Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation of 13C-alanine into newly synthesized glucose by hepatocytes. In vivo Gpt2 knockdown or knockout in liver has no effect on glucose concentrations in lean mice, but Gpt2 suppression alleviates hyperglycemia in db/db mice. These data suggest that ALT2 plays a significant role in hepatic gluconeogenesis from amino acids in diabetes.

Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Monoacylglycerol Acyltransferase 1 Knockdown Exacerbates Hepatic Ischemia/Reperfusion Injury in Mice With Hepatic Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common indication for liver transplantation. The growing prevalence of NAFLD not only increases the demand for liver transplantation, but it also limits the supply of available organs because steatosis predisposes grafts to ischemia/reperfusion injury (IRI) and many steatotic grafts are discarded. We have shown that monoacylglycerol acyltransferase (MGAT) 1, an enzyme that converts monoacylglycerol to diacylglycerol, is highly induced in animal models and patients with NAFLD and is an important mediator in NAFLD-related insulin resistance. Herein, we sought to determine whether Mogat1 (the gene encoding MGAT1) knockdown in mice with hepatic steatosis would reduce liver injury and improve liver regeneration following experimental IRI. Antisense oligonucleotides (ASO) were used to knockdown the expression of Mogat1 in a mouse model of NAFLD. Mice then underwent surgery to induce IRI. We found that Mogat1 knockdown reduced hepatic triacylglycerol accumulation, but it unexpectedly exacerbated liver injury and mortality following experimental ischemia/reperfusion surgery in mice on a high-fat diet. The increased liver injury was associated with robust effects on the hepatic transcriptome following IRI including enhanced expression of proinflammatory cytokines and chemokines and suppression of enzymes involved in intermediary metabolism. These transcriptional changes were accompanied by increased signs of oxidative stress and an impaired regenerative response. We have shown that Mogat1 knockdown in a mouse model of NAFLD exacerbates IRI and inflammation and prolongs injury resolution, suggesting that Mogat1 may be necessary for liver regeneration following IRI and that targeting this metabolic enzyme will not be an effective treatment to reduce steatosis-associated graft dysfunction or failure.

Clinicopathologic Characteristics of Centrilobular Injury in Pediatric Liver Transplantation.

Centrilobular injury (CLI) is defined as the presence of perivenular mononuclear inflammation, hepatocyte dropout, and extravasated erythrocytes. In pediatric liver allografts, CLI has been associated with advanced fibrosis and chronic rejection (CR). We sought to better characterize the clinicopathologic features of CLI in the setting of T cell-mediated rejection (TCMR) and its association with complement component 4d (C4d) deposition. A total of 206 posttransplant pediatric patients (491 allograft liver biopsies) were available from 2000 to 2018, of which 63 patients (102 biopsies) showed evidence of TCMR and were included in the study. Of the patients, 35 (55.6%) had CLI on their initial episode of TCMR; those patients with CLI were significantly associated with the type of immunosuppression treatment (P = 0.03), severity of TCMR (P < 0.001), higher gamma-glutamyltransferase (P = 0.01), and advanced fibrosis (P = 0.03). There was a trend to shorter time interval from transplantation to presentation of CLI compared with those without CLI (P = 0.06). No difference was observed in graft or overall survival in the patients with CLI. In 20 patients with CLI, additional biopsies were available; in 45% of these patients, CLI was a persistent/recurrent finding. C4d deposition was noted in 12% of all biopsies (6 patients) with CLI. No significant correlation was noted in C4d deposition and CLI, CR, or graft/overall survival. In conclusion, CLI, although not significantly associated with worse graft survival, was significantly associated with severe TCMR and degree of fibrosis, which highlights the importance of active clinical management and follow-up for these patients.

Long-term Survival Outcomes of Primary Breast Cancer in Women With or Without Preoperative Magnetic Resonance Imaging: A Matched Cohort Study.

AIMS: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets. RESULTS: In total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratio = 0.98; overall survival hazard ratio = 1.04), larger tumour size (DFS hazard ratio = 1.01; overall survival hazard ratio = 1.02), triple negative breast cancer (DFS hazard ratio = 2.64; overall survival hazard ratio = 3.44) and the presence of lymphovascular invasion (DFS hazard ratio = 2.12; overall survival hazard ratio = 2.70) were independent significant variables for worse DFS and overall survival. CONCLUSION: Preoperative MRI did not result in an improvement in a patient's outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival.

