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Abstract The tumor microenvironment is a key determinant of cancer cell biology. The microenvironment is a complex mixture of tumor cells, stromal cells, and proteins, extracellular matrix, oxygen tension, and pH levels surrounding the cells that regulate the tumor progress. This study identified the prognostic factors associated with hepatocellular carcinoma (HCC) and MCT4 and GLUT1 expression levels in HCC specimens. In this study, we analyzed MCT4 and GLUT1 expression levels in tissue samples from 213 patients with HCC by immunohistochemical analyses and in HCC tumor tissues and matched adjacent nonneoplastic tissues by quantitative real‐time PCR. We conducted a prognostic analysis of the overall survival (OS) and time to recurrence (TTR) using immunoreactivity and other common clinical and pathological parameters. All variables with prognostic impact were further analyzed by multivariate analysis. We found that MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. In patients with HCC, MCT4 expression was an independent negative prognostic factor for OS (hazard ratio [HR] = 1.617; 95% confidence interval [CI] = 1.102–2.374; P = 0.014), and metabolic indicators were independent prognostic factors for OS (HR = 1.617, 95% CI = 1.102−2.374, P = 0.006) and TTR (HR = 1.348, 95% CI = 1.079−1.685, P = 0.009). Interestingly, patients with positive metabolic indicator expression in tumor cells had a significantly shorter OS and earlier TTR than those with negative metabolic indicator expression in tumor cells in the ≤5 cm and >5 cm subgroups. In summary, using the expression of MCT4 and GLUT1 and their metabolic parameters to determine the metabolic status of tumors is promising for predicting the prognosis of patients with HCC.

Objective: Double primary cervical cancer and ovarian cancer refer to the simultaneous or successive appearance of cervical cancer and ovarian cancer in the same patient. Due to the low incidence, there are few relevant reports. Therefore, this study is the first population-based analysis of the clinicopathological features as well as the prognostic status of double primary cervical cancer and ovarian cancer. We look forward to providing a reference for future clinical diagnosis and treatment. Methods: In this study, 473 cases of double primary cervical cancer and ovarian cancer were collected from 1975 to 2019 through the SEER database. Double primary cancers were considered non-synchronous when they were diagnosed more than 6 months apart and were classified as Group A. Double primary cancers were considered synchronous when the interval between diagnosis of the two tumors was less than or equal to 6 months and was classified as group B. Results: In this study, the incidence of double primary cervical cancer and ovarian cancer accounted for 0.39% of primary cervical cancer and 0.24% of primary ovarian cancer in the same period. 80% of patients developed second cancer within 107 months of their first cancer being diagnosed. Compared with non-synchronous cancer, synchronous cancer is mainly characterized by simultaneous bilateral ovarian involvement and early clinical stage, but highly malignant, high lymph node metastasis rate, and poor prognosis. Conclusion: Most patients developed second cancer within 107 months of their first cancer being diagnosed. Age at diagnosis, bilateral ovarian invasion, the interval between diagnoses, pathological type and stage of ovarian cancer, and grade of cervical cancer are important factors affecting survival, which still needs to be confirmed by more extensive studies in future. [ABSTRACT FROM AUTHOR]

