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.

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.

Application of intraoperative frozen section examination in the management of female breast cancer in China: a nationwide, multicenter 10-year epidemiological study.

BACKGROUND: Intraoperative frozen section examination (IFSE) during breast cancer surgery can partly reflect the status of surgical treatment since the surgical method used directly determines the purpose of IFSE use in disease management. This study aims to investigate the application of, changing trends in, and factors influencing IFSE in the management of female breast cancer in China. METHODS: We collected the sociodemographic and clinical data of 4,211 breast cancer patients between 1999 and 2008 and statistically analyzed these data using χ2 or Fisher's exact tests. RESULTS: A total of 2,283 (54.22%) patients with breast cancer underwent IFSE. During the 10-year study period, IFSE use was associated with an increase in the number of sentinel lymph node biopsies (SLNB) and breast-conserving surgeries (BS) performed, with significant regional differences noted in this trend (P < 0.05). Patients' education, occupation, age, tumor size estimated by preoperative palpation, and the use of imaging examinations affected the purpose of IFSE use (P < 0.05). CONCLUSIONS: Our results show that the purpose of IFSE in the surgical treatment of breast cancer in China is gradually approaching that in developed countries. We believe that policymakers must address the differences in breast cancer treatment based on the socioeconomic status of patients. Lastly, the use of IFSE for determining tumor characteristics should be avoided as far as possible, and patient education and breast cancer screening programs tailored to the Chinese population should be established. Our findings may guide the formulation of breast cancer control strategies in China and other low-income countries.

The pathologic characteristics of breast cancer in China and its shift during 1999-2008: a national-wide multicenter cross-sectional image over 10 years.

In China, breast cancer is currently the most common malignancy and the sixth leading cause of cancer death in women. But, the characteristics of breast cancer in the whole population are not determined. The aim of this study was to perform a detailed study on pathologic characteristics of breast cancer representing the whole population in China during 1999-2008 and to compare the difference in invasive breast cancer between the Western and Chinese. We randomly collected 4,211 inpatient at seven hospitals in representative geographical regions of China during 1999-2008. All the hospitals had the ability of comprehensive cancer treatment. The pathologic characters including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were surveyed. The shift of pathologic characters was evaluated and the data from China were also compared with those of the Western, both using Chi-square test. We found as follow. (i) The median age of the patients was 48 years and showed the similar characters of Asia. (ii) Breast cancer in China showed more invasive ductal carcinoma with larger tumor size, later stage, lower ER and PR expression and higher HER2 overexpression than those in the Western (p < 0.001). (iii) Both tumor size and stage at diagnosis decreased year by year (p < 0.001). Breast cancer in China showed more aggressive behavior than those in western countries, although tumor size and stage at diagnosis decreased by year during 1999-2008. We addressed the urgent needs for employ race-specific breast cancer screen, diagnosis methods, and therapeutic models in China.

[10-year changes and development of surgical treatment for breast cancer in China].

OBJECTIVE: To investigate the changes and development of surgical treatment for breast cancer from 1999 to 2008 in China, and compare the differences between the surgical methods used in high-resource and low-resource areas. METHODS: Clinicopathological data of surgical treatment for female primary breast cancer was collected via medical chart review at hospitals in seven geographic areas in China. Chi-square test and chisqure test for linear trends were used to analyze the changes and development of the surgical methods used for breast cancer in the 10 years. RESULTS: A total of 4211 primary breast cancer patients were selected from the 10-year database, including 4078 women (97.5%) treated by surgical operation. Among 3271 women (80.21%) treated with modified radical mastectomy, the surgical rate was rising from 68.89% in 1999 to 80.17% in 2008, ascending by 11.28% (χ(2) = 31.143, P < 0.001). In high-resource areas, the surgical rate of modified radical mastectomy was rising from 45.64% in 1999 to 76.13% in 2008, ascending by 30.49% (χ(2) = 89.393, P < 0.001), while in low-resource areas it kept a steady rate at 80% in the ten years (χ(2) = 2.113,P = 0.146). Among 231 women (5.66%) treated with breast-conserving surgery, the surgical rate was rising from 1.29% in 1999 to 11.57% in 2008, ascending by 10.28% (χ(2) = 102.835, P < 0.001). In high-resource areas, the surgical rate of breast-conserving surgery was rising from 2.68% in 1999 to 16.87% in 2008, ascending by 14.19% (χ(2) = 69.544, P < 0.001), while in low-resource areas it was rising from 0.42% in 1999 to 6.22% in 2008, ascending by 5.80% (χ(2) = 30.003, P < 0.001). Among 469 women (11.50%) treated with Halsted radical mastectomy, the surgical rate was declining from 28.28% in 1999 to 4.96% in 2008, descending by 23.32% (χ(2) = 206.202, P < 0.001). In high-resource areas, the surgical rate of Halsted radical mastectomy was declining from 50.34% in 1999 to 3.29% in 2008, descending by 47.05% (χ(2) = 274.830, P < 0.001), while in low-resource areas it was declining from 14.58% in 1999 to 6.64% in 2008, descending by 7.94% (χ(2) = 8.166, P = 0.004). Among 3786 women treated with breast mastectomy (including modified radical mastectomy and Halsted radical mastectomy), the surgical rate was declining from 98.46% in 1999 to 86.36% in 2008, descending by 12.10% (χ(2) = 95.744, P < 0.001). In high-resource areas, the surgical rate of breast mastectomy was declining from 96.64% in 1999 to 80.66% in 2008, descending by 15.98% (χ(2) = 53.446, P < 0.001), while in low-resource areas it was declining from 99.58% in 1999 to 92.12% in 2008, descending by 7.46% (χ(2) = 36.758,P < 0.001). CONCLUSIONS: The main primary surgical treatment for breast cancer is modified radical mastectomy during the period 1999 - 2008. Halsted radical mastectomy is gradually replaced by modified radical mastectomy and breast-conserving surgery. The rate of changes for breast-conserving surgery and mastectomy is higher in high-resource areas than that in low-resource areas. Breast-conserving surgery will become the main treatment for early-stage breast cancer.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.