloem, Bastiaan R.; Verbeek, Marcel M.; Goraj, Bozena

    2015-01-01

    The aim of this study is to evaluate whether the diagnostic accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of diffusion tensor imaging (DTI), to differentiate between neurodegenerative atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage parkinsonism. We performed a prospective observational cohort study of 60 patients presenting with early stage parkinsonism and initial uncertain diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI. After clinical follow-up (mean 28.3 months), diagnoses could be made in 49 patients (30 PD and 19 AP). Conventional brain MRI was evaluated for regions of atrophy and signal intensity changes. Tract-based spatial statistics and ROI analyses of DTI were performed to analyze group differences in mean diffusivity (MD) and fractional anisotropy (FA), and diagnostic thresholds were determined. Diagnostic accuracy of conventional brain MRI and DTI was assessed with the receiver operating characteristic (ROC). Significantly higher MD of the centrum semiovale, body corpus callosum, putamen, external capsule, midbrain, superior cerebellum, and superior cerebellar peduncles was found in AP. Significantly increased MD of the putamen was found in multiple system atrophy-parkinsonian form (MSA-P) and increased MD in the midbrain and superior cerebellar peduncles in progressive supranuclear palsy (PSP). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by ROI measures of MD, though the diagnostic accuracy to identify MSA-P was slightly increased (AUC 0.82 to 0.85). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by the current analysis approach to DTI, though DTI measures could be of added value to identify AP subgroups. (orig.)

  15. Conventional 3T brain MRI and diffusion tensor imaging in the diagnostic workup of early stage parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Meijer, Frederick J.A. [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Rumund, Anouke van; Tuladhar, Anil M.; Aerts, Marjolein B.; Titulaer, Imke; Esselink, Rianne A.J.; Bloem, Bastiaan R. [Radboud University Nijmegen Medical Center, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen (Netherlands); Verbeek, Marcel M. [Radboud University Nijmegen Medical Center, Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Nijmegen (Netherlands); Radboud University Nijmegen Medical Center, Department of Laboratory Medicine, Nijmegen (Netherlands); Goraj, Bozena [Radboud University Nijmegen Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Medical Center of Postgraduate Education, Department of Diagnostic Imaging, Warsaw (Poland)

    2015-07-15

    The aim of this study is to evaluate whether the diagnostic accuracy of 3 T brain MRI is improved by region of interest (ROI) measures of diffusion tensor imaging (DTI), to differentiate between neurodegenerative atypical parkinsonism (AP) and Parkinson's disease (PD) in early stage parkinsonism. We performed a prospective observational cohort study of 60 patients presenting with early stage parkinsonism and initial uncertain diagnosis. At baseline, patients underwent a 3 T brain MRI including DTI. After clinical follow-up (mean 28.3 months), diagnoses could be made in 49 patients (30 PD and 19 AP). Conventional brain MRI was evaluated for regions of atrophy and signal intensity changes. Tract-based spatial statistics and ROI analyses of DTI were performed to analyze group differences in mean diffusivity (MD) and fractional anisotropy (FA), and diagnostic thresholds were determined. Diagnostic accuracy of conventional brain MRI and DTI was assessed with the receiver operating characteristic (ROC). Significantly higher MD of the centrum semiovale, body corpus callosum, putamen, external capsule, midbrain, superior cerebellum, and superior cerebellar peduncles was found in AP. Significantly increased MD of the putamen was found in multiple system atrophy-parkinsonian form (MSA-P) and increased MD in the midbrain and superior cerebellar peduncles in progressive supranuclear palsy (PSP). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by ROI measures of MD, though the diagnostic accuracy to identify MSA-P was slightly increased (AUC 0.82 to 0.85). The diagnostic accuracy of brain MRI to identify AP as a group was not improved by the current analysis approach to DTI, though DTI measures could be of added value to identify AP subgroups. (orig.)

  16. Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

    Science.gov (United States)

    Petry, Karl Ulrich; Liebrich, Clemens; Luyten, Alexander; Zander, Martina; Iftner, Thomas

    2017-12-01

    We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population. We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping. HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests. The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

    Directory of Open Access Journals (Sweden)

    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

  18. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2016-01-01

    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2...... frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma...

  19. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.

    Science.gov (United States)

    Chapuy, Bjoern; Stewart, Chip; Dunford, Andrew J; Kim, Jaegil; Kamburov, Atanas; Redd, Robert A; Lawrence, Mike S; Roemer, Margaretha G M; Li, Amy J; Ziepert, Marita; Staiger, Annette M; Wala, Jeremiah A; Ducar, Matthew D; Leshchiner, Ignaty; Rheinbay, Ester; Taylor-Weiner, Amaro; Coughlin, Caroline A; Hess, Julian M; Pedamallu, Chandra S; Livitz, Dimitri; Rosebrock, Daniel; Rosenberg, Mara; Tracy, Adam A; Horn, Heike; van Hummelen, Paul; Feldman, Andrew L; Link, Brian K; Novak, Anne J; Cerhan, James R; Habermann, Thomas M; Siebert, Reiner; Rosenwald, Andreas; Thorner, Aaron R; Meyerson, Matthew L; Golub, Todd R; Beroukhim, Rameen; Wulf, Gerald G; Ott, German; Rodig, Scott J; Monti, Stefano; Neuberg, Donna S; Loeffler, Markus; Pfreundschuh, Michael; Trümper, Lorenz; Getz, Gad; Shipp, Margaret A

    2018-04-30

    Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

  20. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    Science.gov (United States)

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

    2016-01-01

    Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

  2. Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

    Science.gov (United States)

    Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

    2017-07-01

    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Central nervous system prophylaxis in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zahid, Mohammad Faizan; Khan, Nadia; Hashmi, Shahrukh K; Kizilbash, Sani Haider; Barta, Stefan K

    2016-08-01

    Central nervous system (CNS) involvement with diffuse large B-cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high-dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Discovery of large-scale diffuse radio emission in low-mass galaxy cluster Abell 1931

    Science.gov (United States)

    Brüggen, M.; Rafferty, D.; Bonafede, A.; van Weeren, R. J.; Shimwell, T.; Intema, H.; Röttgering, H.; Brunetti, G.; Di Gennaro, G.; Savini, F.; Wilber, A.; O'Sullivan, S.; Ensslin, T. A.; De Gasperin, F.; Hoeft, M.

    2018-04-01

    Extended, steep-spectrum radio synchrotron sources are pre-dominantly found in massive galaxy clusters as opposed to groups. LOFAR Two-Metre Sky Survey images have revealed a diffuse, ultra-steep spectrum radio source in the low-mass cluster Abell 1931. The source has a fairly irregular morphology with a largest linear size of about 550 kpc. The source is only seen in LOFAR observations at 143 MHz and GMRT observations at 325 MHz. The spectral index of the total source between 143 MHz and 325 MHz is α _{143}^{325} = -2.86 ± 0.36. The source remains invisible in Very Large Array (1-2 GHz) observations as expected given the spectral index. Chandra X-ray observations of the cluster revealed a bolometric luminosity of LX = (1.65 ± 0.39) × 1043 erg s-1 and a temperature of 2.92_{-0.87}^{+1.89} keV which implies a mass of around ˜1014M⊙. We conclude that the source is a remnant radio galaxy that has shut off around 200 Myr ago. The brightest cluster galaxy, a radio-loud elliptical galaxy, could be the source for this extinct source. Unlike remnant sources studied in the literature, our source has a steep spectrum at low radio frequencies. Studying such remnant radio galaxies at low radio frequencies is important for understanding the scarcity of such sources and their role in feedback processes.

  5. A Diffuse Interface Model for Incompressible Two-Phase Flow with Large Density Ratios

    KAUST Repository

    Xie, Yu; Wodo, Olga; Ganapathysubramanian, Baskar

    2016-01-01

    In this chapter, we explore numerical simulations of incompressible and immiscible two-phase flows. The description of the fluid–fluid interface is introduced via a diffuse interface approach. The two-phase fluid system is represented by a coupled Cahn–Hilliard Navier–Stokes set of equations. We discuss challenges and approaches to solving this coupled set of equations using a stabilized finite element formulation, especially in the case of a large density ratio between the two fluids. Specific features that enabled efficient solution of the equations include: (i) a conservative form of the convective term in the Cahn–Hilliard equation which ensures mass conservation of both fluid components; (ii) a continuous formula to compute the interfacial surface tension which results in lower requirement on the spatial resolution of the interface; and (iii) a four-step fractional scheme to decouple pressure from velocity in the Navier–Stokes equation. These are integrated with standard streamline-upwind Petrov–Galerkin stabilization to avoid spurious oscillations. We perform numerical tests to determine the minimal resolution of spatial discretization. Finally, we illustrate the accuracy of the framework using the analytical results of Prosperetti for a damped oscillating interface between two fluids with a density contrast.

  6. Novel disease targets and management approaches for diffuse large B-cell lymphoma.

    Science.gov (United States)

    Wilson, Wyndham H; Hernandez-Ilizaliturri, Francisco J; Dunleavy, Kieron; Little, Richard F; O'Connor, Owen A

    2010-08-01

    Diffuse large B-cell lymphoma (DLBCL) responds well to treatment with CHOP and the R-CHOP regimen, but a subset of patients still fail to achieve complete or durable responses. Recent advances in gene expression profiling have led to the identification of three different subtypes of DLBCL, and confirmed that patients with the activated B-cell (ABC) disease subtype are less likely to respond well to CHOP-based regimens than those with germinal centre B-cell-type (GCB) disease. This discovery could herald the use of gene expression profiling to aid treatment decisions in DLBCL, and help identify the most effective management strategies for patients. Treatment options for patients with relapsed or refractory DLBCL are limited and several novel agents are being developed to address this unmet clinical need. Novel agents developed to treat plasma cell disorders such as multiple myeloma have shown promising activity in patients with NHL. Indeed, the immunomodulatory agent lenalidomide and the proteasome inhibitors bortezomib and carfilzomib, as single agents or in combination with chemotherapy, have already demonstrated promising activity in patients with the ABC subtype of DLBCL. One should not be complacent however when applying these agents to new disease types, because dose and drug scheduling can have marked effects on the responses achieved with investigational agents. As more targeted agents are developed, the timing of administration with other agents in clinical trials will become increasingly important to ensure maximal efficacy while minimizing side effects.

  7. A Diffuse Interface Model for Incompressible Two-Phase Flow with Large Density Ratios

    KAUST Repository

    Xie, Yu

    2016-10-04

    In this chapter, we explore numerical simulations of incompressible and immiscible two-phase flows. The description of the fluid–fluid interface is introduced via a diffuse interface approach. The two-phase fluid system is represented by a coupled Cahn–Hilliard Navier–Stokes set of equations. We discuss challenges and approaches to solving this coupled set of equations using a stabilized finite element formulation, especially in the case of a large density ratio between the two fluids. Specific features that enabled efficient solution of the equations include: (i) a conservative form of the convective term in the Cahn–Hilliard equation which ensures mass conservation of both fluid components; (ii) a continuous formula to compute the interfacial surface tension which results in lower requirement on the spatial resolution of the interface; and (iii) a four-step fractional scheme to decouple pressure from velocity in the Navier–Stokes equation. These are integrated with standard streamline-upwind Petrov–Galerkin stabilization to avoid spurious oscillations. We perform numerical tests to determine the minimal resolution of spatial discretization. Finally, we illustrate the accuracy of the framework using the analytical results of Prosperetti for a damped oscillating interface between two fluids with a density contrast.

  8. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

    Directory of Open Access Journals (Sweden)

    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  9. Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

    Science.gov (United States)

    Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Hishima, Tsunekazu; Omuro, Yasushi

    2018-06-01

    The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

  10. MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Kwanhian, Wiyada; Lenze, Dido; Alles, Julia; Motsch, Natalie; Barth, Stephanie; Döll, Celina; Imig, Jochen; Hummel, Michael; Tinguely, Marianne; Trivedi, Pankaj; Lulitanond, Viraphong; Meister, Gunter; Renner, Christoph; Grässer, Friedrich A

    2012-01-01

    MicroRNAs (miRNAs) are short 18–23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3′ untranslated region (3′ UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3′ UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype

  11. Electrochemical lysis at the stage of endoresection for large posterior intraocular tumors

    Directory of Open Access Journals (Sweden)

    Yu. A. Belyy

    2012-01-01

    Full Text Available Purpose: to design the new combined technique of endoresection with intraoperative intraocular electrochemical lysis at the tumor destruction stage for large posterior intraocular tumors.Methods: 3 patients (3 eyes with large choroidal melanomas t3N0M0 (tumor thickness — 8-10 mm, base diameter — 13-15 mm, juxtapapillary localization. Mean age was 55.4 years old. Endoresection with intraoperational intraocular electrochemical lysis of the tumor was performed. Electrochemical lysis was performed with use of the technical unit ECU 300 (Soering, Germany and the original method of combined intratumoral positioning of two platinum electrodes: anode and cathode.Results: the tumor was removal completely in all 3 cases. the anatomical retinal reattachment was reached in all patients. Sclera was safe in all 3 cases. Visual acuity was not changed (NLP. At the place of the removal tumor a surgical choroidal coloboma without pigmentation all over scleral bed and periphery was shown in all cases in distant postoperative period (from 1.5 to 3 years. No local recurrences or metastasis were revealed in all patients.Conclusion: Further investigations in clinical group are necessarily to determinate the real possibilities of the combined method and the indications for endoresection with intraoperative intraocular electrochemical lysis for large intraocular tumors. 

  12. Discrimination method of large log-likelihood study in differential diagnosis of pulmonary diffuse mild micro-nodule

    International Nuclear Information System (INIS)

    Chen Budong; Ma Daqing; He Wen; Tang Hongqu; Qian Linxue; Zhou Ronglin

    2001-01-01

    Objective: To analyze HRCT and thin-slice CT scan findings in 150 patients with pulmonary diffuse mild micro-nodule, and to find the features with the purpose of identifying random micro-nodule, peri-lymphatic micro-nodule, and centrilobular micro-nodule. Methods: The useful features i 150 patients with pulmonary diffuse mild micro-nodule were translated into scores by means of discrimination method of large log-likelihood to identify the micro-nodular category. Results: The accuracy of diagnosis was 94.0% for random micro-nodule, 76.0% for peri-lymphatic micro-nodule, and 90.0% for centrilobular micro-nodule. Conclusion: HRCT and thin-slice CT scans were helpful in differential diagnosis of pulmonary diffuse mild micro-nodule. The discrimination method of large log-likelihood was propitious to diagnosis and differential diagnosis

  13. Two-Stage Surgery for a Large Cervical Dumbbell Tumour in Neurofibromatosis 1: A Case Report

    Directory of Open Access Journals (Sweden)

    Mohd Ariff S

    2011-11-01

    Full Text Available Spinal neurofibromas occur sporadically and typically occur in association with neurofibromatosis 1. Patients afflicted with neurofibromatosis 1 usually present with involvement of several nerve roots. This report describes the case of a 14- year-old child with a large intraspinal, but extradural tumour with paraspinal extension, dumbbell neurofibroma of the cervical region extending from the C2 to C4 vertebrae. The lesions were readily detected by MR imaging and were successfully resected in a two-stage surgery. The time interval between the first and second surgery was one month. We provide a brief review of the literature regarding various surgical approaches, emphasising the utility of anterior and posterior approaches.

  14. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 59: Japanese Technological Innovation. Implications for Large Commercial Aircraft and Knowledge Diffusion

    Science.gov (United States)

    Pinelli, Thomas E.; Barclay, Rebecca O.; Kotler, Mindy L.

    1997-01-01

    This paper explores three factors-public policy, the Japanese (national) innovation system, and knowledge-that influence technological innovation in Japan. To establish a context for the paper, we examine Japanese culture and the U.S. and Japanese patent systems in the background section. A brief history of the Japanese aircraft industry as a source of knowledge and technology for other industries is presented. Japanese and U.S. alliances and linkages in three sectors-biotechnology, semiconductors, and large commercial aircraft (LCA)-and the importation, absorption, and diffusion of knowledge and technology are examined next. The paper closes with implications for diffusing knowledge and technology, U.S. public policy, and LCA.

  15. Aberrant methylation of cell-free circulating DNA in plasma predicts poor outcome in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Hansen, Jakob Werner; Kristensen, Søren Sommer

    2016-01-01

    BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients...

  16. AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Wang, Jinfen; Xu-Monette, Zijun Y; Jabbar, Kausar J

    2017-01-01

    AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT...

  17. Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Deng, Q.; Manyam, G.C.; Tzankov, A.; Li, L; Xia, Y.; Wang, X.X.; Zou, D.; Visco, C.; Dybkaer, K.; Li, J.; Zhang, L.; Liang, H.; Montes-Moreno, S.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huh, J.; Ponzoni, M.; Ferreri, A.J.; Parsons, B.M.; Moller, M.B.; Wang, S.A.; Miranda, R.N.; Piris, M.A.; Winter, J.N.; Medeiros, L.J.; Li, Y.; Young, K.H.

    2016-01-01

    PURPOSE: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This study

  18. Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

    NARCIS (Netherlands)

    Rayman, Nazik; Lam, King H.; van der Holt, Bronno; Koss, Clara; Veldhuizen, Dennis; Budel, Leo M.; Mulder, Andries H.; Verdonck, Leo F.; Delwel, Ruud; de Jong, Daphne; van Imhoff, Gustaaf W.; Sonneveld, Pieter

    Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large

  19. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity?

    Science.gov (United States)

    Hong, J Y; Yoon, D H; Suh, C; Huh, J; Do, I-G; Sohn, I; Jo, J; Jung, S-H; Hong, M E; Yoon, H; Ko, Y H; Kim, S J; Kim, W S

    2015-03-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined only in adults older than 50 years. However, EBV-positive DLBCL can affect younger patients. We investigated the prevalence, clinical characteristics and survival outcomes of EBV-positive DLBCL in young adults. We analyzed patients with de novo DLBCL who were registered in the Samsung Medical Center (SMC) retrospective lymphoma cohort and prospective SMC Lymphoma Cohort Study I (ClinicalTrials.gov: NCT00822731). A total of 571 cases were included in the analysis. The prevalence of EBV positivity was 6.7% (13/195) and 9.3% (35/376) in the young group (≤50 years) and in the elderly group (>50 years), respectively. EBV status was closely associated with unique unfavorable clinical characteristics [older age, more advanced stage, two or more sites of extranodal involvement, higher International Prognostic Index (IPI), and age-adjusted IPI risk] only in the elderly group. Poor prognostic impact of EBV positivity on overall survival was observed only in the elderly group [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.83-4.47; P young group (HR 1.17; 95% CI 0.35-3.89; P = 0.801). A substantial proportion of EBV-positive DLBCL of the elderly can occur in young adults. EBV positivity of DLBCL in young adults was not associated with unfavorable clinical characteristics or worse outcomes. We suggest that EBV-positive DLBCL should not be confined only in the elderly and 'EBV-positive DLBCL in young adults' needs to be considered as a clinically distinct disease entity. ClinicalTrials.gov: NCT02060435. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Şerife Hülya Arslan

    2012-09-01

    Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

  1. PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

    Science.gov (United States)

    Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2016-09-13

    Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

  2. Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Hannah ePhipps-Yonas

    2013-12-01

    Full Text Available The MHC class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL, the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT, an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for MHC class II binding and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

  3. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Carmen Bellas

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification was associated with the non-germinal center B subtype (non-GCB. BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.

  4. Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era.

    Science.gov (United States)

    Tao, Li; Clarke, Christina A; Rosenberg, Aaron S; Advani, Ranjana H; Jonas, Brian A; Flowers, Christopher R; Keegan, Theresa H M

    2017-07-01

    With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients. © 2017 John Wiley & Sons Ltd.

  5. Large Time Asymptotics for a Continuous Coagulation-Fragmentation Model with Degenerate Size-Dependent Diffusion

    KAUST Repository

    Desvillettes, Laurent; Fellner, Klemens

    2010-01-01

    We study a continuous coagulation-fragmentation model with constant kernels for reacting polymers (see [M. Aizenman and T. Bak, Comm. Math. Phys., 65 (1979), pp. 203-230]). The polymers are set to diffuse within a smooth bounded one

  6. Diffusion of hydrogen, hydrogen sulfide and large molecular weight anions in bentonite

    International Nuclear Information System (INIS)

    Eriksen, T.E.; Jacobsson, A.

    1982-01-01

    The diffusivities of HS - and H 2 have been determined from profile analysis and steady state transport experiments. The diffusivity of HS - was found to be 9x10 - 12 and 4x10xsec 1 in MX-80 and Erbsloeh bentonite respectively. The results are in fair agreement with the results earlier obtained for Cl - and I - . The H 2 diffusivity calculated from steady state transport was found to be surprisingly low (3.6x10 - 12 m 2 xsec - 1 ). Various heavy anions with molecular weights 290-30x10 3 were found to migrate through MX-80 bentonite with diffusivities in the range (2,1-0,75)x10 - 15 m 2 xsec - 1 . (Author)

  7. Spectrum of the isotropic diffuse gamma-ray emission derived from first-year Fermi Large Area Telescope data.

    Science.gov (United States)

    Abdo, A A; Ackermann, M; Ajello, M; Atwood, W B; Baldini, L; Ballet, J; Barbiellini, G; Bastieri, D; Baughman, B M; Bechtol, K; Bellazzini, R; Berenji, B; Blandford, R D; Bloom, E D; Bonamente, E; Borgland, A W; Bregeon, J; Brez, A; Brigida, M; Bruel, P; Burnett, T H; Buson, S; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Cavazzuti, E; Cecchi, C; Celik, O; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Cominsky, L R; Conrad, J; Cutini, S; Dermer, C D; de Angelis, A; de Palma, F; Digel, S W; Di Bernardo, G; do Couto e Silva, E; Drell, P S; Drlica-Wagner, A; Dubois, R; Dumora, D; Farnier, C; Favuzzi, C; Fegan, S J; Focke, W B; Fortin, P; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gaggero, D; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, T; Godfrey, G; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Gustafsson, M; Hanabata, Y; Harding, A K; Hayashida, M; Hughes, R E; Itoh, R; Jackson, M S; Jóhannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kataoka, J; Kawai, N; Kerr, M; Knödlseder, J; Kocian, M L; Kuehn, F; Kuss, M; Lande, J; Latronico, L; Lemoine-Goumard, M; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Madejski, G M; Makeev, A; Mazziotta, M N; McConville, W; McEnery, J E; Meurer, C; Michelson, P F; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nolan, P L; Norris, J P; Nuss, E; Ohsugi, T; Omodei, N; Orlando, E; Ormes, J F; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Pesce-Rollins, M; Piron, F; Porter, T A; Rainò, S; Rando, R; Razzano, M; Reimer, A; Reimer, O; Reposeur, T; Ritz, S; Rochester, L S; Rodriguez, A Y; Roth, M; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Scargle, J D; Sellerholm, A; Sgrò, C; Shaw, M S; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Starck, J-L; Strickman, M S; Strong, A W; Suson, D J; Tajima, H; Takahashi, H; Takahashi, T; Tanaka, T; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Tramacere, A; Uchiyama, Y; Usher, T L; Vasileiou, V; Vilchez, N; Vitale, V; Waite, A P; Wang, P; Winer, B L; Wood, K S; Ylinen, T; Ziegler, M

    2010-03-12

    We report on the first Fermi Large Area Telescope (LAT) measurements of the so-called "extragalactic" diffuse gamma-ray emission (EGB). This component of the diffuse gamma-ray emission is generally considered to have an isotropic or nearly isotropic distribution on the sky with diverse contributions discussed in the literature. The derivation of the EGB is based on detailed modeling of the bright foreground diffuse Galactic gamma-ray emission, the detected LAT sources, and the solar gamma-ray emission. We find the spectrum of the EGB is consistent with a power law with a differential spectral index gamma = 2.41 +/- 0.05 and intensity I(>100 MeV) = (1.03 +/- 0.17) x 10(-5) cm(-2) s(-1) sr(-1), where the error is systematics dominated. Our EGB spectrum is featureless, less intense, and softer than that derived from EGRET data.

  8. De Novo Nodal Diffuse Large B-Cell Lymphoma: Identification of Biologic Prognostic Factors

    International Nuclear Information System (INIS)

    Abd El-Hameed, A.

    2005-01-01

    Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients. making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t( 14; 18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. Material and Methods: A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formal infixed, paraffin-embedded sections were analyzed for: I) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR). and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. Bcl-2 gene rearrangement was detected in 8 cases (20%). 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (> I 0%) was expressed in 24 cases (60%), irrespective of the presence of t( 14; 18) translocation. The t( 14; 18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (ρ=0.008. and 0.04. respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (ρ=0.04, and 0.01, respectively). The t( 14; 18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the

  9. Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

    International Nuclear Information System (INIS)

    Griffiths, Robert; Gleeson, Michelle; Knopf, Kevin; Danese, Mark

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

  10. Large size self-assembled quantum rings: quantum size effect and modulation on the surface diffusion.

    Science.gov (United States)

    Tong, Cunzhu; Yoon, Soon Fatt; Wang, Lijun

    2012-09-24

    We demonstrate experimentally the submicron size self-assembled (SA) GaAs quantum rings (QRs) by quantum size effect (QSE). An ultrathin In0.1 Ga0.9As layer with different thickness is deposited on the GaAs to modulate the surface nucleus diffusion barrier, and then the SA QRs are grown. It is found that the density of QRs is affected significantly by the thickness of inserted In0.1 Ga0.9As, and the diffusion barrier modulation reflects mainly on the first five monolayer . The physical mechanism behind is discussed. The further analysis shows that about 160 meV decrease in diffusion barrier can be achieved, which allows the SA QRs with density of as low as one QR per 6 μm2. Finally, the QRs with diameters of 438 nm and outer diameters of 736 nm are fabricated using QSE.

  11. Creating large out-of-plane displacement electrothermal motion stage by incorporating beams with step features

    International Nuclear Information System (INIS)

    Kim, Yong-Sik; Dagalakis, Nicholas G; Gupta, Satyandra K

    2013-01-01

    Realizing out-of-plane actuation in micro-electro-mechanical systems (MEMS) is still a challenging task. In this paper, the design, fabrication methods and experimental results for a MEMS-based out-of-plane motion stage are presented based on bulk micromachining technologies. This stage is electrothermally actuated for out-of-plane motion by incorporating beams with step features. The fabricated motion stage has demonstrated displacements of 85 µm with 0.4 µm (mA) −1 rates and generated up to 11.8 mN forces with stiffness of 138.8 N m −1 . These properties obtained from the presented stage are comparable to those for in-plane motion stages, therefore making this out-of-plane stage useful when used in combination with in-plane motion stages. (paper)

  12. Design, development and characterization studies of a large aperture high power Nd : glass rod amplifier stage

    International Nuclear Information System (INIS)

    Gopi, N.; Bapna, R.C.; Murali, C.G.; Narayan, B.S.; Dhareshwar, L.J.

    1992-01-01

    Laser-plasma interaction studies and experiments related to laser driven shocks as well as laser induced inertially confined thermonuclear fusion have resulted in an ever increasing demand for high brightness lasers capable of producing nanosecond pulse with energy of hundreds of kilo joules. High power Nd-glass laser chains with a master oscillator followed by a number of amplifier stages made up of rods, disks, slabs etc. are in operation in many leading laboratories in the world. This report describes the design, development and characterisation studies of a large aperture Nd:glass laser amplifier which is to be incorporated on line with the existing 40 J, 5 ns high power laser chain built for laser-plasma interaction and laser driven shock wave studies in the Laser and Plasma Technology Division. The development work described in this report discusses the design based on optimum material selection, optimisation of various sub components, ease of maintenance and smooth operation. The necessary operational electronics has also been described. The characterization studies mainly include measurement of spatial gain uniformity, thermally induced depolarization effects, and thermal relaxation studies. (author). 37 refs., 14 figs., 5 tabs

  13. Two stage enucleation and deflation of a large unicystic ameloblastoma with mural invasion in mandible.

    Science.gov (United States)

    Sasaki, Ryo; Watanabe, Yorikatsu; Ando, Tomohiro; Akizuki, Tanetaka

    2014-06-01

    A treatment for strategy of unicystic ameloblastoma (UA) should be decided by its pathology type including luminal or mural type. Luminal type of UA can be treated only by enucleation alone, but UA with mural invasion should be treated aggressively like conventional ameloblastomas. However, it is difficult to diagnose the subtype of UA by an initial biopsy. There is a possibility that the lesion is an ordinary cyst or keratocystic odontogenic tumor, leading to a possible overtreatment. Therefore, this study performed the enucleation of the cyst wall and deflation at first, and the pathological finding confirmed mural invasion into the cystic wall, leading to the second surgery. The second surgery enucleated scar tissue, bone curettage, and deflation, and was able to contribute to the reduction of the recurrence rate by removing tumor nest in scar tissue or new bone, enhancing new bone formation, and shrinking the mandibular expanding by fenestration. In this study, a large UA with mural invasion including condyle was treated by "two-stage enucleation and deflation" in a 20-year-old patient.