Objective: To explore the appropriate treatment strategies, clinical outcomes, and prognostic factors of patients with pulmonary‐limited metastases derived from colorectal cancer (CRC), usually manifested as a less aggressive course. Methods: A retrospective review was conducted in 331 CRC patients diagnosed with pulmonary‐limited metastases at a single institution between January 2011 and November 2017. The Kaplan–Meier method was used to calculate the overall survival (OS). Further analysis was conducted according to treatment modalities. Univariate and multivariate analyses were used to determine potential prognostic factors influencing OS. Results: With a median follow‐up time of 38.6 months, the median OS in all patients was 45.2 months. A total of 163 patients received intensive local treatment with a median OS of 76.4 months, whereas 168 patients received palliative systemic treatment with a median OS of 29.7 months. The median OS was 68.9 months for patients treated with radiotherapy/radiofrequency ablation, with similar efficacy compared to surgery group, whose OS had not reached yet. No survival benefits were observed from the additional targeted therapy in systemic treatment group. The prognostic analysis demonstrated unilateral/bilateral lesions, synchronous/metachronous metastases, intensive local treatment, and resection of primary lesion that were significantly associated with survival of patients. Conclusions: Intensive local treatment alone for pulmonary lesions was associated with excellent survival in certain patients with CRC presented with metastases confined to lungs. Doublet systemic chemotherapy as the first‐line treatment also revealed satisfied efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: NOTCH mutations (NOTCHmut) are recognized as major oncogenic drivers associated with controversial clinical impact on T‐cell acute lymphoblastic leukemia (T‐ALL), whereas their clinical value on acute myeloid leukemia (AML) is poorly defined. Methods: A study involving 878 consecutive newly diagnosed patients with AML was undertaken in an institution with available clinical data to unravel the impact of NOTCHmut on prognosis. Results: In the study, NOTCHmut were discovered in 3.6% (32/878) of included patients with AML and composed substitution‐missense, frameshift mutation, substitution‐nonsense, and insertion‐in frame. These mutations were more commonly associated with low platelet (29 vs 42 × 109/L, p =.024) count and coexisted with BCOR/BCORL1 (15.6% vs 3.2%, p =.001), DNMT3A (28.1% vs 12.5%, p =.021), and MPL (9.4% vs 0.8%, p =.004) mutations compared with NOTCH wild‐type (NOTCHwt). No significant difference was observed in treatment responses between NOTCHmut and NOTCHwt. The presence of NOTCHmut was associated with worse overall survival ([OS], 1 year‐OS: 68.0% vs 84.2%; 3 year‐OS: 48.3% vs 59.6%; p =.059) and relapse‐free survival ([RFS], 1 year‐RFS: 78.3% vs 85.4%; 3 year‐RFS: 54.5% vs 76.9%; p =.018), especially within the European Leukemia Net 2017 intermediate‐risk group. Furthermore, allogeneic hematopoietic stem cell transplantation might abrogate the dismal impact of NOTCHmut on RFS. In multivariate analysis, NOTCHmut were found to be an independent factor negatively influencing RFS (hazard ratio, 2.153; 95% CI, 1.166‐3.975; p =.014). Conclusion: This study suggests that NOTCHmut may serve as an indicator for poor prognosis of AML. Plain language summary: Although NOTCH mutations (NOTCHmut) are well studied in T‐cell acute lymphoblastic leukemia (T‐ALL), less is known about their incidence and prognostic implications in acute myeloid leukemia (AML).A total of 878 newly diagnosed patients with AML was retrospectively analyzed; it was found that the frequency of NOTCHmut was relatively low but was associated with an adverse prognosis. A retrospective study in a large cohort of 878 patients with acute myeloid leukemia (AML) was performed, and the study suggested that NOTCH mutations may serve as indicators for poor prognosis of AML. [ABSTRACT FROM AUTHOR]

Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p <.001) and JAK mutation (OR = 17.32, p =.024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p <.001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083–7.207, p =.034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis. What is the context? Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs. Patients with hematological diseases tend to develop PTR. PTR results from immune and nonimmune factors and the latter account for 80–90%. At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear. What is new? In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020. We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation. PTR might affect megakaryocyte reconstitution after transplantation. What is the impact? This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation. Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring. Abbreviations PLT: platelets; PTR: platelet transfusion refractoriness; HSCT: hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD: graft-versus-host disease; BM: bone marrow; PB: peripheral blood [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a complex, heterogeneous malignant hematologic disease. Although multiple prognostic-related genes gave been explored in previous studies, there are still many genes whose prognostic value remains unclear. In this study, a total of 1532 AML patients from three GEO databases were included, five genes with potential prognostic value (DLC1, NF1B, DENND5B, TANC2 and ELAVL4) were screened by weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE). Based on this, we conducted survival analysis of the above five genes through the TCGA database and found that low level of DLC1 was detrimental to the long-term prognosis of AML patients. We also performed external validation in 48 AML patients from our medical center to analyze the impact of DLC1 level on prognosis. In conclusion, DLC1 may be a potential marker affecting the prognosis of AML, and its deficiency is associated with poor prognosis. [ABSTRACT FROM AUTHOR]

