Prognostic prediction of the platelet-to-lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Platelet-to-lymphocyte ratio (PLR) has been used to predict the prognosis of patients with hepatocellular carcinoma (HCC) with inconsistent results. This meta-analysis aimed to clarify the prognostic value of PLR in patients with HCC. Methods: We systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to November 20, 2021. The primary outcomes were the hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), and secondary study outcomes were recurrence-free survival (RFS), disease-free survival (DFS), progression-free survival (PFS). All statistical analyses were conducted by Review Manager 5.4.1 and STATA 16.0 software. Results: A total of 21 studies comprising 8,779 patients were included in this meta-analysis. Pooled results suggested that a high PLR was significantly associated with poor OS (HR: 1.34, 95% CI: 1.18-1.52, P<0.00001; I2=59%, P=0.0005), RFS or DFS (HR: 1.35, 95% CI: 1.13-1.63, P=0.001; I2=69%, P=0.002), and PFS (HR: 1.55, 95% CI: 1.09-2.22, P=0.02; I2=73%, P=0.02). The subgroup analysis for OS showed, when the PLR cutoff value was greater than 150, the heterogeneity decreased to 0 (HR: 1.48, 95% CI: 1.33-1.68, P<0.00001; I2=0%, P=0.56); when the HBsAg positive population was increased to 100%, the heterogeneity decreased to 0 (HR: 1.46, 95% CI: 1.22-1.73, P<0.0001; I2=0%, P=0.45); compared with other regions in the world, it was more significant in China (HR: 1.43, 95% CI: 1.26-1.62, P<0.00001; I2=52%, P=0.01). In addition, scatter plot showed that the HR was negatively correlated with the proportion of patients with liver cirrhosis. Conclusions: This meta-analysis suggests that PLR is a negative correlation prognostic biomarker for HCC, high PLR values indicate poor OS, RFS, DFS and PFS, especially in hepatitis B virus (HBV) related patients.

Metformin With or Without Clomiphene Citrate Versus Laparoscopic Ovarian Drilling With or Without Clomiphene Citrate to Treat Patients With Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views. Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation. Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022. Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable. Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156). Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87-1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46-1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate. Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS. Systematic Review Registration: identifier CRD42021240156.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUND: The liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis. AIM: To analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT. METHODS: From January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed. RESULTS: The mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively. CONCLUSION: Measurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment.

BACKGROUND: CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment. The expression of CD155 is correlated with the prognosis and pathological features of breast cancer. AIM: To investigate the expression status of CD155 and the association with exhausted CD4+ helper and CD8+ cytotoxic tumor infiltrating lymphocytes (TILs) and PD-L1 in the breast cancer microenvironment. METHODS: One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study. Immunohistochemistry was used to detect the expression CD155, PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment. RESULTS: The proportion of patients with CD155 expression was higher in triple negative breast cancer (72.7%) than in Luminal A patients (22.2%, P < 0.05). Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+ helper TILs (30%) than patients with negative CD155 expression (21%, P < 0.05). Patients with positive CD155 expression also had higher cell counts of exhausted CD4+ TILs [47 vs 20/high-power fields (HPF)] and unexhausted CD8+ TILs (30 vs 17/HPF) than patients with negative expression (P < 0.05). CD155 expression was correlated with increased PD-L1 expression in immune cells, 0.8% and 0.02% immune cells expressed PD-L1 in patients with positive and negative CD155 expression, respectively (P < 0.05). CONCLUSION: CD155 was related to an inhibitory immune breast cancer microenvironment. CD155 was associated with a high proportion of exhausted CD4+ and unexhausted CD8+ TILs and high PD-L1 expression in immune cells.

Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study.

PURPOSE: The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. METHODS: 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. RESULTS: 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p < 0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p < 0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p < 0.05). CD155 overexpression was associated with an increased relapse (HR = 13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR = 5.47, 1.42, 20.99). CONCLUSIONS: Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature.

