Discovery of novel 1H-benzo[d]imidazole-4,7-dione based transglutaminase 2 inhibitors as p53 stabilizing anticancer agents in renal cell carcinoma.

Overexpression of transglutaminase 2 (TGase 2; TG2) has been implicated in the progression of renal cell carcinoma (RCC) through the inactivation of p53 by forming a protein complex. Because most p53 in RCC has no mutations, apoptosis can be increased by inhibiting the binding between TG2 and p53 to increase the stability of p53. In the present study, a novel TG2 inhibitor was discovered by investigating the structure of 1H-benzo[d]imidazole-4,7-dione as a simpler chemotype based on the amino-1,4-benzoquinone moiety of streptonigrin, a previously reported inhibitor. Through structure-activity relationship (SAR) studies, compound 8j (MD102) was discovered as a potent TG2 inhibitor with an IC50 value of 0.35 µM, p53 stabilization effect and anticancer effects in the ACHN and Caki-1 RCC cell lines with sulforhodamine B (SRB) GI50 values of 2.15 µM and 1.98 µM, respectively. The binding property of compound 8j (MD102) with TG2 was confirmed to be reversible in a competitive enzyme assay, and the binding interaction was expected to be formed at the ß-sandwich domain, a p53 binding site, in the SPR binding assay with mutant proteins. The mode of binding of compound 8j (MD102) to the ß-sandwich domain of TG2 was analyzed by molecular docking using the crystal structure of the active conformation of human TG2. Compound 8j (MD102) induced a decrease in the downstream signaling of p-AKT and p-mTOR through the stabilization of p53 by TG2 inhibition, resulting in tumor cell apoptosis. In a xenograft animal model using ACHN cancer cells, oral administration and intraperitoneal injection of compound 8j (MD102) showed an inhibitory effect on tumor growth, confirming increased levels of p53 and decreased levels of Ki-67 in tumor tissues through immunohistochemical (IHC) tissue staining. These results indicated that the inhibition of TG2 by compound 8j (MD102) could enhance p53 stabilization, thereby ultimately showing anticancer effects in RCC. Compound 8j (MD102), a novel TG2 inhibitor, can be further applied for the development of an anticancer candidate drug targeting RCC.

Artificial intelligence assistance for women who had spot compression view: reducing recall rates for digital mammography.

BACKGROUND: Mammography yields inevitable recall for indeterminate findings that need to be confirmed with additional views. PURPOSE: To explore whether the artificial intelligence (AI) algorithm for mammography can reduce false-positive recall in patients who undergo the spot compression view. MATERIAL AND METHODS: From January to December 2017, 236 breasts from 225 women who underwent the spot compression view due to focal asymmetry, mass, or architectural distortion on standard digital mammography were included. Three readers who were blinded to the study purpose, patient information, previous mammograms, following spot compression views, and any clinical or pathologic reports retrospectively reviewed 236 standard mammograms and determined the necessity of patient recall and the probability of malignancy per breast, first without and then with AI assistance. The performances of AI and the readers were evaluated with the recall rate, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. RESULTS: Among 236 examinations, 8 (3.4%) were cancers and 228 (96.6%) were benign. The recall rates of all three readers significantly decreased with AI assistance (P < 0.05). The reader-averaged recall rates significantly decreased with AI assistance regardless of breast composition (fatty breasts: 32.7% to 24.1%m P = 0.002; dense breasts: 33.6% to 21.2%, P < 0.001). The reader-averaged AUC increased with AI assistance and was comparable to that of standalone AI (0.835 vs. 0.895; P = 0.234). The reader-averaged specificity (71.2% to 79.8%, P < 0.001) and accuracy (71.3% to 79.7%, P < 0.001) significantly improved with AI assistance. CONCLUSION: AI assistance significantly reduced false-positive recall without compromising cancer detection in women with focal asymmetry, mass, or architectural distortion on standard digital mammography regardless of mammographic breast density.

Geriatric functional assessment for decision-making on adjuvant chemotherapy in older colon cancer patients.