The diagnostic value of procalcitonin and the prognostic role of PCT clearance remain unclear in neutropenic period after allogeneic hematopoietic stem cell transplantation introduction. This study evaluated 219 febrile neutropenic patients (116, retrospectively; 103, prospectively) who underwent allo-HSCT from April 2014 to March 2016. The area under the receiver operator characteristic curve (AUC) of PCT for detecting documented infection (DI) was 0.637, and that of bloodstream infection (BSI) was 0.811. In multivariate analysis, the inability to decrease PCT by more than 80% within 5–7 days after the onset of fever independently predicted poor 100-day survival following allo-HSCT (P = 0.036). Furthermore, the prognostic nomogram combining PCTc and clinical parameters showed a stable predictive performance, supported by the C-index of 0.808 and AUC of 0.813 in the primary cohort, and C-index of 0.691 and AUC of 0.697 in the validation cohort. This study demonstrated the diagnostic role of PCT in documented and bloodstream infection during the neutropenic period after allo-HSCT. PCTc might serve as a predictive indicator of post-HSCT 100-day mortality. A nomogram based on PCTc and several clinical factors effectively predicted the 100-day survival of febrile patients and may help physicians identify high-risk patients in the post-HSCT neutropenic period. [ABSTRACT FROM AUTHOR]

Objective: The objective of this research was to screen prognostic related genes of thyroid papillary carcinoma (PTC) by single-cell RNA sequencing (scRNA-seq), to construct the diagnostic and prognostic models based on The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) data, and to evaluate the association between tumor immune microenvironment and the prognostic model. Method: The differentially expressed genes (DEGs) and tumor evolution were analyzed by scRNA-seq based on public databases. The potential regulatory networks of DEGs related to prognosis were analyzed by multi-omics data in the THCA. Logistic regression and Cox proportional hazards regression were utilized to construct the diagnosis and prognostic model of PTC. The performance of the diagnostic model was verified by bulk RNA sequencing (RNA-seq) of our cohort. The tumor immune microenvironment associated with the prognostic model was evaluated using multi-omics data. In addition, qRT-PCR was performed on tumor tissues and adjacent normal tissues of 20 patients to verify the expression levels of DEGs. Results: The DEGs screened by scRNA-seq can distinguish between tumor and healthy samples. DEGs play different roles in the evolution from normal epithelial cells to malignant cells. Three DEGs ((FN1 , CLU , and ANXA1)) related to prognosis were filtered, which may be regulated by DNA methylation, RNA methylation (m6A) and upstream transcription factors. The area under curve (AUC) of the diagnostic model based on 3-gene in the validation of our RNA-seq was 1. In the prognostic model based on 3-gene, the overall survival (OS) of high-risk patients was shorter. Combined with the clinical information of patients, a nomogram was constructed by using tumor size (pT) and risk score to quantify the prognostic risk. The age and tumor size of high-risk patients in the prognostic model were greater. In addition, the increase of tumor mutation burden (TMB) and diversity of T cell receptor (TCR), and the decrease of CD8+ T cells in high-risk group suggest the existence of immunosuppressive microenvironment. Conclusion: We applied the scRNA-seq pipeline to focus on epithelial cells in PTC, simulated the process of tumor evolution, and revealed a prognostic prediction model based on 3 genes, which is related to tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Severe bleeding is a major cause of death in acute leukemia (AL) patients with graft-versus-host disease (GVHD) after allogene hematopoietic stem-cell transplantation (allo-HSCT). However, the prognostic value and prediction of HSCT-associated severe bleeding in GVHD patients have not been reported in cohort studies. We did a retrospective analysis of 200 AL patients with GVHD after allo-HSCT from Feb 1, 2014, to Dec 1, 2015. Multivariate analysis showed that the severe bleeding class was associated with the risk of death (HR 2.26, 95% CI 1.31–3.92, p<0.001***). In order to predict severe bleeding and figure out the solution to bleeding events, we established a multiple logistic regression model. HLA-DQB1 unmatching, megakaryocyte reconsititution failure, and III or IV GVHD were the independent risk factors for severe bleeding. Among all the variations above, OR of HLA-DQB1 was the highest (OR: 16.02, 95% CI: 11.54–48.68). Adding HLA-DQB1 to other factors improved the reclassification for predicting severe bleeding (NRI=0.195, z=2.634, p=0.008**; IDI=0.289, z=3.249, p<0.001***). Lasso regression was used to select variants. A nomogram of the logistic model was generated and displayed. Calibration curve demonstrated excellent accuracy in estimating severe bleeding (C index of 0.935). HLA-DQB1 showed excellent efficacy of predicting severe bleeding in HSCT patients. [ABSTRACT FROM AUTHOR]