BACKGROUND: Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma (MNT) and micronodular thymic carcinoma with lymphoid hyperplasia (MNC), whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells. This type of tumor is rare; therefore, the corresponding clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. CASE SUMMARY: This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods. Morphologically, this tumor type is a series of benign to malignant pedigrees. We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma: (1) Tumor cells with moderate-to-severe dysplasia; (2) Tumor cell mitotic figures > 2/10 high-power fields; (3) Appearance of neoplastic necrosis; (4) No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor; (5) Tumor cells with a Ki-67 index ≥ 10%; and (6) Tumor cells express CD5. Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT. It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above. CONCLUSION: Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis, which offers a practical reference for oncologists and pathologists.

Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea.

This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: -2.70, -0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.

Distribution of CD4+ and CD8+ exhausted tumor-infiltrating lymphocytes in molecular subtypes of Chinese breast cancer patients.

PURPOSE: Breast cancer (BC) is the leading cancer affecting Chinese women; however, the immune microenvironment between molecular subtypes is less reported. This study aimed to investigate the distribution of tumor-infiltrating lymphocyte (TIL) subpopulations, especially exhausted CD4+ and CD8+ TILs in Chinese BC patients. PATIENTS AND METHODS: A total of 133 patients with breast invasive ductal carcinoma were recruited consecutively from January 1, 2012 to December 31, 2013, and TILs were detected in H&E-stained sections. Expression profiling of PD-1, CD4, and CD8 was determined by immunohistochemistry on 4 µm formalin-fixed paraffin-embedded tissue sections. The distribution of TILs was analyzed based on hormone receptor status and molecular subtypes. RESULTS: PD-1+, CD4+, and CD8+ TILs distributed differently based on molecular subtypes. Compared to Luminal A, triple-negative breast cancer (TNBC) patients had more PD-1+ TILs (39/high-power field [HPF] vs 11/HPF), PD-1+ helper T (CD4+) cells (28/HPF vs 10/HPF), and PD-1+ cytotoxic (CD8+) T-cells (3/HPF vs 2/HPF). CONCLUSION: TILs are distributed differently based on molecular subtypes. TNBC patients exhibit more PD-1+ exhausted TILs, representing an inhibitory immune microenvironment. PD-1/PD-L1 pathway is a potential therapeutic target of TNBC.

High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer.

OBJECTIVE: Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1)+/PD-1- tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer. METHODS: In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment. RESULTS: The median cell counts of the overall TILs, PD-1+ TILs, and PD-1- TILs were 80, 18, and 55/HPF, respectively. The number of PD-1- TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1- TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1+ TILs, and the correlation coefficient was 0.29. CONCLUSIONS: PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1- TILs; however, Ki-67 expression was associated with PD-1+ TILs.

Expression of PD-1 on CD4+ Tumor-Infiltrating Lymphocytes in Tumor Microenvironment Associated with Pathological Characteristics of Breast Cancer.

OBJECTIVE: This study aimed to investigate the correlation of CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes with pathological characteristics in breast cancer patients. METHODS: A cross-sectional study consecutively recruited 133 patients with invasive ductal breast cancer. The expression of CD4, programmed cell death protein 1 (PD-1), CK7, CK20, E-cadherin, or Ki-67 was detected by immunohistochemistry. The associations between CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes and pathological characteristics were evaluated. RESULTS: Elderly patients intended to have a lower level of CD4+/PD-1- tumor-infiltrating lymphocytes (p < 0.05). Patients with positive E-cadherin expression had higher median cell counts of CD4+/PD-1- tumor-infiltrating lymphocytes than patients with negative E-cadherin expression (30/HPF versus 10/HPF, p < 0.05). Counts of CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant correlation with Ki-67 index that the correlation coefficient was 0.29 (p = 0.001). Positive CK20 expression was related to a higher level of CD4+/PD-1- tumor-infiltrating lymphocytes than negative CK20 expression (73/HPF versus 30/HPF, p < 0.05). CONCLUSION: CD4+/PD-1+ or CD4+/PD-1- tumor-infiltrating lymphocytes showed diverse association with pathological features of breast cancer. CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant relationship with Ki-67 expression whereas CD4+/PD-1- tumor-infiltrating lymphocytes had a significant relationship with E-cadherin expression. Further studies are warranted to explore the immunomodulatory effects of phenotypes of CD4+ T cell subsets in breast cancer.