PPARs and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver pathology ranging from simple steatosis to varying degrees of inflammation, hepatocyte injury and fibrosis. Without intervention it can progress to end-stage liver disease and hepatocellular carcinoma. Given its close association with obesity, the prevalence of NAFLD has increased dramatically worldwide. Currently, there are no FDA-approved medications for the treatment of NAFLD and although lifestyle modifications with appropriate diet and exercise have been shown to be beneficial, this has been difficult to achieve and sustain for the majority of patients. As such, the search for effective therapeutic agents is an active area of research. Peroxisome proliferator-activated receptors (PPARs) belong to a class of nuclear receptors. Because of their key role in the transcriptional regulation of mediators of glucose and lipid metabolism, PPAR ligands have been investigated as possible therapeutic agents. Here we review the current evidence from preclinical and clinical studies investigating the therapeutic potential of PPAR ligands for the treatment of NAFLD.

Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles.

BACKGROUND: The degree of neuromuscular blockade is one of the important factors that determine the condition of surgical space during laparoscopic surgery. Magnesium sulfate potentiates the actions of neuromuscular blocking agent, and we hypothesized that intraoperative magnesium sulfate infusion may improve surgical space condition during laparoscopic surgery. METHODS: Eighty-four patients undergoing elective laparoscopic gastrectomy were randomized to receive isotonic saline (group C) or magnesium sulfate (group M, loading dose with 50 mg/kg over 10 min and then 15 mg/kg/h by continuous infusion) to maintain the moderate neuromuscular blockade using rocuronium. Two experienced surgeons scored the quality of surgical space condition using a 5-point surgical rating scale (SRS). The secondary outcomes included recovery profiles, postoperative pain and adverse events. RESULTS: The SRS in group M was higher than that of group C. The proportion of patients with a SRS of 5 (optimal) was 2.7 % in the group C and 40.5 % in the group M (P < 0.0001) although a lower amount of rocuronium was required in group M than group C [24.2 (6.5) mg/h for group M vs. 27.5 (6) mg/h for group C; P = 0.017]. Pain after operation site was less severe in group M than in group C at postoperative 24 h (P = 0.009). Recovery profiles and adverse events were similar between the two groups. CONCLUSION: Intraoperative administration of magnesium sulfate improved the quality of surgical space conditions and decreased neuromuscular blocking agent requirement and postoperative pain in patients undergoing laparoscopic gastrectomy.

Dual mode gelation behavior of silk fibroin microgel embedded poly(ethylene glycol) hydrogels.

Hydrogel formation by more than two cross-linking mechanisms is preferred for the sophisticated manipulation of hydrogel properties. Both chemical and physical crosslinks are often utilized for fabricating stimuli-responsive hydrogels or for compensating the drawbacks of the single crosslinking method. In this study, silk fibroin (SF) microgel embedded poly(ethylene glycol) (PEG) hydrogels were fabricated by dual mode cross-linking based on thiol-ene photo-click chemistry and ß-sheet formation of SF. Norbornene-functionalized SF (SF-NB) was incorporated into PEG hydrogels by photo-cross-linking. The equilibrium shear modulus of SF-PEG hybrid hydrogels decreased with increasing SF-NB content. However, the incorporation of SF-NB caused stiffening of SF-PEG hybrid hydrogels gradually over 5 days and the gel modulus was maintained for 2 weeks. In contrast, the modulus of pure PEG hydrogels decreased continuously owing to hydrolytic degradation of ester bonds in the PEGNB macromers. Structural analysis revealed that such a post-gelation stiffening effect was caused by ß-sheet transition in SF microgels embedded in the PEG hydrogel matrix. PEG hydrogels incorporated with 4 wt% SF microgels exhibited about 2-fold increase in shear modulus compared with the modulus on day 1 post-gelation. To evaluate the compatibility of these hydrogels as cell culture matrices, the cytotoxicity of the hydrogel was examined using in situ encapsulated A549 cells. SF-PEG hybrid hydrogels showed no apparent cytotoxicity and promoted the proliferation of encapsulated A549 cells even at a higher gel modulus compared with cells in pure PEG hydrogels. These results suggest that SF-PEG hybrid hydrogels fabricated by dual mode crosslinking serve as good candidates for three-dimensional cell culture requiring temporal control of hydrogel stiffness.

