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Purpose@#There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL. @*Materials and Methods@#Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test. @*Results@#The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001). @*Conclusion@#Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.
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Purpose@#There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL. @*Materials and Methods@#Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test. @*Results@#The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001). @*Conclusion@#Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.
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Objective@#To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .@*Methods@#The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.@*Results@#The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively.@*Conclusion@#ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.
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Since the outbreak of the new coronavirus pneumonia (NCP) in Wuhan City, China, the main transmission mode as well as the diagnosis and treatment of NCP have become a focus of research in China and World Health Organization.Understanding the mode of infection, transmission and biological behavior of the novel coronavirus (2019-nCoV) is undoubtedly a key of cutting off the spread and prevention of the disease which doctors are fearing to be a worldwide epidemic.In February 2020, Lancet published a correspondence paper, which reviewed a case of NCP patient who first started with conjunctivitis, and raised the issue that the transmission of 2019-nCoV through the ocular surface must not be ignored, causing widespread concern.However, due to a lack of clinical observation data and laboratory research at present, the relationship between NCP pathogen infection and ocular surface infection is not completely clear.So far, there have been many studies and reports on the observation of large-scale epidemic virus infections and eye diseases.This article reviews the eye performance of various types of epidemic virus infections and provides a reference for NCP prevention and control.
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Objective@#To explore the clinical characteristics, the best treatment and prognostic factors of primary pulmonary NK/T-cell lymphoma.@*Methods@#A total of 24 cases with primary pulmonary NK/T-cell lymphoma from April 2011 to May 2019 were analyzed retrospectively. Survival analysis was performed using the Kaplan-Meier method and groups were compared using the log-rank test. Multivariate analysis using Cox proportional hazard regression model was conducted to confirm independent prognostic factors for overall survival (OS) and progression-free survival (PFS) .@*Results@#①The cohort of 24 patients included 16 male and 8 female with a median age of 49 years (range, 4-76 years) old. ②Most patients initially presented with a fever (66.7%) , cough and dyspnea. Chest imaging manifestations were primarily unilateral (45.8%) or bilateral (54.2%) pulmonary consolidation, nodules or mass. ③20 patients received chemotherapy, radiotherapy or hematopoietic stem cell transplantation, the rest 4 cases palliative treatment. Median OS was 9.5 months (range, 0.1-26.0 months) . The estimated 1-year OS rate was 45.8%. Overall response rate of patients treated with asparaginase-based regimen was 88.2%. ④In univariate survival analysis, age≤60 was prognostic for longer OS and PFS, compared with age>60 (P=0.002 and 0.004, respectively) ; ECOG≤2 was prognostic for longer OS and PFS, compared with ECOG>2 (P=0.042 and 0.004, respectively) . In multivariate survival analysis, age>60 and ECOG>2 were significantly correlated with inferior OS and PFS (OS: P=0.024 and 0.024, respectively; PFS: P=0.035 and 0.024, respectively) .@*Conclusions@#Primary pulmonary NK/T-cell lymphoma was a rare disease with poor prognosis. Asparaginase-based regimens appeared to be effective. Age and ECOG served as independent prognostic factors for primary pulmonary NK/T-cell lymphoma patients.
