Prediction of Receptor Status in Radiomics: Recent Advances in Breast Cancer Research.

Breast cancer is a multifactorial heterogeneous disease and the leading cause of cancer-related deaths in women; its diagnosis and treatment require clinical sensitivity and a comprehensive disciplinary research approach. The expression of different receptors on tumor cells not only provides the basis for molecular typing of breast cancer but also has a decisive role in the diagnosis, treatment, and prognosis of breast cancer. To date, immunohistochemistry (IHC), which uses invasive histological sampling, has been extensively used in clinical practice to analyze the status of receptors and to make an accurate diagnosis of breast cancer. As an invasive assay, IHC can provide important biological information on tumors at a single point in time, but cannot predict future changes (due to treatment or tumor mutations) without additional invasive procedures. These issues highlight the need to develop a non-invasive method for predicting receptor status. The emerging field of radiomics may offer a non-invasive approach to identification of receptor status without requiring biopsy. In this paper, we present a review of the latest research results in radiomics for predicting the status of breast cancer receptors, with potential important clinical applications.

Construction and Validation of a Nomogram for Predicting Progression- Free Survival in Patients with Early-Stage Testicular Germ Cell Tumor.

BACKGROUND: Testicular Germ Cell Tumor (TGCT) is the most common malignant tumor in young men, but there is a lack of a prediction model to evaluate the prognosis of patients with TGCT. OBJECTIVE: To explore the prognostic factors for Progression-Free Survival (PFS) and construct a nomogram model for patients with early-stage TGCT after radical orchiectomy. METHODS: Patients with TGCT from The Cancer Genome Atlas (TCGA) database were used as the training cohort; univariate and multivariate cox analysis was performed. A nomogram was constructed based on the independent prognostic factors. Patients from the Nanfang Hospital affiliated with Southern Medical University were used as the cohort to validate the predictive ability using the nomogram model. Harrell's concordance index (C-index) and calibration plots were used to evaluate the nomogram. RESULTS: A total of 110 and 62 patients with TGCT were included in the training cohort and validation cohort, respectively. Lymphatic Vascular Invasion (LVI), American Joint Committee on Cancer (AJCC) stage and adjuvant therapy were independent prognostic factors in multivariate regression analyses and were included to establish a nomogram. The C-index in the training cohort for 1- , 3-, and 5-year PFS were 0.768, 0.74, and 0.689, respectively. While the C-index for 1-, 3-, and 5- year PFS in the external validation cohort were 0.853, 0.663 and 0.609, respectively. The calibration plots for 1-, 3-, and 5-year PFS in the training and validation cohort showed satisfactory consistency between predicted and actual outcomes. The nomogram revealed a better predictive ability for PFS than AJCC staging system. CONCLUSION: The nomogram as a simple and visual tool to predict individual PFS in patients with TGCT could guide clinicians and clinical pharmacists in therapeutic strategy.

[Vascular damage-related risk factors for erectile dysfunction in patients with type 2 diabetes mellitus: Analysis based on a nomogram model].