Influence of occupation and education level on breast cancer stage at diagnosis, and treatment options in China: A nationwide, multicenter 10-year epidemiological study.

The objective of this study was to evaluate the impact of occupation and education level of Chinese female breast cancer patients on their cancer staging at diagnosis, clinical and pathological features, rate of implementation, and selection of treatment.The medical charts of 4211 confirmed female breast cancer cases diagnosed between 1999 and 2008, from 7 breast cancer centers spread across the whole of China, were reviewed. Data including information on the patient's sociodemographic status, clinical and pathological characteristics, implementation of clinical examination and treatment modalities were analyzed. In parallel, the associations between different occupations and level of educational attainment were analyzed in relation to tumor stage through TNM staging, clinical and pathological characteristics, implementation of clinical examination, and treatment patterns. Multivariate logistic regression was used to identify whether the occupation and education level of patients are independent factors of TNM staging at diagnosis.There were significant differences among different occupation groups and the education level of patients in regards to pathological characteristics and treatment choice. Both the occupation and education level of patients were independent factors of TNM staging at diagnosis. For patients within the lower-income occupation or lower educational attainment group, the tumor stage was later, the rates of implementation of relevant investigations were lower, as were the rates of radiotherapy, chemotherapy, and endocrine therapy.This study suggests that strategies should work toward developing more accurate and effective breast cancer prevention and treatment strategies aimed specifically at patients with lower educational attainment levels and at specific occupation groups.

Prevalence and clinical features of adult atopic dermatitis in tertiary hospitals of China.

The prevalence of atopic dermatitis (AD) has increased substantially. Previous studies have focused mostly on pediatric patients, while epidemiological investigation on adult AD has been very limited.The aim of this study was to determine the prevalence and clinical features of adult AD in outpatients with dermatitis and eczema in China mainland.A multicenter cross-sectional study was conducted among outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in China from July 1 to September 30, 2014.Of 8758 patients, 407 were adult AD. Compared with adults with other types of dermatitis, the mean age (41.8 ±â€Š14.3 vs 42.04 ±â€Š15.38 years, P < 0.05) and onset age (35.2 ±â€Š11.2 vs 39.2 ±â€Š14.0 years, P < 0.001) of adult AD were younger, and mean disease duration was longer (5.3 ±â€Š7.1 vs 2.8 ±â€Š4.9 years, P < 0.001). About 53.3% adult AD involved 3 or more body locations, higher than adults with other types of dermatitis (34.4%, P < 0.001), but lower than those with pediatric and adolescent AD (73.8%, P < 0.001). History of asthma (19.2% vs 6.9%, P < 0.001) or allergic conjunctivitis (21.9% vs 14.9%, P < 0.05) was more common in adult AD than pediatric/adolescent AD. Suspected bacterial infection was more frequently in adult AD than adults with other types of dermatitis (24.3% vs 14.6%, P < 0.001) and pediatric/adolescent AD (24.3% vs 14.9%, P < 0.001). More severe itching was observed in 31.4% of adult AD, higher than that of adults with other types of dermatitis (15.4%, P < 0.001), whereas similar to that of pediatric/adolescent AD (28.7%, P > 0.05). The highest (8.7%) and lowest prevalence (3.7%) of adult AD were in 25°N to 30°N and 35°N to 40°N latitude region.A substantial part of adult outpatients with eczema or dermatitis is adult AD. Middle age, more body location involvement, more suspected bacterial infection, and severe itching are the main clinical feathers of adult AD. Geographical environment and economic situation work in synergy to adult AD.

A nomogram to predict the probability of axillary lymph node metastasis in female patients with breast cancer in China: A nationwide, multicenter, 10-year epidemiological study.

Axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) alone may lead to postoperative complications. Among patients with positive ALN in the preoperative examination, approximately 40% patients do not have SLN metastasis. Herein, we aimed to develop a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. We retrospectively analyzed the clinicopathological features of 4211 female patients with breast cancer who were diagnosed in seven breast cancer centers representing entire China, over 10 years (1999-2008). The patients were randomly categorized into a training cohort or validation cohort (3:1 ratio). Multivariate logistic regression analysis was performed for 1869 patients with complete information on the study variables. Age at diagnosis, tumor size, tumor quadrant, clinical nodal status, local invasion status, pathological type, and molecular subtypes were the independent predictors of ALN metastasis. The nomogram was then developed using the seven variables. Further, it was subsequently validated in 642 patients with complete data on variables in the validation cohort. Coefficient of determination (R²) and the area under the receiver-operating characteristic (ROC) curve (AUC) were calculated to be 0.979 and 0.7007, showing good calibration and discrimination of the model, respectively. The false-negative rates of the nomogram were 0 and 6.9% for the predicted risk cut-off values of 14.03% and 20%, respectively. Therefore, when the predicted risk is less than 20%, SLNB may be avoided. After further validation in various patient populations, this model may support increasingly limited axillary surgery in breast cancer.

Cytokine-induced killer cell infusion combined with conventional treatments produced better prognosis for hepatocellular carcinoma patients with barcelona clinic liver cancer B or earlier stage: A systematic review and meta-analysis.

BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies. Egger's test was used to characterize the publication bias. RESULTS: Eight randomized controlled trials and 945 patients with HCC were included in the study. CIK infusion reduced cancer recurrence risk to 0.74 (95% confidence interval [CI] 0.5-0.92), I2 75% (P <0.001), and reduced cancer death risk to 0.76 (95% CI 0.65-0.88), I2 50% (P = 0.09). Among studies blinded for outcome assessment and Barcelona Clinic Liver Cancer stages of 0, A and B, CIK infusion reduced recurrence risk by 18% (relative risk [RR] = 0.82, 95% CI 0.70-0.96) and death risk by 37% (RR = 0.63, 95% CI 0.47-0.85); heterogeneity was 0% and 39%, respectively (P > 0.05). The intercepts of linear regressions for recurrence and death were -2.17 and -2.07, respectively, but the P value was 0.17 and 0.38; no significant publication bias was observed with Egger's test. DISCUSSION: Among hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer score of B or less, CIK cell infusions combined with conventional treatments significantly prolonged recurrence-free and overall survival. This adoptive immunotherapy could be recommended to HCC patients.

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

OBJECTIVE: This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy. METHODS: 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4+CD25+ proportion more than 5% and less than or equal to 5% in peripheral T cells. RESULTS: Peripheral CD4+CD25+ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4+CD25+ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4+CD25+proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients. CONCLUSIONS: Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4+CD25+T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

A suggestion for pathological grossing and reporting based on prognostic indicators of malignancies from a pooled analysis of renal epithelioid angiomyolipoma.

PURPOSE: Epithelioid angiomyolipoma (EAML) is a rare entity of the kidney. The guideline for grossing and reporting of renal EAML has not been established for Chinese patients. We planned this study to provide some preliminary indicators for draft guidelines of pathological diagnosis among Chinese people. METHODS: The histopathological characteristics of 11 EAML cases from Cancer Hospital, Chinese Academy of Medical Sciences, were reviewed, and a pooled analysis based on our cases and cases from published articles was performed on the histopathological characteristics and prognosis of 56 Chinese patients with EAML. All the cases met the criteria of the 2004 World Health Organization classification of renal tumors. RESULTS: The ratio of female to male was 1.2:1 with the mean age of 43.4 in the 11 cases. All the 11 cases were sampled following the guideline of renal cell carcinoma. The mean tumor size was 6.5 cm. Four (36.4 %) cases showed necrosis. Six (54.5 %) cases showed invasive borders. Only one case showed metastases. In pooled analysis of the total 56 cases with EAML, 10 cases (17.9 %) showed adverse prognosis. Tumor size, necrosis and invasive edge showed significant difference between favorite and adverse prognostic groups (P < 0.05). CONCLUSION: The majority of EAML is benign, and true malignant EAML is rare. The sample of EAML should follow the sample guidelines of renal cell carcinoma with some modifications, emphasizing the presence of necrosis and invading edge. The information of tumor size, necrosis and invasive edge should be included in the diagnostic report of each EAML case.