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Objective:To describe corneal endothelial cell density and morphology in cataract eyes in Danzhou city, Hainan province and analyze the influencing factors.Methods:A cross-sectional study was performed.A total of 573 eyes of 573 cataract patients at Danzhou First People＇s Hospital, one of the Poverty Reduction Eye Centres of "Project Vision" , were enrolled from February to December in 2009.TOPCON non-contact corneal endothelial microscope was performed to measure the endothelial cell density, corneal central thickness (CCT), average endothelial cell area, maximum endothelial cell area, minimum endothelial cell area, cell area standard deviation, coefficient of variation in cell area, and percentage of hexagonality.The differences of the above parameters were compared among different genders, eyes and age groups, and the influencing factors were analyzed.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong (No.09-007).Results:The average endothelial cell density of cataract patients was (2 533.00±366.674)/mm 2 (from 846 to 3 969/mm 2), and the CCT was (501.150±31.666) μm.Age ( P<0.01), CCT ( P=0.013), maximum endothelial cell area ( P=0.017), endothelial cell area standard deviation ( P=0.011), coefficient of variation in endothelial cell area ( P=0.001), percentage of hexagonality ( P<0.01), and average endothelial cell area ( P<0.01) were the major influencing factors of endothelial cell density.Endothelial cell density was significanly different in any two age groups (all at P<0.05). The endothelial cell density in cataract patients of 60-79 years old group and ≥80 years old group was lower than that of <60 years old group, whereas the endothelial cell density in patients ≥80 years old subgroups was higher than that in the 60-79 years subgroup, and the difference was statistically significant (all at P<0.01). Gender ( P<0.01), endothelial cell area standard deviation ( P=0.030), coefficient of variation in endothelial cell area ( P=0.012) and endothelial cell density ( P<0.01) were the main influencing factors of CCT.The CCT was (516.27±35.84)μm in male patients, which was significantly higher than (492.20±24.97)μm in female patients, the difference was statistically significant ( t=89.205, P<0.01). The difference of other parameters between different genders was not statistically significant ( P>0.05). There was no significant difference in corneal endothelium parameters between right and left eyes ( P>0.05). Conclusions:Corneal endothelial cell density varies with age, coefficient of variation in cell area, average endothelial cell area and percentage of hexagonality in cataract patients in Danzhou city.The aging degree of corneal endothelial cell is different in patients older than 60 years.
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Objective:To investigate gene basis of primary open angle glaucoma (POAG) by comparing gene expression profile of trabecular meshwork between POAG patients and normal controls by using RNA-sequencing.Methods:Trabecular meshwork specimen were obtained from trabeculectomy (POAG group, n=3) or donated eyes (control group, n=2). RNA was extracted and sequenced in both groups, gene expression profiles were analyzed and compared between them, and different expression genes associated with POAG were revealed by using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Protein Analysis Through Evolutionary Relationships (PANTHER) gene list analysis.Written informed consent was obtained from each patient or the family members prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong [No.EC20140311(3)-P01]. Results:(1)Total of 28 821 genes were obtained from RNA-sequencing, 22 genes were statistically significant between the two groups, of which one gene was up-regulated and 21 genes were down-regulated; (2)Genes that expressed differently had concentrated functions, biological process involved keratinization, epidermis development and intermediate filament cytoskeleton organization, cellular component related to keratin filament, intermediate filament, extracellular exosome and haptoglobin-hemoglobin complex, molecular function related to structural molecule activity and structural constituent of cytoskeleton; (3)Significantly enriched PANTHER pathways were plasminogen activating cascade, p38 MAPK pathway, oxidative stress response and p53 pathway.Conclusions:Trabecular meshwork and extracellular matrix remodeling due to abnormal keratin expression, structural change of intermediate filament cytoskeleton and misregulation of plasminogen activating cascade, p38 MAPK pathway were possible etiology of POAG.Differential expressed genes that related to POAG mainly involve cytoskeleton associated genes and extracellular matrix remodeling genes.Thus, regulation of these genes may have an effect on glaucomatous treatment.
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Objective:To investigate the association of ocular dominance with the severity of chronic primary angle-closure glaucoma (PACG).Methods:Ocular dominance was assessed via the " hole in card" method.The anatomical symmetry (including anterior chamber depth, lens thickness and axial length) in both eyes was analyzed via A scan ultrasound.The severely glaucomatous eye was determined by the mean defect of visual field.The association of ocular dominance with the severity of chronic PACG was then analyzed.This study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong.Written informed consent was obtained from all subjects prior to their entering the study cohort.Results:Visual acuity (LogMAR) was 0.39±0.24 in the dominant eye group, and 0.43±0.29 in the non-dominant eye group.Anterior chamber depth was (2.53±0.26)mm in the dominant eye group, and (2.54±0.29)mm in the non-dominant eye group.Lens thickness was (4.96±0.31)mm in the dominant eye group, and (4.92±0.33)mm in the non-dominant eye group.Axial length was (22.58±0.61)mm in the dominant eye group, and (22.73±1.11)mm in the non-dominant eye group.No significant difference was found in visual acuity, anterior chamber depth, lens thickness or axial length between the dominant and non-dominant eye groups ( t=-1.643, -0.797, 1.867, -1.345; all at P>0.05). The vertical cup-disc ratio of the dominant eye group was lower than that of the non-dominant eye group (0.55 [0.40, 0.80] vs. 0.80 [0.63, 0.90]). The mean defect in the visual field of the dominant eye group was lower than that in the non-dominant eye group (-6.54 [-16.70, -3.85]dB vs.-18.77 [-28.19, -8.55]dB), and the intraocular pressure in the dominant eye group was lower than that in the non-dominant eye group (21.00 [17.00, 27.75]mmHg vs. 24.50 [19.00, 36.25]mmHg) (1 mmHg=0.133 kPa). Significant differences were found in mean defect, vertical cup-disc ratio and intraocular pressure between the two groups ( Z=-3.781, -3.528, -2.126; all at P<0.05). The ratio of the severely glaucomatous eye being the non-dominant eye was 84.09%, which was much higher than that of the severely glaucomatous eye being the dominant eye (15.91%). The non-dominant eye was related to the severity of chronic PACG ( χ2=40.909, P<0.001, Pearson contingency coefficient r=0.563). Conclusions:The non-dominant eye is associated with the severity of chronic PACG.