Background and Aim: It has been reported that serum quantification of anti‐HBc (qAnti‐HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) remains unclear. Its implication in HBV‐ACLF was evaluated in this study. Methods: Baseline serum qAnti‐HBc levels were retrospectively detected in HBV‐ACLF and CHB patients using recently developed double‐sandwich immunoassay. The association of qAnti‐HBc level with clinical outcomes was evaluated by multiple logistic regression. Nomogram was adopted to formulate an algorithm incorporating qAnti‐HBc for the prediction of survival in HBV‐ACLF. The post‐hospitalization of HBV‐ACLF patients were followed‐up for 1 year. Results: Eighty‐eight HBV‐ACLF as training set, 80 HBV‐ACLF as validation set and 216 CHB cases were included. Serum qAnti‐HBc level was significantly higher in HBV‐ACLF (4.95 ± 0.54 log10 IU/mL) than CHB patients (4.47 ± 0.84 log10 IU/mL) (P < 0.01). Among HBV‐ACLF cases, both in training and validation set, patients with poor outcomes had lower qAnti‐HBc level. Area under receiver operating characteristic curve of the novel qAnti‐HBc inclusive model was 0.82, superior to 0.73 from model for end‐stage liver disease scores (P = 0.018), which was confirmed in validation set. During follow‐up, the qAnti‐HBc level declined at month 3 and month 6, then plateaued at 3.84 log10 IU/mL. Conclusions: Serum qAnti‐HBc level was associated with disease severity and might be served as a novel biomarker in the prediction of HBV‐ACLF clinical outcomes. The underlying immunological mechanism warrants further investigation. [ABSTRACT FROM AUTHOR]

Increasing evidence has revealed that plasma fibrinogen levels may serve as prognostic indicators in patients with acute myeloid leukemia (AML), yet the exact association is still elusive. We conducted a systematic review and meta-analysis of all available studies concerning the relationship between plasma fibrinogen level and survival in AML patients. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) were calculated to evaluate the effect. A random-effect model was applied and the robustness of the pooled results was confirmed by subgroup and sensitivity analysis. A total of 9 studies were eligible to assess the association between plasma fibrinogen level and prognosis in AML. Among these investigations above, 5 studies adopted OS as their outcome indicator and were selected for the final meta-analysis. The pooled result suggested that plasma fibrinogen level was significantly relevant to increased mortality risk in AML patients (HR = 1.21, 95% CI: 1.01–1.44, p =.000, I2=85.4%). In conclusion, high plasma fibrinogen level may independently predict worse OS in patients with AML. [ABSTRACT FROM AUTHOR]

Keywords: acute myeloid leukemia; normal karyotype; myocyte enhancer factor 2C; prognosis; adult EN acute myeloid leukemia normal karyotype myocyte enhancer factor 2C prognosis adult e23 e27 5 03/31/20 20200401 NES 200401 Acute myeloid leukaemia (AML) accounts for 80-90% of adult acute leukaemias (Freeman I et al. i , [2]). 2 * The 4th quartile value of I MEF2C i expression in the total population was used as the cut-off point to define the highest relative I MEF2C i expression, while 1st to 3rd quartile was used as the lower I MEF2C i expression. In patients in CR, we found that I MEF2C i expression returned to the normal control levels, whereas I MEF2C i expression of seven relapsed patients was upregulated to the original and even higher levels again upon leukaemia recurrence (Fig C). [Extracted from the article]

HLA-mismatched stem cell microtransplantation is a new form of transplantation reported in recent years. We compared 59 patients undergoing microtransplantation to 66 patients undergoing HLA-matched sibling donor (MSD) transplantation at the same period from April 2012 to December 2016, who all suffered from intermediate/high-risk acute myelogenous leukemia (AML) in first complete remission (CR1). The estimated overall survival (OS) at 2 years was 74.1% ± 6.2% and 34.3% ± 7.9% in MSD and microtransplantation group, respectively (P = 0.001). The estimated leukemia-free survival (LFS) at 2 years was 73.3% ± 6.1% in the MSD group and 31.6% ± 7.6% in the microtransplantation group (P = 0.000). The 2-year cumulative incidence of relapse was 17.6% and 62.3% in the MSD and microtransplantation groups, respectively (P < 0.0001). The 2-year cumulative incidence of nonrelapse mortality was 10.9% in MSD group and 4.2% in the microtransplantation group (P = 0.251). Hematopoietic recovery time was shorter in the microtransplantation group than in the MSD group (P < 0.05). The infection rate was higher in the MSD group than in the microtransplantation group (P = 0.012). The preliminary results suggested that OS and LFS of microtransplantation were inferior to MSD transplantation for intermediate/high-risk AML in CR1. [ABSTRACT FROM AUTHOR]

