Associations between quantitative measures of mammographic density and terminal ductal lobular unit involution in Chinese breast cancer patients.

BACKGROUND: Higher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD. METHODS: In this cohort of 611 invasive breast cancer patients (ages 23-91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype. RESULTS: We found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08-1.51, ptrend = < .0001), TDLU span (highest vs. lowest tertile: Expbeta = 1.23, 95% CI 1.11-1.37, ptrend = < .0001) and acini count/TDLU (highest vs. lowest tertile: Expbeta = 1.22, 95% CI 1.09-1.37, ptrend = 0.0005), while non-dense volume (NDV) was inversely associated with these measures. Similar trend was observed for absolute dense volume (ADV) after the adjustment of total breast volume, although the associations for ADV were in general weaker than those for PDV. The MD-TDLU associations were generally more pronounced among breast cancer patients ≥ 50 years and those with luminal A tumors compared with patients < 50 years and with luminal B tumors. CONCLUSIONS: Our findings based on quantitative MD and TDLU involution measures among Chinese breast cancer patients are largely consistent with those reported in Western populations and may provide additional insights into the complexity of the relationship, which varies by age, and possibly breast cancer subtype.

The relationship between terminal duct lobular unit features and mammographic density among Chinese breast cancer patients.

Extensive mammographic density (MD), a well-established breast cancer risk factor, is a radiological representation of stromal and epithelial breast tissue content. In studies conducted predominantly among Caucasian women, histologic measures of reduced terminal duct lobular unit (TDLU) involution have been correlated with extensive MD, but independently associated with breast cancer risk. We therefore examined associations between TDLU measures and MD among Chinese women, a low-risk population but with high prevalence of dense breasts. Diagnostic pre-treatment digital mammograms were obtained from 144 breast cancer cases at a tertiary hospital in Beijing and scored using the Breast Imaging Reporting and Data System (BI-RADS) density classification. TDLU features were assessed using three standardized measures (count/100 mm2 , span [µm], and acini count/TDLU) in benign tissues. Associations between each of TDLU measures and MD were examined using generalized linear models for TDLU count and span and polytomous logistic regression for acini count with adjustment for potential confounders stratified by age. Among women ≥50 years, 63% had dense breasts; cases with dense breasts (BI-RADS, c-d) had greater TDLU count (21.1 [SE = 2.70] vs. 9.0 [SE = 1.83]; p = 0.0004), longer span (480.6 µm [SE = 24.6] vs. 393.8 µm [SE = 31.8]; p = 0.03), and greater acini count (ORtrend = 16.1; 95%CI = 4.08-63.1; ptrend < 0.0001) compared to those with non-dense breasts (BI-RADS, a-b). Among women <50 years, 91% had dense breasts, precluding our ability to detect associations. Our findings are consistent with previously reported associations between extensive MD and reduced TDLU involution, supporting the hypothesis that breast cancer risk associated with extensive MD may be related to the amount of "at-risk" epithelium.

Associations between mammographic density and tumor characteristics in Chinese women with breast cancer.

PURPOSE: Mammographic density (MD) is a strong risk factor for breast cancer, yet its relationship with tumor characteristics is not well established, particularly in Asian populations. METHODS: MD was assessed from a total of 2001 Chinese breast cancer patients using Breast Imaging Reporting and Data System (BI-RADS) categories. Molecular subtypes were defined using immunohistochemical status on ER, PR, HER2, and Ki-67, as well as tumor grade. Multinomial logistic regression was used to test associations between MD and molecular subtype (luminal A = reference) adjusting for age, body mass index (BMI), menopausal status, parity, and nodal status. RESULTS: The mean age at diagnosis was 51.7 years (SD = 10.7) and the average BMI was 24.7 kg/m2 (SD = 3.8). The distribution of BI-RADS categories was 7.4% A = almost entirely fat, 24.2% B = scattered fibroglandular dense, 49.4% C = heterogeneously dense, and 19.0% D = extremely dense. Compared to women with BI-RADS = A/B, women with BI-RADS = D were more likely to have HER2-enriched tumors (OR = 1.81, 95% CI 1.08-3.06, p = 0.03), regardless of menopausal status. The association was only observed in women with normal (< 25 kg/m2) BMI (OR = 2.43, 95% CI 1.24-4.76, p < 0.01), but not among overweight/obese women (OR: 0.98, 95% CI 0.38-2.52, p = 0.96). CONCLUSIONS: Among Chinese women with normal BMI, higher breast density was associated with HER2-enriched tumors. The results may partially explain the higher proportion of HER2+ tumors previously reported in Asian women.

Temperature-Responsive Electrocatalysis Based on Poly(N-Isopropylacrylamide)-Modified Graphene Oxide (PNIPAm-GO).