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Objective: The expression of CD30 in peripheral lymphoma T cell lymphoma,unspecified (PTCL-U) was analyzed, and the correlations between CD30 and clinical survival and prognosis were studied. Methods: The clinical and pathological indicators of 56 patients with PTCL-U, who were newly treated in The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017, were obtained. Among the 56 patients, the male to female ratio was 1.7∶1. The median age was 60 (16?76) years. The categorical variables were analyzed by the Chi-square test. Kaplan-Meier method was used for the survival analysis along with an assessment of the differences by Log-rank test. Logistic univariate analysis and Cox multivariate regression model analysis were used to analyze the indicators affecting survival. Results: The 3-year and 5-year overall survival (OS) rates of 56 patients were 42.2% and 20.4%, respectively, and the progression-free survival (PFS) rates were 32.1% and 17.8%, respectively. The median overall survival (median-OS, mOS) was 31 months, and the median progression-free survival (median-PFS, mPFS) was 11 months. The positive expression rate of CD30 in PTCL-U patients was 35.7%. The positive expression of CD30 was more common in advanced patients. The LDH level was increased, and the number of extra-nodal lesions was≥2 in the middle-high risk patients. Further, the initial treatment effects in the positive patients were not good (P<0.05). Among the 56 patients, CHOP regimen and GDPT regimen were adopted for chemotherapy, and the two regimens showed no statistically significant effects on OS and PFS (P>0.05). The survivals in the CD30 positive and negative groups were as follows: the 3 years-OS were 16.5% and 54.9%, respectively (P=0.001); and the 3-years PFS were 11.2% and 44.5%, respectively (P=0.016). The univariate analysis showed that advanced disease, CD30-positivity, IPI/aaIPI-high risk, and PIT-high risk (P>0.05) were adverse prognostic factors. The multivariate analysis showed that staging and PIT were correlated with survival. Conclusions: The expression of CD30 in PTCL-U was low, and the prognosis of the positive-expression group was poor. The positive expression was more associated with advanced disease, high level of LDH, and medium-high risk group. The positive group was more prone to extranodal involvement and the objective remission rate was lower. Staging, CD30, IPI/aaIPI, and PIT could affect the prognosis in these patients.
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Objective To evaluate the application of the standard manual labeling on identification of retinopathy of prematurity ( ROP) images in deep learning. Methods According to the International Classification of ROP,different periods of ROP were classified into stage disease and plus disease in this study. From Joint Shantou International Eye Center from August 2009 to July 2018, a total of 1464 labeled fundus retinal photographs were divided randomly by stratified sampling into 3 groups:stage disease group(subgroup 1:173,subgroup 2:117) was used to train for labeling stage disease,whereas plus disease group(subgroup 1:163,subgroup 2:116) was used to train for labeling plus disease,and consistent labels group consisted of 895 consistent labeled images on both disease. Graders consisted of senior experts,3 senior ophthalmologists and 2 interns,and received training for classification and labeling on ROP fundus images. The results were compared among the doctors and doctors with deep learning,and the agreement between non-experts doctors and the reference standards, and deep learning and the reference standards were tested. Results After the first training,the overall agreement rate of the senior ophthalmologist group and the intern group were lower than 90％ for both two disease labeling. After two to three times of training, in image of consistent labels group,overall agreement rates of senior ophthalmologists and intern doctor's were 98. 99％ ( Kappa=0. 979),99. 22％ (Kappa=0. 984) on stage disease,and 97. 43％ (Kappa=0. 914),98. 11％ (Kappa=0. 935) on plus disease,respectively. The agreement on stage disease using deep learning based on human-machine combination was 94. 08％,Kappa value was 0. 880,which achieved good degree. Conclusions Standardized manual labeling can improve the intelligentization of deep learning on identification of ROP images,and be considered as an innovative method of homogenization and standardized training for doctors in ophthalmology.