  14. A large-scale RNA interference screen identifies genes that regulate autophagy at different stages.

    Science.gov (United States)

    Guo, Sujuan; Pridham, Kevin J; Virbasius, Ching-Man; He, Bin; Zhang, Liqing; Varmark, Hanne; Green, Michael R; Sheng, Zhi

    2018-02-12

    Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B. By coupling monodansylcadaverine staining with fluorescence-activated cell sorting, we successfully isolated autophagic K562 cells where we identified 336 short hairpin RNAs. After candidate validation using Cyto-ID fluorescence spectrophotometry, LC3B immunoblotting, and quantitative RT-PCR, 82 genes were identified as autophagy-regulating genes. 20 genes have been reported previously and the remaining 62 candidates are novel autophagy mediators. Bioinformatic analyses revealed that most candidate genes were involved in molecular pathways regulating autophagy, rather than directly participating in the autophagy process. Further autophagy flux assays revealed that 57 autophagy-regulating genes suppressed autophagy initiation, whereas 21 candidates promoted autophagy maturation. Our RNA interference screen identifies identified genes that regulate autophagy at different stages, which helps decode autophagy regulation in cancer and offers novel avenues to develop autophagy-related therapies for cancer.

  15. Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

    Science.gov (United States)

    Ni, Liangping; Liu, Ying

    2018-04-01

    The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( K trans ), flux rate constant between extravascular extracellular space and plasma ( K ep ), the volume of extravascular extracellular space per unit volume of tissue ( V e ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and K trans were analysed. The diagnostic accuracy of K trans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with K trans and negatively with ADC values. Additionally, tumour K trans negatively correlated with ADC value. The sensitivity and accuracy of combined K trans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that K trans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. K trans and ADC in combination were superior than either alone.

  16. The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses.

    Science.gov (United States)

    Kim, Soo Young; Choi, Yoon Young; An, Ji Yeong; Shin, Hyun Beak; Jo, Ara; Choi, Hyeji; Seo, Sang Hyuk; Bang, Hui-Jae; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon

    2015-08-15

    We previously reported that the prognosis of microsatellite instability high (MSI-H) gastric cancer is similar to that of MSI-low/microsatellite stable (MSI-L/MSS) gastric cancer. The reason for this seemed to be related to the effects of chemotherapy. To verify this hypothesis, we expanded the study population and reanalyzed the prognosis of MSI-H gastric cancer. Data from 1,276 patients with Stage II and III gastric cancer who underwent gastrectomy with curative intent between January 2005 and June 2010 were reviewed. The prognosis of MSI-H tumors in comparison with MSI-L/MSS tumors was analyzed, according to the administration of chemotherapy and other clinicopathologic features. A total of 361 (28.3%) patients did not receive chemotherapy (MSI-H = 47 and MSI-L/MSS = 314), whereas 915 (71.7%) patients did receive chemotherapy (MSI-H = 58 and MSI-L/MSS = 857). The hazard ratio of MSI-H versus MSI-L/MSS was 0.49 (95% confidence interval: 0.26-0.94, p = 0.031) when chemotherapy was not received and 1.16 (95% confidence interval: 0.78-1.71, p = 0.466) when chemotherapy was received. In subgroup analyses, the prognosis of MSI-H was better in Stage III, women, with lymph node metastasis, and undifferentiated histology subgroups when chemotherapy was not received. However, in patients treated with chemotherapy, prognosis was worse for MSI-H tumors in Stage III, undifferentiated histology, and diffuse type subgroups of gastric cancer. In conclusion, MSI-H tumors were associated with a good prognosis in Stage II and III gastric cancer when patients were treated by surgery alone, and the benefits of MSI-H status were attenuated by chemotherapy. © 2015 UICC.

  17. Discovery of small-scale-structure in the large molecule/dust distribution in the diffuse ISM

    Science.gov (United States)

    Cordiner, Martin A.; Fossey, Stephen J.; Sarre, Peter J.

    There is mounting evidence that far from being homogeneously distributed, interstellar matter can have a clumpy or filamentary structure on the scale of 10s to a few 1000s of AU and which is commonly described as small scale structure (SSS). Initially confined to VLBI HI observations and HI observations of high-velocity pulsars, evidence for SSS has also come indirectly from molecular radio studies of e.g. HCO+ and infrared absorption by H3+. Much of the recent data on SSS has been obtained through optical/UV detection of atomic and diatomic molecular lines. Is there small scale structure in the large molecule/dust distribution? While this question could in principle be explored by measuring differences in the interstellar extinction towards the components of binary stars, in practice this would be difficult. Rather we chose to investigate this by recording very high signal-to-noise spectra of diffuse interstellar absorption bands. Although the carriers remain unidentified, the diffuse bands are generally considered to be tracers of the large molecule/dust distribution and scale well with reddening. Using the Anglo-Australian Telescope we have made UCLES observations of pairs of stars with separations ranging between 500 and 30000 AU. The signal-to-noise achieved was up to 2000, thus allowing variations in central depth of less than a few tenths of a percent to be discernible. Striking differences in diffuse band strengths for closely spaced lines of sight are found showing clearly that there exists small-scale-structure in the large molecule/dust distribution. For example, in the Ophiuchus star-formation region the central depths for the λ6614 diffuse band towards the ρ Oph stars A, B, C and D/E all differ and range between 0.966 and 0.930. Further interesting behaviour is found when comparing the relative strengths of diffuse bands between closely parallel lines of sight. Taking again the ρ Oph group, for λ5797 the strengths follow the order DE > B > C > A

  18. Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

    Directory of Open Access Journals (Sweden)

    Paul M. Graham, DO

    2018-05-01

    Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

  19. Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    J. Dias Coelho

    2010-01-01

    Full Text Available Primary cutaneous follicle center lymphoma (PCFCL is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

  20. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

  1. Large animal model of functional tricuspid regurgitation in pacing induced end-stage heart failure.

    Science.gov (United States)

    Malinowski, Marcin; Proudfoot, Alistair G; Langholz, David; Eberhart, Lenora; Brown, Michael; Schubert, Hans; Wodarek, Jeremy; Timek, Tomasz A

    2017-06-01

    Functional tricuspid regurgitation (FTR) is common in patients with advanced heart failure and frequently complicates left ventricular assist device implantation yet remains poorly understood. We set out to establish large animal model of FTR that could serve as a research platform to investigate the pathogenesis of FTR associated with end-stage heart failure. : Through right thoracotomy, ten adult sheep underwent implantation of pacemaker with epicardial LV lead, five sonomicrometry crystals on the right ventricle, and left and right ventricular telemetry pressure sensors during a beating heart off-pump procedure. After 5 ± 1 days of recovery, baseline haemodynamic, echocardiographic and sonomicrometry data were collected. Animals were paced thereafter at a rate of 220-240 beats/min until the development of heart failure and concomitant tricuspid regurgitation. : Three animals died during early recovery period and one during the pacing phase. Six surviving animals were paced for a mean of 14 ± 5 days. Cardiac function was significantly depressed compared to baseline, with LV ejection fraction falling from 69 ± 2% to 22 ± 4% ( P  tricuspid annulus (from 29.5 ± 1.6 to 36.5 ± 4.5 mm; P  = 0.01) and right ventricle (from 21.9 ± 0.2 to 30.3 ± 0.6 mm; P  = 0.03). Sonomicrometry derived contractility of RV free wall was depressed and at least moderate tricuspid insufficiency developed in all animals. : Biventricular dysfunction, tricuspid annular dilatation and significant FTR were observed in our model of ovine tachycardia induced cardiomyopathy. This animal model reflects the clinical situation of end-stage heart failure patients presenting for mechanical support. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  2. Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kinowaki, Yuko; Kurata, Morito; Ishibashi, Sachiko; Ikeda, Masumi; Tatsuzawa, Anna; Yamamoto, Masahide; Miura, Osamu; Kitagawa, Masanobu; Yamamoto, Kouhei

    2018-02-20

    Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

  3. Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

    OpenAIRE

    Gromski, Mark A.; Peng, Jennifer L.; Zhou, Jiehao; Masuoka, Howard C.; Suvannasankha, Attaya; Liangpunsakul, Suthat

    2016-01-01

    Primary gastrointestinal (GI) lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL) who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endosco...

  4. Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

    International Nuclear Information System (INIS)

    Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

    2010-01-01

    A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

  5. A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma

    OpenAIRE

    Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

    2015-01-01

    Background Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. Case presentation A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3?months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinica...

  6. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

    OpenAIRE

    Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Link, Brian K.; Zou, Lihua

    2012-01-01

    To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include...

  7. Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

    Science.gov (United States)

    Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

    2011-05-01

    There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

  8. Adsorption and diffusion of Ru adatoms on Ru(0001)-supported graphene: Large-scale first-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yong; Evans, James W. [Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA and Ames Laboratory—U.S. Department of Energy, Iowa State University, Ames, Iowa 50011 (United States)

    2015-10-28

    Large-scale first-principles density functional theory calculations are performed to investigate the adsorption and diffusion of Ru adatoms on monolayer graphene (G) supported on Ru(0001). The G sheet exhibits a periodic moiré-cell superstructure due to lattice mismatch. Within a moiré cell, there are three distinct regions: fcc, hcp, and mound, in which the C{sub 6}-ring center is above a fcc site, a hcp site, and a surface Ru atom of Ru(0001), respectively. The adsorption energy of a Ru adatom is evaluated at specific sites in these distinct regions. We find the strongest binding at an adsorption site above a C atom in the fcc region, next strongest in the hcp region, then the fcc-hcp boundary (ridge) between these regions, and the weakest binding in the mound region. Behavior is similar to that observed from small-unit-cell calculations of Habenicht et al. [Top. Catal. 57, 69 (2014)], which differ from previous large-scale calculations. We determine the minimum-energy path for local diffusion near the center of the fcc region and obtain a local diffusion barrier of ∼0.48 eV. We also estimate a significantly lower local diffusion barrier in the ridge region. These barriers and information on the adsorption energy variation facilitate development of a realistic model for the global potential energy surface for Ru adatoms. This in turn enables simulation studies elucidating diffusion-mediated directed-assembly of Ru nanoclusters during deposition of Ru on G/Ru(0001)

  9. mTOR activity in AIDS-related diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Sara H Browne

    Full Text Available Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K, an extensively studied effector of mTOR Complex 1 (mTORC1 and the phosphorylated phosphatase and tensin homolog (pPTEN, a negative regulator of mTORC1 pathway.We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs supplied by the Aids and Cancer Specimen Resource (ACSR, the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD. The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40. The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features.The majority of the patients evaluated were males (88%; only two cases (1.6% were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group, and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group. We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001. The degree of intensity and percentage of cells positive for pPTEN was positively correlated with

  10. The ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) . I. Project description, survey sample, and quality assessment

    Science.gov (United States)

    Cox, Nick L. J.; Cami, Jan; Farhang, Amin; Smoker, Jonathan; Monreal-Ibero, Ana; Lallement, Rosine; Sarre, Peter J.; Marshall, Charlotte C. M.; Smith, Keith T.; Evans, Christopher J.; Royer, Pierre; Linnartz, Harold; Cordiner, Martin A.; Joblin, Christine; van Loon, Jacco Th.; Foing, Bernard H.; Bhatt, Neil H.; Bron, Emeric; Elyajouri, Meriem; de Koter, Alex; Ehrenfreund, Pascale; Javadi, Atefeh; Kaper, Lex; Khosroshadi, Habib G.; Laverick, Mike; Le Petit, Franck; Mulas, Giacomo; Roueff, Evelyne; Salama, Farid; Spaans, Marco

    2017-10-01

    The carriers of the diffuse interstellar bands (DIBs) are largely unidentified molecules ubiquitously present in the interstellar medium (ISM). After decades of study, two strong and possibly three weak near-infrared DIBs have recently been attributed to the C60^+ fullerene based on observational and laboratory measurements. There is great promise for the identification of the over 400 other known DIBs, as this result could provide chemical hints towards other possible carriers. In an effort tosystematically study the properties of the DIB carriers, we have initiated a new large-scale observational survey: the ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES). The main objective is to build on and extend existing DIB surveys to make a major step forward in characterising the physical and chemical conditions for a statistically significant sample of interstellar lines-of-sight, with the goal to reverse-engineer key molecular properties of the DIB carriers. EDIBLES is a filler Large Programme using the Ultraviolet and Visual Echelle Spectrograph at the Very Large Telescope at Paranal, Chile. It is designed to provide an observationally unbiased view of the presence and behaviour of the DIBs towards early-spectral-type stars whose lines-of-sight probe the diffuse-to-translucent ISM. Such a complete dataset will provide a deep census of the atomic and molecular content, physical conditions, chemical abundances and elemental depletion levels for each sightline. Achieving these goals requires a homogeneous set of high-quality data in terms of resolution (R 70 000-100 000), sensitivity (S/N up to 1000 per resolution element), and spectral coverage (305-1042 nm), as well as a large sample size (100+ sightlines). In this first paper the goals, objectives and methodology of the EDIBLES programme are described and an initial assessment of the data is provided.

  11. Using collaborative two-stage examinations to address test anxiety in a large enrollment gateway course.

    Science.gov (United States)

    Fournier, Kimberly A; Couret, Jannelle; Ramsay, Jason B; Caulkins, Joshua L

    2017-09-01

    Large enrollment foundational courses are perceived as "high stakes" because of their potential to act as barriers for progression to the next course or admittance to a program. The nature of gateway courses makes them ideal settings to explore the relationship between anxiety, pedagogical interventions, and student performance. Here, two-stage collaborative examinations were implemented to improve test-taking skills and address widespread test anxiety in an introductory human anatomy course. Test anxiety data were collected (using the Motivated Strategies for Learning Questionnaire) before the first examination and last examination. Most students experienced decreased test anxiety over the course of the semester; however, some students may have experienced performance limiting conditions due to test anxiety at the end of the semester based on academic ability in the course (in "C" students when compared to "A" students: P < 0.00006 and "B" students: P < 0.05), overall academic ability (in academically weaker students: P < 0.025), and demographic factors (in women: P < 0.025). The strongest performances on examinations were primarily observed in already academically strong students (mean individual performance: P < 0.000, mean group performance: P < 0.000). Furthermore, changes in test anxiety were not significantly associated with the group portion of the examinations. Patterns of changes in test anxiety over the course of the semester underscore a complex interaction between test anxiety, student background, and student performance. Results suggest that pathways for test anxiety in "high stakes" courses may be separate from the mechanisms responsible for the benefits of collaborative testing. Anat Sci Educ 10: 409-422. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

  12. Entanglement is a costly life-history stage in large whales.

    Science.gov (United States)

    van der Hoop, Julie; Corkeron, Peter; Moore, Michael

    2017-01-01

    Individuals store energy to balance deficits in natural cycles; however, unnatural events can also lead to unbalanced energy budgets. Entanglement in fishing gear is one example of an unnatural but relatively common circumstance that imposes energetic demands of a similar order of magnitude and duration of life-history events such as migration and pregnancy in large whales. We present two complementary bioenergetic approaches to estimate the energy associated with entanglement in North Atlantic right whales, and compare these estimates to the natural energetic life history of individual whales. Differences in measured blubber thicknesses and estimated blubber volumes between normal and entangled, emaciated whales indicate between 7.4 × 10 10  J and 1.2 × 10 11  J of energy are consumed during the course to death of a lethal entanglement. Increased thrust power requirements to overcome drag forces suggest that when entangled, whales require 3.95 × 10 9 to 4.08 × 10 10  J more energy to swim. Individuals who died from their entanglements performed significantly more work (energy expenditure × time) than those that survived; entanglement duration is therefore critical in determining whales' survival. Significant sublethal energetic impacts also occur, especially in reproductive females. Drag from fishing gear contributes up to 8% of the 4-year female reproductive energy budget, delaying time of energetic equilibrium (to restore energy lost by a particular entanglement) for reproduction by months to years. In certain populations, chronic entanglement in fishing gear can be viewed as a costly unnatural life-history stage, rather than a rare or short-term incident.

  13. Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

    Energy Technology Data Exchange (ETDEWEB)

    Dhakal, Sughosh; Bates, James E. [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Casulo, Carla; Friedberg, Jonathan W.; Becker, Michael W.; Liesveld, Jane L. [Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States)

    2016-10-01

    Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

  14. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  15. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

    Directory of Open Access Journals (Sweden)

    González-Satué Carlos

    2012-01-01

    Full Text Available Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images.

  16. destiny: diffusion maps for large-scale single-cell data in R.

    Science.gov (United States)

    Angerer, Philipp; Haghverdi, Laleh; Büttner, Maren; Theis, Fabian J; Marr, Carsten; Buettner, Florian

    2016-04-15

    : Diffusion maps are a spectral method for non-linear dimension reduction and have recently been adapted for the visualization of single-cell expression data. Here we present destiny, an efficient R implementation of the diffusion map algorithm. Our package includes a single-cell specific noise model allowing for missing and censored values. In contrast to previous implementations, we further present an efficient nearest-neighbour approximation that allows for the processing of hundreds of thousands of cells and a functionality for projecting new data on existing diffusion maps. We exemplarily apply destiny to a recent time-resolved mass cytometry dataset of cellular reprogramming. destiny is an open-source R/Bioconductor package "bioconductor.org/packages/destiny" also available at www.helmholtz-muenchen.de/icb/destiny A detailed vignette describing functions and workflows is provided with the package. carsten.marr@helmholtz-muenchen.de or f.buettner@helmholtz-muenchen.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Combined effects of multiple large-scale hydraulic engineering on water stages in the middle Yangtze River

    Science.gov (United States)

    Han, Jianqiao; Sun, Zhaohua; Li, Yitian; Yang, Yunping

    2017-12-01

    influence was observed at Hankou owing to its remote location and the short impoundment time of the TGD. (4) Potentially detrimental decreases in low-flow stages and increases in flood stages should be monitored and managed in the future. Our results are of practical significance for river management and the evaluation of the influences of large-scale anthropogenic activities on the hydrological regimes of large rivers.

  18. From gas dynamics with large friction to gradient flows describing diffusion theories

    KAUST Repository

    Lattanzio, Corrado

    2016-12-09

    We study the emergence of gradient flows in Wasserstein distance as high friction limits of an abstract Euler flow generated by an energy functional. We develop a relative energy calculation that connects the Euler flow to the gradient flow in the diffusive limit regime. We apply this approach to prove convergence from the Euler-Poisson system with friction to the Keller-Segel system in the regime that the latter has smooth solutions. The same methodology is used to establish convergence from the Euler-Korteweg theory with monotone pressure laws to the Cahn-Hilliard equation.

  19. From gas dynamics with large friction to gradient flows describing diffusion theories

    KAUST Repository

    Lattanzio, Corrado; Tzavaras, Athanasios

    2016-01-01

    We study the emergence of gradient flows in Wasserstein distance as high friction limits of an abstract Euler flow generated by an energy functional. We develop a relative energy calculation that connects the Euler flow to the gradient flow in the diffusive limit regime. We apply this approach to prove convergence from the Euler-Poisson system with friction to the Keller-Segel system in the regime that the latter has smooth solutions. The same methodology is used to establish convergence from the Euler-Korteweg theory with monotone pressure laws to the Cahn-Hilliard equation.

  20. Prospective study of bone metastasis from prostate cancer: comparison between large field diffusion-weighted imaging and bone scintigraphy

    International Nuclear Information System (INIS)

    Wang Xiaoying; Zhang Chunyan; Jiang Xuexiang

    2009-01-01

    Objective: To evaluate the large field diffusion weighted imaging (DWI) (from head vertex to lower leg) in detection of bone metastases from prostate cancer. Methods: One hundred and sixty- six consecutive patients who were suspected of prostate cancer received pelvic MRI and large field diffusion weighted imaging examination. Forty-nine of them underwent bone scintigraphy within one month of the examination of large field DWI. The images were double-blindly evaluated without the knowledge of the pathology result. Conventional MR T 1 and fat saturation T 2 weighted images were taken as standard for the diagnosis of bone metastasis. The sensitivity, specificity, and area under curve between large field DWI and bone scintigraphy were compared with McNemar test. Five patients with bone metastases exceeding 10 per patient were excluded in the lesion-by-lesion analysis. Results: Ten of the 49 patients were diagnosed as bone metastases. The diagnosis of bone metastasis were made in 15 patients by large field DWI and in 17 patients by bone scintigraphy. With patient number as study units (n=49), the diagnostic sensitivity of bone metastases with large field DWI and bone metastases were both 100% (10/10), and specificity were 87.2% (34/39) vs. 82.1% (32/39), respectively. ROC study showed the area under curve (AUC) of large field DWI and bone scintigraphy were 0.936 vs. 0.910, respectively. Totally 68 abnormal foci were identified from large field DWI and/or bone scintigraphy in 44 patients (while 5 patients with bone metastases exceeding 10 foci per patient were excluded), 20 of them were diagnosed as foci of bone metastasis. The diagnosis of bone metastases was made in 23 foci by large field DWI and in 34 by bone scintigraphy. With lesion numbers as study units (n=68), the diagnostic sensitivity of large field DWI and bone scintigraphy were both 90.0% (18/20), and specificity were 89.6% (43/48) vs. 66.7% (32/48), respectively. ROC study showed the area under curve of

  1. Effectiveness of diffusion tensor imaging in differentiating early-stage subcortical ischemic vascular disease, Alzheimer's disease and normal ageing.

    Directory of Open Access Journals (Sweden)

    Min-Chien Tu

    Full Text Available To describe and compare diffusion tensor imaging (DTI parameters between patients with subcortical ischemic vascular disease (SIVD and Alzheimer's disease (AD diagnosed using structuralized neuropsychiatric assessments, and investigate potential neuronal substrates related to cognitive performance.Thirty-five patients with SIVD, 40 patients with AD, and 33 cognitively normal control (NC subjects matched by age and education level were consecutively recruited and underwent cognitive function assessments and DTI examinations. Comparisons among these three subgroups with regards to cognitive performance and DTI parameters including fractional anisotropy (FA and mean diffusivity (MD values were performed. Partial correlation analysis after controlling for age and education was used to evaluate associations between cognitive performance and DTI parameters.With regards to cognitive performance, the patients with SIVD had lower total scores in frontal assessment battery (FAB compared to those with AD (p < 0.05 in the context of comparable Mini-Mental Status Examination and Cognitive Abilities Screening Instrument scores. With regards to DTI parameters, there were more regions of significant differences in FA among these three subgroups compared with MD. Compared with NC group, the patients with SIVD had significant global reductions in FA (p < 0.001 ~ 0.05, while significant reductions in FA among the patients with AD were regionally confined within the left superior longitudinal fasciculus, genu and splenium of the corpus callosum, and bilateral forceps major, and the anterior thalamic radiation, uncinate fasciculus, and cingulum of the left side (p < 0.01 ~ 0.05. Analysis of FA values within the left forceps major, left anterior thalamic radiation, and genu of the corpus callosum revealed a 71.8% overall correct classification (p < 0.001 with sensitivity of 69.4%, specificity of 73.8%, positive predictive value of 69.4%, and negative predictive value

  2. An Adaptive Large Neighborhood Search-based Three-Stage Matheuristic for the Vehicle Routing Problem with Time Windows

    DEFF Research Database (Denmark)

    Christensen, Jonas Mark; Røpke, Stefan

    that serves all the customers. The second stage usesan Adaptive Large Neighborhood Search (ALNS) algorithm to minimise the travel distance, during the second phase all of the generated routes are considered by solving a set cover problem. The ALNS algorithm uses 4 destroy operators, 2 repair operators...

  3. Late-stage alpha-synuclein accumulation in TNWT-61 mouse model of Parkinson's disease detected by diffusion kurtosis imaging

    Czech Academy of Sciences Publication Activity Database

    Khairnar, A.; Rudá-Kučerová, J.; Dražanová, Eva; Szabó, N.; Latta, P.; Arab, A.; Hutter-Paier, B.; Havas, D.; Windisch, M.; Šulcová, A.; Starčuk jr., Zenon; Király, A.; Rektorová, I.

    2016-01-01

    Roč. 136, č. 6 (2016), s. 1259-1269 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : diffusion kurtosis imaging * diffusion kurtosis imaging * Parkinson's disease * TBSS * TNWT-61 * transgenic mice Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 4.083, year: 2016

  4. Maple syrup urine disease encephalopathy: a follow-up study in the acute stage using diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Ha, Jong Su; Kim, Taik-Kun; Lee, Ki Yeol; Seol, Hae Young; Cha, Sang Hoon; Eun, Baik-Lin; Lee, Hee Sun

    2004-01-01

    Neonatal maple syrup urine disease (MSUD) is associated with diffuse oedema and characteristic MSUD oedema. We present a newborn infant with two coexisting different types of oedema. The myelinated white matter showed a marked decrease in the water apparent diffusion coefficient (ADC) compatible with cytotoxic oedema. The unmyelinated white matter showed an increase in ADC, consistent with vasogenic-interstitial oedema. On follow-up studies, the cytotoxic oedema showed improvement, but the vasogenic-interstitial oedema progressed into brain atrophy. (orig.)

  5. A thermodynamically consistent model of magneto-elastic materials under diffusion at large strains and its analysis

    Science.gov (United States)

    Roubíček, Tomáš; Tomassetti, Giuseppe

    2018-06-01

    A theory of elastic magnets is formulated under possible diffusion and heat flow governed by Fick's and Fourier's laws in the deformed (Eulerian) configuration, respectively. The concepts of nonlocal nonsimple materials and viscous Cahn-Hilliard equations are used. The formulation of the problem uses Lagrangian (reference) configuration while the transport processes are pulled back. Except the static problem, the demagnetizing energy is ignored and only local non-self-penetration is considered. The analysis as far as existence of weak solutions of the (thermo) dynamical problem is performed by a careful regularization and approximation by a Galerkin method, suggesting also a numerical strategy. Either ignoring or combining particular aspects, the model has numerous applications as ferro-to-paramagnetic transformation in elastic ferromagnets, diffusion of solvents in polymers possibly accompanied by magnetic effects (magnetic gels), or metal-hydride phase transformation in some intermetallics under diffusion of hydrogen accompanied possibly by magnetic effects (and in particular ferro-to-antiferromagnetic phase transformation), all in the full thermodynamical context under large strains.

  6. Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

    International Nuclear Information System (INIS)

    Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

    2013-01-01

    Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

  7. Cryopreservation of third-stage larvae of Strongylus vulgaris (large strongyle of horses).

    Science.gov (United States)

    Titoy, G A; Van Rensburg, L J

    1997-06-01

    A technique for the cryopreservation of third-stage larvae of Strongylus vulgaris is described. Infective larvae of S. vulgaris were exsheathed in a 0.16% sodium hypochlorite solution and then transferred into cryotubes containing 0.09% saline. The samples were stored in the gas phase of liquid nitrogen.

  8. Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

    Science.gov (United States)

    Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

    2017-09-18

    Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

  9. Large Cancer Drug Trial Helps Move Precision Medicine Toward the Mainstream | FNLCR Staging

    Science.gov (United States)

    A landmark cancer drug trial is helping set the stage for moving precision medicine into the mainstream of clinical practice, according to a new study. The study, reported in the Journal of Molecular Diagnostics, validates a procedure used in the dru

  10. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

    DEFF Research Database (Denmark)

    Gang, Anne O.; Pedersen, Michael; d'Amore, Francesco

    2015-01-01

    The introduction of rituximab and generally improved health among elderly patients have increased the survival of patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) from 1992 is based on pre-rituximab data from clinical trials including several lymphoma ...... dehydrogenase (LDH), stage and albumin level, and (2) a separate age-adjusted DLBCL-PI for patients 1 extranodal lesion, however excluding stage....... subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...... lesion. The optimal age cut-off was 70 years. In a MVA of albumin, lymphocyte count, sex, immunoglobulin G, bulky disease, hemoglobin and B-symptoms, only albumin was prognostic. We propose: (1) a modified DLBCL prognostic index (DLBCL-PI) including: age (70 years), performance status (PS), lactate...

