Superparamagnetic Iron Oxide-Erastin-Polyethylene Glycol Nanotherapeutic Platform: A Ferroptosis-Based Approach for the Integrated Diagnosis and Treatment of Nasopharyngeal Cancer.

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)-erastin-polyethylene glycol (PEG) nanoparticles prepared by loading SPIO-PEG nanoparticles with erastin on ferroptosis. SPIO-erastin-PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO-erastin-PEG were measured as (-37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T2-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO-erastin-PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO-erastin-PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO-erastin-PEG have been demonstrated in 5-8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO-erastin-PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.

Gelatin nanocarriers assembled by a self-immolative cross-linker for targeted cancer therapy.

With a number of outstanding properties, gelatin is an ideal candidate for assembling nanoplatforms in biomedical applications. Generally, gelatin nanocarriers are cross-linked by aldehydes to improve their stability in water solution. However, aldehydes could cause multiple toxicities and their cross-linking products are uncontrollable. Here, we first used a self-immolative cross-linker to assemble gelatin nanocarriers for the controlled release of drugs and targeted cancer therapy. The cross-linker contains a disulphide bridge and two symmetrical succinimidyl-esters, endowing it with multiple functions: 1) to cross-link the gelatin nanocarriers and thus improve their stability in water; 2) to conjugate the drug and tumor-targeting ligands with nanocarriers through covalent linkage; 3) to redox-responsively degrade the nanocarriers through hydrolysis of disulphide bridge; and 4) to produce traceless drug molecules through self-immolative reaction. Good biocompatibility and controllable drug release were demonstrated by in vitro experiments. Both qualitative and quantitative analyses confirmed the intracellular uptake of the nanocarriers by using doxorubicin (DOX) as a drug model and phenylboronic acid (PBA) as the targeting ligand. In vivo results demonstrated high therapeutic efficiency and low toxic side effects of the DOX loaded nanocarriers against artificial liver tumors.

Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L1 Immunotherapy to Treat Immunotherapy Resistance.

Background: The anti-Programmed Death-Ligand 1 (termed aPD-L1) immune checkpoint blockade therapy has emerged as a promising treatment approach for various advanced solid tumors. However, the effect of aPD-L1 inhibitors limited by the tumor microenvironment makes most patients exhibit immunotherapy resistance. Methods: We conjugated the Sialyl Lewis X with a polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO-PEG) to form UPS nanoparticles (USPIO-PEG-SLex, termed UPS). The physicochemical properties of UPS were tested and characterized. Transmission electron microscopy and ICP-OES were used to observe the cellular uptake and targeting ability of UPS. Flow cytometry, mitochondrial membrane potential staining, live-dead staining and scratch assay were used to verify the in vitro photothermal effect of UPS, and the stimulation of UPS on immune-related pathways at the gene level was analyzed by sequencing. Biological safety analysis and pharmacokinetic analysis of UPS were performed. Finally, the amplification effect of UPS-mediated photothermal therapy on aPD-L1-mediated immunotherapy and the corresponding mechanism were studied. Results: In vitro experiments showed that UPS had strong photothermal therapy ability and was able to stimulate 5 immune-related pathways. In vivo, when the PTT assisted aPD-L1 treatment, it exhibited a significant increase in CD4+ T cell infiltration by 14.46-fold and CD8+ T cell infiltration by 14.79-fold, along with elevated secretion of tumor necrosis factor-alpha and interferon-gamma, comparing with alone aPD-L1. This PTT assisted aPD-L1 therapy achieved a significant inhibition of both primary tumors and distant tumors compared to the alone aPD-L1, demonstrating a significant difference. Conclusion: The nanotheranostic agent UPS has been introduced into immunotherapy, which has effectively broadened its application in biomedicine. This photothermal therapeutic approach of the UPS nanotheranostic agent enhancing the efficacy of aPD-L1 immune checkpoint blockade therapy, can be instructive to address the challenges associated with immunotherapy resistance, thereby offering potential for clinical translation.

A three-gene signature reveals changes in the tumor immune microenvironment in the progression from NAFLD to HCC.