Poly(N-isopropylacrylamide)-modified graphene oxide (PNIPAm-GO), which is a type of thermally responsive GO, was designed and synthesized through a covalent "grafting-from" strategy. The as-prepared modified nanosheets integrated the individual advantages of two components, such as the thermal sensitivity of the PNIPAm terminal as well as the conductivity and the open 2D structure of the GO substrate. PNIPAm-GO was able to perform the reversible regulation of hydrophilicity/hydrophobicity in aqueous solution upon variations in the temperature. Such a unique property might also lead to the utilization of PNIPAm-GO as an intelligent electrode material to achieve a switchable electrochemical response toward a [Fe(CN)6 ]3-/4- probe. The PNIPAm-GO modified glassy carbon electrode (PNIPAm-GO/GC electrode) was able to exhibit better electrochemical performance in an ON/OFF switching effect than the PNIPAm-modified glassy carbon electrode (PNIPAm/GC electrode) without GO owing to the intrinsic properties and large surface area of the introduced GO. Moreover, it was found that the PNIPAm-GO/GC electrode also displayed excellent thermally responsive electrocatalysis toward the detection of 1,4-dihydro-ß-nicotinamide adenine dinucleotide (NADH) and dopamine (DA), which resulted in two different catalytic statuses on the same electrode. This kind of switchable catalytic performance of the PNIPAm-GO/GC electrode might greatly enhance the flexibility of its application, and thus it is expected to have wide potential for applications in the fields of biosensors and biocatalysis.

Generalized linear model (GLM) analysis: Multivariables of microcalcification specimens obtained via X-ray guided by stereotactic wire localization biopsy.

OBJECTIVE: To retrospectively explore correlation of the resected specimen volume of breast microcalcification lesions and endogenous and exogenous factors of stereotactic needle localization biopsy (SNLB). MATERIALS AND METHODS: Totally 214 patients underwent SNLB for non-palpable breast lesion with microcalcification lesions. Of 211 patients, 198 patients underwent single needle localization and 13 patients underwent multi-needle localization (26 lesions). Lesion sizes, distribution characteristics, lesion localization accuracy and resected specimen volumes were recorded and analyzed using a generalized linear model (GLM). RESULTS: The average lesion diameter is 2.63±1.73 cm. The localization accuracy of 187 lesions were moderate, 26 were too deep and 11 were too superficial. The mean resected specimen volume (V) was 17.51±5.14 cm3. One-way ANOVA analysis showed that 3 factors, including lesion sizes, distribution characteristics and the localization accuracy were associated with resected specimen volume (F = 67.56-112.78, P < 0.001). GLM revealed that lesion sizes, single clustered distribution and accurate localization were significant factors for resected specimen volume (F = -4.82-11.36, P < 0.05). The ratio (%) of the resected specimen volume to the involved breast volume (V0) was defined as the degree of breast defect. The mean breast defect of 125 benign patients (V/V0) was 27.5% ranging from 10.1% to 42.3%. CONCLUSION: Average lesion diameter and localization accuracy are highly significant variables for the resected specimen volume. Localization accuracy as a subjective controllable variable is one of the important factors that determine the volume of lesion resection. Single clustered distribution was more susceptible localization accuracy than other characteristic distributions. Improving localization accuracy can reduce resected specimen volume, which can reduce breast defect to a certain extent.

Age-related terminal duct lobular unit involution in benign tissues from Chinese breast cancer patients with luminal and triple-negative tumors.

BACKGROUND: Terminal duct lobular unit (TDLU) involution is a physiological process of breast tissue aging characterized by a reduction in the epithelial component. In studies of women with benign breast disease, researchers have found that age-matched women with lower levels of TDLU involution are at increased risk of developing breast cancer. We previously showed that breast cancer cases with core basal phenotype (CBP; estrogen receptor negative [ER-], progesterone receptor-negative [PR-], human epidermal growth factor receptor 2-negative [HER2-], cytokeratins (CK 5 or CK5/6)-positive [CK5/6+] and/or epidermal growth factor receptor-positive [EGFR+]) tumors had significantly reduced TDLU involution compared with cases with luminal A (ER+ and/or PR+, HER2-, CK5/6-, EGFR-) tumors from a population-based case-control study in Poland. We evaluated the association of TDLU involution with tumor subtypes in an independent population of women in China, where the breast cancer incidence rate, prevalence of known risk factors, and mammographic breast density are thought to be markedly different from those of Polish women. METHODS: We performed morphometric assessment of TDLUs by using three reproducible semiquantitative measures that inversely correlate with TDLU involution (TDLU count/100 mm2, TDLU span in micrometer, and acini count/TDLU) by examining benign tissue blocks from 254 age-matched luminal A and 250 triple-negative (TN; ER-, PR-, HER2-, including 125 CBP) breast cancer cases treated in a tertiary hospital in Beijing, China. RESULTS: Overall, we found that TN and particularly CBP cases tended to have greater TDLU measures (less involution) than luminal A cases in logistic regression models accounting for age, body mass index, parity, and tumor grade. The strongest association was observed for tertiles of acini count among younger women (aged <50 years) (CBP vs. luminal A; ORtrend 2.11, 95% CI 1.22-3.67, P = 0.008). CONCLUSIONS: These data extend previous findings that TN/CBP breast cancers are associated with reduced TDLU involution in surrounding breast parenchyma compared with luminal A cases among Chinese women, providing further support for differences in the pathogenesis of these tumor subtypes.