  11. Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

    Science.gov (United States)

    Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

    2014-06-01

    The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

  12. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-01-25

    B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  13. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Karin E Smedby

    2011-04-01

    Full Text Available Non-Hodgkin lymphoma (NHL represents a diverse group of hematological malignancies, of which follicular lymphoma (FL is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined  = 0.64, P(combined  = 2 × 10(-21 located 962 bp away from rs10484561 (r(2<0.1 in controls. After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted  = 0.70, P(adjusted  =  4 × 10(-12; rs10484561:OR(adjusted  = 1.64, P(adjusted  = 5 × 10(-15. Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined  = 1.36, P(combined  =  1.4 × 10(-7. Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

  14. Routine imaging for diffuse large B-cell lymphoma in first remission is not associated with better survival

    DEFF Research Database (Denmark)

    El-Galaly, Tarec; Jakobsen, Lasse Hjort; Hutchings, Martin

    2015-01-01

    Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients-two neighbour......Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients...... are fully publicly funded. Follow-up (FU) for Swedish patients included symptom assessment, clinical examinations, and blood tests with 3-month intervals for 2 years and with longer intervals later in follow-up. Imaging was only performed in response to suspected relapse. FU for Danish patients...... was equivalent but included additional routine surveillance imaging (usually half-yearly CT for 2 years as a minimum). Clinico-pathological features were retrieved from the national lymphoma registries, and vital status was updated using the civil registries. OS was defined as the time from end of treatment...

  15. Terahertz Conductivity within Colloidal CsPbBr3 Perovskite Nanocrystals: Remarkably High Carrier Mobilities and Large Diffusion Lengths.

    Science.gov (United States)

    Yettapu, Gurivi Reddy; Talukdar, Debnath; Sarkar, Sohini; Swarnkar, Abhishek; Nag, Angshuman; Ghosh, Prasenjit; Mandal, Pankaj

    2016-08-10

    Colloidal CsPbBr3 perovskite nanocrystals (NCs) have emerged as an excellent light emitting material in last one year. Using time domain and time-resolved THz spectroscopy and density functional theory based calculations, we establish 3-fold free carrier recombination mechanism, namely, nonradiative Auger, bimolecular electron-hole recombination, and inefficient trap-assisted recombination in 11 nm sized colloidal CsPbBr3 NCs. Our results confirm a negligible influence of surface defects in trapping charge carriers, which in turn results into desirable intrinsic transport properties, from the perspective of device applications, such as remarkably high carrier mobility (∼4500 cm(2) V(-1) s(-1)), large diffusion length (>9.2 μm), and high luminescence quantum yield (80%). Despite being solution processed and possessing a large surface to volume ratio, this combination of high carrier mobility and diffusion length, along with nearly ideal photoluminescence quantum yield, is unique compared to any other colloidal quantum dot system.

  16. Intravascular Large B-Cell Lymphoma Presenting with Diffuse Gallbladder Wall Thickening: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sayf Al-Katib

    2018-01-01

    Full Text Available Intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse B-cell lymphoma characterized by proliferation of neoplastic cells within the lumen of small and medium sized vessels. Clinical and imaging findings are nebulous as the intravascular subtype of lymphoma can involve a multitude of organs. Involvement of the gallbladder is extremely uncommon, and imaging findings can be easily confused for more prevalent pathologies. We report a case of intravascular large B-cell lymphoma in an 83-year-old male and review clinical presentation and imaging findings on CT, ultrasound, hepatobiliary iminodiacetic acid (HIDA scan, and MRI. It is important for the radiologist to know about this disease as the imaging findings are atypical of other types of lymphoma, and this may lead to a delay in diagnosis and treatment.

  17. Accelerating inference for diffusions observed with measurement error and large sample sizes using approximate Bayesian computation

    DEFF Research Database (Denmark)

    Picchini, Umberto; Forman, Julie Lyng

    2016-01-01

    a nonlinear stochastic differential equation model observed with correlated measurement errors and an application to protein folding modelling. An approximate Bayesian computation (ABC)-MCMC algorithm is suggested to allow inference for model parameters within reasonable time constraints. The ABC algorithm......In recent years, dynamical modelling has been provided with a range of breakthrough methods to perform exact Bayesian inference. However, it is often computationally unfeasible to apply exact statistical methodologies in the context of large data sets and complex models. This paper considers...... applications. A simulation study is conducted to compare our strategy with exact Bayesian inference, the latter resulting two orders of magnitude slower than ABC-MCMC for the considered set-up. Finally, the ABC algorithm is applied to a large size protein data. The suggested methodology is fairly general...

  18. Primary Diffuse Large B-cell Lymphoma of the Uterus Manifesting as a Leiomyoma: A Unique Presentation with Review of Literature

    Directory of Open Access Journals (Sweden)

    Rajan Dewar

    2013-01-01

    Full Text Available We report a primary diffuse large B-cell lymphoma of uterine corpus in a 70-years old woman who presented with symptoms of increased urinary frequency and sense of bloating. Magnetic Resonance Imaging (MRI findings were suggestive of a degenerating intramural fibroid. Histological examination of tissue samples obtained during hysteroscopy showed diffuse infiltration of fibrous stroma by atypical enlarged mononuclear cells. Immunohistochemical studies were consistent with the diagnosis of diffuse large B-cell lymphoma.Further imaging studies showed no evidence of lymphoma outside the uterus. To our knowledge,this represents the first welldocumented case of primary uterine lymphoma presenting as a leiomyoma on imaging studies.

  19. Prediction of temperature and thermal inertia effect in the maturation stage and stockpiling of a large composting mass

    OpenAIRE

    Barrena Gómez, Raquel

    2006-01-01

    A macroscopic non-steady state energy balance was developed and solved for a composting pile of source-selected organic fraction of municipal solid waste during the maturation stage (13,500 kg of compost). Simulated temperature profiles correlated well with temperature experimental data (ranging from 50 to 70 °C) obtained during the maturation process for more than 50 days at full scale. Thermal inertia effect usually found in composting plants and associated to the stockpiling of large compo...

  20. CT and MRI findings of Creutzfeldt-Jakob disease in the early stage. The usefulness of diffusion-weighted images

    International Nuclear Information System (INIS)

    Ukisu, Ryutaro; Kushihashi, Tamio; Gokan, Takehiko

    2001-01-01

    To detect subtle CT and MRI features of Creutzfeldt-Jacob disease (CJD) in the early stage is important to prevent a human-to-human transmission. This study included 10 patients of CJD who underwent CT and/or MRI in its early stage. CT, T1- and T2-weighted MRI, DWI, and FLAIR images were obtained in 10, 6, 4, and 2 patients respectively. On DWI, abnormal hyperintensities were observed in both cerebral cortex, and in basal ganglia in all patients. On FLAIR images, abnormal hyperintensies were observed in one patient. Detection of abnormal intensities may be possible in the early stage of CJD using MRI, particularly with DWI. (author)

  1. CT and MRI findings of Creutzfeldt-Jakob disease in the early stage. The usefulness of diffusion-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Ukisu, Ryutaro; Kushihashi, Tamio; Gokan, Takehiko [Showa Univ., Tokyo (Japan). School of Medicine] [and others

    2001-02-01

    To detect subtle CT and MRI features of Creutzfeldt-Jacob disease (CJD) in the early stage is important to prevent a human-to-human transmission. This study included 10 patients of CJD who underwent CT and/or MRI in its early stage. CT, T1- and T2-weighted MRI, DWI, and FLAIR images were obtained in 10, 6, 4, and 2 patients respectively. On DWI, abnormal hyperintensities were observed in both cerebral cortex, and in basal ganglia in all patients. On FLAIR images, abnormal hyperintensies were observed in one patient. Detection of abnormal intensities may be possible in the early stage of CJD using MRI, particularly with DWI. (author)

  2. Small larvae in large rivers: observations on downstream movement of European grayling Thymallus thymallus during early life stages.

    Science.gov (United States)

    Van Leeuwen, C H A; Dokk, T; Haugen, T O; Kiffney, P M; Museth, J

    2017-06-01

    Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages. © 2017 The Fisheries Society of the British Isles.

  3. Large fluctuations of the macroscopic current in diffusive systems: a numerical test of the additivity principle.

    Science.gov (United States)

    Hurtado, Pablo I; Garrido, Pedro L

    2010-04-01

    Most systems, when pushed out of equilibrium, respond by building up currents of locally conserved observables. Understanding how microscopic dynamics determines the averages and fluctuations of these currents is one of the main open problems in nonequilibrium statistical physics. The additivity principle is a theoretical proposal that allows to compute the current distribution in many one-dimensional nonequilibrium systems. Using simulations, we validate this conjecture in a simple and general model of energy transport, both in the presence of a temperature gradient and in canonical equilibrium. In particular, we show that the current distribution displays a Gaussian regime for small current fluctuations, as prescribed by the central limit theorem, and non-Gaussian (exponential) tails for large current deviations, obeying in all cases the Gallavotti-Cohen fluctuation theorem. In order to facilitate a given current fluctuation, the system adopts a well-defined temperature profile different from that of the steady state and in accordance with the additivity hypothesis predictions. System statistics during a large current fluctuation is independent of the sign of the current, which implies that the optimal profile (as well as higher-order profiles and spatial correlations) are invariant upon current inversion. We also demonstrate that finite-time joint fluctuations of the current and the profile are well described by the additivity functional. These results suggest the additivity hypothesis as a general and powerful tool to compute current distributions in many nonequilibrium systems.

  4. Implementation of Exhaust Gas Recirculation for Double Stage Waste Heat Recovery System on Large Container Vessel

    DEFF Research Database (Denmark)

    Andreasen, Morten; Marissal, Matthieu; Sørensen, Kim

    2014-01-01

    Concerned to push ships to have a lower impact on the environment, the International Maritime Organization are implementing stricter regulation of NOx and SOx emissions, called Tier III, within emission control areas (ECAs). Waste Heat Recovery Systems (WHRS) on container ships consist...... of recovering some of the waste heat from the exhaust gas. This heat is converted into electrical energy used on-board instead of using auxiliary engines. Exhaust Gas Recirculation (EGR) systems, are recirculating a part of the exhaust gas through the engine combustion chamber to reduce emissions. WHRS combined...... with EGR is a potential way to improve system efficiency while reducing emissions. This paper investigates the feasibility of combining the two systems. EGR dilutes the fuel, lowering the combustion temperature and thereby the formation of NOx, to reach Tier III limitation. A double stage WHRS is set up...

  5. CD3+/CD16+CD56+ cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Anna Twardosz

    2011-04-01

    Full Text Available Diffuse large B-cell lymphoma is the commonest histological type of malignant lymphoma, andremains incurable in many cases. Developing more efficient immunotherapy strategies will require betterunderstanding of the disorders of immune responses in cancer patients. NKT (natural killer-like T cells wereoriginally described as a unique population of T cells with the co-expression of NK cell markers. Apart fromtheir role in protecting against microbial pathogens and controlling autoimmune diseases, NKT cells havebeen recently revealed as one of the key players in the immune responses against tumors. The objective of thisstudy was to evaluate the frequency of CD3+/CD16+CD56+ cells in the peripheral blood of 28 diffuse largeB-cell lymphoma (DLBCL patients in correlation with clinical and laboratory parameters. Median percentagesof CD3+/CD16+CD56+ were significantly lower in patients with DLBCL compared to healthy donors(7.37% vs. 9.01%, p = 0.01; 4.60% vs. 5.81%, p = 0.03, although there were no differences in absolute counts.The frequency and the absolute numbers of CD3+/CD16+CD56+ cells were lower in advanced clinical stagesthan in earlier ones. The median percentage of CD3+/CD16+CD56+ cells in patients in Ann Arbor stages 1–2 was5.55% vs. 3.15% in stages 3–4 (p = 0.02, with median absolute counts respectively 0.26 G/L vs. 0.41 G/L (p == 0.02. The percentage and absolute numbers of CD3+/CD16+CD56+ cells were significantly higher in DL-BCL patients without B-symptoms compared to the patients with B-symptoms, (5.51% vs. 2.46%, p = 0.04;0.21 G/L vs. 0.44 G/L, p = 0.04. The percentage of CD3+/CD16+CD56+ cells correlated adversely with serumlactate dehydrogenase (R= –445; p < 0.05 which might influence NKT count. These figures suggest a relationshipbetween higher tumor burden and more aggressive disease and decreased NKT numbers. But it remains tobe explained whether low NKT cell counts in the peripheral blood of patients with DLBCL are the result

  6. Comparison of PET-CT and magnetic resonance diffusion weighted imaging with body suppression (DWIBS) for initial staging of malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Stéphane, Velasco, E-mail: stephane.velasco@chu-poitiers.fr [Department of Radiology, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Samuel, Burg, E-mail: s.burg@chu-poitiers.fr [Department of Nuclear Medicine, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Department of Nuclear Medicine, Saint-Louis Hospital, Paris CHU Saint Louis, 40 rue de Bichat, 75 010 Paris (France); Vincent, Delwail, E-mail: v.delwail@chu-poitiers.fr [Department of Hematology, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Joelle, Guilhot, E-mail: j.guilhot@chu-poitiers.fr [Department of Hematology, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Remy, Perdrisot, E-mail: r.perdrisot@chu-poitiers.fr [Department of Nuclear Medicine, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Francois, Guilhot Gaudeffroy, E-mail: f.guilhot-gaudeffroy@chu-poitiers.fr [Department of Hematology, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France); Jean-Pierre, Tasu, E-mail: j.p.tasu@chu-poitiers.fr [Department of Radiology, CHU de Poitiers, rue de la milétrie, 86000 Poitiers (France)

    2013-11-01

    Objective: To evaluate the clinical impact of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in staging of malignant lymphoma. Methods: Twenty-three patients with proven malignant lymphomas were prospectively enrolled. DWIBS (b = 0, 1000 s/mm{sup 2}) examinations and PET-CT were performed respectively on an Intera 1.5 T unit and a Gyroscan PET-CT scan (Philips Medical system, Best, the Netherland). The criteria for positive node involvement were a size over 10 mm or an apparent diffusion coefficient (ADC) value under 0.75 10{sup −3} mm{sup 2}/s for nodes under 10 mm. For extranodal analysis, a high or heterogeneous signal on DWIBS was considered as positive. In cases of discordance, the reference standard for each region or organ was established at 6 months after the diagnosis according to all available clinical, biological information, as well as histological evidence or follow-up to prove or disprove the presence of disease. Results: DWIBS and PET-CT results were congruent in 333 node regions on the 345 areas analyzed, with excellent agreement (κ = 0.97, P < 0.0001). From 433 organs analyzed (one patient had splenectomy) extranodal disease was detected in 22 organs on DWIBS. The two imaging techniques agreed on 430 organs (κ = 0.99, P < 0.0001). Finally, Ann Arbor stages based on DWIBS and those of PET/CT were in agreement for 23 patients. Conclusions: For malignant lymphoma in a pre-therapeutic context, agreement between diffusion-weighted whole-body imaging and PET/CT is high for Ann Arbor staging.

  7. Comparison of PET-CT and magnetic resonance diffusion weighted imaging with body suppression (DWIBS) for initial staging of malignant lymphomas

    International Nuclear Information System (INIS)

    Stéphane, Velasco; Samuel, Burg; Vincent, Delwail; Joelle, Guilhot; Remy, Perdrisot; Francois, Guilhot Gaudeffroy; Jean-Pierre, Tasu

    2013-01-01

    Objective: To evaluate the clinical impact of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in staging of malignant lymphoma. Methods: Twenty-three patients with proven malignant lymphomas were prospectively enrolled. DWIBS (b = 0, 1000 s/mm 2 ) examinations and PET-CT were performed respectively on an Intera 1.5 T unit and a Gyroscan PET-CT scan (Philips Medical system, Best, the Netherland). The criteria for positive node involvement were a size over 10 mm or an apparent diffusion coefficient (ADC) value under 0.75 10 −3 mm 2 /s for nodes under 10 mm. For extranodal analysis, a high or heterogeneous signal on DWIBS was considered as positive. In cases of discordance, the reference standard for each region or organ was established at 6 months after the diagnosis according to all available clinical, biological information, as well as histological evidence or follow-up to prove or disprove the presence of disease. Results: DWIBS and PET-CT results were congruent in 333 node regions on the 345 areas analyzed, with excellent agreement (κ = 0.97, P < 0.0001). From 433 organs analyzed (one patient had splenectomy) extranodal disease was detected in 22 organs on DWIBS. The two imaging techniques agreed on 430 organs (κ = 0.99, P < 0.0001). Finally, Ann Arbor stages based on DWIBS and those of PET/CT were in agreement for 23 patients. Conclusions: For malignant lymphoma in a pre-therapeutic context, agreement between diffusion-weighted whole-body imaging and PET/CT is high for Ann Arbor staging

  8. Large-scale fluctuations in the diffusive decomposition of solid solutions

    International Nuclear Information System (INIS)

    Karpov, V.G.; Grimsditch, M.

    1995-01-01

    The concept of an instability in the classic Ostwald ripening theory with respect to compositional fluctuations is suggested. We show that small statistical fluctuations in the precipitate phase lead to gigantic Coulomb-like fluctuations in the solute concentration which in turn affect the ripening. As a result large-scale fluctuations in both the precipitate and solute concentrations appear. These fluctuations are characterized by amplitudes of the order of the average values of the corresponding quantities and by a space scale L∼(na) -1/2 which is considerably greater than both the average nuclear radius and internuclear distance. The Lifshitz-Slyozov theory of ripening is shown to remain locally applicable, over length scales much less than L. The implications of these findings for elastic light scattering in solid solutions that have undergone Ostwald ripening are considered

  9. Large-scale fluctuations in the diffusive decomposition of solid solutions

    Science.gov (United States)

    Karpov, V. G.; Grimsditch, M.

    1995-04-01

    The concept of an instability in the classic Ostwald ripening theory with respect to compositional fluctuations is suggested. We show that small statistical fluctuations in the precipitate phase lead to gigantic Coulomb-like fluctuations in the solute concentration which in turn affect the ripening. As a result large-scale fluctuations in both the precipitate and solute concentrations appear. These fluctuations are characterized by amplitudes of the order of the average values of the corresponding quantities and by a space scale L~(na)-1/2 which is considerably greater than both the average nuclear radius and internuclear distance. The Lifshitz-Slyozov theory of ripening is shown to remain locally applicable, over length scales much less than L. The implications of these findings for elastic light scattering in solid solutions that have undergone Ostwald ripening are considered.

  10. Development of Spray on Bag for manufacturing of large composites parts: Diffusivity analysis

    Science.gov (United States)

    Dempah, Maxime Joseph

    Bagging materials are utilized in many composites manufacturing processes. The selection is mainly driven by cost, temperature requirements, chemical compatibility and tear properties of the bag. The air barrier properties of the bag are assumed to be adequate or in many cases are not considered at all. However, the gas barrier property of a bag is the most critical parameter, as it can negatively affect the quality of the final laminate. The barrier property is a function of the bag material, uniformity, thickness and temperature. Improved barrier properties are needed for large parts, high pressure consolidated components and structures where air stays entrapped on the part surface. The air resistance property of the film is defined as permeability and is investigated in this thesis. A model was developed to evaluate the gas transport through the film and an experimental cell was implemented to characterize various commercial films. Understanding and characterizing the transport phenomena through the film allows optimization of the bagging material for various manufacturing processes. Spray-on-Bag is a scalable alternative bagging method compared to standard films. The approach allows in-situ fabrication of the bag on large and complex geometry structures where optimization of the bag properties can be varied on a local level. An experimental setup was developed and implemented using a six axis robot and an automated spraying system. Experiments were performed on a flat surface and specimens were characterized and compared to conventional films. Air barrier properties were within range of standard film approaches showing the potential to fabricate net shape bagging structures in an automated process.

  11. Early stage animal hoarders: are these owners of large numbers of adequately cared for cats?

    OpenAIRE

    Ramos, D.; da Cruz, N. O.; Ellis, Sarah; Hernandez, J. A. E.; Reche-Junior, A.

    2013-01-01

    Animal hoarding is a spectrum-based condition in which hoarders are often reported to have had normal and appropriate pet-keeping habits in childhood and early adulthood. Historically, research has focused largely on well established clinical animal hoarders with little work targeted towards the onset and development of animal hoarding. This study investigated whether a Brazilian population of owners of what might typically be considered an excessive number (20 or more) of cats were more like...

  12. Large-scale and Long-duration Simulation of a Multi-stage Eruptive Solar Event

    Science.gov (United States)

    Jiang, chaowei; Hu, Qiang; Wu, S. T.

    2015-04-01

    We employ a data-driven 3D MHD active region evolution model by using the Conservation Element and Solution Element (CESE) numerical method. This newly developed model retains the full MHD effects, allowing time-dependent boundary conditions and time evolution studies. The time-dependent simulation is driven by measured vector magnetograms and the method of MHD characteristics on the bottom boundary. We have applied the model to investigate the coronal magnetic field evolution of AR11283 which was characterized by a pre-existing sigmoid structure in the core region and multiple eruptions, both in relatively small and large scales. We have succeeded in producing the core magnetic field structure and the subsequent eruptions of flux-rope structures (see https://dl.dropboxusercontent.com/u/96898685/large.mp4 for an animation) as the measured vector magnetograms on the bottom boundary evolve in time with constant flux emergence. The whole process, lasting for about an hour in real time, compares well with the corresponding SDO/AIA and coronagraph imaging observations. From these results, we show the capability of the model, largely data-driven, that is able to simulate complex, topological, and highly dynamic active region evolutions. (We acknowledge partial support of NSF grants AGS 1153323 and AGS 1062050, and data support from SDO/HMI and AIA teams).

  13. [A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

    Science.gov (United States)

    Gorgidze, L A; Vorob'ev, I A

    2009-01-01

    To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

  14. Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Silvio A. Ñamendys-Silva

    2011-01-01

    Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

  15. Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

    Directory of Open Access Journals (Sweden)

    Mark A. Gromski MD

    2016-12-01

    Full Text Available Primary gastrointestinal (GI lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endoscopic biopsies. Multiple treatment modalities including surgery, radiotherapy, and chemotherapy have been used. Advancements in endoscopic and pathologic technology decrease turnaround time for diagnosis and treatment initiation, thus reducing the need for surgery. Health care providers should maintain a high level of suspicion and consider gastric DLBCL as part of the differential diagnosis, especially in those with warning symptoms such as weight loss and early satiety with abnormal endoscopic findings.

  16. Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2016-01-01

    Full Text Available We report a rare case of diffuse large B-cell lymphoma (DLBCL of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities.

  17. Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

    Science.gov (United States)

    Scheinpflug, K; Schalk, E; Reschke, K; Franke, A; Mohren, M

    2006-01-01

    The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

  18. Diffuse Large B-Cell Lymphoma in the Elderly: Real World Outcomes of Immunochemotherapy in Asian Population.

    Science.gov (United States)

    Byun, Ja Min; Lee, Jeong-Ok; Kang, Beodeul; Kim, Ji-Won; Kim, Se Hyun; Kim, Jin Won; Kim, Yu Jung; Lee, Keun-Wook; Bang, Soo-Mee; Lee, Jong Seok

    2016-09-01

    We evaluated the real-life treatment outcomes of elderly patients with diffuse large B-cell lymphoma from a homogenous Asian population and defined the cutoff age for "elderly." The medical records of 192 DLBCL patients aged > 60 years who had received first-line immunochemotherapy were retrospectively evaluated. The treatment schedule, adverse events, and survival outcomes were analyzed overall and stratified by 4 age groups (> 60-64, 65-69, 70-74, and ≥ 75 years). Patient age of ≥ 75 years was associated with a significantly lower complete remission rate (86.5% vs. 81.4% vs. 82.0% vs. 51%; P population, 75 years seems to be a judicious cutoff for predicting treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Advances in the molecular diagnosis of diffuse large B-cell lymphoma in the era of precision medicine.

    Science.gov (United States)

    Araf, Shamzah; Korfi, Koorosh; Rahim, Tahrima; Davies, Andrew; Fitzgibbon, Jude

    2016-10-01

    The adoption of high-throughput technologies has led to a transformation in our ability to classify diffuse large B-cell lymphoma (DLBCL) into unique molecular subtypes. In parallel, the expansion of agents targeting key genetic and gene expression signatures has led to an unprecedented opportunity to personalize cancer therapies, paving the way for precision medicine. Areas covered: This review summarizes the key molecular subtypes of DLBCL and outlines the novel technology platforms in development to discriminate clinically relevant subtypes. Expert commentary: The application of emerging diagnostic tests into routine clinical practise is gaining momentum following the demonstration of subtype specific activity by novel agents. Co-ordinated efforts are required to ensure that these state of the art technologies provide reliable and clinically meaningful results accessible to the wider haematology community.

  20. Large-scale multi-stage constructed wetlands for secondary effluents treatment in northern China: Carbon dynamics.

    Science.gov (United States)

    Wu, Haiming; Fan, Jinlin; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan

    2018-02-01

    Multi-stage constructed wetlands (CWs) have been proved to be a cost-effective alternative in the treatment of various wastewaters for improving the treatment performance as compared with the conventional single-stage CWs. However, few long-term full-scale multi-stage CWs have been performed and evaluated for polishing effluents from domestic wastewater treatment plants (WWTP). This study investigated the seasonal and spatial dynamics of carbon and the effects of the key factors (input loading and temperature) in the large-scale seven-stage Wu River CW polishing domestic WWTP effluents in northern China. The results indicated a significant improvement in water quality. Significant seasonal and spatial variations of organics removal were observed in the Wu River CW with a higher COD removal efficiency of 64-66% in summer and fall. Obvious seasonal and spatial variations of CH 4 and CO 2 emissions were also found with the average CH 4 and CO 2 emission rates of 3.78-35.54 mg m -2 d -1 and 610.78-8992.71 mg m -2 d -1 , respectively, while the higher CH 4 and CO 2 emission flux was obtained in spring and summer. Seasonal air temperatures and inflow COD loading rates significantly affected organics removal and CH 4 emission, but they appeared to have a weak influence on CO 2 emission. Overall, this study suggested that large-scale Wu River CW might be a potential source of GHG, but considering the sustainability of the multi-stage CW, the inflow COD loading rate of 1.8-2.0 g m -2 d -1 and temperature of 15-20 °C may be the suitable condition for achieving the higher organics removal efficiency and lower greenhouse gases (GHG) emission in polishing the domestic WWTP effluent. The obtained knowledge of the carbon dynamics in large-scale Wu River CW will be helpful for understanding the carbon cycles, but also can provide useful field experience for the design, operation and management of multi-stage CW treatments. Copyright © 2017 Elsevier Ltd. All rights

  1. Computational Modelling of Large Scale Phage Production Using a Two-Stage Batch Process

    Directory of Open Access Journals (Sweden)

    Konrad Krysiak-Baltyn

    2018-04-01

    Full Text Available Cost effective and scalable methods for phage production are required to meet an increasing demand for phage, as an alternative to antibiotics. Computational models can assist the optimization of such production processes. A model is developed here that can simulate the dynamics of phage population growth and production in a two-stage, self-cycling process. The model incorporates variable infection parameters as a function of bacterial growth rate and employs ordinary differential equations, allowing application to a setup with multiple reactors. The model provides simple cost estimates as a function of key operational parameters including substrate concentration, feed volume and cycling times. For the phage and bacteria pairing examined, costs and productivity varied by three orders of magnitude, with the lowest cost found to be most sensitive to the influent substrate concentration and low level setting in the first vessel. An example case study of phage production is also presented, showing how parameter values affect the production costs and estimating production times. The approach presented is flexible and can be used to optimize phage production at laboratory or factory scale by minimizing costs or maximizing productivity.

  2. First-principles studies on vacancy-modified interstitial diffusion mechanism of oxygen in nickel, associated with large-scale atomic simulation techniques

    International Nuclear Information System (INIS)

    Fang, H. Z.; Shang, S. L.; Wang, Y.; Liu, Z. K.; Alfonso, D.; Alman, D. E.; Shin, Y. K.; Zou, C. Y.; Duin, A. C. T. van; Lei, Y. K.; Wang, G. F.