Hepatocellular carcinoma (HCC) is one of the most dangerous malignant tumors. The incidence rates of obesity related NAFLD and NASH are increasing year by year, and they are the main risk factors for HCC at present. Finding the mechanism of malignant transformation of NAFLD and NASH is helpful for early prevention and diagnosis. In this study, we performed differential analysis using NAFLD data, NASH data, and HCC data to identify crossover differential genes. Then, using the clinical data of TCGA, a prognostic risk prediction model of three genes (TEAD4, SOCS2, CIT) was constructed, and survival analysis and receiver operating characteristic curves were drawn. The prognostic model was validated using ICGC, GSE116174 and GSE54236 datasets. In addition, we assessed immune status and function in high- and low-risk populations using a prognostic model. Moreover, we assessed the expression of CIT in clinical samples and HCC cell lines and validated its role in HCC development. Our study elucidates the important role of the tumor immune microenvironment in the development of NAFLD/NASH to HCC, deepens the understanding of the pathogenesis of NAFLD/NASH development to HCC, and is helpful for clinical management and decision-making.

Nomogram based on clinical and preoperative CT features for predicting the early recurrence of combined hepatocellular-cholangiocarcinoma: a multicenter study.

PURPOSE: To establish and validate a multiparameter prediction model for early recurrence after radical resection in patients diagnosed with combined hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS: This study reviewed the clinical characteristics and preoperative CT images of 143 cHCC-CC patients who underwent radical resection from three institutions. A total of 110 patients from institution 1 were randomly divided into training set (n = 78) and testing set (n = 32) in the ratio of 7-3. Univariate and multivariate logistic regression analysis were used to construct a nomogram prediction model in the training set, which was internally and externally validated in the testing set and the validation set (n = 33) from institutions 2 and 3. The area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration analysis were used to evaluate the model's performance. RESULTS: The combined model demonstrated superior predictive performance compared to the clinical model, the CT model, the pathological model and the clinic-CT model in predicting the early postoperative recurrence. The nomogram based on the combined model included AST, ALP, tumor size, tumor margin, arterial phase peritumoral enhancement, and MVI (Microvascular invasion). The model had AUCs of 0.89 (95% CI 0.81-0.96), 0.85 (95% CI 0.70-0.99), and 0.86 (95% CI 0.72-1.00) in the training, testing, and validation sets, respectively, indicating high predictive power. DCA showed that the combined model had good clinical value and correction effect. CONCLUSION: A nomogram incorporating clinical characteristics and preoperative CT features can be utilized to effectively predict the early postoperative recurrence in patients with cHCC-CC.

A Reliable and Repeatable Model for Predicting Microvascular Invasion in Patients With Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: The reproducibility of imaging models for predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains questionable due to inconsistent interpretation of image signs. Our aim was to screen for high-consensus MRI features to develop a repeatable model for predicting MVI. MATERIALS AND METHODS: We included 219 patients with HCC who underwent surgical resection, and patients were divided into a training cohort (n = 145) and a validation cohort (n = 74). Morphological characteristics, signal features on hepatobiliary phases, and dynamic enhancement patterns were qualitatively interobserver evaluated. Interobserver agreement was assessed using Cohen's κ for selecting features with high interobserver agreement. Risk factors that were significant in stepwise multivariate analysis and that could be measured with good interobserver agreement were used to construct a predictive model, which was assessed in the validation cohort. The diagnostic performance of the model was evaluated based on area under the receiver operating characteristic curve (AUC). RESULTS: Multivariate analysis identified nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery as independent risk factors of MVI. These MRI-based features showed good or nearly perfect interobserver agreement between radiologists (κ > 0.6). The predictive model predicted MVI well in the training (AUC 0.734) and validation cohorts (AUC 0.759) and fitted well to calibration curves. CONCLUSION: MRI features included nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery that can be assessed with high interobserver agreement can predict MVI in HCC patients. The predictive model described here may be useful to radiologists, regardless of experience level.

Breast Magnetic Resonance Imaging Can Predict Ki67 Discordance Between Core Needle Biopsy and Surgical Samples.