OBJECTIVE: To analyze vascular damage-related risk factors for ED in patients with type 2 diabetes mellitus (DM) and develop a nomogram for the prediction of the factors. METHODS: A total of 181 patients with type 2 DM were included for sexual function assessment, and the clinical data on vascular damage were retrieved from the patients system. After preprocessing, the data were described by the number and percentage of different types of cases and subjected to statistical analysis with the R software. The Lasso regression model was used to optimize feature selection. On the premise of the sample size required for logistic regression analysis according to the number of events per variable, multivariable logistic regression analysis was performed on the selected variables and a nomogram was developed for diabetes-induced erectile dysfunction (DIED). Then, the performance of the nomogram was evaluated with respect to its calibration, discrimination and clinical utility using Harrell's concordance index (C-index), the calibration plot and decision curve analysis, as well as bootstrapping for internal validation. RESULTS: ED was diagnosed in 90 (49.7%) of the 181 patients. The risk factors subjected to logistic regression analysis included the duration of DM (OR = 4.440, 95% CI: 1.594－13.105; OR = 7.667, 95% CI: 1.444－48.733), status of carotid intima-media thickness (c-IMT) (OR = 3.767, 95% CI: 1.194－12.691), diabetic retinopathy (DR) (OR = 5.382, 95% CI: 1.373－28.301), diabetic kidney disease (DKD) (OR = 4.959, 95% CI: 1.156－27.728), low-density lipoprotein cholesterol (LDL-C) (OR = 8.210, 95% CI: 2.027－43.507), red blood cell distribution width (RDW) (OR = 2.418, 95% CI: 1.021－5.826), and plasma fibrinogen (Fbg) (OR = 4.649, 95% CI: 2.001－11.339). The C-index of the DIED model was 0.911 (95% CI: 0.869－0.954). The curve representing the performance of the nomogram fit in well with that representing a perfect prediction by the calibration plot. Decision curve analysis indicated that the nomogram was clinically useful for predicting DIED in the type 2 DM patients at the possibility threshold of 6% to 93%. CONCLUSIONS: A nomogram was preliminarily developed for predicting the risk of DIED in type 2 DM patients with respect to the seven independent influencing factors, including the duration of DM, status of c-IMT, DR, DKD, LDL-C, RDW, and Fbg.

[Surgical intervention in adult varicocele: An update].

Varicocele is one of the common causes of infertility in adult males. Surgical intervention can improve the semen quality of some of the patients and significantly increase the pregnancy rate, but fails to benefit them all. Therefore, it is of great practical significance to identify the patients who can significantly benefit from surgical interventions to maximize the effectiveness of surgery and avoid medical waste. This article summarizes the recent progress in surgical indications and strategies for varicocele in adult males, and provides some reference for the management of the disease.

[Gene characteristics and changing trend of neonatal thalassemia in Dongguan, China].

OBJECTIVE: To study the gene distribution characteristics of neonatal thalassemia in Dongguan, China and the changing trend of the gene distribution characteristics of neonates with thalassemia in Dongguan in 2014-2018. METHODS: A retrospective analysis was performed for the data on neonatal thalassemia screening from the Dongguan Neonatal Disease Screening System between January 2014 and December 2018. A total of 616 718 neonates were enrolled who were born in Dongguan. RESULTS: Among the 616 718 neonates, 52 308 were positive for primary screening, 10 366 were recalled, 8 576 underwent genetic diagnosis, and 6 432 were confirmed with thalassemia by genetic diagnosis. The carrying rates of thalassemia genes in 2014-2018 were 5.81%, 5.47%, 5.96%, 6.91%, and 7.90% respectively, and showed an upward trend (P<0.001). The positive rates of neonatal thalassemia screening in 2014-2018 were 9.12%, 8.34%, 7.54%, 8.13%, and 9.32% respectively (P<0.001). The positive rates of genetic diagnosis of neonatal thalassemia in 2014-2018 were 0.89%, 1.11%, 1.24%, 0.90%, and 1.09% respectively (P<0.001). In 2014-2018, 5 098 cases of α-thalassemia were detected, accounting for 79.26% of all cases, and 1 230 cases of ß-thalassemia were detected, accounting for 19.12% of all cases. The detection rate of α-thalassemia was significantly higher than that of ß-thalassemia in each year (P<0.001). In 2014-2018, static α-thalassemia, mild α-thalassemia, and mild ß-thalassemia were the main types observed in neonates. CONCLUSIONS: Most of the neonates with thalassemia have α-thalassemia in Dongguan, with static α-thalassemia and mild α-thalassemia as the main types. The carrying rate of thalassemia genes keeps increasing in neonates in Dongguan, and the prevention and treatment of thalassemia is still challenging.

Clinical outcome after management of unprotected left main in-stent restenosis after bare metal or drug-eluting stents.