BACKGROUND/AIMS: Despite the increasing need for geriatric assessment prior to chemotherapy, the method for this assessment remains inadequate for older cancer patients. We aimed to propose a simple assessment method to predict the performance of adjuvant chemotherapy in older patients after colon cancer surgery. METHODS: This prospective study included patients over 65 years of age who were scheduled for adjuvant chemotherapy after colon cancer surgery. Before initiating chemotherapy, their functional status was assessed on the basis of activities of daily living (ADL)/instrumental activities of daily living (IADL). These parameters were analyzed with clinical characteristics and the patterns of adjuvant chemotherapy. The focus was on the completion rate of adjuvant chemotherapy. RESULTS: A total of 89 patients with a median age of 72 years were analyzed. Among them, 54 (61%) were non-impaired and 35 (39%) were impaired regarding their ADL/IADL classification. Low body mass index and impairment of ADL/IADLs were significantly associated with chemotherapy interruption. Among toxicities, fatigue and hand-foot syndrome were independent prognostic factors for chemotherapy interruption. Impairments of ADL/IADL were significantly associated with fatigue regardless of age. Based on age and ADL/IADL stratification, younger patients (≤ 72 years) and/or those who were ADL/IADL non-impaired were significantly more likely to complete adjuvant chemotherapy than older patients (> 72 years) and ADL/IADL impaired patients (p = 0.038). This was regardless of the chemotherapy regimen. CONCLUSION: Functional assessment using ADL/IADL is a convenient method to predict chemotherapy toxicity and performance. These results suggested that routine screening for ADL/IADLs could guide appropriate patient selection for the completion of adjuvant chemotherapy and predict expected outcomes.

Feasibility study using multifocal Doppler twinkling artifacts to detect suspicious microcalcifications in ex vivo specimens of breast cancer on US.

Multifocal Doppler twinkling artifact (MDTA) imaging has shown high detection rates of microcalcifications in phantom studies. We aimed to evaluate its performance in detecting suspicious microcalcifications in comparison with mammography by using ex vivo breast cancer specimens. We prospectively included ten women with breast cancer that presented with calcifications on mammography. Both digital specimen mammography and MDTA imaging were performed for ex vivo breast cancer specimens on the day of surgery. Five breast radiologists marked cells that included suspicious microcalcifications (referred to as 'positive cell') on specimen mammographic images using a grid of 5-mm cells. Cells that were marked by at least three readers were considered as 'consensus-positive'. Matched color Doppler twinkling artifact (CDTA) signals were compared between reconstructed US-MDTA projection images and mammographic images. The median detection rate for each case was 74.7% for positive cells and 96.7% for consensus-positive cells. Of the 10 cases, 90% showed a detection rate of ≥ 80%, with 50% of cases showing a 100% detection rate for consensus-positive cells. The proposed MDTA imaging method showed high performance for detecting suspicious microcalcifications in ex vivo breast cancer specimens, and may be a feasible approach for detecting suspicious breast microcalcifications with US.

US, Mammography, and Histopathologic Evaluation to Identify Low Nuclear Grade Ductal Carcinoma in Situ.

Background Low nuclear grade ductal carcinoma in situ (DCIS) identified at biopsy can be upgraded to intermediate to high nuclear grade DCIS at surgery. Methods that confirm low nuclear grade are needed to consider nonsurgical approaches for these patients. Purpose To develop a preoperative model to identify low nuclear grade DCIS and to evaluate factors associated with low nuclear grade DCIS at biopsy that was not upgraded to intermediate to high nuclear grade DCIS at surgery. Materials and Methods In this retrospective study, 470 women (median age, 50 years; interquartile range, 44-58 years) with 477 pure DCIS lesions at surgical histopathologic evaluation were included (January 2010 to December 2015). Patients were divided into the training set (n = 330) or validation set (n = 147) to develop a preoperative model to identify low nuclear grade DCIS. Features at US (mass, nonmass) and at mammography (morphologic characteristics, distribution of microcalcification) were reviewed. The upgrade rate of low nuclear grade DCIS was calculated, and multivariable regression was used to evaluate factors for associations with low nuclear grade DCIS that was not upgraded later. Results A preoperative model that included lesions manifesting as a mass at US without microcalcification and no comedonecrosis at biopsy was used to identify low nuclear grade DCIS, with a high area under the receiver operating characteristic curve of 0.97 (95% CI: 0.94, 1.00) in the validation set. The upgrade rate of low nuclear grade DCIS at biopsy was 38.8% (50 of 129). Ki-67 positivity (odds ratio, 0.04; 95% CI: 0.0003, 0.43; P = .005) was inversely associated with constant low nuclear grade DCIS. Conclusion The upgrade rate of low nuclear grade ductal carcinoma in situ (DCIS) at biopsy to intermediate to high nuclear grade DCIS at surgery occurred in more than a third of patients; low nuclear grade DCIS at final histopathologic evaluation could be identified if the mass was viewed at US without microcalcifications and had no comedonecrosis at histopathologic evaluation of biopsy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Rahbar in this issue. An earlier incorrect version appeared online. This article was corrected on April 14, 2022.