Bortezomib Inhibits Osteoclastogenesis and Porphyromonas gingivalis Lipopolysaccharide-induced Alveolar Bone Resorption.

Healthy bone is maintained by the coordinated activities of osteoblast-mediated bone formation and osteoclast-dependent bone resorption. Pathologic conditions such as hormonal imbalance and inflammation cause increased osteoclastogenesis resulting in osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is novel antimyeloma agent that has a direct beneficial effect on bone formation. However, the role of bortezomib in osteoclastogenesis and underlying mechanisms remains to be fully comprehended. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)- and lipopolysaccharide-dependent osteoclast differentiation. Interestingly, the bortezomib-mediated inhibition of osteoclastogenesis was transient, since the removal of bortezomib from culture completely restored osteoclast differentiation. Bortezomib impeded the induction and nuclear localization of nuclear factor of activated T cells, cytoplasmic 1 and reduced both macrophage colony-stimulating factor- and RANKL-induced extracellular-signal-regulated kinase (ERK) phosphorylation. In a mouse model of periodontitis, bortezomib prevented alveolar bone erosion induced by Porphyromonas gingivalis lipopolysaccharide. These data not only suggest a previously unappreciated mechanism by which bortezomib regulates bone resorption but also propose novel applications of bortezomib beyond its use as an antimyeloma agent.

Scoring system for traumatic liver injury (SSTLI) in polytraumatic patients: a predictor of mortality.

PURPOSE: The aim of this study was to examine prognostic factors in polytraumatic patients with liver injury and to develop a scoring system for traumatic liver injury (SSTLI) to predict mortality. METHODS: The medical records of 175 patients treated for traumatic liver injury from July 2009 to April 2013 were reviewed. The primary outcome variable was hospital mortality. All risk factors were analyzed by multivariate logistic regression analysis. The SSTLI was created based on the predictive power of each factor. RESULTS: Age, injury severity score (ISS), trauma and injury severity score, the shock index, and the volume of packed red blood cells transfused were strong predictors of mortality. We hypothesized that the SSTLI would use five clinical measures (total bilirubin, prothrombin time, serum creatinine, age, and ISS). Each measure was scored 0-1 (age and ISS) or 0-3 (total bilirubin, prothrombin time, and creatinine), with 3 indicating the most severe derangement. The receiver-operating characteristic curve of the SSTLI was significant at post-traumatic days 0, 1, 3, and 5 [area under the curve (AUC), 0.830; AUC, 0.912; AUC, 0.941; and AUC, 0.930, respectively]. A value of 5 points was the threshold for reliability dividing low-risk (<5) from high-risk (≥5) patients. CONCLUSIONS: The SSTLI may be available to predict mortality in polytraumatic patients with liver injury, although external validation is needed before widespread implementation.

A lazy learning-based QSAR classification study for screening potential histone deacetylase 8 (HDAC8) inhibitors.

Histone deacetylases 8 (HDAC8) is an enzyme repressing the transcription of various genes including tumour suppressor gene and has already become a target of human cancer treatment. In an effort to facilitate the discovery of HDAC8 inhibitors, two quantitative structure-activity relationship (QSAR) classification models were developed using K nearest neighbours (KNN) and neighbourhood classifier (NEC). Molecular descriptors were calculated for the data set and database compounds using ADRIANA.Code of Molecular Networks. Principal components analysis (PCA) was used to select the descriptors. The developed models were validated by leave-one-out cross validation (LOO CV). The performances of the developed models were evaluated with an external test set. Highly predictive models were used for database virtual screening. Furthermore, hit compounds were subsequently subject to molecular docking. Five hits were obtained based on consensus scoring function and binding affinity as potential HDAC8 inhibitors. Finally, HDAC8 structures in complex with five hits were also subjected to 5 ns molecular dynamics (MD) simulations to evaluate the complex structure stability. To the best of our knowledge, the NEC classification model used in this study is the first application of NEC to virtual screening for drug discovery.