BACKGROUND: Disagreement in assessments of Ki67 expression based on core-needle biopsy and matched surgical samples complicates decisions in the treatment of breast cancer. PURPOSE: To examine whether preoperative breast MRI could be useful in predicting Ki67 discordance between core-needle biopsy and surgical samples. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixty-five breast cancer patients with MRI scans and having both core-needle biopsy and surgical samples from 2017 to 2019. FIELD STRENGTH/SEQUENCE: 3.0 T, T2-weighted iterative decomposition of water and fat with echo asymmetry and least squares estimation sequence, diffusion-weighted sequence using b-values 0/1000, dynamic contrast enhanced image by volume imaged breast assessme NT. ASSESSMENT: We collected clinicopathologic variables and preoperative MRI features (tumor size, lesion type, shape of mass, spiculated margin, internal enhancement, peri-tumoral edema, intra-tumoral necrosis, multifocal/multicentric, apparent diffusion coefficient [ADC] minimum, ADC mean, ADC maximum, ADC difference). STATISTICAL TESTS: K-means clustering, multivariable logistic regression, receiver operating characteristic curve. RESULTS: Sixty-one patients showed Ki67 discordance and 304 patients show Ki67 concordance according to our definition using K-means clustering. Multivariable regression analysis showed that the following parameters were independently associated with Ki67 discordance: peri-tumoral edema, odds ratio (OR) 2.662, 95% confidence interval (CI) 1.432-4.948; ADCmin ≤ 0.829 × 10-3  mm2 /sec, OR 2.180, 95% CI 1.075-4.418; and ADCdiff > 0.317 × 10-3  mm2 /sec, OR 3.365, 95% CI 1.698-6.669. This multivariable model resulted in an AUC of 0.758 (95% CI 0.711-0.802) with sensitivity and specificity being 0.803 and 0.621, respectively. CONCLUSION: Presence of peri-tumoral edema, smaller ADCmin and greater ADCdiff in preoperative breast MRI may indicate high risk of Ki67 discordance between core-needle biopsy and surgical samples. For patients with these MRI-based risk factors, clinicians should not rely on Ki67 assessment only from core-needle biopsy.

A Dual-Mode Imaging Nanoparticle Probe Targeting PD-L1 for Triple-Negative Breast Cancer.

Chemotherapy has remained the mainstay of treatment of triple-negative breast cancer; however, it is significantly limited by the associated side effects. PD-1/PD-L1 immune checkpoint inhibition therapy (ICI) has been a breakthrough for this patient population in recent years. PD-L1 expression is crucial in immunotherapy since it is a major predictor of PD-1/PD-L1 antibody response, emphasizing the significance of monitoring PD-L1 expression. Nonetheless, it is hard to assess the expression of PD-L1 before surgery, which has highlighted the urgency for a precise and noninvasive approach. Herein, we prepared a dual-mode imaging nanoparticle probe to detect PD-L1. The particle size, zeta potential, biocompatibility, and imaging ability of NPs were characterized. The synthesized NPs showed slight cytotoxicity and good T2 relaxivity. The targeted NPs accumulated more in 4T1 cells than nontargeted NPs in vitro. The in vivo experiment further demonstrated the distribution of targeted NPs in tumor tissues, with changes in NIRF and MR signals observed. Our study indicated that SPIO-aPD-L1-Cy5.5 NPs can be used to monitor PD-L1 expression in breast cancer as NIRF/MR contrast agents.

A functional liver imaging score for preoperative prediction of liver failure after hepatocellular carcinoma resection.

OBJECTIVES: Posthepatectomy liver failure (PHLF) is a challenging complication after resection to treat hepatocellular carcinoma (HCC), and it is associated with high mortality. Preoperative prediction of PHLF may improve patient subsequent and reduce such mortality. This study examined whether a functional liver imaging score (FLIS) based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) could predict PHLF. MATERIALS AND METHODS: The study included 502 patients who underwent preoperative gadoxetic acid-enhanced MRI, followed by HCC resection. Significant preoperative predictors of PHLF were identified using logistic regression analysis. The ability of FLIS to predict PHLF was evaluated using receiver operating characteristic curves, and its predictive power was compared to that of the model for end-stage liver disease (MELD) score, albumin-bilirubin (ALBI) score, and indocyanine green 15-min retention rate (ICG-R15). RESULTS: In multivariate analysis, PHLF was independently associated with FLIS (OR 0.452, 95% CI 0.361 to 0.568, p < 0.001) and major resection (OR 1.898, 95% CI 1.057 to 3.408, p = 0.032). FLIS was associated with a higher area under the receiver operating characteristic curve (0.752) than the MELD score (0.557), ALBI score (0.609), or ICG-R15 (0.605) (all p < 0.05). Patients with FLIS ≤ 4 who underwent major resection were at 9.4-fold higher risk of PHLF than patients with lower FLIS who underwent minor resection. CONCLUSION: FLIS is an independent predictor of PHLF, and it may perform better than the MELD score, ALBI score, and ICG-R15 clearance. We propose treating elevated FLIS and major resection as risk factors for PHLF. KEY POINTS: • A functional liver imaging score can independently predict posthepatectomy liver failure in patients with HCC. • The score may predict such failure better than MELD and ALBI scores and ICG-R15. • Patients with scores ≤ 4 who undergo major hepatic resection may be at nearly tenfold higher risk of posthepatectomy liver failure.