Mammographic Surveillance After Breast-Conserving Therapy: Impact of Digital Breast Tomosynthesis and Artificial Intelligence-Based Computer-Aided Detection.

BACKGROUND. Postoperative mammograms present interpretive challenges due to postoperative distortion and hematomas. The application of digital breast tomosyn-thesis (DBT) and artificial intelligence-based computer-aided detection (AI-CAD) after breast-conserving therapy (BCT) has not been widely investigated. OBJECTIVE. The purpose of our study was to assess the impact of additional DBT or AI-CAD on recall rate and diagnostic performance in women undergoing mammographic surveillance after BCT. METHODS. This retrospective study included 314 women (mean age, 53.3 ± 10.6 [SD] years; four with bilateral breast cancer) who underwent BCT followed by DBT (mean interval from surgery to DBT, 15.2 ± 15.4 months). Three breast radiologists independently reviewed images in three sessions: digital mammography (DM), DM with DBT (DM plus DBT), and DM with AI-CAD (DM plus AI-CAD). Recall rates and diagnostic performance were compared between DM, DM plus DBT, and DM plus AI-CAD using the readers' mean results. RESULTS. Of the 314 women, six breast recurrences (three ipsilateral and three contralateral) had developed at the time of surveillance mammography. The ipsilateral breast recall rate was lower for DM plus AI-CAD (1.9%) than for DM (11.2%) or DM plus DBT (4.1%) (p < .001). The contralateral breast recall rate was significantly lower for DM plus AI-CAD (1.5%, p < .001) than for DM (6.6%) but for not DM plus DBT (2.7%, p = .08). In the ipsilateral breast, accuracy was higher for DM plus AI-CAD (97.0%) than for DM (88.5%) or DM plus DBT (94.8%) (p < .05); specificity was higher for DM plus AI-CAD (98.3%) than for DM (89.3%) or DM plus DBT (96.1%) (p < .05); sensitivity was significantly lower for DM plus AI-CAD (22.2%) than for DM (66.7%, p = .03) but not DM plus DBT (22.2%, p > .99). In the contralateral breast, accuracy was significantly higher for DM plus AI-CAD (97.1%) than for DM (92.5%, p < .001) but not DM plus DBT (96.1%, p = .25); specificity was significantly higher for DM plus AI-CAD (98.6%) than for DM (93.7%, p < .001) but not DM plus DBT (97.5%) (p = .09); sensitivity was not different between DM (33.3%), DM plus DBT (22.2%), and DM plus AI-CAD (11.1%) (p > .05). CONCLUSION. After BCT, adjunct DBT or AI-CAD reduced recall rates and improved accuracy in the ipsilateral and contralateral breasts compared with DM. In the ipsilateral breast, the addition of AI-CAD resulted in a lower recall rate and higher accuracy than the addition of DBT. CLINICAL IMPACT. AI-CAD may help address the challenges of interpreting post-BCT surveillance mammograms.

Chronological Trends of Breast Ductal Carcinoma In Situ: Clinical, Radiologic, and Pathologic Perspectives.