    2014-01-01

    This paper is concerned with the prediction of oxygen diffusivities in fcc nickel from first-principles calculations and large-scale atomic simulations. Considering only the interstitial octahedral to tetrahedral to octahedral minimum energy pathway for oxygen diffusion in fcc lattice, greatly underestimates the migration barrier and overestimates the diffusivities by several orders of magnitude. The results indicate that vacancies in the Ni-lattice significantly impact the migration barrier of oxygen in nickel. Incorporation of the effect of vacancies results in predicted diffusivities consistent with available experimental data. First-principles calculations show that at high temperatures the vacancy concentration is comparable to the oxygen solubility, and there is a strong binding energy and a redistribution of charge density between the oxygen atom and vacancy. Consequently, there is a strong attraction between the oxygen and vacancy in the Ni lattice, which impacts diffusion

  3. MR imaging of urinary bladder cancer for T-staging: a review and a pictorial essay of diffusion-weighted imaging.

    Science.gov (United States)

    Takeuchi, Mitsuru; Sasaki, Shigeru; Naiki, Taku; Kawai, Noriyasu; Kohri, Kenjiro; Hara, Masaki; Shibamoto, Yuta

    2013-12-01

    Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion-weighted imaging (DWI) of urinary bladder cancer for T-staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T-stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2-weighted imaging or enhanced MRI and could lead to over-staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy. Copyright © 2013 Wiley Periodicals, Inc.

  4. Obtaining high-resolution stage forecasts by coupling large-scale hydrologic models with sensor data

    Science.gov (United States)

    Fries, K. J.; Kerkez, B.

    2017-12-01

    We investigate how "big" quantities of distributed sensor data can be coupled with a large-scale hydrologic model, in particular the National Water Model (NWM), to obtain hyper-resolution forecasts. The recent launch of the NWM provides a great example of how growing computational capacity is enabling a new generation of massive hydrologic models. While the NWM spans an unprecedented spatial extent, there remain many questions about how to improve forecast at the street-level, the resolution at which many stakeholders make critical decisions. Further, the NWM runs on supercomputers, so water managers who may have access to their own high-resolution measurements may not readily be able to assimilate them into the model. To that end, we ask the question: how can the advances of the large-scale NWM be coupled with new local observations to enable hyper-resolution hydrologic forecasts? A methodology is proposed whereby the flow forecasts of the NWM are directly mapped to high-resolution stream levels using Dynamical System Identification. We apply the methodology across a sensor network of 182 gages in Iowa. Of these sites, approximately one third have shown to perform well in high-resolution flood forecasting when coupled with the outputs of the NWM. The quality of these forecasts is characterized using Principal Component Analysis and Random Forests to identify where the NWM may benefit from new sources of local observations. We also discuss how this approach can help municipalities identify where they should place low-cost sensors to most benefit from flood forecasts of the NWM.

  5. Design and analysis of a 3-DOF planar micromanipulation stage with large rotational displacement for micromanipulation system

    Directory of Open Access Journals (Sweden)

    B. Ding

    2017-05-01

    Full Text Available Flexure-based mechanisms have been widely used for scanning tunneling microscopy, nanoimprint lithography, fast servo tool system and micro/nano manipulation. In this paper, a novel planar micromanipulation stage with large rotational displacement is proposed. The designed monolithic manipulator has three degrees of freedom (DOF, i.e. two translations along the X and Y axes and one rotation around Z axis. In order to get a large workspace, the lever mechanism is adopted to magnify the stroke of the piezoelectric actuators and also the leaf beam flexure is utilized due to its large rotational scope. Different from conventional pre-tightening mechanism, a modified pre-tightening mechanism, which is less harmful to the stacked actuators, is proposed in this paper. Taking the circular flexure hinges and leaf beam flexures hinges as revolute joints, the forward kinematics and inverse kinematics models of this stage are derived. The workspace of the micromanipulator is finally obtained, which is based on the derived kinematic models.

  6. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients.

    Science.gov (United States)

    Parikh, Sameer A; Rabe, Kari G; Call, Timothy G; Zent, Clive S; Habermann, Thomas M; Ding, Wei; Leis, Jose F; Schwager, Susan M; Hanson, Curtis A; Macon, William R; Kay, Neil E; Slager, Susan L; Shanafelt, Tait D

    2013-09-01

    Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy-proven RS during follow-up were identified. After a median follow-up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed. © 2013 John Wiley & Sons Ltd.

  7. How breast cancer chemotherapy increases the risk of leukemia: Thoughts about a case of diffuse large B-cell lymphoma and leukemia after breast cancer chemotherapy.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Li, Minghuan; Kong, Li; Deng, Xiaoqin; Yu, Jinming

    2016-01-01

    The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukemia after breast cancer treatment associated with chemotherapy? Can these types of leukemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together and we hope to attract the attention of other clinicians.

  8. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xia, Yi; Xu-Monette, Z Y; Tzankov, A

    2017-01-01

    PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBC...

  9. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Møller, Michael B; Tzankov, Alexander

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cycloph...

  10. Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

    Directory of Open Access Journals (Sweden)

    İkbal Cansu Barış

    2015-12-01

    Full Text Available INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0% in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041. In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040. DISCUSSION AND CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.

  11. Diffusion-weighted MR imaging in comparison to integrated [18F]-FDG PET/CT for N-staging in patients with lung cancer

    International Nuclear Information System (INIS)

    Pauls, Sandra; Schmidt, Stefan A.; Juchems, Markus S.; Klass, Oliver; Luster, Markus; Reske, Sven Norbert; Brambs, Hans-Juergen; Feuerlein, Sebastian

    2012-01-01

    Purpose The purpose of this study was to prospectively determine the diagnostic accuracy of diffusion-weighted imaging (DWI) using MRI in the staging of thoracic lymph nodes in patients with lung cancer, and to compare the performance to that of PET/CT. Patients and Method 20 consecutive patients (pts) with histologically proven lung cancer were included in this study. In all pts FDG-PET/CT was routinely performed to stage lung carcinoma. Additionally, MRI (1.5 T) was performed including native T1w, T1w post contrast medium, T2w, and DWI sequences. Regarding the N stage based on the results of the PET/CT there were 5 patients with N0, 3 patients with N1, 5 patients with N2 and 7 patients with N3. Image analysis was performed by two radiologists (R1 and R2), respectively. The reviewers had to chose between 1 (at least one lymph node within a station is malignant) or 0 (no lymph nodes suspicious for malignancy). First the T1 post contrast sequence was analyzed. In a second step the DWI sequence (b = 800) was analyzed. Both steps were performed in a blinded fashion. Results MR imaging with or without DWI only agreed with the results of the PET/CT regarding the N stage in 80% of the patients—15% were understaged and 5% overstaged. There was excellent interobserver agreement; the N-staging result only differed in 1 patient for DWI, resulting in correlation coefficients of 0.98 for DWI and 1.0 for MRI. Compared to PET-CT MRI overstaged one and understaged 4 patients, while DWI overstaged one and understaged 3 patients. This resulted in correlation coefficients of 0.814 (R1 and R2) for MRI and 0.815 (R1) and 0.804 (R2) for DWI. Regarding the ADC values there were no significant differences between ipsilateral hilar (1.03 mm 2 /s ± 0.13), subcarinal (0.96 mm 2 /s ± 0.24), ipsilateral mediastinal (1.0 mm 2 /s ± 0.18), contralateral mediastinal (0.93 mm 2 /s ± 0.23) and supraclavicular (0.9 mm 2 /s ± 0.23) lymph nodes. Conclusion Diffusion-weighted imaging does not

  12. Myometrial invasion and overall staging of endometrial carcinoma: assessment using fusion of T2-weighted magnetic resonance imaging and diffusion-weighted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Guo Y

    2017-12-01

    Full Text Available Yu Guo,1,2 Ping Wang,2 Penghui Wang,2 Wei Gao,1 Fenge Li,3 Xueling Yang,1 Hongyan Ni,2 Wen Shen,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 2Department of Radiology, Tianjin First Center Hospital, The First Central Clinical College of Tianjin Medical University, Tianjin, 3Department of Gynecology, Tianjin First Center Hospital, Tianjin, People’s Republic of China Background: The age of onset of endometrial carcinoma has been decreasing in recent years. In endometrial carcinoma, it is important to accurately assess invasion depth and preoperative staging. Fusion of T2-weighted magnetic resonance imaging (T2WI and diffusion-weighted magnetic resonance imaging (DWI may contribute to the improvement of anatomical localization of lesions.Materials and methods: In our study, a total of 58 endometrial carcinoma cases were included. Based on the revised 2009 International Federation of Gynecology and Obstetrics staging system, a fusion of T2WI and DWI was utilized for the evaluation of invasion depth and determination of the overall stage. Postoperative pathologic assessment was considered as the reference standard. The consistency of T2WI image staging and pathologic staging, and the consistency of fused T2WI and DWI and pathologic staging were all analyzed using Kappa statistics.Results: Compared with the T2WI group, a significantly higher diagnostic accuracy was observed for myometrial invasion with fusion of T2WI and DWI (77.6% for T2WI; 94.8% for T2WI-DWI. For the identification of deep invasion, we calculated values for diagnostic sensitivity (69.2% for T2WI; 92.3% for T2WI-DWI, specificity (80% for T2WI; 95.6% for T2WI-DWI, positive predictive value (50% for T2WI; 85.7% for T2WI-DWI, and negative predictive value (90% for

  13. A finite element simulation on transient large deformation and mass diffusion in electrodes for lithium ion batteries

    International Nuclear Information System (INIS)

    An, Yonghao; Jiang, Hanqing

    2013-01-01

    Lithium-ion batteries have attracted great deal of attention recently. Silicon is one of the most promising anode materials for high-performance lithium-ion batteries, due to its highest theoretical specific capacity. However, the short lifetime confined by mechanical failure in the silicon anode is now considered to be the biggest challenge in desired applications. High stress induced by the huge volume change due to lithium insertion/extraction is the main reason underlying this problem. Some theoretical models have been developed to address this issue. In order to properly implement these models, we develop a finite element based numerical method using a commercial software package, ABAQUS, as a platform at the continuum level to study fully coupled large deformation and mass diffusion problem. Using this method, large deformation, elasticity–plasticity of the electrodes, various spatial and temporal conditions, arbitrary geometry and dimension could be fulfilled. The interaction between anode and other components of the lithium ion batteries can also be studied as an integrated system. Several specific examples are presented to demonstrate the capability of this numerical platform. (paper)

  14. Large Conization and Laparoendoscopic Single-Port Pelvic Lymphadenectomy in Early-Stage Cervical Cancer for Fertility Preservation

    Directory of Open Access Journals (Sweden)

    Polat Dursun

    2013-01-01

    Full Text Available Fertility preservation in early-stage cervical cancer is a hot topic in gynecologic oncology. Although radical vaginal trachelectomy (RVT is suggested as a fertility preserving approach, there are some serious concerns like cervical stenosis, second trimester loss, preterm delivery in survivors, and lack of residual tumor in the majority of the surgical specimens. Therefore, less radical surgical operations have been proposed in early-stage cervical carcinomas. On the other hand, single-incision laparoscopic surgery (SILS is an evolving endoscopic approach for minimal access surgery. In this report, we present a case with early-stage cervical cancer who wishes to preserve fertility. We successfully performed single-port pelvic lymphadenectomy and large conization to preserve fertility potential of the patient. We think that combination of less radical approach like conization and single-port pelvic lymphadenectomy might be less minimally invasive and is still an effective surgical approach in well-selected cases with cervical carcinomas. Incorporation of single-port laparoscopy into the minimally invasive fertility sparing management of the cervical cancer will improve patients outcome with less complications and better cosmesis. Further studies are needed to reach a clear conclusion.

  15. PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

    Directory of Open Access Journals (Sweden)

    Cui W

    2017-04-01

    Full Text Available Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3 1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL. In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8 and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS

  16. Combination of Bcl-2 and MYC protein expression improves high-risk stratification in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Wang J

    2015-09-01

    Full Text Available Jing Wang,* Min Zhou,* Jing-Yan Xu,* Bing Chen, Jian OuyangDepartment of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this work and should be considered as cofirst authorsPurpose: To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL.Method: Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The patients were classified according to four risk groups: low (0–1, low-intermediate (2–3, high-intermediate (4, and high (5–7. Only high-risk patients with DLBCL were included in this analysis. We retrospectively examined 20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital.Results: The median expression of MYC protein was 60%, and 17 of 20 (65% evaluable cases overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen of 20 (90% evaluable cases showed BCL-2 overexpression. Additionally, 12 out of 20 cases (60% demonstrated coexpression of MYC and BCL-2 proteins. The percentages of overall survival and progression-free survival at the median follow-up time (36 months were 33.3%±16.1% and 16.9%±13.5%, respectively. By comparison, nine, four, and 20 patients were classified as high risk based on the International Prognostic Index (IPI, National Comprehensive Cancer Network(NCCN-IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI stratification, the risk groups demonstrated closely overlapping survival curves. In addition, four out of 20 cases were identified as low-intermediate risk according to the NCCN-IPI criteria.Conclusion: The addition of MYC and BCL-2 protein expression to the IPI could identify a subset of DLBCL patients with high-risk clinicopathological characteristics and

  17. Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

    Science.gov (United States)

    Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

    2018-04-01

    To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

  18. Preoperative staging of endometrial cancer using reduced field-of-view diffusion-weighted imaging: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Takashi; Hori, Masatoshi; Onishi, Hiromitsu; Sakane, Makoto; Tsuboyama, Takahiro; Tatsumi, Mitsuaki; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Suita, Osaka (Japan); Nakamoto, Atsushi; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Osaka (Japan); Kimura, Tadashi [Osaka University Graduate School of Medicine, Department of Obstetrics and Gynaecology, Osaka (Japan)

    2017-12-15

    To compare the image quality and diagnostic performance of reduced field-of-view (rFOV) versus conventional full field-of-view (fFOV) diffusion-weighted (DW) imaging of endometrial cancer. Fifty women with endometrial cancer underwent preoperative rFOV and fFOV DW imaging. Two radiologists compared the image qualities of both techniques, and five radiologists assessed superficial and deep myometrial invasion using both techniques. The statistical analysis included the Wilcoxon signed-rank test and paired t-test for comparisons of image quality and mean diagnostic values. Distortion, tumour delineation, and overall image quality were significantly better with rFOV DW imaging, compared to fFOV DW imaging (P < 0.05); however, the former was inferior in noise (P < 0.05). Regarding superficial invasion, the mean accuracies of the techniques did not differ statistically (rFOV, 58.0% versus fFOV, 56.0%; P = 0.30). Regarding deep myometrial invasion, rFOV DW imaging yielded significantly better mean accuracy, specificity, and positive predictive values (88.4%, 97.8%, and 91.7%, respectively), compared with fFOV DW imaging (84.8%, 94.1%, and 77.4%, respectively; P = 0.009, 0.005, and 0.011, respectively). Compared with fFOV DW imaging, rFOV DW imaging yielded less distortion, improved image quality and, consequently, better diagnostic performance for deep myometrial invasion of endometrial cancer. (orig.)

  19. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

    Science.gov (United States)

    Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

    2012-03-22

    Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

  20. Numerical and analytical approaches to an advection-diffusion problem at small Reynolds number and large Péclet number

    Science.gov (United States)

    Fuller, Nathaniel J.; Licata, Nicholas A.

    2018-05-01

    Obtaining a detailed understanding of the physical interactions between a cell and its environment often requires information about the flow of fluid surrounding the cell. Cells must be able to effectively absorb and discard material in order to survive. Strategies for nutrient acquisition and toxin disposal, which have been evolutionarily selected for their efficacy, should reflect knowledge of the physics underlying this mass transport problem. Motivated by these considerations, in this paper we discuss the results from an undergraduate research project on the advection-diffusion equation at small Reynolds number and large Péclet number. In particular, we consider the problem of mass transport for a Stokesian spherical swimmer. We approach the problem numerically and analytically through a rescaling of the concentration boundary layer. A biophysically motivated first-passage problem for the absorption of material by the swimming cell demonstrates quantitative agreement between the numerical and analytical approaches. We conclude by discussing the connections between our results and the design of smart toxin disposal systems.

  1. Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

    Science.gov (United States)

    Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

    2017-03-22

    The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  2. EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies

    Directory of Open Access Journals (Sweden)

    Marshall Williams

    2018-05-01

    Full Text Available The Epstein-Barr virus (EBV, which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2, which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function. Furthermore, examination of serum samples from diffuse large B-cell lymphoma (DLBCL and chronic lymphocytic leukemia patients revealed the presence of increased levels of anti-dUTPase antibodies in both cohorts compared to controls with the highest levels (3.67-fold increase observed in DLBCL female cases and the lowest (2.12-fold increase in DLBCL males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, and functional studies of BLLF3 mutants, we identified a putative amino acid motif involved with TLR2 interaction. These findings suggest that the EBV-dUTPase: TLR2 interaction is a potential molecular target that could be used for developing novel therapeutics (small molecules/vaccines.

  3. Data-Driven Diffusion Of Innovations: Successes And Challenges In 3 Large-Scale Innovative Delivery Models.

    Science.gov (United States)

    Dorr, David A; Cohen, Deborah J; Adler-Milstein, Julia

    2018-02-01

    Failed diffusion of innovations may be linked to an inability to use and apply data, information, and knowledge to change perceptions of current practice and motivate change. Using qualitative and quantitative data from three large-scale health care delivery innovations-accountable care organizations, advanced primary care practice, and EvidenceNOW-we assessed where data-driven innovation is occurring and where challenges lie. We found that implementation of some technological components of innovation (for example, electronic health records) has occurred among health care organizations, but core functions needed to use data to drive innovation are lacking. Deficits include the inability to extract and aggregate data from the records; gaps in sharing data; and challenges in adopting advanced data functions, particularly those related to timely reporting of performance data. The unexpectedly high costs and burden incurred during implementation of the innovations have limited organizations' ability to address these and other deficits. Solutions that could help speed progress in data-driven innovation include facilitating peer-to-peer technical assistance, providing tailored feedback reports to providers from data aggregators, and using practice facilitators skilled in using data technology for quality improvement to help practices transform. Policy efforts that promote these solutions may enable more rapid uptake of and successful participation in innovative delivery system reforms.

  4. Large eddy simulation of turbulent diffusion flame with hybrid fuel of CH4/H2 in various background conditions

    Science.gov (United States)

    Hong, Sungmin; Lee, Wook; Song, Han Ho; Kang, Seongwon

    2014-11-01

    A turbulent diffusion flame with hybrid fuel of methane and hydrogen is analyzed to investigate the effects of operating conditions on flame shape, rate of fuel consumption and pollutant formation. Various combinations of operating parameter, i.e. hydrogen concentration, background pressure and temperature, are examined in relatively high pressure and temperature conditions that can be found at the end of compression stroke in an internal combustion engine. A flamelet-progress variable approach (FPVA) and a dynamic subgrid scale (SGS) model are used for large eddy simulation (LES). A comparison with previous experiments and simulations in the standard condition shows a good agreement in the statistics of flow fields and chemical compositions, as well as in the resultant trends by similar parametric studies. As a result, the effects of added hydrogen are found to be consistent for most of the chemical species in the range of background pressure and temperature conditions. However, the flow fields of some species such as OH, NO, CO at a higher pressure and temperature state show a behavior different from the standard condition. Finally, hydrogen addition is shown to improve flame stability which is measured by the pressure fluctuations in all the tested conditions.

  5. Metabolic fingerprinting of fresh lymphoma samples used to discriminate between follicular and diffuse large B-cell lymphomas.

    Science.gov (United States)

    Barba, Ignasi; Sanz, Carolina; Barbera, Angels; Tapia, Gustavo; Mate, José-Luis; Garcia-Dorado, David; Ribera, Josep-Maria; Oriol, Albert

    2009-11-01

    To investigate if proton nuclear magnetic resonance ((1)H NMR) spectroscopy-based metabolic profiling was able to differentiate follicular lymphoma (FL) from diffuse large B-cell lymphoma (DLBCL) and to study which metabolites were responsible for the differences. High-resolution (1)H NMR spectra was obtained from fresh samples of lymph node biopsies obtained consecutively at one center (14 FL and 17 DLBCL). Spectra were processed using pattern-recognition methods. Discriminant models were able to differentiate between the two tumor types with a 86% sensitivity and a 76% specificity; the metabolites that most contributed to the discrimination were a relative increase of alanine in the case of DLBCL and a relative increase of taurine in FL. Metabolic models had a significant but weak correlation with Ki67 expression (r(2)=0.42; p=0.002) We have proved that it is possible to differentiate between FL and DLBCL based on their NMR metabolic profiles. This approach may potentially be applicable as a noninvasive tool for diagnostic and treatment follow-up in the clinical setting using conventional magnetic resonance systems.

  6. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

    Science.gov (United States)

    Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

    2016-01-01

    The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

  7. The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

    Science.gov (United States)

    Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

    2018-04-01

    Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

  8. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  9. Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

    Directory of Open Access Journals (Sweden)

    S. V. Voloshin

    2013-01-01

    Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

  10. Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

    Directory of Open Access Journals (Sweden)

    S. V. Voloshin

    2014-07-01

    Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

  11. Evidence of solitary chemosensory cells in a large mammal: the diffuse chemosensory system in Bos taurus airways

    Science.gov (United States)

    Tizzano, Marco; Merigo, Flavia; Sbarbati, Andrea

    2006-01-01

    The diffuse chemosensory system (DCS) of the respiratory apparatus is composed of solitary chemosensory cells (SCCs) that resemble taste cells but are not organized in end organs. The discovery of the DCS may open up new approaches to respiratory diseases. However, available data on mammalian SCCs have so far been collected from rodents, the airways of which display some differences from those of large mammals. Here we investigated the presence of the DCS and of SCCs in cows and bulls (Bos taurus), in which the airway cytology is similar to that in humans, focusing our attention on detection in the airways of molecules involved in the transduction cascade of taste [i.e. α-gustducin and phospholipase C of the β2 subtype (PLCβ2)]. The aim of the research was to extend our understanding of airway chemoreceptors and to compare the organization of the DCS in a large mammal with that in rodents. Using immunocytochemistry for α-gustducin, the taste buds of the tongue and arytenoid were visualized. In the trachea and bronchi, α-gustducin-immunoreactive SCCs were frequently found. Using immunocytochemistry for PLCβ2, the staining pattern was generally similar to those seen for α-gustducin. Immunoblotting confirmed the expression of α-gustducin in the tongue and in all the airway regions tested. The study demonstrated the presence of SCCs in cows and bulls, suggesting that DCSs are present in many mammalian species. The description of areas with a high density of SCCs in bovine bronchi seems to indicate that the view of the DCS as made up of isolated cells totally devoid of ancillary elements is probably an oversimplification. PMID:16928202

  12. Analysis and experimental study on formation conditions of large-scale barrier-free diffuse atmospheric pressure air plasmas in repetitive pulse mode

    Science.gov (United States)

    Li, Lee; Liu, Lun; Liu, Yun-Long; Bin, Yu; Ge, Ya-Feng; Lin, Fo-Chang

    2014-01-01

    Atmospheric air diffuse plasmas have enormous application potential in various fields of science and technology. Without dielectric barrier, generating large-scale air diffuse plasmas is always a challenging issue. This paper discusses and analyses the formation mechanism of cold homogenous plasma. It is proposed that generating stable diffuse atmospheric plasmas in open air should meet the three conditions: high transient power with low average power, excitation in low average E-field with locally high E-field region, and multiple overlapping electron avalanches. Accordingly, an experimental configuration of generating large-scale barrier-free diffuse air plasmas is designed. Based on runaway electron theory, a low duty-ratio, high voltage repetitive nanosecond pulse generator is chosen as a discharge excitation source. Using the wire-electrodes with small curvature radius, the gaps with highly non-uniform E-field are structured. Experimental results show that the volume-scaleable, barrier-free, homogeneous air non-thermal plasmas have been obtained between the gap spacing with the copper-wire electrodes. The area of air cold plasmas has been up to hundreds of square centimeters. The proposed formation conditions of large-scale barrier-free diffuse air plasmas are proved to be reasonable and feasible.

  13. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

    2016-01-01

    CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

  14. Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma : Systematic review and meta-analysis

    NARCIS (Netherlands)

    Adams, Hugo J A; Kwee, Thomas C.

    2016-01-01

    This study aimed to systematically review and meta-analyze the prognostic value of interim 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone

  15. Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    van Imhoff, Gustaaf W.; Boerma, Evert-Jan G.; van der Holt, Bronno; Schuuring, Ed; Verdonck, Leo F.; Kluin-Nelemans, Hanneke C.; Kluin, Philip M.

    2006-01-01

    Purpose Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy

  16. Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

    NARCIS (Netherlands)

    de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

    2018-01-01

    Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

  17. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...... for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies....

  18. The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Villa, Diego; Michaelsen, Thomas Yssing

    2017-01-01

    Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknow...

  19. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  20. Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features

    NARCIS (Netherlands)

    de Jong, Daphne; Glas, Annuska M.; Boerrigter, Lucie; Hermus, Marie-Christine; Dalesio, Otilia; Willemse, Els; Nederlof, Petra M.; Kersten, Marie José

    2003-01-01

    Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic

  1. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries

    DEFF Research Database (Denmark)

    Ok, Chi Young; Li, Ling; Xu-Monette, Zijun Y

    2014-01-01

    PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV(+) DLBCL, independent of age...

  2. Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

    DEFF Research Database (Denmark)

    Yao, Zhilei; Deng, Lijuan; Xu-Monette, Z Y

    2018-01-01

    In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positiv...

  3. Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

    Science.gov (United States)

    Tan, Hung-Jui; Meyer, Anne-Marie; Kuo, Tzy-Mey; Smith, Angela B; Wheeler, Stephanie B; Carpenter, William R; Nielsen, Matthew E

    2015-03-15

    Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care. © 2014 American Cancer Society.

  4. Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Song, Yoo Sung; Lee, Won Woo; Lee, Jong Seok; Kim, Sang Eun

    2015-11-01

    Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan-Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients.

  5. Large birth size does not reduce the negative latent effects of harsh environmental conditions across life stages in two coral species.

    NARCIS (Netherlands)

    Hartmann, A.C.; Marhaver, K.L.; Chamberland, V.F.; Sandin, S.A.; Vermeij, M.J.A.

    2013-01-01

    When juveniles must tolerate harsh environments early in life, the disproportionate success of certain phenotypes across multiple early life stages will dramatically influence adult community composition and dynamics. In many species, large offspring have a higher tolerance for stressful

  6. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Science.gov (United States)

    Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2014-04-01

    Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

  7. Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy

    Directory of Open Access Journals (Sweden)

    Lucy C. Fox

    2018-06-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus, representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

  8. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    Science.gov (United States)

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  9. Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients.

    Science.gov (United States)

    Culpin, Rachel E; Sieniawski, Michal; Angus, Brian; Menon, Geetha K; Proctor, Stephen J; Milne, Paul; McCabe, Kate; Mainou-Fowler, Tryfonia

    2013-12-01

    To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized. © 2013 John Wiley & Sons Ltd.

  10. Determining the correlation of Epstein-Barr virus with diffuse large B-cell lymphoma by chromogenic in situ hybridization

    Directory of Open Access Journals (Sweden)

    Kosari F

    2012-09-01

    Full Text Available Background: Diffuse large B-cell lymphoma (DLBCL is the most common type of lymphoma. There are various types of DLBCL including immunoblastic and centroblastic. Epstein-Barr virus (EBV is a member of Herpes virus family found in all human populations inducing different lymphoproliferative disorders. The role of EBV in the development of DLBCL is known. Multiple laboratory methods are available for detecting EBV. This study was conducted to determine the correlation of EBV with DLBCL in samples referred to pathology ward in Shariati and Sina Hospitals by chromogenic in situ hybridization (CISH method.Methods: In this case/control study, pathological specimens of 50 patients with DLBCL as well as 50 reactive lymph nodes and tonsils (control group were collected from archives of Shariati and Sina Hospitals and were evaluated for EBV encoded RNA (EBER expression based on CISH method. A peptide nucleic acid (PNA EBV probe (Dakocytomatin was used while all the processes were done in RNAase-free conditions using RNAase-free water, sterile gloves and samplers. Results: Out of fifty specimens in the case group, eight were positive for EBER in comparison with two in the control group (P=0.046. No statistically significant difference was observed between intranodal or extranodal samples (P=0.736 or between males and females (P=0.0746.Conclusion: Our study showed that EBV positivity for EBER in patient with DLBCL could be determined more effectively by CISH method than immunohistochemistry (IHC. Comparative analysis between CISH, PCR and IHC methods is recommended.