Peritumoral edema in preoperative magnetic resonance imaging is an independent prognostic factor for hepatocellular carcinoma.

BACKGROUND: Peritumoral edema is an independent prognostic risk factor for malignant tumors. Therefore, assessment of peritumoral edema in preoperative magnetic resonance imaging (MRI) may provide better prognostic information in patients with hepatocellular carcinoma (HCC). AIM: To determine whether peritumoral edema in preoperative MRI is a prognostic factor for HCC. METHODS: A retrospective analysis of 90 patients with HCC confirmed by surgical pathology was performed. All patients' peritumoral edema in preoperative MRI was reviewed by two radiologists. The association of disease recurrence with peritumoral edema and clinicopathological features was assessed using the Cox proportional hazards model. Interobserver agreement for evaluating peritumoral edema was determined using Cohen's κ coefficient. RESULTS: Recurrence and non-recurrence after an average 20.8 month follow-up was 25.6% (23/90) and 74.4% (67/90), respectively. The ratio of peritumoral edema of 90 patients with HCC in preoperative MRI was 35.6% (32/90). In univariate Cox regression analysis, peritumoral edema [hazard ratio (HR) 11.08, P < 0.001], tumor diameter (HR 4.12, P = 0.001), microvascular invasion (HR 2.78, P = 0.020), gender (HR 0.29, P = 0.006), cirrhosis (HR 2.45, P = 0.049), ascites syndrome (HR 2.83, P = 0.022), aspartate aminotransferase(AST)/alanine aminotransferase(ALT) (HR 5.07, P = 0.003) were indicators for HCC recurrence. In multivariate Cox regression analysis, the tumor diameter (HR 2.53, P = 0.032) and peritumoral edema (HR 8.71, P < 0.001) were independent prognostic factors of HCC. The sensitivity, specificity, positive predictive value and negative predictive value of peritumoral edema and tumor diameter were 82.6%&60.9%, 80.6%&77.6%, 59.4%&48.3%, and 93.1%&85.3%, respectively. CONCLUSION: Peritumoral edema in preoperative MRI may be considered as a biomarker of prognostic information for patients with HCC.

Preoperative normalized iodine concentration derived from spectral CT is correlated with early recurrence of hepatocellular carcinoma after curative resection.

OBJECTIVES: To investigate whether normalized iodine concentration (NIC) correlates with tumor microvessel density and early recurrence in patients with HCC. MATERIALS AND METHODS: We included 71 patients with surgically resected single HCC in this prospective study who underwent preoperative spectral CT between November 2014 and June 2016. Two observers independently measured the NIC in the arterial phase (AP) and portal venous phase (PVP). The relationship between NIC and microvessel density was evaluated. Univariate and multivariate logistic regression was performed to evaluate independent predictors of early recurrence. RESULTS: Early recurrence occurred in 28 of 71 patients (39.4%) during the 2-year follow-up. NIC-AP positively correlated with microvessel density for the two observers (r = 0.593 and 0.527). Based on multivariate analysis, independent risk factors for early HCC recurrence were tumor size (odds ratio, 1.200; p = 0.043) and NIC-AP (odds ratio, 2.522; p = 0.005). For the two observers, areas under the receiver operating characteristic curve for predicting early HCC recurrence were 0.719 and 0.677. Early recurrence rates were significantly higher among patients with NIC-AP values higher than the optimal cutoff than among those with values below the cutoff. CONCLUSION: Normalized iodine concentration in the arterial phase from spectral CT reflects tumor-derived angiogenesis and is a potential predictive biomarker for early recurrence of hepatocellular carcinoma. KEY POINTS: • Normalized iodine concentration in the arterial phase positively correlated with microvessel density of hepatocellular carcinoma. • In the patients with hepatocellular carcinoma, tumor size and normalized iodine concentration in the arterial phase were independent risk factors for early hepatocellular carcinoma recurrence. • Early hepatocellular carcinoma recurrence rates were significantly higher when normalized iodine concentration in the arterial phase values was above the optimal cutoff.