BACKGROUND: Because no prior studies have evaluated the chronological trends of ductal carcinoma in situ (DCIS) despite the increasing number of surgeries performed for DCIS, this study analyzed how the clinical, radiologic, and pathologic characteristics of DCIS changed during a 10-year period. METHODS: Of 7123 patients who underwent primary breast cancer surgery at a single institution from 2006 to 2015, 792 patients with pure DCIS were included in this study. The chronological trends of age, symptoms, method for detecting either mammography or ultrasonography, tumor size, nuclear grade, comedonecrosis, and molecular markers were calculated using Poisson regression for all patients and asymptomatic patients. RESULTS: During 10 years, DCIS surgery rates significantly increased (p < 0.001). Despite the high percentage of DCIS detected on mammography, the detection rate for DCIS by mammography significantly decreased (97.3% in 2006 to 67.6% in 2015; p = 0.025), whereas the detection rate by ultrasound significantly increased (2.7% to 31.0%; p < 0.001). Conservation surgery rates (odds ratio [OR], 1.058), low-to-intermediate nuclear grade rates (OR, 1.069), and the absence of comedonecrosis (OR, 1.104) significantly increased over time (all p < 0.05). Estrogen receptor (ER) negativity (OR, 0.935) and human epidermal growth factor receptor 2 (HER2) positivity rates (OR, 0.953) significantly decreased (all p < 0.05). The same trends were observed for the 613 asymptomatic patients. CONCLUSION: The rate of DCIS detected on ultrasound only significantly increased during 10 years. Low-to-intermediate nuclear grade rates significantly increased, whereas ER negativity and HER2 positivity rates significantly decreased during the same period. These findings suggest that DCIS detected on screening ultrasound is less aggressive than DCIS detected on mammography.

Interval Cancers after Negative Supplemental Screening Breast MRI Results in Women with a Personal History of Breast Cancer.

Background There are few interval cancer studies of incident screening MRI for women with a personal history of breast cancer (PHBC). Purpose To evaluate the performance measures of screening breast MRI in women with a PHBC across multiple rounds and to identify subgroups who might be more at risk for interval cancer. Materials and Methods Between January 2008 and March 2019, consecutive screening breast MRI studies for women who had undergone breast-conserving surgery because of breast cancer were retrospectively identified. Inclusion criteria were negative or benign findings at mammography with US, availability of at least 1 year of follow-up data, and examinations having been performed within 12 months after the initial cancer surgery. Performance measures were calculated for each round. Multivariable logistic regression analysis was performed to determine factors associated with the risk of interval cancer. Results Among the 6603 MRI examinations for 2809 women (median age, 47 years; interquartile range, 42-53 years), the cancer detection rate was 8.3 per 1000 screening examinations (55 of 6603 examinations) and the interval cancer rate was 1.5 per 1000 screening examinations (10 of 6603 examinations). The sensitivity and specificity were 85% (55 of 65 examinations; 95% CI: 76, 93) and 88.3% (5775 of 6538 examinations; 95% CI: 87.6, 89.1), respectively. At multivariable analysis, interval cancers were associated with a first-degree family history of breast cancer (odds ratio [OR], 5.4; 95% CI: 1.3, 22.5; P = .02), estrogen receptor- and progesterone receptor-negative primary cancers (OR, 3.6; 95% CI: 1.1, 12.2; P = .04), and moderate or marked background parenchymal enhancement (OR, 10.8; 95% CI: 3.3, 35.7; P < .001). Conclusion Performance of screening breast MRI in women with a personal history of breast cancer was sustained across multiple rounds, and a first-degree family history of breast cancer, estrogen receptor- and progesterone receptor-negative primary cancers, and moderate or marked background parenchymal enhancement at MRI were independently associated with the risk of developing interval cancers. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Slanetz in this issue.

Outcomes Following Negative Screening MRI Results in Korean Women with a Personal History of Breast Cancer: Implications for the Next MRI Interval.

Background There are limited data on outcomes following screening breast MRI in women with a personal history of breast cancer (PHBC). Purpose To investigate outcomes and factors associated with subsequent cancers following a negative screening MRI study in women with a PHBC. Materials and Methods Consecutive women with a PHBC and a negative prevalence screening breast MRI result between August 2014 and December 2016 were retrospectively identified. Inclusion criteria were prevalence screening MRI performed as part of routine surveillance protocol (1-3 years after treatment) and follow-up data for at least 12 months. The incidence and characteristics of subsequent cancers were reviewed. Logistic regression analysis was used to investigate associations between clinical-pathologic characteristics and subsequent cancers. Performance metrics were compared among screening MRI, mammography, and US. Results A total of 993 women (mean age ± standard deviation, 53 years ± 10) were evaluated. Ten second in-breast cancers (ie, ipsilateral or contralateral) occurred at a median interval of 31.8 months (range, 13.3-44.8 months) after MRI, of which eight (80%) were ductal carcinoma in situ (DCIS) or node-negative T1 cancers. Only one node-negative T1mi (tumor ≤1 mm) second in-breast cancer visible on a mammogram was detected within 24 months of MRI. Of second in-breast cancers, 40% (four of 10) were detected only at subsequent screening MRI, which was performed a median of 30.5 months after negative prevalence screening MRI. Ten local-regional recurrences occurred at a median interval of 16.9 months (range, 6-35 months). Previous treatment for DCIS was associated with second in-breast cancers (odds ratio, 3.73; 95% CI: 1.04, 13.38; P = .04). In 1048 women who underwent prevalence screening MRI (including all Breast Imaging Reporting and Data System categories), MRI showed a lower abnormal interpretation rate and higher specificity than mammography or US (P < .001 for all). Conclusion After a negative screening MRI result, 90% of subsequent cancers were detected at intervals longer than 24 months and there was a low second in-breast cancer rate (1%). © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Chang in this issue.