BACKGROUND: Implantation of either bare metal stent (BMS) or drug-eluting stent (DES) has been used in every day practice for patients with unprotected left main stenosis (UPLMS). There are still a lack of data regarding the subsequent results of UPLMS in-stent restenosis (ISR). The present study aimed at determining the clinical outcome of UPLMS ISR patients after implantation of either BMS or DES. METHODS: Patients with UPLMS ISR after stenting were included. The primary endpoint was the cumulative major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). RESULTS: UPLMS ISR rate was 14.8% (n = 73, 15.7% after BMS, 14.5% for DES) after average of (3.89 +/- 2.01) years (range from 1 to 10.5 years) follow-up. Angiographic follow-up between 6 - 8 months was available in 85.3%. Of these, repeat percutaneous coronary intervention (PCI) was used in 62 (84.9%) patients, with medicine only in 9 (12.4%) and coronary artery bypass graft (CABG) in 2 (2.7%). Most repeat PCI patients were with unstable angina (87.0%), and had decreased left ventricular ejection fraction ((42.58 +/- 5.12)%), fewer focal/ostial left circumflex branch (LCX) lesions, in relative to medicine only group. After (31.9 +/- 23.3) months, the MACE, MI, TVR and cardiac death were 31.5%, 1.4%, 24.1% and 8.2%, respectively. Definite and possible stent thrombosis occurred in 1 (1.4%) patient. CONCLUSIONS: Medical therapy for asymptomatic isolated ostial LCX was safe. Repeat PCI for UPLMS ISR was associated with acceptable early and short-term clinical outcome. Further study was needed to elucidate the role of CABG in treating UPLMS ISR.

[Situation of impaired glucose regulation and metabolic syndrome in overweight or obesity adolescent students in Dongguan city].

OBJECTIVE: To understand the occurrence and development of adolescent students' type 2 diabetes mellitus (T2DM) by researching the characteristics of the adolescent students' impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) effected by overweight or obesity. METHODS: From May to November 2007, 3856 middle school students aged 11 to 18 years old in Dongguan city were enrolled in the study. Overweight or obesity (b/Ob) depended on three indexes: the national unified school-age children and adolescent students' body mass index (BMI) and the temporary screening classification standard II established by the Working Group on Obesity in China, BP > or = 140/90 mm Hg (1mm Hg = 0.133 kPa) and fasting capillary whole glucose which was greater than or equal to 5.6 mmol/L. The fasting capillary whole glucose was screened by blood glucose meter from fingertips. Students who had any abnormal indexes were brought into this study. On basis of voluntary principle, blood lipid, fasting blood glucose (FPG) and 2-hour postprandial blood glucose (2 h PG), fasting insulin (FIns) of 368 male and 326 female students who conformed to these conditions were measured using their venous blood. By temporary BMI standard II, they were divided into overweight group (b) and obesity group (Ob). Data of different age groups (11 to 14; 15 to 18 years old) was analyzed. RESULTS: The BMI, low density lipoprotein cholesterol (LDL-C), insulin resistance index (IR), IFG and IGT of the same age stage in two groups were compared. The BMI value was (22.1 +/- 2.4) kg/m2, LDL-C was (2.38 +/- 0.65) mmol/L, IR was 1.15 +/- 0.58 and the detection rates of IFG and IGT were 3.5% and 1.4% respectively in female students aged 11 to 14 years old in b group. In Ob group, BMI value was (24.4 +/- 3.9) kg/m2, LDL-C was (2.70 +/- 0.73) mmol/L, IR was 1.36 +/- 0.67 and the detection rates of IFG and IGT were 14.6% and 6.3% respectively. t or chi2 values of two groups which were compared were 4.83, 2.45, 2.10, 7.41 and 7.99 (P < 0.01 or P < 0.05). BMI value was (25.8 +/- 3.1) kg/m2, LDL-C was (2.35 +/- 0.62) mmol/L, IR was 1.14 +/- 0.64 and the detection rates of IFG and IGT were 3.1% and 4.1% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.0 +/- 4.3) kg/m2, LDL-C was (2.69 +/- 0.69) mmol/L, IR was 1.43 +/- 0.84 and the detection rates of IFG and IGT were 12.8% and 15.4% respectively. t or chi2 values of two groups which were compared were 3.33, 2.79, 1.87, 4.75 and 5.17 (P < 0.01 or P < 0.05). BMI value was (22.4 +/- 2.3) kg/m2, LDL-C was (2.36 +/- 0.67) mmol/L, IR was 1.19 +/- 0.65 and the detection rates of IFG and IGT were 3.6% and 1.8% respectively in male students of 11 to 14 years old in b group. In Ob group, BMI value was (24.6 +/- 4.2) kg/m2, LDL-C was (2.68 +/- 0.71) mmol/L, IR was 1.44 +/- 0.89 and the detection rates of IFG and IGT were 13.3% and 9.4% respectively. t or chi2 values of two groups which were compared were 4.85, 2.72, 2.19, 6.75 and 6.76 (P < 0.01 or P < 0.05). BMI value was (26.4 +/- 2.8) kg/m2, LDL-C was (2.35 +/- 0.70) mmol/L, IR was 1.24 +/- 0.68 and the detection rates of IFG and IGT were 4.7% and 5.6% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.2 +/- 4.8) kg/m2, LDL-C was (2.71 +/- 0.73) mmol/L, IR was 1.50 +/- 0.95 and the detection rates of IFG and IGT were 17.9% and 17.9% respectively. t or chi2 values of two groups which were compared were 2.80, 2.69, 1.84, 6.68 and 6.27 (P < 0.01 or P < 0.05). The male students' FPG of 11 to 14 years old in b group was (4.88 +/- 0.76) mmol/L and FPG of Ob group was (5.09 +/- 0.80) mmol/L. Two groups were compared and t = 1.84 (P < 0.05). The statistical differences were all observed. We compared different age stages and found that the male students' 2-hour PG of 11 to 14 years old in Ob group was (5.13 +/- 1.18) mmol/L and the 2-hour PG of 15 to 18 years old was (5.36 +/- 1.24) mmol/L. Two groups were compared and t = 1.78 (P < 0.05) near the adults value. Male students' IGT of 11 to 14 years old (b/Ob) had 8 positive cases and the positive detection rate was 3.6%. IGT of 15 to 18 years old (b/Ob) had 13 positive cases and the positive detection rate was 8.9%. Two age stages were compared and chi2 = 6.86 (P < 0.01). Female students' IGT of 11 to 14 years old (b/Ob) had 5 positive cases and the positive detection rate was 2.6%. IGT of 15 to 18 years old (b/Ob) had 10 positive cases and the positive detection rate was 7.4%. Two age stages were compared and chi2 = 4.02 (P < 0.05). All had statistical significance. The high IGT incidence rate of b/Ob group's male and female students was in the stage of 15 - 18 years old. Male students were more obvious. CONCLUSION: T2DM prevention among adolescent students should start with body overweight control. Meanwhile, the adolescent students with high risk factors should be screened regularly and early measures should be taken to prevent the impaired glucose regulation (IFG, IGT) transforming into T2DM.