The tumor microenvironment is a key determinant of cancer cell biology. The microenvironment is a complex mixture of tumor cells, stromal cells, and proteins, extracellular matrix, oxygen tension, and pH levels surrounding the cells that regulate the tumor progress. This study identified the prognostic factors associated with hepatocellular carcinoma (HCC) and MCT4 and GLUT1 expression levels in HCC specimens. In this study, we analyzed MCT4 and GLUT1 expression levels in tissue samples from 213 patients with HCC by immunohistochemical analyses and in HCC tumor tissues and matched adjacent nonneoplastic tissues by quantitative real‐time PCR. We conducted a prognostic analysis of the overall survival (OS) and time to recurrence (TTR) using immunoreactivity and other common clinical and pathological parameters. All variables with prognostic impact were further analyzed by multivariate analysis. We found that MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. In patients with HCC, MCT4 expression was an independent negative prognostic factor for OS (hazard ratio [HR] = 1.617; 95% confidence interval [CI] = 1.102–2.374; P = 0.014), and metabolic indicators were independent prognostic factors for OS (HR = 1.617, 95% CI = 1.102−2.374, P = 0.006) and TTR (HR = 1.348, 95% CI = 1.079−1.685, P = 0.009). Interestingly, patients with positive metabolic indicator expression in tumor cells had a significantly shorter OS and earlier TTR than those with negative metabolic indicator expression in tumor cells in the ≤5 cm and >5 cm subgroups. In summary, using the expression of MCT4 and GLUT1 and their metabolic parameters to determine the metabolic status of tumors is promising for predicting the prognosis of patients with HCC. MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is among the most fatal types of cancer worldwide due to its high rates of recurrence and metastasis. The molecular processes involved in HCC progression require further investigation to identify biomarkers for use in diagnosis and treatment. In the present study, the significance and prognostic value of matrix metallopeptidase 12 (MMP12) expression in human HCC was investigated. MMP12 mRNA expression was investigated using reverse transcription-quantitative polymerase chain reaction analysis of 42 pairs of tumor and non-tumor liver tissues obtained from patients with HCC following surgical treatment. Immunohistochemical staining was used to detect MMP12 and forkhead box P3 (FOXP3) expression in 158 paraffin-embedded HCC tissues. The prognostic value of MMP12 expression was determined using Kaplan-Meier analysis and the Cox proportional hazards model. MMP12 mRNA levels were significantly higher in liver tumor tissues compared with matched non-tumor liver tissues. MMP12 expression and FOXP3+ regulatory T cell (Treg) infiltration was positively correlated (r=0.302; P<0.001). MMP12 protein overexpression was positively correlated with tumor size (P=0.018), high serum alpha-fetoprotein levels (P=0.005) and poor overall survival time (P=0.012) in patients with HCC. Furthermore, MMP12 protein level was an independent predictive factor for overall survival time of patients with HCC who underwent curative resection. In conclusion, these results suggest that MMP12 may increase FOXP3+ Treg infiltration into tumor tissues, and promote tumor progression and immune evasion of HCC. The overexpression of MMP12 protein is, therefore, a valuable prognostic indicator in patients with HCC. [ABSTRACT FROM AUTHOR]