Inhibitory Effect of LGS and ODE Isolated from the Twigs of Syringa oblata subsp. dilatata on RANKL-Induced Osteoclastogenesis in Macrophage Cells.

Osteoblasts and osteoclasts play a pivotal role in maintaining bone homeostasis, of which excessive bone resorption by osteoclasts can cause osteoporosis and various bone diseases. However, current osteoporosis treatments have many side effects, and research on new treatments that can replace these treatments is ongoing. Therefore, in this study, the roles of ligustroside (LGS) and oleoside dimethylester (ODE), a natural product-derived compound isolated from Syringa oblata subsp. dilatata as a novel, natural product-derived osteoporosis treatments were investigated. In the results of this study, LGS and ODE inhibited the differentiation of receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced RAW264.7 cells into osteoclasts without cytotoxicity, and down-regulated the activity of TRAP, a specific biomarker of osteoclasts. In addition, it inhibited bone resorption and actin ring formation, which are important functions and features of osteoclasts. Also, the effects of LGS and ODE on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and phosphoinositide 3-kinases (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways that play important roles in osteoclast differentiation were evaluated. In the results, LGS and ODE downregulated the phosphorylation of RANKL-induced MAPK and PI3K/Akt/mTOR proteins in a concentration-dependent manner, translocation of NF-κB into the nucleus was inhibited. As a result, the compounds LGS and ODE isolated from S. oblate subsp. dilatata effectively regulated the differentiation of RANKL-induced osteoclasts and inhibited the phosphorylation of signaling pathways that play a pivotal role in osteoclast differentiation. Therefore, these results suggest the possibility of LGS and ODE as new natural product treatments for bone diseases caused by excessive osteoclasts.

Persimmon leaf extract protects mice from atopic dermatitis by inhibiting T cell activation via regulation of the JNK pathway.

Persimmon leaf extracts (PLE) have been widely used as a traditional medicine in East Asian countries. The effects of persimmon leaves, including antioxidant, antiinflammatory, hypotensive, and anti-allergy effects, have been investigated; however, there is little evidence on the inhibition of T cell activation in vitro and effects on T cell-related diseases, such as atopic dermatitis (AD), in vivo by persimmon leaves. PLE (50 µg/mL) effectively attenuated the mRNA levels of IL-2 in Jurkat T cells stimulated with PMA/A23187 and Staphylococcus enterotoxin E-loaded Raji B cells without causing cytotoxicity. In Jurkat T cells stimulated with PMA/A23187, treatment with 50 µg/mL PLE blocked the translocation of p65 and IκBα degradation. Moreover, the JNK signaling pathway in Jurkat T cells stimulated with PMA/A23187 was affected by treatment with PLE. The oral administration of PLE markedly attenuated AD manifestations in mice, including ear thickness, IgE levels, and lymph node sizes. These results indicate PLE significantly blocked T cell activation via NF-κB signaling and the JNK pathway. This suggests underlying mechanisms of PLE involving the control of effector cytokines produced by activated T cells in ear tissue and lymph nodes, as well as the infiltration of mast cells and the therapeutic potential of AD.

Combining radiomics with ultrasound-based risk stratification systems for thyroid nodules: an approach for improving performance.