Dual-Mode Contrast Agents with RGD-Modified Polymer for Tumour-Targeted US/NIRF Imaging.

BACKGROUND: Cancer diagnosis and treatment during the early stages of disease remain extremely challenging clinical tasks. The development of effective multimode contrast agents could greatly facilitate the early detection of cancer. MATERIALS AND METHODS: We prepared dual-mode contrast agents using a biotin/avidin bioamplification system. Through in vivo and in vitro experiments, we verified the imaging performance of this contrast agents in both fluorescence and ultrasound and its targeting specificity for MDA-MB-231 cells. RESULTS: The RGD peptide-labelled microbubbles showed excellent targeting of αvß3 integrin expressed by MDA-MB-231 cells in vitro and in vivo. The signal intensity and time duration of ultrasound imaging using these particles were superior to those obtained with a typical ultrasound contrast agent in the clinic. The tumour areas also demonstrated high Cy5.5 accumulation by fluorescence imaging. CONCLUSION: The results show that this targeted dual-mode imaging system yields outstanding US/NIRF imaging results, possibly allowing the early clinical diagnosis of cancer.

Multi-mode biodegradable tumour-microenvironment sensitive nanoparticles for targeted breast cancer imaging.

Gas-filled ultrasound (US) contrast agents easily collapse in the body, and the gas can easily overflow, which limits the effectiveness of US imaging. To address this issue, an injectable gas-generating multi-mode system was developed that carries the MR negative contrast agent Fe3O4, the fluorescent dye Cy5.5, and the CO2 releasing donor (Na2CO3). The nanoparticles can continuously generate carbon dioxide (CO2) gas in acidic tumour tissue in the body, giving the tumour a strong echo signal under ultrasonic imaging. In addition, the nanoparticles confer excellent effects for MR and fluorescence imaging of the tumour tissue. The results indicate that this pH-responsive NP system provides good effects in MR/US/fluorescent imaging. This study provides a useful reference for multi-mode tumour imaging.

Changes in Apparent Diffusion Coefficient as Surrogate Marker for Changes in Ki-67 Index Due to Neoadjuvant Chemotherapy in Patients with Invasive Breast Cancer.

RATIONALE AND OBJECTIVES: To evaluate possible correlation between changes in apparent diffusion coefficient (ADC) and Ki-67 index as a result of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. METHODS AND MATERIALS: Between February 2016 and October 2017, 87 patients with breast cancer underwent diffusion-weighted magnetic resonance imaging (b = 0 and 800 sec/mm2) before and after NAC. ADC and tumor diameter before and after NAC were compared to the Ki-67 index determined from biopsy or surgical specimens. RESULTS: Ki-67 index did not correlate significantly with ADC before NAC (p = 0.862) or afterwards (p = 0.292), nor did it correlate with tumor diameter before (p = 0.545) or afterwards (p = 0.478). However, change in ADC as a result of NAC correlated inversely with change in Ki-67 index (r = -0.326, p = 0.002). The percentage change in Ki-67 index did not correlate with the percentage change in ADC (p = 0.404). Similarly, the change in Ki-67 index or percentage change in that index did not correlate with the change in tumor diameter (p = 0.075) or percentage change in tumor diameter (p = 0.233). CONCLUSION: Comparison of pre- and post-NAC ADC can be used to estimate the change in Ki-67 index in patients with invasive breast cancer.

Diagnostic value of diffusion-weighted magnetic resonance imaging for local and skull base recurrence of nasopharyngeal carcinoma after radiotherapy.