The clinical significance of the sodium‑potassium ATPase regulator FXYD domain‑containing ion transport regulator 3 (FXYD3) has been demonstrated in a number of types of cancer. However, the role of this protein in human hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, 217 HCC tissue samples were analyzed to evaluate the expression and prognostic significance of FXYD3 in HCC. Reverse transcription‑quantitative polymerase chain reaction was used to analyze the mRNA expression of FXYD3 in 80 primary HCC specimens and paired non‑cancerous liver tissue samples, while western blotting was used to analyze the protein expression level of FXYD3 in another 24 pairs. These analyses demonstrated that the expression level of FXYD3 was significantly increasedb at the mRNA and protein levels in HCC tumor tissues compared with adjacent non‑cancerous tissues. Immunohistochemical analysis of 137 paraffin‑embedded HCC tissue samples indicated that the expression of FXYD3 was associated with HCC clinicopathological characteristics. Kaplan‑Meier analysis demonstrated that patients with high FXYD3 protein expression (n=60) experienced significantly poorer overall survival time compared with patients with low FXYD3 protein expression (n=77) (P<0.001). Multivariate analysis demonstrated that FYXD3 protein expression level (hazard ratio, 2.137; 95% confidence interval, 1.224‑3.732; P=0.008) was an independent prognostic factor in patients with HCC. Overall, the results indicated that FXYD3 expression levels were higher in HCC tumor tissues than in adjacent non‑cancerous tissues, and that the FXYD3 protein may serve as a prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

Aim The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. Methods The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. Results The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test. Conclusions The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted. [ABSTRACT FROM AUTHOR]

Assessing the prognosis of patients with hepatocellular carcinoma (HCC) by the number and size of tumors is sometimes difficult. The main purpose of the study was to evaluate the prognostic value of total tumor volume (TTV), which combines the two factors, in patients with HCC who underwent liver resection. We retrospectively reviewed 521 HCC patients from January 2001 to December 2008 in our center. Patients were categorized using the tertiles of TTV. The prognostic value of TTV was assessed. With a median follow-up of 116 months, the 1-, 3-, and 5-year overall survival (OS) rates of the patients were 93.1 , 69.9, and 46.3 %, respectively. OS was significantly differed by TTV tertile groups, and higher TTV was associated with shorter OS ( P < 0.001). Multivariate analysis revealed that TTV was an independent prognostic factor for OS. Larger TTV was significantly associated with higher alpha-fetoprotein level, presence of macrovascular invasion, multiple tumor lesions, larger tumor size, and advanced tumor stages (all P < 0.05). Within the first and second tertiles of TTV (TTV ≤ 73.5 cm), no significant differences in OS were detected in patients within and beyond Milan criteria ( P = 0.183). TTV-based Cancer of the Liver Italian Program (CLIP) score gained the lowest Akaike information criterion value, the highest χ value of likelihood ratio test, and the highest C-index among the tested staging systems. Our results suggested that TTV is a good indicator of tumor burden in patients with HCC. Further studies are warranted to validate the prognostic value of TTV. [ABSTRACT FROM AUTHOR]

Objective: The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers. Methods: We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated. Results: A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR=1.809, 95% CI: 1.442-2.270, P<0.001) and DFS (HR=1.481, 95% CI: 1.028-2.133, P= 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) =1.895, 95% CI: 1.364-2.632, P<0.001) and lymph node metastases (OR=2.108, 95% CI: 1.104-4.024, P=0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger’s tests revealed there was no significant publication bias in the meta-analysis. Conclusion: Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3. [ABSTRACT FROM AUTHOR]

The article discusses research which was conducted to analyze the prognostic factors for survival in 75 Chinese patients with peripheral T-cell lymphoma (PTCL). Researchers evaluated patients with PTCL who were newly diagnosed between April 2004 and November 2011 at the First Affiliated Hospital of Soochow University. They found that the three year overall survival rate of all patients was 49% and that age and bone marrow involvement were factors which affected overall survival.

Severe thrombocytopenia is a serious condition that frequently arises in patients with myelodysplastic syndrome (MDS) and is associated with poor prognosis. Few studies have investigated the prognostic significance of platelet recovery in patients with MDS having thrombocytopenia. We retrospectively analyzed 117 patients with de novo MDS complicated with thrombocytopenia (platelet count [PLT] < 100 × 109/L). Patients received decitabine treatment (schedule A) or decitabine followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT; schedule B). Severe thrombocytopenia (PLT < 20 × 109/L), identified in 31 (26.5%) patients, was associated with poor survival. The PLT increased significantly after decitabine treatment in the 2 groups. Patients with thrombocytopenia treated with schedule B showed a superior prognosis compared to those treated with schedule A. On analysis of overall survival by platelet response in patients with severe thrombocytopenia, a significant survival advantage was observed in patients who achieved a platelet response, who would further benefit from allo-HSCT following decitabine therapy. The results indicate a potentially favorable prognostic impact of platelet response achieved with decitabine. Patients with MDS having severe thrombocytopenia may benefit from the effective recovery of platelets and further allo-HSCT following decitabine therapy. [ABSTRACT FROM AUTHOR]