OBJECTIVES: To develop a radiomics score using ultrasound images to predict thyroid malignancy and to investigate its potential as a complementary tool to improve the performance of risk stratification systems. METHODS: We retrospectively included consecutive patients who underwent fine-needle aspiration (FNA) for thyroid nodules that were cytopathologically diagnosed as benign or malignant. Nodules were randomly assigned to a training and test set (8:2 ratio). A radiomics score was developed from the training set, and cutoff values based on the maximum Youden index (Rad_maxY) and for 5%, 10%, and 20% predicted malignancy risk (Rad_5%, Rad_10%, Rad_20%, respectively) were applied to the test set. The performances of the American College of Radiology (ACR) and the American Thyroid Association (ATA) guidelines were compared with the combined performances of the guidelines and radiomics score with interpretations from expert and nonexpert readers. RESULTS: A total of 1624 thyroid nodules from 1609 patients (mean age, 50.1 years [range, 18-90 years]) were included. The radiomics score yielded an AUC of 0.85 (95% CI: 0.83, 0.87) in the training set and 0.75 (95% CI: 0.69, 0.81) in the test set (Rad_maxY). When the radiomics score was combined with the ACR or ATA guidelines (Rad_5%), all readers showed increased specificity, accuracy, and PPV and decreased unnecessary FNA rates (all p < .05), with no difference in sensitivity (p > .05). CONCLUSION: Radiomics help predict thyroid malignancy and improve specificity, accuracy, PPV, and unnecessary FNA rate while maintaining the sensitivity of the ACR and ATA guidelines for both expert and nonexpert readers. KEY POINTS: • The radiomics score yielded an AUC of 0.85 and 0.75 in the training and test set, respectively. • For all readers, combining a 5% predicted malignancy risk cutoff for the radiomics score with the ACR and ATA guidelines significantly increased specificity, accuracy, and PPV and decreased unnecessary FNA rates, with no decrease in sensitivity. • Radiomics can help predict malignancy in thyroid nodules in combination with risk stratification systems, by improving specificity, accuracy, and PPV and unnecessary FNA rates while maintaining sensitivity for both expert and nonexpert readers.

Inhibitory Effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside on RANKL-Induced Osteoclast Differentiation and ROS Generation in Macrophages.

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin ß3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κß translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

Comparing recall rates following implementation of digital breast tomosynthesis to synthetic 2D images and digital mammography on women with breast-conserving surgery.

OBJECTIVES: To evaluate the recall rates of digital mammography (DM) and synthetic images after adding digital breast tomosynthesis (DBT) in patients with breast-conserving surgery. METHODS: From November 2015 to April 2017, 229 women with breast-conserving surgery due to breast cancer who underwent DBT after surgery were included (mean interval, 12.9 ± 1.4 months). All women underwent combo-mode DBT examinations including full-field DM, tomosynthesis, and reconstructed synthetic 2D images. Three board-certified breast radiologists reviewed the images sequentially: synthetic 2D+DBT and, 1 month later, DM and then DM+DBT. Recall rates and the abnormality type causing the recall were calculated and compared for each mammographic modality and breast density. RESULTS: Of the 229 patients included, 230 mammography images were reviewed. One patient (0.4%) developed locoregional recurrences during follow-up (mean duration, 25.8 ± 4.5 months). Recall rates for synthetic 2D+DBT were significantly lower than for DM alone (4.1% (2.6-6.2) vs. 11.6% (9.2-14.5), respectively; p < 0.001). Recall rates did not differ between synthetic 2D+DBT and DM+DBT (4.1% (2.6-6.2) vs. 2.9% (1.9-4.5), respectively; p = 0.234). Recall rates of synthetic 2D+DBT and DM+DBT were significantly lower than those of DM alone, regardless of mammographic breast density (all p < 0.05, respectively). CONCLUSION: Adding DBT to synthetic 2D images or DM shows significant reduction in recall rates compared with DM alone for women who undergo breast-conserving surgery for breast cancer, regardless of mammographic density. KEY POINTS: • Recall rates for synthetic 2D+DBT were significantly lower than those of DM alone (4.1% (2.6-6.2) vs. 11.6% (9.2-14.5), respectively; p < 0.001). • No significant differences were seen in recall rates between synthetic 2D+DBT and DM+DBT (4.1 (2.6-6.2) vs. 2.9 (1.9-4.5), respectively; p = 0.234). • Reader-averaged recall rates after adding DBT to synthetic 2D or DM were significantly lower than those of DM alone, regardless of mammographic breast density (all p < 0.05, respectively).

Significance of Radial Margin in Patients Undergoing Complete Mesocolic Excision for Colon Cancer.