Short-term effect of gastric resection on circulating levels of ghrelin, peptide YY3-36 and obestatin in patients with early gastric cancer.

The short-term responses of gut hormones and the compensative interaction during a one-week period after subtotal gastrectomy in early gastric cancer (EGC) patients were assessed. Previous studies have reported gut hormonal changes after Roux-en-Y gastric bypass surgery. Blood samples were collected from 40 patients with EGC preoperatively, at 1 h after gastric resection, and on postoperative day (POD) 1, 3, and 7. Levels of active ghrelin, total ghrelin, obestatin, and PYY3-36 were measured. Total ghrelin level rapidly reached a nadir of 69.1%, while active ghrelin level had increased to 135.5% at 1 h after resection. Then, both returned to preoperative level. On the contrary, active/total ghrelin reached its nadir quickly at 1 h after resection and had returned to the preoperative level by POD 3. The nadir PYY3-36 level was 71.4% on POD 1, followed by a gradual recovery, and had increased to 116.5% by POD 7. The same pattern was observed for obestatin. Active ghrelin/obestatin showed an increase on POD 1 while total ghrelin/obestatin showed a decrease on POD 3. Then, both returned to preoperative level. These results suggest that a rapid interactive compensatory mechanism of gut hormones does exist in the remnant gastrointestinal tract after abrupt changes in the production reservoir in nonobese people.

The prognostic value of pretreatment of systemic inflammatory responses in patients with urothelial carcinoma undergoing radical cystectomy.

BACKGROUND: Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy. METHODS: The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability. RESULTS: Multivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR. CONCLUSIONS: Cellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.

Effect of neoadjuvant chemotherapy on postoperative morbidity and mortality in patients with locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has been shown to improve the rate of complete (R0) resection and downstaging in patients with localized gastric cancer. There are few reports, however, regarding its impact on postoperative morbidity and mortality. The aims of this study were to analyse complication and mortality rates after neoadjuvant chemotherapy using a modified regimen of folinic acid, 5-fluorouracil and oxaliplatin (mFOLFOX6) for locally advanced gastric cancer (AGC), compared with rates in patients who underwent surgery without neoadjuvant chemotherapy. METHODS: Data were collected from patients with AGC enrolled in a phase II trial of four cycles of neoadjuvant mFOLFOX6 followed by surgery, between January 2005 and June 2008 at two of three institutions, and compared with those from a cohort of patients with AGC who underwent surgery alone at one of the institutions in 2006. RESULTS: Among 51 patients who received neoadjuvant chemotherapy, there were no deaths and a morbidity rate of 24 per cent after surgery. Comparison of 48 patients in one institution who received neoadjuvant chemotherapy with 92 patients who had surgery alone in the same institution showed no increase in postoperative morbidity (23 versus 29 per cent; P = 0·417). Combined resection was the only risk factor for postoperative morbidity after neoadjuvant chemotherapy. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOX is a safe treatment for patients with localized AGC, and does not increase postoperative morbidity or mortality.

Prediction of pathological complete response of breast cancer patients undergoing neoadjuvant chemotherapy: usefulness of breast MRI computer-aided detection.

OBJECTIVE: To evaluate the usefulness of MR computer-aided detection (CAD) in patients undergoing neoadjuvant chemotherapy for prediction of the pathological complete response of tumours. METHODS: 148 patients with breast cancer (mean age, 47.3 years; range, 29-72 years) who underwent neoadjuvant chemotherapy were included in our study. They underwent MRI before and after neoadjuvant chemotherapy, and we reviewed the pathological result as the gold standard. The computer-generated kinetic features for each lesion were recorded, and the features analysed included "threshold enhancement" at 50% and 100% minimum thresholds; degree of initial peak enhancement; and enhancement profiles comprising lesion percentages of washout, plateau and persistent enhancement. The final pathological size and character of tumours were correlated with post-chemotherapy mammography, ultrasonography and MR CAD findings. Kruskal-Wallis test and intraclass correlation coefficient were used to analyse the findings. RESULTS: We divided the 148 patients into complete pathological response and non-complete pathological response groups. A complete pathological response was defined as no histopathological evidence of any residual invasive cancer cells in the breast or axillary lymph nodes. 39 patients showed complete pathological response, and 109 patients showed non-complete pathological response. Between enhancement profiles of MR CAD, plateau proportion of tumours was significantly correlated with the pathological response of tumours (mean proportion of plateau on complete pathological response group was 27%, p = 0.007). CONCLUSION: When plateau proportion of tumours is high, we can predict non-complete pathological response of neoadjuvant chemotherapy. ADVANCES IN KNOWLEDGE: MR CAD can be a useful tool for the assessment of response to neoadjuvant chemotherapy and prediction of pathological results.