Tumor recurrence is a major cause of nasopharyngeal carcinoma (NPC) treatment failure. Diffusion-weighted imaging (DWI) is used for a variety of cancers, but few data are available for NPC.The aim of the study was to investigate the DWI features of recurrent NPC after radiotherapy and apparent diffusion coefficient (ADC) thresholds for the diagnosis of recurrent NPC.This was a retrospective study of 160 patients with NPC treated by radiotherapy at the Cancer Hospital affiliated to Guangxi Medical University from May 2012 to March 2015. The patients were divided into the local recurrence (n = 39), fibrosis (n = 51), clivus recurrence (n = 22), and clivus nonrecurrence (n = 48) groups. The patients underwent magnetic resonance imaging (MRI), enhanced MRI, and DWI. Receiver operating characteristics curves were used to determine sensitivity, specificity, and negative predictive values.ADC values were significantly different between the recurrence and fibrosis groups (P < .0001). Using ADC threshold values of 0.887 × 10 mm/s for local recurrence, the area under the curve (AUC) of DWI was 0.967 (87.2% sensitivity and 94.1% specificity), compared with 0.732 for routine MRI (71.8% sensitivity and 74.5% specificity) (P < .001). Using ADC threshold values of 1.018 × 10 mm/s for the diagnosis of clivus recurrent NPC, the AUC of DWI was 0.984 (95.5% sensitivity and 91.7% specificity) compared with 0.558 for routine MRI (63.6% sensitivity and 47.9% specificity) (P < .001).DWI has a higher diagnostic value for recurrent NPC than MRI. DWI can increase the diagnosis sensitivity and specificity of locally recurrent NPC.

Non-enhanced MRI in combination with color Doppler flow imaging for improving diagnostic accuracy of parotid gland lesions.

PURPOSE: To determine the value of non-enhanced MRI in combination with color Doppler flow imaging (CDFI) for differentiating malignant parotid tumors from benign ones. METHODS: This retrospective study analyzed 51 parotid gland lesions (39 benign and 12 malignant) in 51 patients who underwent preoperative CDFI as well as non-enhanced MRI including T1-weighted, T2-weighted, and diffusion-weighted imaging (DWI). Degrees of intratumor vascularity were categorized into four grades basing on CDFI findings. The relationships between the lesion and its adjacent external carotid artery and retromandibular vein were inspected on T1-weighted and T2-weighted images. Apparent diffusion coefficient (ADC) values were calculated from diffusion-weighted images, and were used to classify the parotid gland lesions with and without reference to the CDFI findings. The classification results were compared using the McNemar test. Sensitivity, specificity, and accuracy percentages were calculated when the non-enhanced MRI/CDFI findings were used to differentiate benign lesions from malignant ones. RESULTS: The diagnostic accuracy (96.1 vs 82.4%) was significantly improved when ADCs were used together with CDFI findings for classifying parotid gland lesions compared to when ADCs were used alone. Pleomorphic adenomas had the highest ADCs. The ADC thresholds were 1.425 × 10-3 mm2/s for differentiating pleomorphic adenomas from carcinomas, 0.999 × 10-3 mm2/s for differentiating pleomorphic adenomas from other benign lesions, and 0.590 × 10-3 mm2/s for differentiating benign lesions other than pleomorphic adenomas from lymphomas. CONCLUSION: Combining CDFI with non-enhanced MRI can improve the diagnostic accuracy of MRI for classifying parotid gland lesions.

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer.

BACKGROUND: Indocyanine green (ICG) is widely used as a tracer in sentinel lymph node biopsy (SLNB) of patients with breast cancer. Whether SLNB performance can be improved by supplementing ICG with methylene blue dye remains controversial. This study compared the performance of SLNB when ICG was used alone or with blue dye. MATERIALS AND METHODS: Consecutive patients with T1-3 primary breast cancer at our hospital were recruited into our study and randomized to undergo SLNB with ICG alone (n = 62) or with the combination of ICG and blue dye (n = 65). We compared the two methods in terms of identification rate, number and detection time of sentinel lymph nodes (SLNs) removed. RESULTS: SLN identification rate were similar in the absence (95.2%) or presence of blue dye (98.5%, P = 0.578) but significantly, more average nodes were removed when blue dye was used (3.8 ± 1.5 versus 2.7 ± 1.2, P = 0.000), and the average time for detecting each SLN was significantly shorter (3.91 ± 1.87 versus 5.65 ± 2.95 min; P = 0.000). No patient in the study experienced severe adverse reactions or complications. Recurrence of axillary node was detected in one patient (1.6%) using ICG alone but not in any patients using ICG and blue dye. CONCLUSIONS: The efficiency and sensitivity of SLNB can be improved by combining ICG with blue dye.

GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Diagnostic performance of ADCs in different ROIs for breast lesions.

OBJECTIVE: The purpose of this study was to explore the diagnostic performance of apparent diffusion coefficient (ADC) values for breast lesions by different measuring methods and find out the optimum measuring method. METHODS: ADCW-mean and ADCW-min were obtained by whole-measurement method, while ADCmean and ADCmin were extracted by spot-measurement method. Four ADCs were analyzed by One-way ANOVA and Independent T-test. The diagnostic performances of these four ADCs were calculated by receiver operating characteristics (ROC) curves and the area under the curves (AUC) were compared through Z-test. RESULTS: For the whole-measurement method, there were significant differences between malignant and benign lesions (ADCW-mean=1.014±0.197 for malignant, ADCW-mean=1.650±0.348 for benign, F=37.511, P<0.001; ADCW-min=0.627±0.144 for malignant, ADCW-min=1.245±0.290 for benign, F=41.446, P<0.001), as well as the spot-measurement method (ADCmean=1.010±0.234 for malignant, ADCmean=1.648±0.392 for benign, F=34.580, P<0.001; ADCmin=0.817±0.203 for malignant, ADCmin=1.411±0.357 for benign, F=40.039, P<0.001). The optimal diagnostic threshold of ADCW-mean, ADCW-min, ADCmean, and ADCmin values were 1.223×10(-3) mm(2)/s, 0.897×10(-3) mm(2)/s, 1.315×10(-3) mm(2)/s, and 1.111×10(-3) mm(2)/s, respectively. ROC curves indicated that the AUC for ADCW-min (0.969) was statistically significant higher than the AUC for ADCW-mean (0.940; Z=2.473, p=0.013), ADCmean (0.919; Z=3.691, P=0.000), and ADCmin (0.928; Z=3.634, P=0.000). The AUC for ADCW-mean was also significantly higher than the AUC for ADCmean (Z=2.863, P=0.004). CONCLUSION: The results provided evidence that the most reliable and accurate value in demonstrating the limitation of diffusion may be ADCW-min, and it has the highest diagnostic value in distinguishing breast lesions from malignant to benign.

Apparent diffusion coefficient ratio between axillary lymph node with primary tumor to detect nodal metastasis in breast cancer patients.

PURPOSE: To evaluate the ratios of apparent diffusion coefficient (ADC) calculated from diffusion weighted imaging (DWI) between axillary lymph nodes with primary breast tumor lesions in the detection of axillary lymph nodes metastasis in breast cancer patients. MATERIALS AND METHODS: A total of 36 patients with breast tumors and their axillary lymph nodes were included in this study for MR image scan. The ADC values were calculated using DW-MR imaging software. The ADC values and the ADC ratios of axillary lymph nodes in patients with primary breast lesion were compared among benign and metastatic axillary lymph nodes. All the diagnosis were confirmed by histopathological examination. RESULTS: The mean ADC value of metastatic lymph nodes was significantly lower than those of benign lymph nodes (0.787 × 10(-3) mm(2)/s ± 0.145 versus 1.043 × 10(-3) mm(2)/s ± 0.257) (P < 0.05). In addition, ADC ratio of metastatic lymph nodes with breast lesion was significantly lower than those of benign lymph nodes with breast tumor lesions (0.986 ± 0.17 versus 1.375 ± 0.417) (P < 0.05). Once the ADC ratio was fixed at 0.889 × 10(-3) mm(2)/s, the sensitivity, specificity, and accuracy were 82.22%, 82.35% and 82.28%, respectively. The cutoff of ADC ratio was at 1.097 × 10(-3) mm(2)/s, the sensitivity, specificity, and accuracy can be up to 84.44%, 88.24%, and 86.08%. CONCLUSION: ADC value and ADC ratio could be used as a reliable parameter to detect the axillary lymph nodes metastasis in breast cancer patients, and ADC ratio has a higher accuracy.