BACKGROUND: Comparable to circumferential resection margin in rectal cancer, radial margin is a potential prognostic factor in colon cancer that has just begun to be studied. No previous studies have investigated the influence of radial margin in the context of complete mesocolic excision. OBJECTIVE: This study aimed to examine the impact of radial margin on oncologic outcomes after complete mesocolic excision for colon cancer. DESIGN: We retrospectively reviewed patients with stage I to III colon cancer who underwent curative resection from October 2010 to March 2013. SETTINGS: This study was conducted using the prospective colorectal cancer registry of Severance hospital. PATIENTS: A total of 834 consecutive patients who underwent complete mesocolic excision for colon adenocarcinoma were included. INTERVENTIONS: We assigned patients into 3 groups according to radial margin distance: group A, radial margin ≥2.0 mm; group B, 1.0 ≤ radial margin < 2.0 mm; group C, radial margin <1 mm. MAIN OUTCOMES AND MEASURES: Overall survival and disease-free survival were estimated. RESULTS: On adjusted Cox regression analysis, only group C was predictive of reduced overall survival (HR, 1.90; 95% CI, 1.11-3.25; p = 0.018) and disease-free survival (HR, 1.93; 95% CI, 1.28-2.89; p = 0.001). We thereby defined radial margin threatening as radial margin <1 mm. Postoperative 5-fluorouracil (HR, 0.86; 95% CI, 0.35-2.10; p = 0.743) and FOLFOX (HR, 1.23; 95% CI, 0.57-2.64; p = 0.581) chemotherapy did not affect disease-free survival in patients with radial margin threatening. LIMITATIONS: This study has the limitations inherent in all retrospective, single-institution studies. CONCLUSIONS: Even with complete mesocolic excision, radial margin <1 mm was an independent predictor of survival and recurrence. This finding suggests that special efforts for obtaining a clear radial margin may be necessary in locally advanced colon cancer. See Video Abstract at http://links.lww.com/DCR/B125. IMPORTANCIA DEL MARGEN RADIAL EN PACIENTES SOMETIDOS A ESCISIÓN MESOCÓLICA COMPLETA PARA CÁNCER DEL COLON: Comparable al margen de resección circunferencial en cáncer rectal, el margen radial en cáncer de colon, es un factor pronóstico potencial, que recientemente comienza a estudiarse. Ningún estudio previo ha investigado la influencia del margen radial, en el contexto de la escisión mesocólica completa.Examinar en cáncer de colon, el impacto del margen radial en los resultados oncológicos, después de la escisión mesocólica completa.Revisión retrospectiva de pacientes con cáncer de colon en estadio I-III, sometidos a resección curativa de octubre 2010 a marzo 2013.Este estudio se realizó utilizando un registro prospectivo de cáncer colorrectal del hospital Severance.Se incluyeron un total de 834 pacientes consecutivos con adenocarcinoma de colon, sometidos a escisión mesocólica completa. Dividimos a los pacientes en 3 grupos según la distancia del margen radial: grupo A, margen radial ≥ 2.0 mm; grupo B, 1.0 ≤ margen radial <2.0 mm; grupo C, margen radial <1 mm.Se estimó la supervivencia general y la supervivencia libre de enfermedad.En el análisis de regresión de Cox ajustado, solo el grupo C fue predictivo de supervivencia global reducida (HR, 1.90; IC 95%, 1.11-3.25; p = 0.018) y supervivencia libre de enfermedad (HR, 1.93; IC 95%, 1.28-2.89; p = 0.001). Definimos como margen radial amenazante, un margen radial <1 mm. La quimioterapia posoperatoria con 5-FU (HR, 0,86; IC 95%, 0,35-2,10; p = 0.743) y FOLFOX (HR, 1,23; IC 95%, 0,57-2,64; p = 0,581), no afectó la supervivencia libre de enfermedad en pacientes con riesgo de margen radial.Este estudio tiene limitaciones inherentes a todos los estudios retrospectivos de una sola institución.Aun con la escisión mesocólica completa, el margen radial <1 mm fue un predictor independiente de supervivencia y recurrencia. Este hallazgo sugiere que pueden ser necesarios esfuerzos especiales para obtener un claro margen radial, en cáncer de colon localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B125.

Correlation between MR Image-Based Radiomics Features and Risk Scores Associated with Gene Expression Profiles in Breast Cancer.