• Adverse karyotype, CEBPA mut, and FLT3 -ITDmut were correlated with prognosis in acute myelogenous leukemia (AML). • Hematopoietic stem cell transplantation (HSCT) can overcome the prognostic effect of karyotype at diagnosis. • FLT3 -ITD and CEBPA mutations are predictive of prognosis in AML irrespective of HSCT. Cytogenetic and genetic changes have prognostic significance in acute myelogenous leukemia (AML). In our study, we compared the cytogenetic changes and gene mutations (NPM1, CEBPA, DNMT3A, FLT3 -ITD, FLT3 -TKD, and C-KIT) with clinical outcomes in 1132 patients with AML enrolled at our center over a 10-year period. A total of 977 patients provided gene mutation data. There were subsets of patients who exhibited mutations in NPM1 (17.9%), CEBPA (16.4%), FLT3 -ITD (18.5%), FLT3 -TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). A total of 557 patients (49.2%) underwent hematopoietic stem cell transplantation (HSCT) as consolidation therapy. Multivariate analysis identified an adverse karyotype (hazard ratio [HR], 1.48; P =.001), the presence of FLT3 -ITD (HR, 1.90; P <.001), and receipt of nonstandard first-line induction chemotherapy (HR, 1.45; P =.003) as significant risk factors for poor overall survival (OS), and the presence of CEBPA mut (HR,.42; P <.001) and receipt of HSCT (HR,.35; P <.001) as prognostic factors for favorable OS. In addition, the presence of FLT3 -ITDmut (HR, 2.11; P <.001) was identified as an independent risk factor for poor disease-free survival (DFS), and receipt of HSCT was correlated with improved DFS (HR,.74; P =.046). Compared with chemotherapy as consolidation therapy, HSCT improved the prognosis and overcame the prognostic effect of karyotype from the initial diagnosis; however, the presence of FLT3 -ITD or CEBPA mutation can predict prognosis in AML irrespective of HSCT. [ABSTRACT FROM AUTHOR]

Abstract Introduction Disseminated intravascular coagulation (DIC) is a severe complication of critical conditions. There are several scoring systems used for the diagnosis of DIC, including the International Society on Thrombosis and Hemostasis (ISTH) Overt-DIC criteria, the Japanese Ministry of Health and Welfare (JMHW) criteria and the Chinese Society of Thrombosis and Hemostasis scoring system for DIC (CDSS). The objective of this prospective study was to evaluate the accuracy and predictive value of the CDSS. Materials and methods 1318 patients, aged 18–70 years old and suspected of DIC were enrolled from 18 hospitals across China. Participants were divided into two groups for analysis (group 1, non-hematological diseases; group 2, hematological diseases). 242 patients were excluded because of incomplete data collection and failure to follow-up. Results and conclusions The rates of concordance of diagnosis of DIC between the CDSS and two other scoring systems were close to 80%. The area under ROC curves of CDSS had a slight advantage when using the ISTH, JMHW criteria or prognosis as gold standard, respectively. The CDSS DIC was an independent predictor of mortality, and its odds-ratio was superior or comparable to that of the ISTH and JMHW criteria in the two groups. The CDSS DIC score also had a significant correlation with the APACHE II and SOFA score (p < 0.05). In summary, as a quantification standard of the Chinese experts' consensus, the CDSS is conducive to the standardized diagnosis of DIC because of its favorable diagnostic and prognostic utility. Highlights • The diagnostic rates for DIC from the three scoring systems varied with different illnesses. • The rates of concordance in the diagnosis of DIC between the CDSS and other two scoring systems were close to 80%. • When the ISTH, JMHW and prognosis was used as the gold standard, the AUC for CDSS had a slight advantage over the two others. • The CDSS DIC was an independent predictor of mortality, and the CDSS score may reflect DIC severity. [ABSTRACT FROM AUTHOR]