  11. An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

    Science.gov (United States)

    Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

    2018-01-02

    Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

  12. A strategy for full interrogation of prognostic gene expression patterns: exploring the biology of diffuse large B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Lisa M Rimsza

    Full Text Available Gene expression profiling yields quantitative data on gene expression used to create prognostic models that accurately predict patient outcome in diffuse large B cell lymphoma (DLBCL. Often, data are analyzed with genes classified by whether they fall above or below the median expression level. We sought to determine whether examining multiple cut-points might be a more powerful technique to investigate the association of gene expression with outcome.We explored gene expression profiling data using variable cut-point analysis for 36 genes with reported prognostic value in DLBCL. We plotted two-group survival logrank test statistics against corresponding cut-points of the gene expression levels and smooth estimates of the hazard ratio of death versus gene expression levels. To facilitate comparisons we also standardized the expression of each of the genes by the fraction of patients that would be identified by any cut-point. A multiple comparison adjusted permutation p-value identified 3 different patterns of significance: 1 genes with significant cut-point points below the median, whose loss is associated with poor outcome (e.g. HLA-DR; 2 genes with significant cut-points above the median, whose over-expression is associated with poor outcome (e.g. CCND2; and 3 genes with significant cut-points on either side of the median, (e.g. extracellular molecules such as FN1.Variable cut-point analysis with permutation p-value calculation can be used to identify significant genes that would not otherwise be identified with median cut-points and may suggest biological patterns of gene effects.

  13. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Loo, Suet Kee; Ab Hamid, Suzina Sheikh; Musa, Mustaffa; Wong, Kah Keng

    2018-01-01

    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) 0.8) with DNMT1 expression and significantly downregulated (log fold-change <-1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Peroja Pekka

    2012-03-01

    Full Text Available Abstract Background Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL, although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx, manganese superoxide dismutase (MnSOD and glutamate-cysteine ligase (GCL via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL. Results Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002, a high International Prognostic Index (p = 0.002 and strong Trx (p = 0.011 and GCL (p = 0.0003 expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046 and poor disease-specific survival (p = 0.015. Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049. Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003 and disease-specific survival (p = 0.031 compared with the other patients. Conclusions The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

  15. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

    Science.gov (United States)

    Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Rangel-Escareño, Claudia; Fernandez-Lopez, Juan Carlos; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernández-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Habermann, Thomas M.; Cerhan, James R.; Shipp, Margaret A.; Getz, Gad; Golub, Todd R.

    2012-01-01

    To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. PMID:22343534

  16. Prediction of temperature and thermal inertia effect in the maturation stage and stockpiling of a large composting mass

    International Nuclear Information System (INIS)

    Barrena, R.; Canovas, C.; Sanchez, A.

    2006-01-01

    A macroscopic non-steady state energy balance was developed and solved for a composting pile of source-selected organic fraction of municipal solid waste during the maturation stage (13,500 kg of compost). Simulated temperature profiles correlated well with temperature experimental data (ranging from 50 to 70 deg. C) obtained during the maturation process for more than 50 days at full scale. Thermal inertia effect usually found in composting plants and associated to the stockpiling of large composting masses could be predicted by means of this simplified energy balance, which takes into account terms of convective, conductive and radiation heat dissipation. Heat losses in a large composting mass are not significant due to the similar temperatures found at the surroundings and at the surface of the pile (ranging from 15 to 40 deg. C). In contrast, thermophilic temperature in the core of the pile was maintained during the whole maturation process. Heat generation was estimated with the static respiration index, a parameter that is typically used to monitor the biological activity and stability of composting processes. In this study, the static respiration index is presented as a parameter to estimate the metabolic heat that can be generated according to the biodegradable organic matter content of a compost sample, which can be useful in predicting the temperature of the composting process

  17. Continuous and discreet methods in the aggregation and des fuzzy stages of a diffuse controller of neutron power; Metodos continuo y discreto en las etapas de agregacion y desdifusificacion de un controlador disfuso de potencia neutronica

    Energy Technology Data Exchange (ETDEWEB)

    Najera H, M.C.; Benitez R, J.S. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2003-07-01

    The results of a comparative study are presented of: to) A denominated diffuse controller 'exact', designed by means of an innovative method that determines analytically so much the group of exit resultant in the aggregation stage like the de fuzzy process, and b) a diffuse controller denominated 'discreet' based on the discretization of the variable of having left as much for the aggregation as for the de fuzzy. These stages incorporated to the control algorithms whose objective is the ascent and regulation of the neutron power, carrying out an analysis of its performance. (Author)

  18. Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center

    International Nuclear Information System (INIS)

    Mac Manus, Michael P.; Wong, Kevin; Hicks, Rodney J.; Matthews, Jane P.; Wirth, Andrew; Ball, David L.

    2002-01-01

    Purpose: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. Methods and Materials: Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I-III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. Results: Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p=0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. Conclusion: Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging

  19. Gaseous diffusion system

    International Nuclear Information System (INIS)

    Garrett, G.A.; Shacter, J.

    1978-01-01

    A gaseous diffusion system is described comprising a plurality of diffusers connected in cascade to form a series of stages, each of the diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof

  20. Diagnostic and prognostic value of baseline FDG PET/CT skeletal textural features in diffuse large B cell lymphoma.

    Science.gov (United States)

    Aide, Nicolas; Talbot, Marjolaine; Fruchart, Christophe; Damaj, Gandhi; Lasnon, Charline

    2018-05-01

    Our purpose was to evaluate the diagnostic and prognostic value of skeletal textural features (TFs) on baseline FDG PET in diffuse large B cell lymphoma (DLBCL) patients. Eighty-two patients with DLBCL who underwent a bone marrow biopsy (BMB) and a PET scan between December 2008 and December 2015 were included. Two readers blinded to the BMB results visually assessed PET images for bone marrow involvement (BMI) in consensus, and a third observer drew a volume of interest (VOI) encompassing the axial skeleton and the pelvis, which was used to assess skeletal TFs. ROC analysis was used to determine the best TF able to diagnose BMI among four first-order, six second-order and 11 third-order metrics, which was then compared for diagnosis and prognosis in disease-free patients (BMB-/PET-) versus patients considered to have BMI (BMB+/PET-, BMB-/PET+, and BMB+/PET+). Twenty-two out of 82 patients (26.8%) had BMI: 13 BMB-/PET+, eight BMB+/PET+ and one BMB+/PET-. Among the nine BMB+ patients, one had discordant BMI identified by both visual and TF PET assessment. ROC analysis showed that SkewnessH, a first-order metric, was the best parameter for identifying BMI with sensitivity and specificity of 81.8% and 81.7%, respectively. SkewnessH demonstrated better discriminative power over BMB and PET visual analysis for patient stratification: hazard ratios (HR), 3.78 (P = 0.02) versus 2.81 (P = 0.06) for overall survival (OS) and HR, 3.17 (P = 0.03) versus 1.26 (P = 0.70) for progression-free survival (PFS). In multivariate analysis accounting for IPI score, bulky status, haemoglobin and SkewnessH, the only independent predictor of OS was the IPI score, while the only independent predictor of PFS was SkewnessH. The better discriminative power of skeletal heterogeneity for risk stratification compared to BMB and PET visual analysis in the overall population, and more specifically in BMB-/PET- patients, suggests that it can be useful to identify diagnostically

  1. Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Kung-Chao Chang

    Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

  2. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

    International Nuclear Information System (INIS)

    Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

    2016-01-01

    The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

  3. A two-stage compound parabolic concentrator system with a large entrance over the exit aperture ratio

    International Nuclear Information System (INIS)

    Angelescu, Tatiana; Radu, A. A.

    2000-01-01

    Certain optical designs in the field of high energy gamma ray astronomy components of the Cherenkov light, collected by the mirror of telescope, be concentrated on the photo-cathodes of the photomultiplier tubes, with the help of the light collectors having large entrance and small exit apertures. Mathematical restrictions imposed by the design of the compound parabolic concentrator (CPC) implied that for a given cut-off angle and an entrance aperture, the exit aperture of the CPC should not exceed a limit value. If this value is larger than the active diameter of the photocathode, an additional concentrator must be added to the system in order to transfer the light collected, from the exit aperture of the compound parabolic concentrator to the photocathode of the photomultiplier tube. Different designs of a two-stage system composed by a a hollow compound parabolic concentrator and a solid, dielectric filled concentrator are evaluated in this paper, from the point of view of optical efficiency and manufacturability. (authors)

  4. Prevalence and intensity of third stage Gnathostoma spinigerum larvae in swamp eels sold in three large markets in Bangkok, Thailand.

    Science.gov (United States)

    Saksirisampant, Wilai; Nuchprayoon, Surang; Wiwanitkit, Viroj; Kraivichian, Kanyarat; Suwansaksri, Jamsai

    2002-01-01

    Gnathostoma spinigerum is a common human tissue parasite in Thailand. The swamp eel is the major intermediate or paratenic host for this parasite. The high prevalence of the infective third stage larvae (L3) of this parasite in the rainy season has been noted in previous studies. During June 1999 (rainy season), we performed a cross-sectional survey of the prevalence and the intensity of G. spinigerum L3s in the livers of swamp eels that were obtained from three large Bangkok markets (Klong Toey, Pran Nok, and Tevej). Of a total of 785 livers, G. spinigerum L3s were found in 97: an infection rate of 12%. The prevalence rates in Klong Toey, Pran Nok, and Tevej markets were 13%, 10% and 14% respectively. There was no significant difference in the proportion of infected eels between the markets (p > 0.05). The intensity of L3 burden in the livers ranged from 1-17 larvae, with an average of 2.60 +/- 0.24 larvae (mean +/- SE). In this study a high prevalence of G. spinigerum L3s was found; there was no significant difference in the intensity of larvae in swamp eels between markets. These findings emphasize the importance of public health education: people need to be aware of the dangers of consuming raw or undercooked food.

  5. Diffusion-weighted imaging as part of hybrid PET/MRI protocols for whole-body cancer staging: Does it benefit lesion detection?

    Energy Technology Data Exchange (ETDEWEB)

    Buchbender, Christian, E-mail: christian.buchbender@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Moorenstr. 5, D-40225 Dusseldorf (Germany); Hartung-Knemeyer, Verena, E-mail: verena.hartung@uk-essen.de [Univ Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Hufelandstr. 55, D-45147 Essen (Germany); Beiderwellen, Karsten, E-mail: karsten.beiderwellen@uk-essen.de [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Hufelandstr. 55, D-45147 Essen (Germany); Heusch, Philipp, E-mail: philipp.heusch@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Moorenstr. 5, D-40225 Dusseldorf (Germany); Kühl, Hilmar, E-mail: hilmar.kuehl@uni-due.de [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Hufelandstr. 55, D-45147 Essen (Germany); Lauenstein, Thomas C., E-mail: thomas.lauenstein@uk-essen.de [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Hufelandstr. 55, D-45147 Essen (Germany); Forsting, Michael, E-mail: michael.forsting@uk-essen.de [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Hufelandstr. 55, D-45147 Essen (Germany); Antoch, Gerald, E-mail: antoch@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Moorenstr. 5, D-40225 Dusseldorf (Germany); Heusner, Till A., E-mail: heusner@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Moorenstr. 5, D-40225 Dusseldorf (Germany)

    2013-05-15

    Purpose: Positron emission tomography/magnetic resonance imaging (PET/MRI) requires efficient scan protocols for whole-body cancer staging. The aim of this study was to evaluate if the application of diffusion-weighted MR imaging (DWI) results in a diagnostic benefit for lesion detection in oncologic patients if added to a whole-body [18F]-fluorodesoxyglucose ([18F]-FDG) PET/MRI protocol. Methods: 25 consecutive oncologic patients (16 men, 9 women; age 57 ± 12 years) prospectively underwent whole-body [18F]-FDG-PET/MRI including DWI on a hybrid PET/MRI scanner. A team of two readers assessed [18F]-FDG PET/MRI without DWI for primary tumors and metastases. In a second session, now considering DWI, readers reassessed [18F]-FDG PET/MRI accordingly. Additionally, the lesion-to-background contrast on [18F]-FDG PET and DWI was rated qualitatively (0, invisible; 1, low; 2, intermediate; 3, high). Wilcoxon's signed-rank test was performed to test for differences in the lesion-to-background contrast. Results: 49 lesions were detected in 16 patients (5 primaries, 44 metastases). All 49 lesions were concordantly detected by [18F]-FDG PET/MRI alone and [18F]-FDG PET/MRI with DWI. The lesion-to-background contrast on DWI compared to [18F]-FDG PET was rated lower in 22 (44.9%) of 49 detected lesions resulting in a significantly higher lesion-to-background contrast on [18F]-FDG PET compared to DWI (P = 0.001). Conclusions: DWI as part of whole-body [18F]-FDG PET/MRI does not benefit lesion detection. Given the necessity to optimize imaging protocols with regard to patient comfort and efficacy, DWI has to be questioned as a standard tool for whole-body staging in oncologic PET/MRI.

  6. Sulphate leaching from diffuse agricultural and forest sources in a large central European catchment during 1900-2010

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Jiří; Hejzlar, Josef; Porcal, Petr; Posch, M.

    470, February (2014), s. 543-550 ISSN 0048-9697 R&D Projects: GA ČR(CZ) GAP504/12/1218; GA ČR(CZ) GA526/09/0567 Institutional support: RVO:60077344 Keywords : modelling * sulphate leaching * sulphur mineralization * diffuse sources Subject RIV: DJ - Water Pollution ; Quality Impact factor: 4.099, year: 2014

  7. CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Elham Vali Betts

    2016-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

  8. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 62: The Influence of Knowledge Diffusion on Aeronautics Innovation: The Research, Development, and Production of Large Commercial Aircraft in France, Germany, and the United Kingdom

    Science.gov (United States)

    Golich, Vicki L.; Pinelli, Thomas E.

    1997-01-01

    This paper focuses on how European public policies-individually and collectively - influence the diffusion of knowledge and technology. It begins with an overview of the roles played historically and currently by European governments in the Research, Development and Production (RD&P) of Large Commercial Aircraft (LCA). The analytical framework brings together literature from global political economy, comparative politics, business management, and science and technology policy studies. It distinguishes between the production of knowledge, on the one hand, and the dissemination of knowledge, on the other. France, Germany, and the United Kingdom serve as the analytical cases. The paper concludes with a call for additional research in this area, some tentative lessons learned, and a discussion of the consequences of national strategies and policies for the diffusion of knowledge and technology in an era of globalizaton.

  9. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    Science.gov (United States)

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

  10. High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

    Science.gov (United States)

    Cardesa-Salzmann, Teresa M.; Colomo, Luis; Gutierrez, Gonzalo; Chan, Wing C.; Weisenburger, Dennis; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Arenillas, Leonor; Serrano, Sergio; Tubbs, Ray; Delabie, Jan; Gascoyne, Randy D.; Connors, Joseph M; Mate, Jose L.; Rimsza, Lisa; Braziel, Rita; Rosenwald, Andreas; Lenz, Georg; Wright, George; Jaffe, Elaine S.; Staudt, Louis; Jares, Pedro; López-Guillermo, Armando; Campo, Elias

    2011-01-01

    Background Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions These findings highlight the impact of angiogenesis in the outcome of patients with

  11. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD3...... value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL....

  12. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    OpenAIRE

    Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

    2016-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

  13. Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Hollmann, Annette; Aloyz, Raquel; Baker, Kristi

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression...... as a potential marker to identify tumours likely to respond to CD40-targeted therapies. Copyright (c) 2010 John Wiley & Sons, Ltd....

  14. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Science.gov (United States)

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L; Salamero, Olga; Sancho, Juan M; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

    2013-10-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

  15. Primary diffuse large B-cell lymphoma of the oral cavity Linfoma difuso de grandes células B primário de boca

    Directory of Open Access Journals (Sweden)

    Bruno Correia Jham

    2007-10-01

    Full Text Available Lymphomas arising within the oral cavity account for only 3.5% of all oral malignancies. Diffuse large B-cell lymphoma is a non-Hodgkin lymphoma subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells. This paper reports a case of diffuse large B-cell lymphoma affecting the oral cavity of a Brazilian woman, along with its clinical, microscopical, immunohistochemical, and molecular features.Linfomas correspondem a 3,5% de todos os casos de lesões malignas de boca. O linfoma difuso de grandes células B é um subtipo de linfoma não-Hodgkin caracterizado pela proliferação difusa de células linfóides B. Este artigo relata um caso de linfoma difuso de grandes células B localizado na cavidade bucal de uma mulher brasileira, incluindo os achados clínicos, microscópicos, imuno-histoquímicos e moleculares.

  16. Large-scale expression analysis reveals distinct microRNA profiles at different stages of human neurodevelopment.

    Directory of Open Access Journals (Sweden)

    Brandon Smith

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short non-coding RNAs predicted to regulate one third of protein coding genes via mRNA targeting. In conjunction with key transcription factors, such as the repressor REST (RE1 silencing transcription factor, miRNAs play crucial roles in neurogenesis, which requires a highly orchestrated program of gene expression to ensure the appropriate development and function of diverse neural cell types. Whilst previous studies have highlighted select groups of miRNAs during neural development, there remains a need for amenable models in which miRNA expression and function can be analyzed over the duration of neurogenesis. PRINCIPAL FINDINGS: We performed large-scale expression profiling of miRNAs in human NTera2/D1 (NT2 cells during retinoic acid (RA-induced transition from progenitors to fully differentiated neural phenotypes. Our results revealed dynamic changes of miRNA patterns, resulting in distinct miRNA subsets that could be linked to specific neurodevelopmental stages. Moreover, the cell-type specific miRNA subsets were very similar in NT2-derived differentiated cells and human primary neurons and astrocytes. Further analysis identified miRNAs as putative regulators of REST, as well as candidate miRNAs targeted by REST. Finally, we confirmed the existence of two predicted miRNAs; pred-MIR191 and pred-MIR222 associated with SLAIN1 and FOXP2, respectively, and provided some evidence of their potential co-regulation. CONCLUSIONS: In the present study, we demonstrate that regulation of miRNAs occurs in precise patterns indicative of their roles in cell fate commitment, progenitor expansion and differentiation into neurons and glia. Furthermore, the similarity between our NT2 system and primary human cells suggests their roles in molecular pathways critical for human in vivo neurogenesis.

  17. Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-06-01

    Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

  18. Measurements of beam halo diffusion and population density in the Tevatron and in the Large Hadron Collider

    CERN Document Server

    Stancari, Giulio

    Halo dynamics influences global accelerator performance: beam lifetimes, emittance growth, dynamic aperture, and collimation efficiency. Halo monitoring and control are also critical for the operation of high-power machines. For instance, in the high-luminosity upgrade of the LHC, the energy stored in the beam tails may reach several megajoules. Fast losses can result in superconducting magnet quenches, magnet damage, or even collimator deformation. The need arises to measure the beam halo and to remove it at controllable rates. In the Tevatron and in the LHC, halo population densities and diffusivities were measured with collimator scans by observing the time evolution of losses following small inward or outward collimator steps, under different experimental conditions: with single beams and in collision, and, in the case of the Tevatron, with a hollow electron lens acting on a subset of bunches. After the LHC resumes operations, it is planned to compare measured diffusivities with the known strength of tran...

  19. On the group approximation errors in description of neutron slowing-down at large distances from a source. Diffusion approach

    International Nuclear Information System (INIS)

    Kulakovskij, M.Ya.; Savitskij, V.I.

    1981-01-01

    The errors of multigroup calculating the neutron flux spatial and energy distribution in the fast reactor shield caused by using group and age approximations are considered. It is shown that at small distances from a source the age theory rather well describes the distribution of the slowing-down density. With the distance increase the age approximation leads to underestimating the neutron fluxes, and the error quickly increases at that. At small distances from the source (up to 15 lengths of free path in graphite) the multigroup diffusion approximation describes the distribution of slowing down density quite satisfactorily and at that the results almost do not depend on the number of groups. With the distance increase the multigroup diffusion calculations lead to considerable overestimating of the slowing-down density. The conclusion is drawn that the group approximation proper errors are opposite in sign to the error introduced by the age approximation and to some extent compensate each other

  20. Molecular analysis of immunoglobulin variable genes supports a germinal center experienced normal counterpart in primary cutaneous diffuse large B-cell lymphoma, leg-type.

    Science.gov (United States)

    Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Deveza, Mélanie; Laforet, Marie-Pierre; Beylot-Barry, Marie; Vergier, Béatrice; Parrens, Marie; Feuillard, Jean; Merlio, Jean-Philippe; Gachard, Nathalie

    2017-11-01

    Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. These data suggest that cell-of origin is

  1. Prognostic value of negative interim 2-["1"8F]-fluoro-2-deoxy-D-glucose PET/CT in diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Kwon, S.H.; Kang, D.R.; Kim, J.; Yoon, J.-K.; Lee, S.J.; Jeong, S.H.; Lee, H.W.; An, Y.-S.

    2016-01-01

    Aim: To assess the prognostic value of negative interim combined 2-["1"8F]-fluoro-2-deoxy-D-glucose ("1"8F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent "1"8F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal "1"8F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. Results: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0–2; p<0.001). Conclusion: Despite a negative interim "1"8F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score. - Highlights: • About 39% of patients showed progression after negative interim PET/CT. • The IPI score was an independent predictor for PFS. • It is important to closely follow-up with high IPI score

  2. Fully implicit solution of large-scale non-equilibrium radiation diffusion with high order time integration

    International Nuclear Information System (INIS)

    Brown, Peter N.; Shumaker, Dana E.; Woodward, Carol S.

    2005-01-01

    We present a solution method for fully implicit radiation diffusion problems discretized on meshes having millions of spatial zones. This solution method makes use of high order in time integration techniques, inexact Newton-Krylov nonlinear solvers, and multigrid preconditioners. We explore the advantages and disadvantages of high order time integration methods for the fully implicit formulation on both two- and three-dimensional problems with tabulated opacities and highly nonlinear fusion source terms

  3. Numerical simulation of nonstationary dissipative structures in 3D double-diffusive convection at large Rayleigh numbers

    Science.gov (United States)

    Kozitskiy, Sergey

    2018-05-01

    Numerical simulation of nonstationary dissipative structures in 3D double-diffusive convection has been performed by using the previously derived system of complex Ginzburg-Landau type amplitude equations, valid in a neighborhood of Hopf bifurcation points. Simulation has shown that the state of spatiotemporal chaos develops in the system. It has the form of nonstationary structures that depend on the parameters of the system. The shape of structures does not depend on the initial conditions, and a limited number of spectral components participate in their formation.

  4. Measurements of beam halo diffusion and population density in the Tevatron and in the Large Hadron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Stancari, Giulio [Fermilab

    2015-03-01

    Halo dynamics influences global accelerator performance: beam lifetimes, emittance growth, dynamic aperture, and collimation efficiency. Halo monitoring and control are also critical for the operation of high-power machines. For instance, in the high-luminosity upgrade of the LHC, the energy stored in the beam tails may reach several megajoules. Fast losses can result in superconducting magnet quenches, magnet damage, or even collimator deformation. The need arises to measure the beam halo and to remove it at controllable rates. In the Tevatron and in the LHC, halo population densities and diffusivities were measured with collimator scans by observing the time evolution of losses following small inward or outward collimator steps, under different experimental conditions: with single beams and in collision, and, in the case of the Tevatron, with a hollow electron lens acting on a subset of bunches. After the LHC resumes operations, it is planned to compare measured diffusivities with the known strength of transverse damper excitations. New proposals for nondestructive halo population density measurements are also briefly discussed.

  5. Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients.

    Science.gov (United States)

    Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Toyoda, Kosuke; Yamauchi, Nobuhiko; Makita, Shinichi; Fukuhara, Suguru; Munakata, Wataru; Maruyama, Dai; Kobayashi, Yukio; Tobinai, Kensei

    2016-09-01

    This study analysed incidence, patient outcome, immunophenotype and prognostic factors of histological transformation (HT) from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) to diffuse large B-cell lymphoma (DLBCL) in 467 patients (median age, 61 years). The primary sites of MALT lymphoma were the stomach (43%), ocular adnexa (25%), lung (8%), systemic (8%) and other tissues (16%). HT occurred in 8% of MALT lymphomas. Risk of HT by 15 years was 5%: 4% in limited-stage diseases (n = 385) and 16% in advanced-stage diseases (n = 56) (P = 0·02). The median time to HT was 48 months (range, 4-139). Five-year progression-free survival (PFS) and overall survival (OS) rates after HT were 80% and 94%, respectively. Immunohistochemical results of DLBCL were as follows: germinal centre B-cell (GCB)/non-GCB, 37%/63%; CD10, 9%; BCL6, 59%; MUM1, 38%; MYC, 42%; BCL2, 35%; Ki67 ≥ 90%, 23%; and CD5, 3%. The majority (75%, 9/12) of GCB-type DLBCLs exhibited CD10(-) , BCL6(+) and MUM1(-) immunophenotypes; the remainder had CD10(+) immunophenotypes. Multivariate analysis revealed that only advanced stage at HT was a significant adverse factor for PFS (P = 0·037). Thus, overall risk of HT was low and prognosis after HT was favourable; however, in advanced-stage cases, risk of HT was relatively high and prognosis was unfavourable. © 2016 John Wiley & Sons Ltd.

  6. Attachment site selection of life stages of Ixodes ricinus ticks on a main large host in Europe, the red deer (Cervus elaphus).

    Science.gov (United States)

    Mysterud, Atle; Hatlegjerde, Idar Lauge; Sørensen, Ole Jakob

    2014-11-13

    Ticks and tick-borne diseases are increasing in many areas of Europe and North America due to climate change, while land use and the increased abundances of large hosts play a more controversial role. The pattern of host selection involves a crucial component for tick abundance. While the larvae and nymphs feed on a wide range of different sized hosts, the adult female ticks require blood meal from a large host (>1 kg), typically a deer, to fulfil the life cycle. Understanding the role of different hosts for abundances of ticks is therefore important, and also the extent to which different life stages attach to large hosts. We studied attachment site selection of life stages of I. ricinus ticks on a main large host in Europe, the red deer (Cervus elaphus). We collected from 33 felled red deer pieces of skin from five body parts: leg, groin, neck, back and ear. We counted the number of larval, nymphal, adult male and adult female ticks. Nymphs (42.2%) and adult (48.7%) ticks dominated over larvae (9.1%). There were more larvae on the legs (40.9%), more nymphs on the ears (83.7%), while adults dominated in the groins (89.2%) and neck (94.9%). Large mammalian hosts are thus a diverse habitat suitable for different life stages of ticks. The attachment site selection reflected the life stages differing ability to move. The spatial separation of life stages may partly limit the role of deer in co-feeding transmission cycles.

  7. Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zhao, K-X; Dai, G-Z; Zhu, J-F

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

  8. The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on 'EBV-positive DLBCL of the elderly'.

    Science.gov (United States)

    Uner, Aysegul; Akyurek, Nalan; Saglam, Arzu; Abdullazade, Samir; Uzum, Nuket; Onder, Sevgen; Barista, Ibrahim; Benekli, Mustafa

    2011-04-01

    Accumulated evidence has shown the importance of Epstein-Barr virus in the pathogenesis of various lymphomas. This study aimed to determine the prevalence of Epstein-Barr virus expression and its effect on survival amongst diffuse large B-cell lymphoma (DLBCL) cases from two large tertiary care centres in Turkey with a particular interest in identifying cases of 'Epstein-Barr virus-positive DLBCL of the elderly'. Diffuse large B-cell lymphoma cases diagnosed between 1999 and 2009 were retrieved and 340 cases were used to construct tissue microarrays. The presence of Epstein-Barr virus small ribonucleic acids was examined by in situ hybridization using Epstein-Barr virus (EBV)-encoded small RNA (EBER) oligonucleotides. A total of 18 cases (5.3%) showed Epstein-Barr virus expression. Twelve cases were classified as Epstein-Barr virus-positive DLBCL of the elderly. Epstein-Barr virus-positive DLBCL cases showed a significantly inferior overall survival as compared with Epstein-Barr virus-negative cases (p < 0.001). In our study group Epstein-Barr virus expression is not prevalent in DLBCLs. Epstein-Barr virus-positive DLBCL of the elderly is also rare in the Turkish population. The presence of Epstein-Barr virus, however, is associated with poor prognosis. © 2011 The Authors. APMIS © 2011 APMIS.

  9. L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation

    NARCIS (Netherlands)

    Zeimet, A.G.; Reimer, D.; Huszar, M.; Winterhoff, B.; Puistola, U.; Azim, S.A.; Muller-Holzner, E.; Ben-Arie, A.; Kempen, L.C.L.T. van; Petru, E.; Jahn, S.; Geels, Y.P.; Massuger, L.F.A.G.; Amant, F.; Polterauer, S.; Lappi-Blanco, E.; Bulten, J.; Meuter, A.; Tanouye, S.; Oppelt, P.; Stroh-Weigert, M.; Reinthaller, A.; Mariani, A.; Hackl, W.; Netzer, M.; Schirmer, U.; Vergote, I.; Altevogt, P.; Marth, C.; Fogel, M.