Purpose: To investigate the correlation between magnetic resonance (MR) image-based radiomics features and the genomic features of breast cancer by focusing on biomolecular intrinsic subtypes and gene expression profiles based on risk scores. Materials and Methods: We used the publicly available datasets from the Cancer Genome Atlas and the Cancer Imaging Archive to extract the radiomics features of 122 breast cancers on MR images. Furthermore, PAM50 intrinsic subtypes were classified and their risk scores were determined from gene expression profiles. The relationship between radiomics features and biomolecular characteristics was analyzed. A penalized generalized regression analysis was performed to build prediction models. Results: The PAM50 subtype demonstrated a statistically significant association with the maximum 2D diameter (p = 0.0189), degree of correlation (p = 0.0386), and inverse difference moment normalized (p = 0.0337). Among risk score systems, GGI and GENE70 shared 8 correlated radiomic features (p = 0.0008-0.0492) that were statistically significant. Although the maximum 2D diameter was most significantly correlated to both score systems (p = 0.0139, and p = 0.0008), the overall degree of correlation of the prediction models was weak with the highest correlation coefficient of GENE70 being 0.2171. Conclusion: Maximum 2D diameter, degree of correlation, and inverse difference moment normalized demonstrated significant relationships with the PAM50 intrinsic subtypes along with gene expression profile-based risk scores such as GENE70, despite weak correlations.

Outcomes of Ductal Carcinoma In Situ According to Detection Modality: A Multicenter Study Comparing Recurrence Between Mammography and Breast US.

The purpose of this study was to determine whether disease recurrence and intrinsic characteristics of ductal carcinoma in situ (DCIS) are associated with the imaging method of detection in asymptomatic women. This multicenter, retrospective study included 844 women treated for asymptomatic DCIS who had pre-operative mammography and breast ultrasonography (US) studies available. Of the 844 women, 25 (3.0%) developed recurrences. Patients in the US group had significantly lower 5- and 10-y recurrence-free survival (RFS) rates compared with patients in the mammography group (p = 0.011). US-detected DCIS showed significantly lower 5-and 10-y RFS rates compared with mammography-detected DCIS in patients <50 y or with mammographically dense breasts (p = 0.002 and 0.002, respectively). US as the detection modality (hazard ratio [HR]: 4.451; 95% confidence interval [CI]: 1.530, 12.950; p = 0.006) and HER2 positivity (HR: 4.036; 95% CI: 1.438; 11.330; p = 0.008) were significantly associated with recurrence. We concluded that US as the detection modality and HER2 positivity were significantly associated with recurrence in patients treated for asymptomatic DCIS.

Characteristics, trend, and methodological quality of systematic reviews and meta-analyses in nuclear medicine: A bibliometric analysis of studies published between 2005 and 2016.

To evaluate the characteristics, trend, and quality of systematic reviews and meta-analyses in nuclear medicine.We performed a PubMed search to identify systematic reviews and meta-analyses published between 2005 and 2016 in the field of nuclear medicine. The following data were extracted: journal name, impact factor, type of study, topics with cancer type, imaging modalities, authors (number, country, affiliation, presence of nuclear medicine specialists and statisticians, discordance between the first and corresponding authors), funding, methodological quality, methods used for quality assessment, and statistical methods.We included 185 nuclear medicine articles. Meta-analyses (n = 164; 88.6%) were published about 7 times more frequently than systematic reviews. Oncology was the most commonly studied topic (n = 125, 67.6%). The first authors were most frequently located in China (n = 73; 39.5%). PET was the most commonly used modality (n = 150; 81.1%). Both the number of authors and the ratio of discordance between the first and corresponding authors tended to progressively increase over time.The mean AMSTAR score increased over time (5.77 in 2005-2008, 6.71 in 2009-2012, and 7.44 in 2013-2016). The proportion of articles with quality assessment increased significantly (20/26 in 2005-2008, 54/65 in 2009-2012, and 79/94 in 2013-2016). The most commonly used assessment tool was quality assessment of diagnostic accuracy studies (n = 85; 54.9%).The number and quality of systematic reviews and meta-analyses in nuclear medicine have significantly increased over the review period; however, the quality of these articles varies. Efforts to overcome specific weaknesses of the methodologies can provide opportunities for quality improvement.

Clinicopathological and biomolecular characteristics of stage IIB/IIC and stage IIIA colon cancer: Insight into the survival paradox.

BACKGROUND: A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS: Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS: Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. CONCLUSIONS: The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.