External validation of an online nomogram in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma.

BACKGROUND: The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort. METHODS: The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan-Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis. RESULTS: The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan-Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis. CONCLUSION: The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.

Assessment of extent of breast cancer: comparison between digital breast tomosynthesis and full-field digital mammography.

AIM: To compare the accuracy of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) in preoperative assessment of local extent of breast cancer. MATERIALS AND METHODS: Lesion sizes of breast cancers on DBT and FFDM images were independently evaluated by breast radiologists. Each lesion was flagged as either mis-sized or not depending on whether the assessment of size at imaging was within 1 cm of the lesion size at surgery. Additional analyses were made by mammographic parenchymal density and by lesion size, using 2 cm as the boundary to separate the two subgroups. Statistical comparisons were performed using a repeated measures linear model on the percent mis-sized. P-values < 0.05 were considered statistically significant. RESULTS: The dataset included 173 malignant breast lesions (mean size 23.8 mm, 43% of lesions were ≤2 cm in size) in 169 patients, two-thirds of which had heterogeneously or extremely dense breasts. Overall, the percentage of lesions mis-sized at DBT was significantly lower than at FFDM (19% versus 29%, p = 0.003). There was significantly less mis-sizing at DBT in both heterogeneously dense breasts (11.1% difference between DBT and FFDM, p = 0.016) and extremely dense breasts (15.8% difference, p = 0.024). DBT also had significantly less mis-sizing than FFDM in the subgroup of lesions that were ≤2 cm in size (14.7% difference, p = 0.005). CONCLUSION: DBT was significantly superior to FFDM for the evaluation of lesion size overall, and specifically for small lesions and for lesions in dense breasts. The superiority of DBT versus FFDM increased with parenchymal density.

Screening-detected calcified and non-calcified ductal carcinoma in situ: differences in the imaging and histopathological features.

AIM: To compare the imaging and histopathological features of screening-detected calcified and non-calcified ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: The study involved 217 DCIS cases in 212 asymptomatic patients admitted between May 2007 and December 2010. All lesions were divided into calcified and non-calcified DCIS according to the presence of calcifications on mammography. Two radiologists reviewed the findings from mammography, ultrasound, and magnetic resonance imaging (MRI) in consensus according to the Breast Imaging Reporting and Data System. The histopathological features of the lesions were obtained from medical records. Statistical comparisons were performed using the chi-square, Fisher's exact test, and intraclass correlation coefficient (ICC) analyses. RESULTS: On mammography, most non-calcified DCIS presented as either a false-negative finding (49%) or mass lesion (30%), whereas most calcified DCIS (68.5%) presented as calcification alone (p < 0.001). At ultrasound, all of the non-calcified DCIS appeared as a mass, whereas 62% of the calcified DCIS appeared as a mass (p < 0.001). At histopathology, high nuclear grade (p = 0.017), necrosis (p < 0.001), positive progesterone receptor (p = 0.027), and presence of the HER-2/neu oncogene (p < 0.001) were more common in the calcified DCIS than in the non-calcified DCIS. There were no significant differences in the MRI features between the two groups. The ICC values of the non-calcified and calcified DCIS between predicted tumour size and pathologic size were 0.625 versus 0.705 for mammography, 0.801 versus 0.552 for ultrasound, and 0.760 versus 0.767 for MRI. CONCLUSIONS: Screening-detected calcified and non-calcified DCIS have different mammographic and sonographic features. Ultrasound could be helpful to predict the pathological size of the non-calcified DCIS.