    2013-01-01

    BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to

  10. Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

    Science.gov (United States)

    Ida, K; Funaba, H; Kado, S; Narihara, K; Tanaka, K; Takeiri, Y; Nakamura, Y; Ohyabu, N; Yamazaki, K; Yokoyama, M; Murakami, S; Ashikawa, N; deVries, P C; Emoto, M; Goto, M; Idei, H; Ikeda, K; Inagaki, S; Inoue, N; Isobe, M; Itoh, K; Kaneko, O; Kawahata, K; Khlopenkov, K; Komori, A; Kubo, S; Kumazawa, R; Liang, Y; Masuzaki, S; Minami, T; Miyazawa, J; Morisaki, T; Morita, S; Mutoh, T; Muto, S; Nagayama, Y; Nakanishi, H; Nishimura, K; Noda, N; Notake, T; Kobuchi, T; Ohdachi, S; Ohkubo, K; Oka, Y; Osakabe, M; Ozaki, T; Pavlichenko, R O; Peterson, B J; Sagara, A; Saito, K; Sakakibara, S; Sakamoto, R; Sanuki, H; Sasao, H; Sasao, M; Sato, K; Sato, M; Seki, T; Shimozuma, T; Shoji, M; Suzuki, H; Sudo, S; Tamura, N; Toi, K; Tokuzawa, T; Torii, Y; Tsumori, K; Yamamoto, T; Yamada, H; Yamada, I; Yamaguchi, S; Yamamoto, S; Yoshimura, Y; Watanabe, K Y; Watari, T; Hamada, Y; Motojima, O; Fujiwara, M

    2001-06-04

    Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

  11. Minimal Loss of Lifetime for Patients With Diffuse Large B-Cell Lymphoma in Remission and Event Free 24 Months After Treatment

    DEFF Research Database (Denmark)

    Jakobsen, Lasse Hjort; Bøgsted, Martin; Brown, Peter de Nully

    2017-01-01

    Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched......). During the first 8 years after pEFS24, the average loss of lifetime was 0.31 mo/y (95% CI, 0.11 to 0.50 mo/y). Excess mortality diminished when analyzing death from lymphoma as competing event to death from other causes, suggesting that early and late relapse is responsible for increased mortality...

  12. An International Collaborative Study of Outcome and Prognostic Factors in Patients with Secondary CNS Involvement By Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Cheah, Chan Yoon; Bendtsen, Mette Dahl

    2016-01-01

    ) determine prognostic factors after SCNS.Patients and methods: We performed a retrospective study of patients diagnosed with SCNS during or after frontline immunochemotherapy (R-CHOP or equivalently effective regimens). SCNS was defined as new involvement of the CNS (parenchymal, leptomeningeal, and/or eye......Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically lt;6 months. However, data in patients...

  13. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Science.gov (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  14. Stages of Change, Smoking Behaviour and Readiness to Quit in a Large Sample of Indigenous Australians Living in Eight Remote North Queensland Communities

    Directory of Open Access Journals (Sweden)

    Robyn McDermott

    2013-04-01

    Full Text Available Tobacco smoking is a major health issue for Indigenous Australians, however there are few interventions with demonstrated efficacy in this population. The Transtheoretical Model may provide a useful framework for describing smoking behaviour and assessing readiness to quit, with the aim of developing better interventions. Interviews were conducted with 593 Indigenous Australians in eight rural and remote communities in north Queensland, to examine stages of change and smoking behaviour. Among current smokers, 39.6% and 43.4% were in Precontemplation and Contemplation stages respectively. A further 13.9% were making preparations to quit (Preparation whilst only 3.2% said they were actively trying to quit (Action. When analysed by stage of change, the pattern of smoking-related behaviours conformed to the results of past research using the model. Importantly however, distribution of individuals across the stages opposes those observed in investigations of smoking behaviour in non-Indigenous Australian populations. The Transtheoretical Model can be used to meaningfully classify Indigenous smokers in remote north Queensland according to stages along the behaviour change continuum. Importantly, in this large sample across eight communities, most Indigenous smokers were not making preparations to change their smoking behaviour. This suggests that interventions should focus on promoting movement toward the Preparation and Action stages of change.

  15. Diagnosis, clinical staging, and treatment of breast cancer: a retrospective multiyear study of a large controlled population.

    Science.gov (United States)

    Legorreta, Antonio P; Chernicoff, Helen O; Trinh, Jennifer B; Parker, Robert G

    2004-04-01

    This study compares diagnosis, staging, and treatment of newly diagnosed breast cancer cases over a several-year period. The study design was a retrospective, multiyear comparison between new breast cancer cases diagnosed in 1995 (n = 827) and 1997 (n = 815). Cases were identified through claims data, and medical record abstraction was used to verify each case and to identify clinical staging and type of treatment. All medical records were reviewed by one physician to maximize internal reliability. Both cohorts were predominantly 40 and older, white, married, and postmenopausal. The latter cohort (1997) had a higher proportion of women aged 70 to 79 and a lower proportion of women aged 40 to 49. In both cohorts, women age 40 and older were likely to be diagnosed with breast cancer at the time of mammographic screening, while women younger than 40 were more likely to be diagnosed by clinical breast examination. In logistic regression analyses, controlling for confounding factors such as age, undergoing mammographic screening increased the likelihood of having a low cancer stage at diagnosis by more than three and a half times. Mammographic screening was statistically significantly positively associated with having eligibility for breast-conserving treatment (BCT); however, although an increase in BCT eligibility was observed, actual use of BCT did not change. Mammography leads to a lower clinical stage as well as a greater likelihood of BCT eligibility at time of breast cancer diagnosis, but may not have a substantial effect on treatment choice (lumpectomy vs. mastectomy). Between 1995 and 1997, a trend was observed toward downstaging of disease at diagnosis; further research is warranted to observe whether this trend continues over time.

  16. Large-Scale Liquid Hydrogen Tank Rapid Chill and Fill Testing for the Advanced Shuttle Upper Stage Concept

    Science.gov (United States)

    Flachbart, R. H.; Hedayat, A.; Holt, K. A.; Sims, J.; Johnson, E. F.; Hastings, L. J.; Lak, T.

    2013-01-01

    Cryogenic upper stages in the Space Shuttle program were prohibited primarily due to a safety risk of a 'return to launch site' abort. An upper stage concept addressed this concern by proposing that the stage be launched empty and filled using shuttle external tank residuals after the atmospheric pressure could no longer sustain an explosion. However, only about 5 minutes was allowed for tank fill. Liquid hydrogen testing was conducted within a near-ambient environment using the multipurpose hydrogen test bed 638.5 ft3 (18m3) cylindrical tank with a spray bar mounted longitudinally inside. Although the tank was filled within 5 minutes, chilldown of the tank structure was incomplete, and excessive tank pressures occurred upon vent valve closure. Elevated tank wall temperatures below the liquid level were clearly characteristic of film boiling. The test results have substantial implications for on-orbit cryogen transfer since the formation of a vapor film would be much less inhibited due to the reduced gravity. However, the heavy tank walls could become an asset in normal gravity testing for on-orbit transfer, i.e., if film boiling in a nonflight weight tank can be inhibited in normal gravity, then analytical modeling anchored with the data could be applied to reduced gravity environments with increased confidence.

  17. Indoor NO/sub 2/ sampling in a large university campus in Benin city, southern Nigeria, using flames diffusion tubes

    International Nuclear Information System (INIS)

    Ukpebor, E.E.; Sadiku, Y.T.; Ahonkhai, S.I.

    2005-01-01

    Monitoring of NO/sub 2/ in different indoor environments (without cooking and with cooking using different fuels) was done. Flames diffusion tubes were used for the monitoring. The sampling duration was two weeks. The highest NO/sub 2/ concentration of 38.61 ppb (73.74 mug/m3) was monitored in the room where the cooking was done with a gas burner. This was followed by the room with firewood cooking, where the concentration was 36.75 ppb (70.19 mug/m3) and the least concentration of 24.05 ppb (46.80 mug/m3) was noted in the room, where kerosene stove was used for cooking. It is of significance to observe that the WHO annual average guideline value of 40 mug/m3 was exceeded in al the rooms where cooking was done. Levels obtained in this study, therefore, suggest a need for precautionary mitigation. However, the outdoor concentration of NO/sub 2/ was almost the same as that obtained indoors in the rooms without cooking. This suggests high penetration indoors of outdoor NO/sub 2/. A background level of 3.40 ppb (6.49 mug/m3) was established for the environment in Ugbowo, Benin City, Nigeria. (author)

  18. Excellent outcome of immunomodulation or Bruton’s tyrosine kinase inhibition in highly refractory primary cutaneous diffuse large B-cell lymphoma, leg type

    Directory of Open Access Journals (Sweden)

    Eva Gupta

    2015-12-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton’s tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

  19. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  20. STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

    Science.gov (United States)

    Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2015-09-01

    Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

  1. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    A León-Suárez

    2016-12-01

    Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

  2. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Georg Lenz

    2015-05-01

    Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  3. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Energy Technology Data Exchange (ETDEWEB)

    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  4. Too fresh is unattractive! The attraction of newly emerged Nicrophorus vespilloides females to odour bouquets of large cadavers at various stages of decomposition.

    Directory of Open Access Journals (Sweden)

    Christian von Hoermann

    Full Text Available The necrophagous burying beetle Nicrophorus vespilloides reproduces on small carcasses that are buried underground to serve as food for their offspring. Cadavers that are too large to bury have previously been postulated to be important food sources for newly emerged beetles; however, the attractiveness of distinct successive stages of decomposition were not further specified. Therefore, we investigated the potential preference of newly emerged N. vespilloides females for odour bouquets of piglet cadavers at specific stages of decomposition. Analyses of walking tracks on a Kramer sphere revealed a significantly higher mean walking speed and, consequently, a higher mean total track length when beetles were confronted with odour plumes of the decomposition stages 'post-bloating', 'advanced decay' or 'dry remains' in comparison with the solvent control. Such a change of the walking speed of newly emerged N. vespilloides females indicates a higher motivation to locate such food sources. In contrast to less discriminating individuals this behaviour provides the advantage of not wasting time at unsuitable food sources. Furthermore, in the advanced decay stage, we registered a significantly higher preference of beetles for upwind directions to its specific odour plume when compared with the solvent control. Such a change to upwind walking behaviour increases the likelihood that a large cadaver will be quickly located. Our findings are of general importance for applied forensic entomology: newly emerged N. vespilloides females on large cadavers can and should be regarded as potential indicators of prolonged post mortem intervals as our results clearly show that they prefer emitted odour bouquets of later decomposition stages.

  5. Standardized uptake value for (18)F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Akkas, B E; Vural, G U

    2014-01-01

    The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). 77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. PET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0-1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. FDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  6. No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort.

    Science.gov (United States)

    Muether, Philipp S; Kribs, Angela; Hahn, Moritz; Schumacher, Jasmin; Eifinger, Frank; Kirchhof, Bernd; Roth, Bernhard; Fauser, Sascha

    2012-03-01

    Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of 3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.

  7. Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

    Directory of Open Access Journals (Sweden)

    Mark op den Winkel

    Full Text Available HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival.Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC and the concordance-index (c-index: BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4% was the leading etiological factor followed by viral hepatitis C (18.8%. Median survival was 18.1 months (95%-CI: 15.2-22.2. Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71, surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66. The unidimensional scores TNM (AIC 2342, c-index 0.64 and Child-Pugh (AIC 2369, c-index 0.63 performed in an inferior fashion.Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.

  8. Too Fresh Is Unattractive! The Attraction of Newly Emerged Nicrophorus vespilloides Females to Odour Bouquets of Large Cadavers at Various Stages of Decomposition

    OpenAIRE

    von Hoermann, Christian; Steiger, Sandra; M?ller, Josef K.; Ayasse, Manfred

    2013-01-01

    The necrophagous burying beetle Nicrophorus vespilloides reproduces on small carcasses that are buried underground to serve as food for their offspring. Cadavers that are too large to bury have previously been postulated to be important food sources for newly emerged beetles; however, the attractiveness of distinct successive stages of decomposition were not further specified. Therefore, we investigated the potential preference of newly emerged N. vespilloides females for odour bouquets of pi...

  9. A second stage homogenization method

    International Nuclear Information System (INIS)

    Makai, M.

    1981-01-01

    A second homogenization is needed before the diffusion calculation of the core of large reactors. Such a second stage homogenization is outlined here. Our starting point is the Floquet theorem for it states that the diffusion equation for a periodic core always has a particular solution of the form esup(j)sup(B)sup(x) u (x). It is pointed out that the perturbation series expansion of function u can be derived by solving eigenvalue problems and the eigenvalues serve to define homogenized cross sections. With the help of these eigenvalues a homogenized diffusion equation can be derived the solution of which is cos Bx, the macroflux. It is shown that the flux can be expressed as a series of buckling. The leading term in this series is the well known Wigner-Seitz formula. Finally three examples are given: periodic absorption, a cell with an absorber pin in the cell centre, and a cell of three regions. (orig.)

  10. Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

    Science.gov (United States)

    Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

    2015-10-01

    Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

  11. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report.

    Science.gov (United States)

    Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

    2006-10-19

    Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

  12. Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

    Science.gov (United States)

    Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

    2017-07-01

    The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

  13. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

    Directory of Open Access Journals (Sweden)

    Dehghani Mehdi

    2006-01-01

    Full Text Available Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

  14. Local Recurrence in Women With Stage I Breast Cancer: Declining Rates Over Time in a Large, Population-Based Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, Joycelin, E-mail: canavanjoycelin@gmail.com [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Truong, Pauline T.; Smith, Sally L. [Radiation Therapy Program and Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, British Columbia (Canada); Lu, Linghong; Lesperance, Mary [Department of Mathematics and Statistics, University of Victoria, British Columbia (Canada); Olivotto, Ivo A. [Department of Radiation Oncology, Tom Baker Cancer Centre, University of Calgary (Canada)

    2014-01-01

    Purpose: To evaluate whether local recurrence (LR) risk has changed over time among women with stage I breast cancer treated with breast-conserving therapy. Methods and Materials: Subjects were 5974 women aged ≥50 years diagnosis with pT1N0 breast cancer from 1989 to 2006, treated with breast-conserving surgery and radiation therapy. Clinicopathologic characteristics, treatment, and LR outcomes were compared among 4 cohorts stratified by year of diagnosis: 1989 to 1993 (n=1077), 1994 to 1998 (n=1633), 1999 to 2002 (n=1622), and 2003 to 2006 (n=1642). Multivariable analysis was performed, with year of diagnosis as a continuous variable. Results: Median follow-up time was 8.6 years. Among patients diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the proportions of grade 1 tumors increased (16% vs 29% vs 40% vs 39%, respectively, P<.001). Surgical margin clearance rates increased from 82% to 93% to 95% and 88%, respectively (P<.001). Over time, the proportions of unknown estrogen receptor (ER) status decreased (29% vs 10% vs 1.2% vs 0.5%, respectively, P<.001), whereas ER-positive tumors increased (56% vs 77% vs 86% vs 86%, respectively, P<.001). Hormone therapy use increased (23% vs 23% vs 62% vs 73%, respectively, P<.001), and chemotherapy use increased (2% vs 5% vs 10% vs 13%, respectively, P<.001). The 5-year cumulative incidence rates of LR over the 4 time periods were 2.8% vs 1.7% vs 0.9% vs 0.8%, respectively (Gray's test, P<.001). On competing risk multivariable analysis, year of diagnosis was significantly associated with decreased LR (hazard ratio, 0.92 per year, P=.0003). Relative to grade 1 histology, grades 2, 3, and unknown were associated with increased LR. Hormone therapy use was associated with reduced LR. Conclusion: Significant changes in the multimodality management of stage I breast cancer have occurred over the past 2 decades. More favorable-risk tumors were diagnosed, and margin clearance and systemic therapy use

  15. Local Recurrence in Women With Stage I Breast Cancer: Declining Rates Over Time in a Large, Population-Based Cohort

    International Nuclear Information System (INIS)

    Canavan, Joycelin; Truong, Pauline T.; Smith, Sally L.; Lu, Linghong; Lesperance, Mary; Olivotto, Ivo A.

    2014-01-01

    Purpose: To evaluate whether local recurrence (LR) risk has changed over time among women with stage I breast cancer treated with breast-conserving therapy. Methods and Materials: Subjects were 5974 women aged ≥50 years diagnosis with pT1N0 breast cancer from 1989 to 2006, treated with breast-conserving surgery and radiation therapy. Clinicopathologic characteristics, treatment, and LR outcomes were compared among 4 cohorts stratified by year of diagnosis: 1989 to 1993 (n=1077), 1994 to 1998 (n=1633), 1999 to 2002 (n=1622), and 2003 to 2006 (n=1642). Multivariable analysis was performed, with year of diagnosis as a continuous variable. Results: Median follow-up time was 8.6 years. Among patients diagnosed in 1989 to 1993, 1994 to 1998, 1999 to 2002, and 2003 to 2006, the proportions of grade 1 tumors increased (16% vs 29% vs 40% vs 39%, respectively, P<.001). Surgical margin clearance rates increased from 82% to 93% to 95% and 88%, respectively (P<.001). Over time, the proportions of unknown estrogen receptor (ER) status decreased (29% vs 10% vs 1.2% vs 0.5%, respectively, P<.001), whereas ER-positive tumors increased (56% vs 77% vs 86% vs 86%, respectively, P<.001). Hormone therapy use increased (23% vs 23% vs 62% vs 73%, respectively, P<.001), and chemotherapy use increased (2% vs 5% vs 10% vs 13%, respectively, P<.001). The 5-year cumulative incidence rates of LR over the 4 time periods were 2.8% vs 1.7% vs 0.9% vs 0.8%, respectively (Gray's test, P<.001). On competing risk multivariable analysis, year of diagnosis was significantly associated with decreased LR (hazard ratio, 0.92 per year, P=.0003). Relative to grade 1 histology, grades 2, 3, and unknown were associated with increased LR. Hormone therapy use was associated with reduced LR. Conclusion: Significant changes in the multimodality management of stage I breast cancer have occurred over the past 2 decades. More favorable-risk tumors were diagnosed, and margin clearance and systemic therapy use

  16. Shades of white : diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia

    NARCIS (Netherlands)

    Riphagen, Joost M.; Gronenschild, Ed HBM; Salat, David H.; Freeze, Whitney M.; Ivanov, Dimo; Clerx, Lies; Verhey, Frans R. J.; Aalten, Pauline; Jacobs, Heidi I. L.

    The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on

  17. Neurocognitive stages of spatial cognitive mapping measured during free exploration of a large-scale virtual environment.

    Science.gov (United States)

    Plank, Markus; Snider, Joseph; Kaestner, Erik; Halgren, Eric; Poizner, Howard

    2015-02-01

    Using a novel, fully mobile virtual reality paradigm, we investigated the EEG correlates of spatial representations formed during unsupervised exploration. On day 1, subjects implicitly learned the location of 39 objects by exploring a room and popping bubbles that hid the objects. On day 2, they again popped bubbles in the same environment. In most cases, the objects hidden underneath the bubbles were in the same place as on day 1. However, a varying third of them were misplaced in each block. Subjects indicated their certainty that the object was in the same location as the day before. Compared with bubble pops revealing correctly placed objects, bubble pops revealing misplaced objects evoked a decreased negativity starting at 145 ms, with scalp topography consistent with generation in medial parietal cortex. There was also an increased negativity starting at 515 ms to misplaced objects, with scalp topography consistent with generation in inferior temporal cortex. Additionally, misplaced objects elicited an increase in frontal midline theta power. These findings suggest that the successive neurocognitive stages of processing allocentric space may include an initial template matching, integration of the object within its spatial cognitive map, and memory recall, analogous to the processing negativity N400 and theta that support verbal cognitive maps in humans. Copyright © 2015 the American Physiological Society.

  18. Large-Time Behavior of Solutions to Vlasov-Poisson-Fokker-Planck Equations: From Evanescent Collisions to Diffusive Limit

    Science.gov (United States)

    Herda, Maxime; Rodrigues, L. Miguel

    2018-03-01

    The present contribution investigates the dynamics generated by the two-dimensional Vlasov-Poisson-Fokker-Planck equation for charged particles in a steady inhomogeneous background of opposite charges. We provide global in time estimates that are uniform with respect to initial data taken in a bounded set of a weighted L^2 space, and where dependencies on the mean-free path τ and the Debye length δ are made explicit. In our analysis the mean free path covers the full range of possible values: from the regime of evanescent collisions τ → ∞ to the strongly collisional regime τ → 0. As a counterpart, the largeness of the Debye length, that enforces a weakly nonlinear regime, is used to close our nonlinear estimates. Accordingly we pay a special attention to relax as much as possible the τ -dependent constraint on δ ensuring exponential decay with explicit τ -dependent rates towards the stationary solution. In the strongly collisional limit τ → 0, we also examine all possible asymptotic regimes selected by a choice of observation time scale. Here also, our emphasis is on strong convergence, uniformity with respect to time and to initial data in bounded sets of a L^2 space. Our proofs rely on a detailed study of the nonlinear elliptic equation defining stationary solutions and a careful tracking and optimization of parameter dependencies of hypocoercive/hypoelliptic estimates.

  19. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    Science.gov (United States)

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  20. Synchronous Microscopic Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Adrenal and Lymphoplasmacytic Lymphoma: De Novo Disease or Transformation?

    Science.gov (United States)

    Moonim, Mufaddal T; Nasir, Alia; Hubbard, Jonathan; Ketley, Nicholas; Fields, Paul

    2017-06-01

    Lymphomas arising in the adrenal are rare, and to our knowledge, 2 cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (DLBCL) in an adrenal pseudocyst have been reported. We report an incidental EBV-positive DLBCL arising in an adrenal pseudocyst in a 58-year-old man with a 7-year history of lymphoplasmacytic lymphoma (LPL). The DLBCL was present in the fibrinous exudate, while the LPL resided in the cyst wall. The patient underwent de-roofing of the same cyst 3 years previously; review of histology revealed foci of LPL in the cyst wall, but not of DLBCL. There have been reports of similar microscopic EBV-positive DLBCLs within enclosed cystic spaces. However, all these cases were incidental extranodal primary DLBCLs. Since residual LPL was present alongside DLBCL, with similar light chain restriction, we propose that this may represent transformation, rather than a de novo primary EBV-driven lymphoma.

  1. Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease

    DEFF Research Database (Denmark)

    Brauner, S; Zhou, W; Backlin, C

    2015-01-01

    OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21...... in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated...... with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR...

  2. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Brown, P J; Wong, K K; Felce, S L

    2016-01-01

    The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II......) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes......, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (PABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone...

  3. DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Loo, Suet Kee; Ch'ng, Ewe Seng; Lawrie, Charles H

    2017-01-01

    .9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p p ...DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90......% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p

  4. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

    Science.gov (United States)

    Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

    2016-11-20

    Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

  5. The impact of changes in parameterizations of surface drag and vertical diffusion on the large-scale circulation in the Community Atmosphere Model (CAM5)

    Science.gov (United States)

    Lindvall, Jenny; Svensson, Gunilla; Caballero, Rodrigo

    2017-06-01

    Simulations with the Community Atmosphere Model version 5 (CAM5) are used to analyze the sensitivity of the large-scale circulation to changes in parameterizations of orographic surface drag and vertical diffusion. Many GCMs and NWP models use enhanced turbulent mixing in stable conditions to improve simulations, while CAM5 cuts off all turbulence at high stabilities and instead employs a strong orographic surface stress parameterization, known as turbulent mountain stress (TMS). TMS completely dominates the surface stress over land and reduces the near-surface wind speeds compared to simulations without TMS. It is found that TMS is generally beneficial for the large-scale circulation as it improves zonal wind speeds, Arctic sea level pressure and zonal anomalies of the 500-hPa stream function, compared to ERA-Interim. It also alleviates atmospheric blocking frequency biases in the Northern Hemisphere. Using a scheme that instead allows for a modest increase of turbulent diffusion at higher stabilities only in the planetary boundary layer (PBL) appears to in some aspects have a similar, although much smaller, beneficial effect as TMS. Enhanced mixing throughout the atmospheric column, however, degrades the CAM5 simulation. Evaluating the simulations in comparison with detailed measurements at two locations reveals that TMS is detrimental for the PBL at the flat grassland ARM Southern Great Plains site, giving too strong wind turning and too deep PBLs. At the Sodankylä forest site, the effect of TMS is smaller due to the larger local vegetation roughness. At both sites, all simulations substantially overestimate the boundary layer ageostrophic flow.

  6. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

    Directory of Open Access Journals (Sweden)

    Song G

    2016-06-01

    Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

  7. Experimental investigations on bubble turbulent diffusion in a vertical large diameter pipe by means of wire-mesh sensors and correlation techniques

    International Nuclear Information System (INIS)

    Annalisa Manera; Horst-Michael Prasser; Dirk Lucas

    2005-01-01

    Full text of publication follows: A large number of experiments for water-air vertical flows in a large-diameter pipe has been carried out at the TOPFLOW facility (Forschunszentrum Rossendorf). The experiments cover a wide range of liquid and superficial gas velocity. The test section consists of a vertical pipe of ∼194 mm and 8.5 m long. At a distance of 7.6 m from the air injection, two wire-mesh sensors are installed. The two sensors are mounted at a distance of 63.3 mm from each other. The wire-mesh sensors measure sequences of instantaneous two-dimensional gas-fraction distributions in the cross-section in which they are mounted with a spatial resolution of 3 mm and a frequency of 2500 Hz. The total dimension of the matrix of measuring points for each mesh sensor is 64 x 64. In a central region of the measuring plane, where the void-fraction gradients are small, points of the first wire-mesh sensor are individually cross-correlated in time domain with measuring points belonging to the second wire-mesh sensor. The cross-correlation functions were calculated for pairs of points that are located accurately above each other as well as for points with a lateral distance. The lateral distance was varied from 0 to 48 mm (16 points), which is still within 50% of the pipe radius, i.e. in the region of small void-fraction gradients. The maximum of each of the 17 correlations is selected in order to derive a spatial correlation in the radial direction. The obtained spatial cross-correlations shows a maximum at zero lateral distance and decrease with growing lateral shift. In a region without gradients, the lateral displacement of bubbles is dominated by turbulent diffusion. This gives the opportunity to derive bubble turbulent diffusion coefficients from the spreading of the spatial correlations. At this aim, the spatial correlations have been first corrected to take into account the finite spatial resolution of the sensor and the finite dimension of the bubbles. The

  8. Large scale simulation of liquid water transport in a gas diffusion layer of polymer electrolyte membrane fuel cells using the lattice Boltzmann method

    Science.gov (United States)

    Sakaida, Satoshi; Tabe, Yutaka; Chikahisa, Takemi

    2017-09-01

    A method for the large-scale simulation with the lattice Boltzmann method (LBM) is proposed for liquid water movement in a gas diffusion layer (GDL) of polymer electrolyte membrane fuel cells. The LBM is able to analyze two-phase flows in complex structures, however the simulation domain is limited due to heavy computational loads. This study investigates a variety means to reduce computational loads and increase the simulation areas. One is applying an LBM treating two-phases as having the same density, together with keeping numerical stability with large time steps. The applicability of this approach is confirmed by comparing the results with rigorous simulations using actual density. The second is establishing the maximum limit of the Capillary number that maintains flow patterns similar to the precise simulation; this is attempted as the computational load is inversely proportional to the Capillary number. The results show that the Capillary number can be increased to 3.0 × 10-3, where the actual operation corresponds to Ca = 10-5∼10-8. The limit is also investigated experimentally using an enlarged scale model satisfying similarity conditions for the flow. Finally, a demonstration is made of the effects of pore uniformity in GDL as an example of a large-scale simulation covering a channel.

  9. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

    Directory of Open Access Journals (Sweden)

    Lina Quan

    Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

  10. Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

    International Nuclear Information System (INIS)

    Paone, Gaetano; Itti, Emmanuel; Lin, Chieh; Meignan, Michel; Haioun, Corinne; Dupuis, Jehan; Gaulard, Philippe

    2009-01-01

    To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

  11. Large Interstellar Polarisation Survey. II. UV/optical study of cloud-to-cloud variations of dust in the diffuse ISM

    Science.gov (United States)

    Siebenmorgen, R.; Voshchinnikov, N. V.; Bagnulo, S.; Cox, N. L. J.; Cami, J.; Peest, C.