Effect of coronary bifurcation angle on clinical outcomes in Chinese patients treated with crush stenting: a subgroup analysis from DKCRUSH-1 bifurcation study.

BACKGROUND: Bifurcation angles may have an impact on the clinical outcomes of crush stenting. We sought to compare high (> or = 60 degrees ) with low (< 60 degrees ) bifurcation angle in patients who underwent either classical or double kissing (DK) crush stenting for bifurcation lesions from the DKCRUSH-1 data base. METHODS: There were 212 patients with 220 lesions, some with low-angle (n = 138) and some with high-angle (n = 74). Angiography was indexed at 8-month after procedure. Primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and target lesion revascularization (TLR). Secondary endpoint included late lumen loss, the rate of restenosis, and final kissing balloon inflation (FKBI). RESULTS: At 8 months, clinical follow-up was 100%; angiographic follow-up was 75% in the low-angle group and 83.3% in the high-angle group. There were no significant differences in the FKBI between the high-angle group (91.43%) and the low-angle group (82.39%). In the high angle group, there was a significant difference in contrast volume used (P = 0.005) but no significant difference in acute gain, minimum lumen diameter (MLD), late loss and diameter stenosis in the pre-bifurcation segment, post-bifurcation segment or side branch. When lesions were assigned into with-(n = 133) and without-FKBI (n = 42), significant side-branch late loss was seen in the group without-FKBI ((0.65 +/- 0.49) mm vs (0.47 +/- 0.62) mm, P = 0.02), with a resultant greater restenosis rate (37.68% vs 18.32%, P = 0.001). No difference was detected in the MACE free survival rate between the high and low angle groups (82.39% vs 82.36%, P = 0.84). The rate of stent thrombosis tended to be higher in the lower-angle group although there was no significant difference (P = 0.38). The TLR free survival rate was 87.2% in the with-FKBI group vs 73.5% in the without-FKBI group (P = 0.001). Cox regression analysis showed that the independent predictors for target vessel revascularization were the side branch stent MLD post stenting (hazard ratios (HR) 1.028, 95% CI 2.357 - 16.233, P = 0.002), lack of FKBI (HR 4.910, 95% CI 4.706 - 8.459, P = 0.001) and unsatisfactory kissing (HR 3.120, 95% CI 2.975 - 5.431, P = 0.001). CONCLUSIONS: Bifurcation angles do not influence the clinical outcome of crush stenting. Successful final kissing balloon inflation, regardless of bifurcation angles, can predict TLR.