Catalytic Emulsion Based on Janus Nanosheets for Ultra-Deep Desulfurization.

Catalytic Janus nanosheets were synthesized by using an anion-exchange reaction between heteropolyacids (HPAs) and the modified ionic-liquid (IL) moieties of Janus nanosheets. Their morphology and surface properties were characterized by using SEM, energy-dispersive spectroscopy (EDS), FTIR spectroscopy, and X-ray photoelectron spectroscopy (XPS) studies. Because of their inherent Janus structure, the nanosheets exhibited good amphipathic character with ILs and oil to form a stable ILs-in-oil emulsion. Therefore, these Janus nanosheets can be used as both emulsifiers and catalysts to perform emulsive desulfurization. During this process, sulfur-containing compounds at the interface could be easily oxidized and efficiently removed from a model oil. Application of this Janus emulsion brings an efficient, useful, and green procedure to the desulfurization process. Compared with the desulfurization catalyzed by using HPAs in a conventional two-phase system, the sulfur removal of dibenzothiophene (DBT) achieved in a Janus emulsion system was improved from 68 to 97 % within 1.5 h. Moreover, this emulsion system could be demulsified easily by simple centrifugation to recover both the nanosheets and the ILs. Owing to the good structural stability of the Janus nanosheets, the sulfur removal efficiency of DBT could still reach 99.9 % after the catalytic nanosheets had been recycled at least six times.

Quantitative Mammographic Density Measurements and Molecular Subtypes in Chinese Women With Breast Cancer.

Background: Studies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the human epidermal growth factor receptor-2 (HER2)-enriched subtype in Chinese breast cancer patients. Methods: In this study, we reevaluated the MD-subtype association in 1549 Chinese breast cancer patients, using VolparaDensity software to obtain quantitative MD measures. All statistical tests were 2-sided. Results: Compared with women with luminal A tumors, women with luminal B/HER2- (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.04 to 1.38; P = .01), luminal B/HER2+ (OR = 1.22, 95% CI = 1.03 to 1.46; P = .03), and HER2-enriched tumors (OR = 1.30, 95% CI = 1.06 to 1.59; P = .01) had higher fibroglandular dense volume. These associations were stronger in patients with smaller tumors (<2 cm). In contrast, the triple-negative subtype was associated with lower nondense volume (OR = 0.82, 95% CI = 0.68 to 0.99; P = .04), and the association was only seen among older women (age 50 years or older). Conclusion: Although biological mechanisms remain to be investigated, the associations for the HER2-enriched and luminal B subtypes with increasing MD may partially explain the higher prevalence of luminal B and HER2+ breast cancers previously reported in Asian women.

Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer.

BACKGROUND: As one effective treatment for lateral pelvic lymph node (LPLN) metastasis (LPNM), laparoscopic LPLN dissection (LPND) is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery. With regard to improving the accuracy and completeness of LPND as well as safety, we tried an innovative method using indocyanine green (ICG) visualized with a near-infrared (NIR) camera system to guide the detection of LPLNs in patients with middle-low rectal cancer. AIM: To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer. METHODS: A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision (TME) and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group. Clinical characteristics, operative outcomes, pathological outcomes, and postoperative complication information were compared and analysed between the two groups. RESULTS: Compared to the non-ICG group, the ICG group had significantly lower intraoperative blood loss (55.8 ± 37.5 mL vs 108.0 ± 52.7 mL, P = 0.003) and a significantly larger number of LPLNs harvested (11.5 ± 5.9 vs 7.1 ± 4.8, P = 0.017). The LPLNs of two patients in the non-IVG group were residual during LPND. In addition, no significant difference was found in terms of LPND, LPNM, operative time, conversion to laparotomy, preoperative complication, or hospital stay (P > 0.05). CONCLUSION: ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.