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Objective@#To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .@*Methods@#From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.@*Results@#Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) .@*Conclusion@#Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.
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Objective@#To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC).@*Methods@#The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed.@*Results@#Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006).@*Conclusions@#PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.
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Objective@#To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) .@*Methods@#The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot.@*Results@#①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels.@*Conclusions@#14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.
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Objective To investigate the clinical manifestations, treatment outcomes and prognosis factors of the patients with primary systemic anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCL). Methods The clinical data of 32 patients histologically confirmed with ALK-ALCL from January 2011 to December 2017 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Kaplan-Meier method, Log-rank test and Cox proportional hazards model were used for the survival analysis. Results There were 19 males and 13 females in 32 patients, and the median age of onset was 50 years old (14-78 years old). The proportion of the patients with B symptom, extranodal involved, stageⅢ-Ⅳ, International Prognostic Index (IPI) sore 2-3 were 34.4 % (11 cases), 53.1 % (17 cases), 59.4 % (19 cases) and 50.0 % (16 cases) respectively. Chemotherapy alone and chemotherapy plus radiotherapy were the main methods, and a few patients received surgery alone, surgery plus chemotherapy, chemotherapy plus autologous stem cell transplantation or palliative care. The efficacy of 28 cases could be evaluated. The objective effective rate was 85.7 % (24/28), the complete remission (CR) rate was 42.9 % (12/28), and the partial remission (PR) rate was 42.9 % (12/28). The median progression-free survival (PFS) time was 28 months (95 % CI 13-42 months) and the median overall survival (OS) time was 43 months (95 % CI 24-61 months). The anticipated 5-year OS rate was 36.6 % . Single factor analysis results revealed that patients who was female (χ2＝7.654, P＝0.006), with normal serum lactic dehydrogenase (LDH) level (χ2＝7.575, P＝0.006), normal serum β2microglobulin level (χ2＝4.770, P＝0.029) and without B symptom (χ2＝9.418, P＝0.002), IPI score 0-1 (χ2＝4.119, P＝0.042) had a better prognosis. Multivariate survival analysis indicated that symptoms B ( HR＝ 12.460, 95 % CI 2.645-58.708, P＝ 0.001) and IPI score ( HR＝7.521, 95 % CI 1.624-34.841, P＝0.010) were the independent factors for prognosis. Conclusion The prognosis of the patients with primary systemic ALK-ALCL is poor, especially for the worse prognosis of the patients with symptoms B and IPI sore 2-3.
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Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.
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To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.
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Objective: To investigate the clinical characteristics, treatment regimens, and outcomes of patients with primary breast dif-fuse large B-cell lymphoma (PB-DLBCL). Methods: Between January 2010 and January 2018, 21 patients with PB-DLBCL were diag-nosed, treated, and followed up at the First Affiliated Hospital of Zhengzhou University. All patients were female, with a median age of 49 years (ranging from 21 to 77 years) at presentation. All patients received chemotherapy, of which 17 patients received the CHOP regimen and 4 received the EPOCH regimen. Eight patients received chemotherapy followed by radiotherapy, and 13 received chemo-therapy alone. Six patients received prophylactic intrathecal injections. The incidences of refractory and progressive disease between patients who received different regimens were analyzed using the Chi-square test. The overall survival (OS) and progression-free sur-vival (PFS) rates were calculated using the Kaplan-Meier method, and differences in survival were compared using the Log-rank test. Multivariate analysis was performed with the Cox-regression model for those factors that were confirmed as significant in the univari-ate analysis. Results: The most common presentation was a painless mass. The 5-year OS and PFS rates were 74% and 66%, respective-ly. There was no significant difference in the incidence of refractory or progressive disease between the EPOCH and CHOP groups (P=0.603). Six of those who received prophylactic intrathecal injections had no central nervous system recurrence, and 2 patients who did not receive prophylactic intrathecal injections had central nervous system recurrence. Univariate and multivariate analyses showed that both the level of serum β2 microglobulin [P=0.044, hazard ratio (HR)=0.431, 95% confidence interval (CI): 0.432-0.967] and radio-therapy (P=0.002, HR=0.495, 95% CI: 1.073-2.508) were related to the OS of PB-DLBCL. Conclusions: PB-DLBCL often occurs in women, mostly involving the unilateral breast, which manifests mainly as a painless mass. The level of serum β2 microglobulin is a factor of poor prognosis in PB-DLBCL. The treatment modality of chemotherapy combined with radiotherapy can significantly improve the OS of PB-DLBCL. Prophylactic intrathecal injections may be useful to reduce the incidence of refractory disease or recurrence in the central nervous system.