    2018-03-01

    It is well known that the dust properties of the diffuse interstellar medium exhibit variations towards different sight-lines on a large scale. We have investigated the variability of the dust characteristics on a small scale, and from cloud-to-cloud. We use low-resolution spectro-polarimetric data obtained in the context of the Large Interstellar Polarisation Survey (LIPS) towards 59 sight-lines in the Southern Hemisphere, and we fit these data using a dust model composed of silicate and carbon particles with sizes from the molecular to the sub-micrometre domain. Large (≥6 nm) silicates of prolate shape account for the observed polarisation. For 32 sight-lines we complement our data set with UVES archive high-resolution spectra, which enable us to establish the presence of single-cloud or multiple-clouds towards individual sight-lines. We find that the majority of these 35 sight-lines intersect two or more clouds, while eight of them are dominated by a single absorbing cloud. We confirm several correlations between extinction and parameters of the Serkowski law with dust parameters, but we also find previously undetected correlations between these parameters that are valid only in single-cloud sight-lines. We find that interstellar polarisation from multiple-clouds is smaller than from single-cloud sight-lines, showing that the presence of a second or more clouds depolarises the incoming radiation. We find large variations of the dust characteristics from cloud-to-cloud. However, when we average a sufficiently large number of clouds in single-cloud or multiple-cloud sight-lines, we always retrieve similar mean dust parameters. The typical dust abundances of the single-cloud cases are [C]/[H] = 92 ppm and [Si]/[H] = 20 ppm.

  12. Evaluation of single and two-stage adaptive sampling designs for estimation of density and abundance of freshwater mussels in a large river

    Science.gov (United States)

    Smith, D.R.; Rogala, J.T.; Gray, B.R.; Zigler, S.J.; Newton, T.J.

    2011-01-01

    Reliable estimates of abundance are needed to assess consequences of proposed habitat restoration and enhancement projects on freshwater mussels in the Upper Mississippi River (UMR). Although there is general guidance on sampling techniques for population assessment of freshwater mussels, the actual performance of sampling designs can depend critically on the population density and spatial distribution at the project site. To evaluate various sampling designs, we simulated sampling of populations, which varied in density and degree of spatial clustering. Because of logistics and costs of large river sampling and spatial clustering of freshwater mussels, we focused on adaptive and non-adaptive versions of single and two-stage sampling. The candidate designs performed similarly in terms of precision (CV) and probability of species detection for fixed sample size. Both CV and species detection were determined largely by density, spatial distribution and sample size. However, designs did differ in the rate that occupied quadrats were encountered. Occupied units had a higher probability of selection using adaptive designs than conventional designs. We used two measures of cost: sample size (i.e. number of quadrats) and distance travelled between the quadrats. Adaptive and two-stage designs tended to reduce distance between sampling units, and thus performed better when distance travelled was considered. Based on the comparisons, we provide general recommendations on the sampling designs for the freshwater mussels in the UMR, and presumably other large rivers.

  13. NASA/DOD Aerospace Knowledge Diffusion Research Project. Report 34: How early career-stage US aerospace engineers and scientists produce and use information

    Science.gov (United States)

    Pinelli, Thomas E.; Barclay, Rebecca O.; Kennedy, John M.

    1995-01-01

    The U.S. government technical report is a primary means by which the results of federally funded research and development (R&D) are transferred to the U.S. aerospace industry. However, little is known about this information product in terms of its actual use, importance, and value in the transfer of federally funded R&D. To help establish a body of knowledge, the U.S. government technical report is being investigated as part of the NASA/DOD Aerospace Knowledge Diffusion Research Project. In this report, we summarize the literature on technical reports and provide a model that depicts the transfer of federally funded aerospace R&D via the U.S. government technical report. We present results from our investigation of aerospace knowledge diffusion vis-a-vis the U.S. government technical report, and present the results of research that investigated aerospace knowledge diffusion vis-a-vis the production and use of information by U.S. aerospace engineers and scientists who had changed their American Institute of Aeronautics and Astronautics (AIAA) membership from student to professional in the past five years.

  14. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Moller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkaer, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab,

  15. Consecutive Short-Scan CT for Geological Structure Analog Models with Large Size on In-Situ Stage.

    Science.gov (United States)

    Yang, Min; Zhang, Wen; Wu, Xiaojun; Wei, Dongtao; Zhao, Yixin; Zhao, Gang; Han, Xu; Zhang, Shunli

    2016-01-01

    For the analysis of interior geometry and property changes of a large-sized analog model during a loading or other medium (water or oil) injection process with a non-destructive way, a consecutive X-ray computed tomography (XCT) short-scan method is developed to realize an in-situ tomography imaging. With this method, the X-ray tube and detector rotate 270° around the center of the guide rail synchronously by switching positive and negative directions alternately on the way of translation until all the needed cross-sectional slices are obtained. Compared with traditional industrial XCTs, this method well solves the winding problems of high voltage cables and oil cooling service pipes during the course of rotation, also promotes the convenience of the installation of high voltage generator and cooling system. Furthermore, hardware costs are also significantly decreased. This kind of scanner has higher spatial resolution and penetrating ability than medical XCTs. To obtain an effective sinogram which matches rotation angles accurately, a structural similarity based method is applied to elimination of invalid projection data which do not contribute to the image reconstruction. Finally, on the basis of geometrical symmetry property of fan-beam CT scanning, a whole sinogram filling a full 360° range is produced and a standard filtered back-projection (FBP) algorithm is performed to reconstruct artifacts-free images.

  16. Safety and efficacy of staged retrograde intrarenal surgery for large stone burden of renal stones in selected patients: A single-center experience

    Directory of Open Access Journals (Sweden)

    Cheng-Feng Lin

    2017-06-01

    Conclusion: To the best of our knowledge, RIRS for large renal stone manipulation is an effective and safe treatment modality currently. In our study, the single RIRS SFR was superior to PNL or SWL even when the stone burden was between 2.0 cm and 3.0 cm (80.2%. For those patients whose stone burden was over 3.0 cm or for those with comorbidities, staged RIRS resulted in a lower complication rate, reduced hospital stay, and better SFR (76.5%.

  17. A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2016-08-01

    Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

  18. Promoter methylation patterns in Richter syndrome affect stem-cell maintenance and cell cycle regulation and differ from de novo diffuse large B-cell lymphoma.

    Science.gov (United States)

    Rinaldi, Andrea; Mensah, Afua Adjeiwaa; Kwee, Ivo; Forconi, Francesco; Orlandi, Ester M; Lucioni, Marco; Gattei, Valter; Marasca, Roberto; Berger, Françoise; Cogliatti, Sergio; Cavalli, Franco; Zucca, Emanuele; Gaidano, Gianluca; Rossi, Davide; Bertoni, Francesco

    2013-10-01

    In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We studied genome-wide promoter DNA methylation in RS and clonally related CLL-phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B type), untransformed-CLL and normal B-cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. RS was more highly methylated for genes involved in cell cycle regulation. When RS was compared to the preceding CLL-phase and with untransformed-CLL, RS presented a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2 targets, as well as for gene targets of TP53 and RB1. Comparison of the methylation levels of individual genes revealed that OSM, a stem cell regulatory gene, exhibited significantly higher methylation levels in RS compared to CLL-phases. Its transcriptional repression by DNA methylation was confirmed by 5-aza-2'deoxycytidine treatment of DLBCL cells, determining an increased OSM expression. Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell-related genes and cell cycle regulation genes are targets of DNA methylation in RS. © 2013 John Wiley & Sons Ltd.

  19. Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

    Directory of Open Access Journals (Sweden)

    Tirado Carlos A

    2012-09-01

    Full Text Available Abstract Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH, as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS. The advent of microarray-based studies (chromosome, RNA, gene expression, etc has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1 array based CGH; 2 classical CGH; and 3 gene expression profiling studies. The aims of this review were three-fold: (1 to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2 to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3 to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such

  20. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  1. Return to work for patients with diffuse large B-cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Arboe, Bente; Olsen, Maja Halgren; Goerloev, Jette Soenderskov

    2017-01-01

    BACKGROUND: Autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL) or transformed indolent lymphoma (TIL). The treatment is mainly considered for younger patients still available for the work market. In this study...... to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5]) and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]). In all, 56 (27%) patients were granted disability pension. Being...... on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]). CONCLUSION: Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore...

  2. A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

    Directory of Open Access Journals (Sweden)

    Geoffrey Shouse

    2018-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

  3. EBV-positive diffuse large B-cell lymphoma in a patient with primary Sjögren’s syndrome and membranous glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Kim Chang

    2012-11-01

    Full Text Available Abstract Background Sjögren’s syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren’s syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren’s syndrome has seldom been reported. Case presentation A 52-year-old woman with primary Sjögren’s syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL. She was diagnosed with Sjögren’s syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL. Conclusions We observed the first case of primary Sjögren’s syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren’s syndrome, we should be careful and examine such patients for hidden malignancy.

  4. Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

    Science.gov (United States)

    Park, Young Hoon; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo; Lim, Joo Han

    2017-01-01

    The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy. © 2017 S. Karger AG, Basel.

  5. Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A.; Nievelstein, Rutger A.J.; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Heggelman, Ben G.F. [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Dubois, Stefan V. [Meander Medical Center, Department of Pathology, Amersfoort (Netherlands)

    2015-05-01

    To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL. (orig.)

  6. The truncate mutation of Notch2 enhances cell proliferation through activating the NF-κB signal pathway in the diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Xinxia Zhang

    Full Text Available The Notch2 is a critical membrane receptor for B-cell functions, and also displays various biological roles in lymphoma pathogenesis. In this article, we reported that 3 of 69 (4.3% diffuse large B-cell lymphomas (DLBCLs exhibited a truncate NOTCH2 mutation at the nucleotide 7605 (G/A in the cDNA sequence, which led to partial deletion of the C-terminal of PEST (proline-, glutamic acid-, serine- and threonine-rich domain. The truncate Notch2 activated both the Notch2 and the NF-κB signals and promoted the proliferation of B-cell lymphoma cell lines, including DLBCL and Burkitt's lymphoma cell lines. Moreover, the ectopic proliferation was completely inhibited by ammonium pyrrolidinedithiocarbamate (PDTC, an NF-κB inhibitor. Simultaneously, PDTC also reduced the expression level of Notch2. Based on these results, we conclude that the Notch2 receptor with PEST domain truncation enhances cell proliferation which may be associated with the activation of the Notch2 and the NF-κB signaling. Our results are expected to provide a possible target for new DLBCL therapies by suppressing the Notch2 and the NF-κB signaling.

  7. Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

    Science.gov (United States)

    Zhang, Yaping; Wang, Xinfeng; Liu, Yifei; Sun, Chunfeng; Shi, Wenyu; Huang, Hongming

    2018-07-03

    CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

  8. Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

    Science.gov (United States)

    Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

    2017-02-01

    The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

  9. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    Science.gov (United States)

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  10. The Glasgow Prognostic Score as a significant predictor of diffuse large B cell lymphoma treated with R-CHOP in China.

    Science.gov (United States)

    Li, Xiaoyang; Zhang, Yunxiang; Zhao, Weili; Liu, Zhao; Shen, Yang; Li, Junmin; Shen, Zhixiang

    2015-01-01

    The Glasgow Prognostic Score (GPS) incorporates C-reactive protein and albumin as clinically useful markers of tumor behavior and shows significant prognostic value in several types of solid tumors. The accuracy of the GPS in predicting outcomes in diffuse large B cell lymphoma (DLBCL) remains unknown. We performed this study to evaluate the prognostic significance of the GPS in DLBCL in China. We retrospectively analyzed 160 patients with newly diagnosed DLBCL at the Shanghai Ruijin Hospital (China). The prognostic value of the GPS was evaluated and compared with that of the International Prognostic Index (IPI) and immunohistochemical subtyping. The GPS was defined as follows: GPS-0, C-reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L; GPS-1, CRP >10 mg/L or albumin L; and GPS-2, CRP >10 mg/L and albumin L. Patients with lower GPS tended to have better outcomes including progression-free survival (PFS, P GPS and high IPI score were independent adverse predictors of OS. Similar to several other tumors, GPS is a reliable predictor of survival outcomes in DLBCL patients treated with R-CHOP therapy. Inflammatory responses are implicated in the progression and survival of patients with DLBCL.

  11. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  12. Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

    Science.gov (United States)

    Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

    2017-05-01

    Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

  13. Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Green, Tina M; Jensen, Andreas K; Holst, René

    2016-01-01

    We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de...... models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B....... This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs...

  14. [Use of archival formalin-fixed, paraffin-embedded (FFPE) tissue samples for molecular genetic analysis in diffuse large B-cell lymphoma (DLBCL)].

    Science.gov (United States)

    Jarošová, Marie; Kučerová, Jana; Flodr, Patrik; Mikešová, Michaela; Procházka, Vít; Papajík, Tomáš

    2014-04-01

    The currently valid molecular genetic subclassification of patients with diffuse large B-cell lymphoma (DLBCL) into three prognostic subgroups based on expression profiling has been the objective of numerous genetic studies. In routine clinical practice, however, expression profiling technology remains unavailable for the most of centers. Apart from the technology, in some cases molecular genetic laboratories have problems obtaining high-quality material, i.e. fresh tissues, for RNA isolation to determine gene expression. One possibility is to determine the gene expression from RNA obtained by isolation from formalin-fixed, paraffin-embedded (FFPE) tissue. This pilot study aimed at isolating RNA from FFPE in patients diagnosed with DLBCL and verifying the potential use of such RNA for the expression analysis of 7 selected genes. Although the study showed that it is possible to isolate RNA and determine the expression of the selected genes from archival material, the values of relative expression of some genes in the set were too variable to be used for unambiguous prognostic classification. It was confirmed that retrospective analyses of selected genes may be performed with sufficient material obtained, and that properly archived blocks may be used for molecular biology analyses even after 8 years.

  15. Diffusion-weighted magnetic resonance imaging of thymoma: ability of the Apparent Diffusion Coefficient in predicting the World Health Organization (WHO) classification and the Masaoka-Koga staging system and its prognostic significance on disease-free survival

    International Nuclear Information System (INIS)

    Priola, Adriano Massimiliano; Priola, Sandro Massimo; Gned, Dario; Ducco, Lorena; Veltri, Andrea; Giraudo, Maria Teresa; Fornari, Alessandro; Ferrero, Bruno

    2016-01-01

    To evaluate the usefulness of diffusion-weighted magnetic resonance for distinguishing thymomas according to WHO and Masaoka-Koga classifications and in predicting disease-free survival (DFS) by using the apparent diffusion coefficient (ADC). Forty-one patients were grouped based on WHO (low-risk vs. high-risk) and Masaoka-Koga (early vs. advanced) classifications. For prognosis, seven patients with recurrence at follow-up were grouped separately from healthy subjects. Differences on ADC levels between groups were tested using Student-t testing. Logistic regression models and areas under the ROC curve (AUROC) were estimated. Mean ADC values were different between groups of WHO (low-risk = 1.58 ± 0.20 x 10 -3 mm 2 /sec; high-risk = 1.21 ± 0.23 x 10 -3 mm 2 /sec; p < 0.0001) and Masaoka-Koga (early = 1.43 ± 0.26 x 10 -3 mm 2 /sec; advanced = 1.31 ± 0.31 x 10 -3 mm 2 /sec; p = 0.016) classifications. Mean ADC of type-B3 (1.05 ± 0.17 x 10 -3 mm 2 /sec) was lower than type-B2 (1.32 ± 0.20 x 10 -3 mm 2 /sec; p = 0.023). AUROC in discriminating groups was 0.864 for WHO classification (cut-point = 1.309 x 10 -3 mm 2 /sec; accuracy = 78.1 %) and 0.730 for Masaoka-Koga classification (cut-point = 1.243 x 10 -3 mm 2 /sec; accuracy = 73.2 %). Logistic regression models and two-way ANOVA were significant for WHO classification (odds ratio[OR] = 0.93, p = 0.007; p < 0.001), but not for Masaoka-Koga classification (OR = 0.98, p = 0.31; p = 0.38). ADC levels were significantly associated with DFS recurrence rate being higher for patients with ADC ≤ 1.299 x 10 -3 mm 2 /sec (p = 0.001; AUROC, 0.834; accuracy = 78.0 %). ADC helps to differentiate high-risk from low-risk thymomas and discriminates the more aggressive type-B3. Primary tumour ADC is a prognostic indicator of recurrence. (orig.)

  16. Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

    2016-08-02

    In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

  17. Managing oral phosphate binder medication expenditures within the Medicare bundled end-stage renal disease prospective payment system: economic implications for large U.S. dialysis organizations.

    Science.gov (United States)

    Park, Haesuk; Rascati, Karen L; Keith, Michael S

    2015-06-01

    From January 2016, payment for oral-only renal medications (including phosphate binders and cinacalcet) was expected to be included in the new Medicare bundled end-stage renal disease (ESRD) prospective payment system (PPS). The implementation of the ESRD PPS has generated concern within the nephrology community because of the potential for inadequate funding and the impact on patient quality of care. To estimate the potential economic impact of the new Medicare bundled ESRD PPS reimbursement from the perspective of a large dialysis organization in the United States. We developed an interactive budget impact model to evaluate the potential economic implications of Medicare payment changes to large dialysis organizations treating patients with ESRD who are receiving phosphate binders. In this analysis, we focused on the budget impact of the intended 2016 integration of oral renal drugs, specifically oral phosphate binders, into the PPS. We also utilized the model to explore the budgetary impact of a variety of potential shifts in phosphate binder market shares under the bundled PPS from 2013 to 2016. The base model predicts that phosphate binder costs will increase to $34.48 per dialysis session in 2016, with estimated U.S. total costs for phosphate binders of over $682 million. Based on these estimates, a projected Medicare PPS $33.44 reimbursement rate for coverage of all oral-only renal medications (i.e., phosphate binders and cinacalcet) would be insufficient to cover these costs. A potential renal drugs and services budget shortfall for large dialysis organizations of almost $346 million was projected. Our findings suggest that large dialysis organizations will be challenged to manage phosphate binder expenditures within the planned Medicare bundled rate structure. As a result, large dialysis organizations may have to make treatment choices in light of potential inadequate funding, which could have important implications for the quality of care for patients

  18. REVIEWS OF TOPICAL PROBLEMS Rotational explosion mechanism for collapsing supernovae and the two-stage neutrino signal from supernova 1987A in the Large Magellanic Cloud

    Science.gov (United States)

    Imshennik, Vladimir S.

    2011-02-01

    The two-stage (double) signal produced by the outburst of the close supernova (SN) in the Large Magellanic Cloud, which started on and involved two neutrino signals during the night of 23 February 1987 UT, is theoretically interpreted in terms of a scenario of rotationally exploding collapsing SNs, to whose class the outburst undoubtedly belongs. This scenario consists of a set of hydrodynamic and kinetic models in which key results are obtained by numerically solving non-one-dimensional and nonstationary problems. Of vital importance in this context is the inclusion of rotation effects, their role being particularly significant precisely in terms of the question of the transformation of the original collapse of the presupernova iron core to the explosion of the SN shell, with an energy release on a familiar scale of 1051 erg. The collapse in itself leads to the birth of neutron stars (black holes) emitting neutrino and gravitational radiation signals of gigantic intensity, whose total energy significantly (by a factor of hundreds) exceeds the above-cited SN burst energy. The proposed rotational scenario is described briefly by artificially dividing it into three (or four) characteristic stages. This division is dictated by the physical meaning of the chain of events a rotating iron core of a sufficiently massive (more than 10M) star triggers when it collapses. An attempt is made to quantitatively describe the properties of the associated neutrino and gravitational radiations. The review highlights the interpretation of the two-stage neutrino signal from SN 1987A, a problem which, given the present status of theoretical astrophysics, cannot, in the author's view, be solved without including rotation effects.

  19. Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

    Science.gov (United States)

    Abidin, Anas Z.; Chockanathan, Udaysankar; DSouza, Adora M.; Inglese, Matilde; Wismüller, Axel

    2017-03-01

    Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with Multiple sclerosis (MS). At an early stage the inflammatory demyelination occurring in the CNS can manifest as a change in neuronal metabolism, with multiple asymptomatic white matter lesions detected in clinical MRI. Such damage may induce topological changes of brain networks, which can be captured by advanced functional MRI (fMRI) analysis techniques. We test this hypothesis by capturing the effective relationships of 90 brain regions, defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale Granger Causality (lsGC) framework. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We study for differences in these properties in network graphs obtained for 18 subjects (10 male and 8 female, 9 with CIS and 9 healthy controls). Global network properties captured trending differences with modularity and clustering coefficient (pdifferences in some regions of the inferior frontal and parietal lobe. We conclude that multivariate analysis of fMRI time-series can reveal interesting information about changes occurring in the brain in early stages of MS.

  20. Diffuse γ-ray emission observed by the Fermi large area telescope: massive stars, cosmic rays and the census of the interstellar medium in the galaxy

    International Nuclear Information System (INIS)

    Tibaldo, L.

    2011-01-01

    Galactic diffuse γ-ray emission is produced by interactions of cosmic rays (CRs) with interstellar gas and low-energy radiation fields. This is the brightest component of the high-energy γ-ray sky, surveyed since 2008 with unprecedented sensitivity and angular resolution by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. Galactic diffuse emission constitutes not only a bright and structured background which needs to be modeled in order to study individual sources and fainter diffuse components, but it can be used also as a probe of the interstellar environment of the Milky Way. We present in-depth studies of LAT γ-ray observations of selected regions in the local and outer Galaxy. LAT data are compared with multiwavelength tracers of the interstellar medium (ISM), including radio/mm-wave lines of gas and infrared emission/extinction from dust. The impact of the HI optical depth, often overlooked in the past, is carefully examined and recognized currently as the dominant source of uncertainty in the interpretation of observations. On one hand, we discuss the constraints provided by the γ-ray data on the census of the interstellar gas. We determine the X C O = N(H 2 )/W C O ratio for several clouds, finding no significant gradients in the Galactic disc over a range of ∼ 3.5 kpc in Galactocentric radius, and variations of a factor ≤ 2 in nearby local clouds. We also find evidence for an ubiquitous dark phase of interstellar gas which does not shine at radio/mm wavelengths and which provides a mass ∼ 50% of that traced by CO. For the first time we determine its γ-ray spectrum which is found to be well correlated with that of HI, thus further confirming that the emission originates from interstellar gas. On the other hand, we use the emissivity per hydrogen atom to infer the distribution of CRs in distant locations not accessible by direct measurements. While the local HI emissivity is consistent with the CR spectra measured near

  1. Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Dabaja, Bouthaina S; Wang, Xiaoxiao

    2015-01-01

    MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about...

  2. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.

    NARCIS (Netherlands)

    Visco, C.; Tzankov, A.; Xu-Monette, Z.Y.; Miranda, R.N.; Tai, Y.C.; Li, Y.; Liu, W.M.; d'Amore, E.S.; Li, Y.O.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Wang, H.Y.; Dunphy, C.H.; His, E.D.; Zhao, X.F.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Ai, W.; O'Neill, S.; Ponzoni, M.; Ferreri, A.J.; Kahl, B.S.; Winter, J.N.; Go, R.S.; Dirnhofer, S.; Piris, M.A.; Moller, M.B.; Wu, L.; Medeiros, L.J.; Young, K.H.

    2013-01-01

    Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has

  3. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

  4. Linfoma Difuso de Grandes Células  de Intestino Delgado: Relato de Caso Diffuse Large -Cell Lymphoma of Small Bowel: Case Report

    Directory of Open Access Journals (Sweden)

    Gustavo Nunes Medina Coeli

    2012-06-01

    are subtype B cell. Case Report: It´s presented a case of rare small bowel lymphoma in a female patient of 77 years who sought medical care with nonspecific symptoms and an anemic framework. Radiological examinations were essential for diagnosis for diagnostic enlightenment and propaedeutics. Tumor markers were negative and the inflamatorious tests activities were positives. In hospitalization, the patient had an abrupt worsening in her clinic picture, needing a surgery. During the operation was identified in the proximal jejunum a perfurative damage with an ulcerated aspect with ulcers, adhesions in the bladder and in fundus of the uterus. The patient did not evaluated well and died after three days. The pathology confirmed a diffuse No Hodgkin lymphoma of Large B-cells with a high rate of cell proliferation. Discussion: The preoperative radiological diagnosis of tumor of the small intestine is only obtained in a small percentage of symptomatic patients. Imaging studies show infiltrative, polypoid, or aneurysmatic morphologicals types .Usually occurs circumferential involvement of the handle, with irregular thickening of the folds of variable length. Conclusion: The intent of this study is to document a rare tumor of the small bowel Non-Hodgkin Lymphoma Diffuse Large B-Cell type, multicentric, that was difficult to diagnose and with a rapid evolution of symptoms, which resulted in acute intestinal obstruction, requiring emergency surgery.

  5. Prognostic significances of overexpression MYC and/or BCL2 in R-CHOP-treated diffuse large B-cell lymphoma: A Systematic review and meta-analysis.

    Science.gov (United States)

    Li, Lu; Li, Yanyan; Que, Ximei; Gao, Xue; Gao, Qian; Yu, Mingxing; Ma, Kaili; Xi, Yanfeng; Wang, Tong

    2018-04-19

    Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69-2.27)without heterogeneity(I 2  = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43-1.89, I 2  = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19-3.04, I 2  = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.

  6. The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi-Ae Lyu

    2010-05-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

  7. Loss of function mutations in PTPN6 promote STAT3 deregulation via JAK3 kinase in diffuse large B-cell lymphoma

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Hu, Guangzhen; Stenson, Mary; Gupta, Mamta

    2015-01-01

    PTPN6 (SHP1) is a tyrosine phosphatase that negatively controls the activity of multiple signaling pathways including STAT signaling, however role of mutated PTPN6 is not much known. Here we investigated whether PTPN6 might also be a potential target for diffuse large B cell lymphoma (DLBCL) and performed Sanger sequencing of the PTPN6 gene. We have identified missense mutations within PTPN6 (N225K and A550V) in 5% (2/38) of DLBCL tumors. Site directed mutagenesis was performed to mutate wild type (WT) PTPN6 and stable cell lines were generated by lentiviral transduction of PTPN6WT, PTPN6N225K and PTPN6A550V constructs, and effects of WT or mutated PTPN6 on STAT3 signaling were analyzed. WT PTPN6 dephosphorylated STAT3, but had no effect on STAT1, STAT5 or STAT6 phosphorylation. Both PTPN6 mutants were unable to inhibit constitutive, as well as cytokines induced STAT3 activation. Both PTPN6 mutants also demonstrated reduced tyrosine phosphatase activity and exhibited enhanced STAT3 transactivation activity. Intriguingly, a lack of direct binding between STAT3 and WT or mutated PTPN6 was observed. However, compared to WT PTPN6, cells expressing PTPN6 mutants exhibited increased binding between JAK3 and PTPN6 suggesting a more dynamic interaction of PTPN6 with upstream regulators of STAT3. Consistent with this notion, both the mutants demonstrated increased resistance to JAK3 inhibitor, WHIP-154 relative to WT PTPN6. Overall, this is the first study, which demonstrates that N225K and A550V PTPN6 mutations cause loss-of-function leading to JAK3 mediated deregulation of STAT3 pathway and uncovers a mechanism that tumor cells can use to control PTPN6 substrate specificity. PMID:26565811

  8. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP.

    Science.gov (United States)

    Gupta, Mamta; Maurer, Matthew J; Wellik, Linda E; Law, Mark E; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N; Dogan, Ahmet; Witzig, Thomas E

    2012-11-22

    STAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

  9. Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

    Science.gov (United States)

    Howlader, Nadia; Mariotto, Angela B; Besson, Caroline; Suneja, Gita; Robien, Kim; Younes, Naji; Engels, Eric A

    2017-09-01

    Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017;123:3326-34. © 2017 American Cancer Society. © 2017 American Cancer Society.

  10. P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Vega, Gabriel G.; Avilés-Salas, Alejandro; Chalapud, J. Ramón; Martinez-Paniagua, Melisa; Pelayo, Rosana; Mayani, Héctor; Hernandez-Pando, Rogelio; Martinez-Maza, Otoniel; Huerta-Yepez, Sara; Bonavida, Benjamin; Vega, Mario I.