Post-radiation CT changes and recurrent nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Asia. Radiation therapy remains the mainstay of treatment strategies for NPC. Although approximately 19% - 56% of patients develop a recurrent disease 5 years after their primary treatment, recognition of post-radiation changes and early detection of relapse are important in improving the outcome of NPC. Our aim was to analyze the post-radiation changes and recurrent diseases related to NPC using computed tomography (CT) scans and to investigate their relationship. METHODS: CT scans of 510 pathologically proven NPC patients who have been followed up for more than 2 years after radiation were reviewed. The tumor's response to the radiation therapy and its relevance to recurrence were evaluated. RESULTS: For patients who were followed up for more than 2 years, their CT scans-obtained within 3 months, during the 4th to the 6th month, and beyond 7 months after radiation therapy, showed a normal nasopharyngeal cavity with a slight thickening in the wall in 93.5%, 95.0% and 84.8% of the patients respectively. The degree of tumor regression had no significant relevance to the risk of recurrence within the initial 3 months (P = 0.094). During this term, the relapse rates in the cases in which the nasopharyngeal walls were displayed as normal, slightly or moderately thickening, or with obvious residual masses on CT scans were 7.1%, 11.7%, 23.5% and 23.1% respectively. The degree of tumor regression beyond 3 months after radiation therapy had a considerable reverse relevance to the risk of recurrence (P = 0.000). The relapse rates were 13.2%, 14.1%, 10.2% and 2.1%, respectively, in the cases with a normal and a slightly thickening nasopharyngeal wall during the 4th to the 6th month, the 7th to the 12th month, the 13th to the 24th month, and beyond 25 months after radiation. In contrast, the percents in cases with moderate or more aggressive thickening walls in the corresponding periods were 62.5%, 88.9%, 100% and 100%. Within 6 months after radiation therapy, shown by CT scans, the metastatic lymph nodes disappeared, markedly decreased, slightly decreased, or enlarged in 37.4%, 51.8%, 4.7%, and 0.4%, respectively, of the patients. During 6 to 12 months after radiation therapy, the proportions were 78.5%, 19.2%, 0.6% and 1.7% correspondingly. Beyond 12 months, the proportions were 83.7%, 7.9%, 0%, and 8.4%. The regression degree of the malignant nodes after radiation therapy showed a remarkable reverse relevance to the risk of recurrence in lymph nodes (P = 0.000). In the cases with disappearing, markedly decreased, slightly decreased, or enlarged malignant nodes within six months after radiation, the relapse rates were 2.9%, 4.5%, 12.5% and 100%, respectively. CONCLUSIONS: If the nasopharyngeal walls are shown to remain moderately thick on a CT scan beyond 6 months after radiotherapy, the risk of relapse will increase. The baseline images taken within 3 months after radiotherapy and regular follow-up studies are the key to pick up the tumor recurrences in an earlier stage.

Thermally responsive reduced graphene oxide with designable secondary functionality.

Both dual responsive and thermal responsive reduced graphene oxide (rGO) with a strategically inbuilt function have been successfully synthesized by utilizing non-covalent modified poly(NIPAm-co-ViEtImBr) combined with anion exchange.

A comparative study of the diagnostic value of contrast-enhanced breast MR imaging and mammography on patients with BI-RADS 3-5 microcalcifications.

OBJECTIVE: To retrospectively investigate the diagnostic value of breast MRI in patients with BI-RADS 3-5 microcalcifications in mammography. METHODS: Eighty-four patients with BI-RADS 3-5 microcalcifications on mammography underwent breast MR exams before surgical biopsy with a hookwire position under mammographic guidance. Two radiologists reviewed each lesion with BI-RADS by consensus. The diagnostic value of mammography and MRI was compared. RESULTS: Histopathological examination revealed 49 benign lesions and 42 malignant lesions. In the assessments of mammography, 21 lesions (23.1%) were assigned to category 3, 51 lesions (56.0%) to category 4, and 19 lesions (20.9%) to category 5. The area under the receiver operating characteristic(ROC) curve for mammography and MR assessment was 0.844, and 0.945, respectively (p<0.05). In cases of category 3 microcalcifications, the specificity of mammography and MR was 100%, and 95.2% (p = 1.000), respectively. In cases of category 4 microcalcifications, the specificity, PPV and accuracy of mammography was 0%, 45.1% and 45.1%; whereas those for MR was 82.1% (p<0.05), 80.8% (P = 0.003) and 86.3% (p<0.05). All microcalcifications of category 5 were correctly diagnosed by mammography and MR. CONCLUSIONS: Breast MRI has the potential to significantly improve the diagnosis of category 4 microcalcifications on mammography. Among mammographic category 4 microcalcifications, about 82% of benign lesions can be degraded to BI-RADS 1∼3 by MRI. However for microcalcifications of category 3 and 5, MR exams do not show significant improvement over mammography.