ABSTRACT
Objective:To investigate the treatment,clinical characteristics,and outcomes of patients with primary central nervous sys-tem lymphoma(PCNSL).Methods:A total of 75 patients histologically confirmed with PCNSL from November 2011 to November 2015 in the frist affiliated hospital of Zhengzhou Unversity were enrolled in this retrospective study.The clinical characteristics,treatment outcomes and prognostic factors of the patients were analyzed.The Kaplan-Meier method was used for univariate analysis of survival, with assessment of differences by the Log-rank test.Multivariate analysis was performed using the Cox proportional hazards model. Results:The median age at diagnosis of the 75 patients with PCNSL was 55 years(range:9-79 years),and a male-to-female ratio of 1.1:1 was observed.Major clinical characteristics observed in the patients were increased intracranial pressure and focal neurological defi-cits.All patients were diagnosed with diffuse large B-cell lymphoma(DLBCL).Of the 69 patients with follow-up data,the median pro-gression-free survival(PFS)of the chemotherapy combined with radiotherapy group(n=25),chemotherapy group(n=28),radiotherapy group(n=9)and surgery group(n=7)were 23.6(95% CI:16.0-31.3),6.4(1.0-11.8),9.8(4.7-14.9),and 5.0(4.9-5.2)months,respective-ly.The median overall survival(OS)of these four groups was 45.7(95% CI:44.2-47.2),11.0(7.1-15.0),16.1(15.3-17.0),and 6.9(1.9-12.0)months,respectively.All differences in PFS and OS between the groups were statistically significant(all P<0.01).No statistical dif-ferences were observed in the incidence of treatment-induced toxicity among these groups(P>0.05).Survival analysis showed that both age and Eastern Cooperative Oncology Group(ECOG)performance status were significantly associated with OS,and thus were in-dependent risk factors.Conclusions:PCNSL predominantly occurred in elderly people.Diffuse large B-cell lymphoma was the main type of PCNSL diagnosed.Increased intracranial pressure and focal neurological deficits were the major clinical characteristics of the patients.Age(60 years or younger),ECOG performance status score≤1,and the comprehensive treatment modality were significantly associated with improved OS.
ABSTRACT
High grade B-cell lymphoma was defined as an independent disease in the 2016 new version of the World Health Organization lymphoma classification, including double-hit high grade B-cell lymphoma with myc and bcl-2 or bcl-6 gene rearrangements and high grade B-cell lymphoma, not otherwise specified without myc and bcl-2 or bcl-6 gene rearrangements, both of them are invasive in clinical features. In recent years, there have many studies on it, double-hit lymphoma (DHL) has relatively unique clinical features and poor prognosis. Although high-intensity chemotherapy can prolong the survival of patients, current treatment options have poor efficacy, and specific targeted drug therapies are still required. Single-agent or combination therapy of signal pathway inhibitors can improve the poor prognosis of patients. Immunotherapy is expected to become the direction of future research. This article reviews the definition, diagnosis, prognosis, and latest treatment progress of DHL.
ABSTRACT
Lymphomatoid granulomatosis (LG) is a kind of Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease. Pathologically, it is characterized by angioinvasion and large EBV-positive atypical B cells in an inflammatory background with numerous T cells. Clinically, it mainly involves the bilateral lungs in the mid and lower lung fields, extra-pulmonary sites such as central nervous system, skin have also been reported. There are still no uniform treatment protocols about the disease, and pathological grading is a main reference. Overall, the prognosis is poor. Because of the rarity, lack of typical symptoms and special imaging characteristics, LG was often misdiagnosed. The article summarizes the diagnosis, treatment and prospects of LG to improve the clinician's understanding of the disease.