Breast Cancer Challenges and Screening in China: Lessons From Current Registry Data and Population Screening Studies.

BACKGROUND: As one of its responses to the increasing global burden of breast cancer (BC), China has deployed a national registration and BC screening campaign. The present report describes these programs and the initial results of these national BC control strategies, highlighting the challenges to be considered. MATERIALS AND METHODS: The primary BC incidence and prevalence data were obtained from the Chinese National Central Cancer Registry. MapInfo software was used to map the geographic distribution and variation. The time trends were estimated by the annual percentage of change from 2003 to 2009. The description of the screening plans and preliminary results were provided by the Ministry of Health. RESULTS: Chinese cancer registries were primarily developed and activated in the East and Coastal regions of China, with only 12.5% of the registries located in West China. Geographic variation was noted, with the incidence of BC higher in North China than in South China and in urban areas compared with rural areas. Of great interest, these registries reported that the overall BC incidence has been increasing in China, with an earlier age of onset compared with Western countries and a peak incidence rate at age 50. In response to this increasing incidence and early age of onset, BC screening programs assessed 1.46 million women aged 35-59 years, using clinical breast examinations and ultrasound as primary screening tools between 2009 and 2011. The diagnostic rate for this screening program was only 48.0/10(5) with 440 cases of early stage BC. Early stage BC was detected in nearly 70% of screened patients. Subsequently, a second-generation screening program was conducted that included older women aged 35-64 years and an additional 6 million women were screened. CONCLUSION: The cancer registration system in China has been uneven, with a greater focus on East rather than West China. The data from these registries demonstrate regional variation, an increasing BC incidence, and an early age of onset. The 2009 to 2011 BC screening program targeting women aged 35-59 years had a low detection rate that resulted in a second-generation screening program that extended the cohort size and ages screened to 35-64 years. IMPLICATIONS FOR PRACTICE: Cancer registration has been active in China for decades; however, a national survey of registries has not been routinely reported. This study used MapInfo to describe the reported data and found asymmetric registration activities, geographic variations in breast cancer (BC) burdens, and an increasing incidence with a peak at age 50. The initial Chinese BC screening programs focused on a relatively young population of women aged 35-59 years and had a low detection rate, but 69.7% of patients had early stage BC. Older women were included in the second-generation screening programs, and an additional 6 million women were screened. Consideration of regional variations and age is necessary to optimize the efficiency and utility of BC screening in China, with the ultimate goal to reduce BC mortality.

A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases.

OBJECTIVE: The potential benefit of adjuvant hepatic arterial infusion remains unknown for patients with colorectal liver metastases after radical hepatic resection. The principle aim of this study was to investigate the long-term outcome of adjuvant hepatic arterial infusion. METHODS: Eligible trials were identified from Embase, PubMed, the Web of Science, and the Cochrane library since their inception to June 1, 2014. Patients with colorectal liver metastases, who underwent radical hepatic resection and received adjuvant hepatic arterial infusion, were enrolled. The study outcomes included 5-year disease-free and overall survival rate, respectively. Hazard ratio with a 95 % confidence interval was used to measure the pooled effect according to a random effects model or fixed effects model, depending on the heterogeneity between the included studies. The statistical heterogeneity between trials was detected by I (2) test. Sensitivity analyses were also carried out. RESULTS: A total of nine studies containing 1057 patients were included. The comparison indicated that the overall pooled hazard ratio for 5-year overall survival was 0.75 (95 % CI: 0.56-0.99, p = 0.048). The hazard ratio for 5-year disease-free survival rate was 0.61 (95 % CI: 0.48-0.79, p = 0.001). When compared with systemic chemotherapy alone, adjuvant hepatic arterial infusion plus systemic chemotherapy also improved the long-term survival. CONCLUSIONS: Adjuvant hepatic arterial infusion improved the 5-year disease-free and overall survival rate, respectively. It should be recommended for patients with a high risk of recurrence, but these findings require prospective confirmation.

Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

BACKGROUND: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. MATERIALS AND METHODS: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. RESULTS: An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). CONCLUSIONS: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.