Distal left main coronary bifurcation lesions predict worse outcome in patients undergoing percutaneous implantation of drug-eluting stents: results from the Drug-Eluting Stent for the Treatment of Left Main Disease (DISTAL) Study.

OBJECTIVES: We investigated the clinical outcome of stenting of unprotected left main coronary artery (LMCA). METHODS: We studied 164 patients with nonbifurcated LMCA lesions (group A) and 96 patients with distal bifurcated lesions (group B). RESULTS: Clinical follow-up was available in 100%. Angiographic follow-up was 87.3% in group A and 86% in group B (p = 0.922). There were significant differences in major adverse cardiac events at 1 (p = 0.014) and 2 years (p = 0.002) between group B (19.8%, 25.0%) and group A (9.1%, 10.4%), mainly due to increased target-vessel revascularization (16.7, 21.9% in group B vs. 6.1, 7.3% in group A, p = 0.006 and 0.001, respectively). The double-stent technique was associated with worse outcomes at 1 year in group B compared to group A. Bifurcation lesions (HR 3.42, 95% CI 1.34-5.61, p = 0.001), diabetes (HR 2.68, 95% CI 2.01-12.11, p = 0.015), three-vessel disease (HR 0.83, 95% CI 0.27-0.96, p = 0.001), incomplete revascularization (HR 0.15, 95% CI 0.11-0.35, p = 0.001) and stent diameter (HR 5.05, 95% CI 2.71-10.01, p = 0.03) were the independent factors of major adverse cardiac events in the whole patient cohort. CONCLUSION: Stenting unprotected distal bifurcated LMCA was associated with unfavorable results when compared to stenting other LMCA lesions.

[Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].

OBJECTIVE: To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions. METHODS: 311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE). RESULTS: Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique. CONCLUSION: DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

[Expression of PH20 in primary and metastatic breast cancer and its pathological significance].

OBJECTIVE: To evaluate the expression pattern of PH20 in primary and metastatic breast cancer and its relationship to tumor metastatic potential. METHODS: Anti-PH20 antibody was synthesized by injection of conjugated human PH20 peptides into rabbits. Immunohistochemical study was performed on 53 cases of human breast cancer. Western blot was used to detect PH20 expression in 5 cases of breast cancer with available fresh tissue. Two oligonucleotide probes were prepared for in-situ hybridization using breast tissue microarray. RESULTS: Normal breast tissue did not express PH20 (0/3), while 58.4% (31/53) of breast cancer cases did. The highest expression rate was found in metastatic foci in regional lymph nodes (83.3%), followed by primary breast cancer tissue in cases with lymph node secondaries (70.8%). The breast cancer cases with no any metastasis had an expression rate of 48.2%. The immunohistochemical staining results were further confirmed by Western blotting. In-situ hybridization showed PH20 RNA in 75% of the breast cancer tissue (21/28). Two of the 17 cases of normal breast tissue showed weak expression in some ductolobular units. CONCLUSIONS: The expression of PH20 has a positive correlation with metastatic potential in breast cancer. It is possible that PH20 may play an important role in the invasive growth and metastasis of breast cancer cells, via mechanisms such as digestion of surrounding stromal tissue and release of FGF-2.