    2015-01-01

    The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed. Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38 − and 34 % for p38 + and for OS was 83 % for p38 − and 47 % for p38 + . The p-p38 + tissues expressed Bcl-2 and 90 % of p-p38 − where Bcl-2 − . The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB. The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors. The online version of this article (doi:10.1186/s12885-015-1778-8) contains supplementary material, which is available to authorized users

  11. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  12. Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

    Science.gov (United States)

    Rink, Jonathan S; Yang, Shuo; Cen, Osman; Taxter, Tim; McMahon, Kaylin M; Misener, Sol; Behdad, Amir; Longnecker, Richard; Gordon, Leo I; Thaxton, C Shad

    2017-11-06

    Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

  13. Putative cruciform DNA structures at BCL6 breakpoint region may explain BCL6 translocation in diffuse large B-Cell lymphoma

    International Nuclear Information System (INIS)

    Bhatelia, Khyati D.; Nambiar, Mridula; Choudhary, Bibha; Raghvan, Sathees C.

    2010-01-01

    Cancer is a disease characterized by uncontrolled proliferation of cells, caused by genetic alterations such as chromosomal translocations, which are present in almost all hematological malignancies. Diffuse Large B-cell Lymphoma (DLBL) is the most common non-Hodgkin's lymphoma, comprising 40-50% of all lymphomas both in India and worldwide, and is characterized by BCL6 chromosomal translocation. However, the mechanism of this translocation is completely unknown. By mapping of translocation breakpoints from patients, we have identified three breakpoint cluster regions at 5' UTR of BCL6 gene. Bioinformatics analysis of cluster II, which possesses majority of breakpoints, this region may form cruciform DNA structures. Gel mobility shift assays using oligomeric DNA from the region suggested that a portion of cluster II folded into hairpin structures. Mutations to the wild type sequences disrupted hairpin formation. Circular dichroism studies on BCL6 oligomers resulted in a spectra containing two overlapping peaks at 265 nm and 285 nm, confirming hairpin structure. Further, the structure was destroyed upon heating, and reformed when appropriate conditions were provided. P1 nuclease assay in conjunction with KMnO 4 probing suggested that the structure possessed an eight nucleotide double-stranded stem and a nine nucleotide loop. To further understand the mechanism of BCL6 translocation in vivo, human cells were transfected with episomes harboring cluster II region and the results obtained will be discussed. Hence, our results suggest the formation of a putative cruciform DNA structure at BCL6 breakpoint region and that may facilitate breakage at BCL6 gene explaining chromosomal translocations in DLBL. (author)

  14. Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH: revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Lu Xin-Yan

    2009-11-01

    Full Text Available Abstract Background Plasmablastic lymphoma (PL is a subtype of diffuse large B-cell lymphoma (DLBCL. Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM. The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related and PCM using array-based comparative genomic hybridization. Results Examination of genomic data in PL revealed that the most frequent segmental gain (> 40% include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.

  15. Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2015-01-01

    We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

  16. Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

    2016-12-01

    Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

  17. A comparison of pectoralis versus lumbar skeletal muscle indices for defining sarcopenia in diffuse large B-cell lymphoma - two are better than one.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Kang, Jung Hun; Kim, Hye Ree; Lee, Gyeong-Won

    2017-07-18

    Sarcopenia is known to be associated with poor clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). There is no consensus concerning the optimal method to define sarcopenia in DLBCL. We retrospectively reviewed 193 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Sarcopenia was classified by the region where the pretreatment skeletal muscle index (SMI) was measured. Both the sarcopenia-L3 and sarcopenia-pectoralis muscle (PM) groups had increased incidences of severe treatment-related toxicities and treatment discontinuation compared with the non-sarcopenia-L3 and non-sarcopenia-PM groups, respectively. The sarcopenia-L3 and non-sarcopenia-L3 groups had 5-year overall survival (OS) rates of 40.5% and 67.8% (p sarcopenia-PM and non-sarcopenia-PM groups had 5-year OS rates of 35.9% and 69.0% (p sarcopenia-L3 alone and sarcopenia-PM alone groups were compared, there were no differences in baseline characteristics, treatment toxicity, or survival. In multivariate analysis, when compared with the non-sarcopenia-both group, OS was significantly worse in the sarcopenia-both group (HR, 2.480; 95% CI, 1.284 - 4.792; p = 0.007), but not in patients with either sarcopenia-L3 alone or sarcopenia-PM alone (p = 0.151). L3- and PM-SMIs are equally useful to define sarcopenia, which is related to intolerance to R-CHOP therapy and to worse survival in patients with DLBCL. More prognostic information can be obtained when these two SMIs are combined to define sarcopenia.

  18. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

    Science.gov (United States)

    Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

    2017-10-01

    Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhai, Linzhu; Zhao, Yuanyuan; Peng, Songguo; Zhu, Ke; Yu, Rongjian; Chen, Hailong; Lin, Tongyu; Lin, Lizhu

    2016-12-01

    There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

  20. Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations.

    Science.gov (United States)

    Cao, Xin-Xin; Li, Jian; Cai, Hao; Zhang, Wei; Duan, Ming-Hui; Zhou, Dao-Bin

    2017-11-01

    This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

  1. Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity.

    Science.gov (United States)

    Zha, Xianfeng; Yin, Qingsong; Tan, Huo; Wang, Chunyan; Chen, Shaohua; Yang, Lijian; Li, Bo; Wu, Xiuli; Li, Yangqiu

    2013-05-01

    Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs) that target tumors are an attractive strategy for specific adoptive immunotherapy. Little is known about whether there are any alterations in the gene expression profile after TCR gene transduction in T cells. We constructed TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene-redirected T-cells, and we further analyzed the gene expression profile pattern of these redirected T-cells by Affymetrix microarrays. The resulting data were analyzed using Bioconductor software, a two-fold cut-off expression change was applied together with anti-correlation of the profile ratios to render the microarray analysis set. The fold change of all genes was calculated by comparing the three TCR gene-modified T-cells and a negative control counterpart. The gene pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and Genomes. Identical genes whose fold change was greater than or equal to 2.0 in all three TCR gene-redirected T-cell groups in comparison with the negative control were identified as the differentially expressed genes. The differentially expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene including JUNB, FOS, TNF, INF-γ, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2, CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen-activated protein kinase signaling, and cytokine-cytokine receptor interaction pathways. In conclusion, we characterized the gene expression profile of DLBCL-specific TCR gene-redirected T-cells. The changes corresponded to an up-regulation in the differentiation and proliferation of the T-cells. These data may help to explain some of the characteristics of the redirected T-cells.

  2. Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

    2017-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on malignant CD19+ B cells in diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhou, Yong; Zha, Jie; Lin, Zhijuan; Fang, Zhihong; Zeng, Hanyan; Zhao, Jintao; Luo, Yiming; Li, Zhifeng; Xu, Bing

    2018-01-15

    Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4 + T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19 + cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19 + cells than patients who did not show recurrence. Examining cytotoxic CD4 + T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4 + T cells. Also, frequency of cytotoxic CD4 + T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4 + T cells against autologous CD19 + cells was investigated. We found that the cytotoxic potential of CD4 + T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19 + cells presented a significant reduction after longer incubation with cytotoxic CD4 + T cells, suggesting that cytotoxic CD4 + T cells preferentially eliminated MHC II-expressing CD19 + cells. Blocking MHC II on CD19 + cells significantly reduced the cytolytic capacity of CD4 + T cells. Despite these discoveries, the frequency of cytotoxic CD4 + T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4 + T cells presented an MHC II-dependent cytotoxic potential against autologous CD19 + cells and could potentially represent a future treatment option for DLBCL. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  5. Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

    Science.gov (United States)

    Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

    2013-01-01

    Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

  6. Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis.

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    Chen-Ge Song

    Full Text Available Epstein-Barr virus (EBV-positive diffuse large B-cell lymphoma (DLBCL in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.In situ hybridization (ISH analysis of Epstein-Barr virus (EBV and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3 was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.A total of 16 patients (7.0% were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB subtypes (87.5% and high Ki67 (75% and CD30 expression (93.8%. For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8% had complete remission, 2 (12.5% had partial remission, 2 (12.5% had stable disease, and 5 (31.3% had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001.EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.

  7. Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort.

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    Wang, Han-I; Smith, Alexandra; Aas, Eline; Roman, Eve; Crouch, Simon; Burton, Cathy; Patmore, Russell

    2017-03-01

    Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on a specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL. All patients newly diagnosed with DLBCL in the UK's population-based Haematological Malignancy Research Network ( www.hmrn.org ) in 2007 were followed until 2013 (n = 271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient-level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5 % per annum. Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7376 for first-, second- and third-line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million. This is the first cost modelling study using empirical data to provide 'real world' evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine.

  8. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

    Science.gov (United States)

    Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim

    2012-09-01

    Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.

  9. The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.

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    Ryan C Thompson

    Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's as monotherapy or in combination with other agents. METHODOLOGY/PRINCIPAL FINDINGS: We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6 that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. CONCLUSIONS/SIGNIFICANCE: These studies indicate that the sensitivity of DLBCL to treatment with HDACi's is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

  10. A multi-stage approach to maximizing geocoding success in a large population-based cohort study through automated and interactive processes

    Directory of Open Access Journals (Sweden)

    Jennifer S. Sonderman

    2012-05-01

    Full Text Available To enable spatial analyses within a large, prospective cohort study of nearly 86,000 adults enrolled in a 12-state area in the southeastern United States of America from 2002-2009, a multi-stage geocoding protocol was developed to efficiently maximize the proportion of participants assigned an address level geographic coordinate. Addresses were parsed, cleaned and standardized before applying a combination of automated and interactive geocoding tools. Our full protocol increased the non-Post Office (PO Box match rate from 74.5% to 97.6%. Overall, we geocoded 99.96% of participant addresses, with only 5.2% at the ZIP code centroid level (2.8% PO Box and 2.3% non-PO Box addresses. One key to reducing the need for interactive geocoding was the use of multiple base maps. Still, addresses in areas with population density 920 persons/km2 (odds ratio (OR = 5.24; 95% confidence interval (CI = 4.23, 6.49, as were addresses collected from participants during in-person interviews compared with mailed questionnaires (OR = 1.83; 95% CI = 1.59, 2.11. This study demonstrates that population density and address ascertainment method can influence automated geocoding results and that high success in address level geocoding is achievable for large-scale studies covering wide geographical areas.

  11. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

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    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

  12. Intra-patient variability of FDG standardized uptake values in mediastinal blood pool, liver, and myocardium during R-CHOP chemotherapy in patients with diffuse large B- cell lymphoma

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    Kim, Soo Jeong; Yi, Hyun Kyung; Lim, Chae Hong; Cho, Young Seok; Choi, Joon Young; Choe, Yeam Seong; Lee, Kyung Han; Moon, Seung Hwan [Dept. of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    {sup 18}F-fluorodeoxyglucose (FDG) PET/CT is useful for staging and evaluating treatment response in patients with diffuse large B-cell lymphoma (DLBCL). A five-point scale model using the mediastinal blood pool (MBP) and liver as references is a recommended method for interpreting treatment response. We evaluated the variability in standardized uptake values (SUVs) of the MBP, liver, and myocardium during chemotherapy in patients with DLBCL. We analyzed 60 patients with DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment and underwent baseline, interim, and final FDG PET/CT scans. The FDG uptakes of lymphoma lesions, MBP, liver, and myocardium were assessed, and changes in the MBP and liver SUV and possible associated factors were evaluated. The SUV of the liver did not change significantly during the chemotherapy. However, the SUV{sub mean} of MBP showed a significant change though the difference was small (p = 0.019). SUV{sub mean} of MBP and liver at baseline and interim scans was significantly lower in patients with advanced Ann Arbor stage on diagnosis. The SUV{sub mean} of the MBP and liver was negatively correlated with the volumetric index of lymphoma lesions in baseline scans (r = -0.547, p < 0.001; r = -0.502, p < 0.001). Positive myocardial FDG uptake was more frequently observed in interim and final scans than in the baseline scan, but there was no significant association between the MBP and liver uptake and myocardial uptake. The SUV of the liver was not significantly changed during R-CHOP chemotherapy in patients with DLBCL, whereas the MBP SUV of the interim scan decreased slightly. However, the SUV of the reference organs may be affected by tumor burden, and this should be considered when assessing follow-up scans. Although myocardial FDG uptake was more frequently observed after R-CHOP chemotherapy, it did not affect the SUV of the MBP and liver.

  13. Assessing the initiation and completion of adjuvant chemotherapy in a large nationwide and population-based cohort of elderly patients with stage-III colon cancer.

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    Hu, Chung-Yuan; Delclos, George L; Chan, Wenyaw; Du, Xianglin L

    2011-12-01

    Randomized trials conducted in the 1980s have established the effectiveness of 5-fluorouracil-based adjuvant chemotherapy in treating stage-III colon cancer. However, the initiation of adjuvant chemotherapy is just the first step for survival improvement. Little is known about the actual completion rate of such a therapy in the community. The objectives of this study were to measure the initiation and completion rate of adjuvant chemotherapy and to identify the associated factors. We studied 12,265 patients aged 65+ diagnosed with stage-III colon cancer between 1991 and 2005 who were identified from the Surveillance, Epidemiology, and End Results-Medicare linked database. Chemotherapy initiation was defined as at least one claim indicating the use of chemotherapy. The first and last claims were used to measure the length of chemotherapy. A complete course of chemotherapy was defined as 8-13 months for 1991-1995 cohort and 5-7 months for 1996-2005 cohort according to clinical guideline. Of the 12,265 patients, 64.4% received adjuvant chemotherapy within 3 months after tumor resection. Among those who had chemotherapy initiated, 62.2% (or 38.0% of 12,265 patients) received a complete course of chemotherapy. Patient's age at diagnosis, marital status, and comorbidity score were the significant predictors for chemotherapy initiation. These variables remained significant in predicting chemotherapy completion after adjusting for year of diagnosis and other factors. In conclusion, initiation and completion of chemotherapy was largely influenced by patient's age, marital status and comorbidity. Further investigation is needed to explore the cause of these differences in adherence to standard treatment that is essential for better quality of cancer care.

  14. Correlated diffusion imaging

    International Nuclear Information System (INIS)

    Wong, Alexander; Glaister, Jeffrey; Cameron, Andrew; Haider, Masoom

    2013-01-01

    Prostate cancer is one of the leading causes of cancer death in the male population. Fortunately, the prognosis is excellent if detected at an early stage. Hence, the detection and localization of prostate cancer is crucial for diagnosis, as well as treatment via targeted focal therapy. New imaging techniques can potentially be invaluable tools for improving prostate cancer detection and localization. In this study, we introduce a new form of diffusion magnetic resonance imaging called correlated diffusion imaging, where the tissue being imaged is characterized by the joint correlation of diffusion signal attenuation across multiple gradient pulse strengths and timings. By taking into account signal attenuation at different water diffusion motion sensitivities, correlated diffusion imaging can provide improved delineation between cancerous tissue and healthy tissue when compared to existing diffusion imaging modalities. Quantitative evaluation using receiver operating characteristic (ROC) curve analysis, tissue class separability analysis, and visual assessment by an expert radiologist were performed to study correlated diffusion imaging for the task of prostate cancer diagnosis. These results are compared with that obtained using T2-weighted imaging and standard diffusion imaging (via the apparent diffusion coefficient (ADC)). Experimental results suggest that correlated diffusion imaging provide improved delineation between healthy and cancerous tissue and may have potential as a diagnostic tool for cancer detection and localization in the prostate gland. A new form of diffusion magnetic resonance imaging called correlated diffusion imaging (CDI) was developed for the purpose of aiding radiologists in cancer detection and localization in the prostate gland. Preliminary results show CDI shows considerable promise as a diagnostic aid for radiologists in the detection and localization of prostate cancer

  15. Diffusion in molybdenum disilicide

    International Nuclear Information System (INIS)

    Salamon, M.; Mehrer, H.

    2005-01-01

    The diffusion behaviour of the high-temperature material molybdenum disilicide (MoSi 2 ) was completely unknown until recently. In this paper we present studies of Mo self-diffusion and compare our present results with our already published studies of Si and Ge diffusion in MoSi 2 . Self-diffusion of molybdenum in monocrystalline MoSi 2 was studied by the radiotracer technique using the radioisotope 99 Mo. Deposition of the radiotracer and serial sectioning after the diffusion anneals to determine the concentration-depth profiles was performed using a sputtering device. Diffusion of Mo is a very slow process. In the entire temperature region investigated (1437 to 2173 K), the 99 Mo diffusivities in both principal directions of the tetragonal MoSi 2 crystals obey Arrhenius laws, where the diffusion perpendicular to the tetragonal axis is faster by two to three orders of magnitude than parallel to it. The activation enthalpies for diffusion perpendicular and parallel to the tetragonal axis are Q perpendicular to = 468 kJ mol -1 (4.85 eV) and Q parallel = 586 kJ mol -1 (6.07 eV), respectively. Diffusion of Si and its homologous element Ge is fast and is mediated by thermal vacancies of the Si sublattice of MoSi 2 . The diffusion of Mo is by several orders of magnitude slower than the diffusion of Si and Ge. This large difference suggests that Si and Mo diffusion are decoupled and that the diffusion of Mo likely takes place via vacancies on the Mo sublattice. (orig.)

  16. Return to work for patients with diffuse large B-cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation

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    Arboe B

    2017-06-01

    Full Text Available Bente Arboe,1,2 Maja Halgren Olsen,2 Jette Soenderskov Goerloev,1 Anne Katrine Duun-Henriksen,2 Christoffer Johansen,2,3 Susanne Oksbjerg Dalton,2 Peter de Nully Brown1 1Department of Hematology, Copenhagen University Hospital, Rigshospitalet, 2Unit of Survivorship Research, The Danish Cancer Society Research Center, 3Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Background: Autologous stem cell transplantation (ASCT is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL or transformed indolent lymphoma (TIL. The treatment is mainly considered for younger patients still available for the work market. In this study, social outcomes after ASCT in terms of return to work (RTW are described.Patients and methods: Information from national administrative registers was combined with clinical information on patients, who received ASCT for relapse of DLBCL or TIL between 2000 and 2012. A total of 164 patients were followed until RTW, disability or old-age pension, death, or December 31, 2015, whichever came first. A total of 205 patients were followed with disability pension as the event of interest. Cox models were used to determine cause-specific hazards. Results: During follow-up, 82 (50% patients returned to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5] and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]. In all, 56 (27% patients were granted disability pension. Being on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]. Conclusion: Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore, patients >55 are more likely to RTW compared to younger patients. These

  17. NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

    Science.gov (United States)

    Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

    2016-01-01

    Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, Puric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

  18. Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ando, Kiyoshi; Niitsu, Nozomi; Kim, Won Seog; Suh, Cheolwon; Ogura, Michinori; Tobinai, Kensei

    2015-02-01

    The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F-18] fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with bendamustine-rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of (18) F-FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty-five patients with relapsed or refractory DLBCL were enrolled. The (18) F-FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value-volume histogram was significantly greater in complete response patients than in non-complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression-free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression-free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine-rituximab. © 2014 The Authors. Cancer Science

  19. Prognostic impact of pre-transplantation computed tomography and 67gallium scanning in chemosensitive diffuse large B cell lymphoma patients undergoing hematopoietic stem-cell transplantation

    International Nuclear Information System (INIS)

    Escobar, Ignacio G.; Alonso, Pilar T.; Barrigon, Dolores C.; Perez-Simon, Jose A.; Mateos Manteca, Maria V.; San Miguel Izquierdo, Jesus F.

    2008-01-01

    In the present study, we evaluated computed tomography (CT) and 67 gallium scanning ( 67 Ga scan) pre-transplant as prognostic factors for overall survival (OS) and event-free survival (EFS) in patients with diffuse large B cell lymphoma, undergoing high-dose chemotherapy and stem-cell transplantation. Forty-two patients were included. Of these, 9 (21%) had both positive CT and 67 Ga scans, 17 (41%) negative results with both techniques, and 16 (38%) positive CT/negative 67 Ga scan. Whole-body planar imaging and single-photon emission computed tomography (SPECT) were performed 72 h after an intravenous administration of 67 Ga citrate measuring between 7 mCi and 10 mCi (259-370 MBq). Patients with positive CT/positive 67 Ga scan had a significantly worse EFS and OS at 5 years than those with negative 67 Ga scan regardless of whether it was associated with a positive or a negative CT scan (29% and 16% vs. 81% and 93% vs. 88% and 100%, respectively, P 67 Ga scan and those with positive CT/negative 67 Ga scan, with an EFS and OS at 5 years of 88% versus 81% and 100% versus 93%, respectively. In multivariate analysis, the presence of a pre-transplant positive CT/ 67 Ga scans adversely influenced both EFS and OS [HR 8, 95% confidence interval (CI) (1.4-38), P=0.03 and HR 2; 95% CI (1.3-8), P=0.02, respectively]. 67 Ga scan helps to identify, in the pre-transplant evaluation, two groups with a different outcome: one group of patients with positive CT and negative 67 Ga scans pre-transplant, who showed a favorable outcome with a low rate of relapse, and the other group of patients with both positive CT and 67 Ga scans pre-transplant, who showed a poor prognosis and did not benefit from autologous stem-cell transplantation. They should have been offered other therapeutic strategies. (author)

  20. Increased expression of IRF8 in tumor cells inhibits the generation of Th17 cells and predicts unfavorable survival of diffuse large B cell lymphoma patients.

    Science.gov (United States)

    Zhong, Weijie; Xu, Xin; Zhu, Zhigang; Du, Qinghua; Du, Hong; Yang, Li; Ling, Yanying; Xiong, Huabao; Li, Qingshan

    2017-07-25

    The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients. Two DLBCL cell lines (OCI-LY10 and OCI-LY1) with IRF8 knockdown or overexpression and two human B lymphoblast cell lines were co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the effect of IRF8 on the generation of Th17 cells. Quantitative real-time PCR and Western blotting were used to investigate the involvement of retinoic acid receptor-related orphan receptor gamma t (RORγt) in the effect of IRF8 on Th17 cell generation. The survival of 67 DLBCL patients was estimated using the Kaplan-Meier method and log-rank analysis. The percentage of Th17 cells was lower in DLBCL tumor tissues than in PBMCs and corresponding adjacent benign tissues. Relative expression of interleukin (IL)-17A was lower, whereas that of interferon (IFN)-γ was higher in tumor tissues than in benign tissues. Co-culture with DLBCL cell lines inhibited the generation of Th17 cells in vitro. IRF8 upregulation was detected in DLBCL tumor tissues, and it was associated with decreased DLBCL patient survival. Investigation of the underlying mechanism suggested that IRF8 upregulation in DLBCL, through an unknown mechanism, inhibited Th17 cell generation by suppressing RORγt in neighboring CD4+ T cells. Tumor cells may express soluble or membrane-bound factors that inhibit the expression of RORγt in T cells within the tumor microenvironment. Our findings suggest that IRF8 expression could

  1. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  2. Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

    Science.gov (United States)

    Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

    2014-08-12

    Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

  3. Experimental study of the possibility of reducing the resistance and unevenness of output field of velocities in flat diffuser channels with large opening angles

    Science.gov (United States)

    Dmitriev, S. S.; Vasil'ev, K. E.; Mokhamed, S. M. S. O.; Gusev, A. A.; Barbashin, A. V.

    2017-11-01

    In modern combined cycle gas turbines (CCGT), when designing the reducers from the output diffuser of a gas turbine to a boiler-utilizer, wide-angle diffusers are used, in which practically from the input a flow separation and transition to jet stream regime occurs. In such channels, the energy loss in the field of velocities sharply rise and the field of velocities in the output from them is characterized by considerable unevenness that worsens the heat transfer process in the first by motion tube bundles of the boiler-utilizer. The results of experimental research of the method for reducing the energy loss and alignment of the field of velocities at the output from a flat asymmetrical diffuser channel with one deflecting wall with the opening angle of 40° by means of placing inside the channel the flat plate parallel to the deflecting wall are presented in the paper. It is revealed that, at this placement of the plate in the channel, it has a chance to reduce the energy loss by 20%, considerably align the output field of velocities, and decrease the dynamic loads on the walls in the output cross-section. The studied method of resistance reduction and alignment of the fields of velocities in the flat diffuser channels was used for optimization of the reducer from the output diffuser of the gas turbine to the boiler-utilizer of CCGT of PGU-450T type of Kaliningrad Thermal Power Plant-2. The obtained results are evidence that the configuration of the reducer installed in the PGU-450T of Kaliningrad Thermal Power Plant-2 is not optimal. It follows also from the obtained data that working-off the reducer should be necessarily conducted by the test results of the channel consisting of the model of reducer with the model of boiler-utilizer installed behind it. Application of the method of alignment of output field of velocities and reducing the resistance in the wide-angle diffusers investigated in the work made it possible—when using the known model of diffusion

  4. Th1/2 Immune Response Signature Predicts Outcome after Dose-Dense Immunochemotherapy in Patients with High Risk Diffuse Large B-Cell Lymphoma – Results from Nordic Lymphoma Group Trials

    DEFF Research Database (Denmark)

    M, Autio; Jørgensen, Judit Meszaros; SK, Leivonen

    treatment-specific roles in diffuse large B-cell lymphoma. For the high risk DLBCL patients treated with dose-dense immunochemotherapy, high expression of type 1/2 immune response signature genes predicts a poor outcome. A detailed characterization of immune cell composition in the tumor microenvironment......Introduction: Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients still relapse and have dismal prognosis. Recently, the impact of genomic aberrations, allowing lymphoma cells to escape immune recognition on DLBCL pathogenesis...... has been recognized. However, whether immune related signatures could be used as determinants for treatment outcome has not been rigorously evaluated. Here, our aim was to elucidate the immunologic characteristics of the tumor microenvironment, and associate the findings with outcome in patients...

  5. TU-F-CAMPUS-J-02: Evaluation of Textural Feature Extraction for Radiotherapy Response Assessment of Early Stage Breast Cancer Patients Using Diffusion Weighted MRI and Dynamic Contrast Enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Y; Wang, C; Horton, J; Chang, Z [Duke University Medical Center, Durham, NC (United States)

    2015-06-15

    Purpose: To investigate the feasibility of using classic textural feature extraction in radiotherapy response assessment, we studied a unique cohort of early stage breast cancer patients with paired pre - and post-radiation Diffusion Weighted MRI (DWI-MRI) and Dynamic Contrast Enhanced MRI (DCE-MRI). Methods: 15 female patients from our prospective phase I trial evaluating preoperative radiotherapy were included in this retrospective study. Each patient received a single-fraction radiation treatment, and DWI and DCE scans were conducted before and after the radiotherapy. DWI scans were acquired using a spin-echo EPI sequence with diffusion weighting factors of b = 0 and b = 500 mm{sup 2} /s, and the apparent diffusion coefficient (ADC) maps were calculated. DCE-MRI scans were acquired using a T{sub 1}-weighted 3D SPGR sequence with a temporal resolution of about 1 minute. The contrast agent (CA) was intravenously injected with a 0.1 mmol/kg bodyweight dose at 2 ml/s. Two parameters, volume transfer constant (K{sup trans} ) and k{sub ep} were analyzed using the two-compartment Tofts kinetic model. For DCE parametric maps and ADC maps, 33 textural features were generated from the clinical target volume (CTV) in a 3D fashion using the classic gray level co-occurrence matrix (GLCOM) and gray level run length matrix (GLRLM). Wilcoxon signed-rank test was used to determine the significance of each texture feature’s change after the radiotherapy. The significance was set to 0.05 with Bonferroni correction. Results: For ADC maps calculated from DWI-MRI, 24 out of 33 CTV features changed significantly after the radiotherapy. For DCE-MRI pharmacokinetic parameters, all 33 CTV features of K{sup trans} and 33 features of k{sub ep} changed significantly. Conclusion: Initial results indicate that those significantly changed classic texture features are sensitive to radiation-induced changes and can be used for assessment of radiotherapy response in breast cancer.

  6. Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

    Science.gov (United States)

    Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

    2017-06-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Fractional diffusion equations and anomalous diffusion

    CERN Document Server

    Evangelista, Luiz Roberto

    2018-01-01

    Anomalous diffusion has been detected in a wide variety of scenarios, from fractal media, systems with memory, transport processes in porous media, to fluctuations of financial markets, tumour growth, and complex fluids. Providing a contemporary treatment of this process, this book examines the recent literature on anomalous diffusion and covers a rich class of problems in which surface effects are important, offering detailed mathematical tools of usual and fractional calculus for a wide audience of scientists and graduate students in physics, mathematics, chemistry and engineering. Including the basic mathematical tools needed to understand the rules for operating with the fractional derivatives and fractional differential equations, this self-contained text presents the possibility of using fractional diffusion equations with anomalous diffusion phenomena to propose powerful mathematical models for a large variety of fundamental and pract