Aim To compare the efficacy and safety between hypomethylating agent (HMA) alone and the combination of HMA and histone deacetylase inhibitor (HDACi) in myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Methods We performed a systematic review and meta-analysis of all available cohort studies regarding the comparison of HMA alone and in combination with HDACi for MDS and AML. Embase and Pubmed databases were searched for relevant studies. The overall hazard ratios for the HMA alone and HDACi combination were extracted. Heterogeneity among the included studies was evaluated by Cochrane’s Q Test and I 2 statistics. A random-effect model or a fixed-effect model was applied depending on the heterogeneity. Subgroup analysis was used to evaluate the source of heterogeneity. Results Seven studies comprising 922 patients (458 patients treated with HMA alone and 464 with HMA and HDACi) were included in the analysis. Pooled data showed no significant differences in complete remission (CR) rates, hematologic improvement (HI), overall response rate (ORR), overall survival (OS), and toxicities between HMA alone treatment and HMA with HDACi regimens. Conclusions HDACi and HMA combination does not appear to be more effective and better tolerated than HMA alone. Future randomized controlled trials are needed to confirm its efficacy and safety. [ABSTRACT FROM AUTHOR]

Poor platelet graft function (PPGF) is a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no optimal treatment has been recommended. This study investigated aspects of platelet recovery after allo-HSCT, including prognostic value and the effect of recombinant human thrombopoietin (rhTPO). We retrospectively analyzed 275 patients who received allo-HSCT in our center. Of them, 135 (49.1%) patients had good platelet graft function (GPGF) and 140 (50.9%) had PPGF. The latter included 59 (21.5%) patients with primary PPGF and 81 (29.4%) with secondary PPGF. Multivariate analysis showed that male gender ( P  = .024), lower CD34 + cell count ( P  = .04), and no use of rhTPO ( P  <   .001) were associated with PPGF. The 3-year overall survival rate of patients with PPGF (58%) was significantly less than that of patients with GPGF (82%; P  <   .001). We further analyzed the effect of rhTPO on prognosis of patients after allo-HSCT. Although no advantage was apparent when analyzing the entire cohort, for patients with myelodysplastic syndromes and aplastic anemia, rhTPO was associated with a significant survival advantage ( P  = .014). [ABSTRACT FROM AUTHOR]

To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n = 42) or matched unrelated donor transplantation (MUD-HCT) (n = 16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation. At the 3-year follow-up, the overall survival (OS), leukemia-free survival (LFS), the cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) rates in Haplo-HCT group were 69.1, 64.3, 19.0, and 14.3%, respectively, without significant differences from that of MUD-HCT. Haplo-HCT was not related to higher incidences of severe acute graft-versus-host disease (GvHD) (17.6 ± 5.2% vs. 20.0 ± 10.0%, P = 0.603) or chronic GvHD (19.5 ± 7.1% vs. 13.3 ± 8.6%, P = 0.637) as compared to MUD-HCT. Multivariate analysis showed that chronic GvHD was associated with lower relapse rate in Haplo-HCT group. Haplo-HCT is a promising choice for improving the long-term survival in Ph+ ALL patients. [ABSTRACT FROM AUTHOR]

Background Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. Materials and methods We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. Results A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542–2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030–4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. Conclusions Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized. [ABSTRACT FROM AUTHOR]

The optimal treatment approach for mixed phenotype acute leukemia (MPAL) remains unknown, and prognostic factors for treatment outcomes need to be identified. In this study, 66 patients diagnosed with MPAL according to criteria published by the WHO in 2008 were retrospectively assessed to evaluate the effectiveness of treatment and identify predictive variables. Five patients died of severe infection after the first induction chemotherapy, 29 received alloHSCT after induction (HSCT group), and 32 received only chemotherapy (chemotherapy group). The 3-year OS and DFS estimates for the entire cohort were 45% and 38%, respectively, and the 3-year OS differed significantly between the HSCT and chemotherapy-only groups (77% versus 16%). Using multivariate analyses, we identified disease burden as a prognostic factor for transplantation outcome, with the 3-year OS being 80% among patients who achieved remission and only 45% among patients in cases of nonremission. Our results indicate that alloHSCT after chemotherapy offers a survival advantage compared with chemotherapy only, and patients in remission before transplantation may experience a better outcome. [ABSTRACT FROM AUTHOR]