Preoperative evaluation of mammographic microcalcifications after neoadjuvant chemotherapy for breast cancer.

AIM: To assess the predictive value of preoperative residual mammographic microcalcifications for residual tumours after neoadjuvant chemotherapy (NAC) for breast cancer. MATERIALS AND METHODS: This single-centre retrospective study included breast cancer patients who underwent NAC and demonstrated suspicious microcalcifications within or near the tumour bed on mammography from June 2015 to August 2018. The residual microcalcifications and remnant lesion on magnetic resonance imaging (MRI) were correlated with histopathological findings of residual tumours and immunohistochemical markers. RESULTS: A total of 96 patients were included. Ten patients achieved pathological complete response (pCR) and previous suspicious microcalcifications were associated with benign pathology in 10.4% (10/96) of the patients. In the remaining 86 patients who did not achieve pCR, 61.5% (59/96) of the residual microcalcifications were associated with invasive or in situ carcinoma and 28.1% (27/96) with benign pathology. Hormone receptor-positive (HR+) patients had the highest proportion of residual malignant microcalcifications compared to HR- patients (48.9% versus 13.5%, respectively; p=0.019). MRI correlated better than residual microcalcifications on mammography in predicting residual tumour extent in all subtypes (ICC=0.709 versus 0.365). MRI also showed higher correlation with residual tumour size for the HR-/HER2+ and HR-/HER2- subtype (ICC=0.925 and 0.876, respectively). CONCLUSION: The extent of microcalcifications on mammography after NAC did not correlate with the extent of residual cancer in 38.5% of women. Regardless of the extent of microcalcifications, residual tumour extent on MRI after NAC and molecular subtype could be an accurate tool in evaluating residual cancer after NAC.

Smad4 in osteoblasts exerts a differential impact on HSC fate depending on osteoblast maturation stage.

Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4 in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1 mutants displayed senescence-associated phenotypes. OC mutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1 mutants than control littermates, suggesting potential impairment of CXCR4-CXCL12-mediated HSC retention. Disruption of the CXCR4-CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated ß-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4 in OBs differentially modulates HSC fate in a stage-dependent manner.

Usefulness of the oblique coronal plane in ankle MRI of the calcaneofibular ligament.

AIM: To evaluate the usefulness and diagnostic accuracy of oblique coronal MRI of the calcaneofibular ligament (CFL) view for diagnosis of CFL injury. MATERIAL AND METHODS: This retrospective study included 91 patients who were suspected to have CFL injury who underwent CFL view imaging. Anatomical identification of the CFL on orthogonal MRI sequences and CFL views was evaluated. Two radiologists evaluated the CFL based on an entire length view, an entire width view, and margin sharpness using a four-point scale. Diagnostic accuracy using orthogonal and CFL views was evaluated by calculating sensitivity, specificity, and accuracy. Arthroscopic or clinical findings were used as the reference standard. RESULTS: Both readers found identification of lesions using the entire length, entire width, and sharp margin from CFL view images to be superior to that based on orthogonal images. The sensitivity and accuracy of diagnosing CFL injury were significantly higher when using the CFL view compared to the orthogonal view, although specificity was not significantly different between the CFL view and orthogonal view images. CONCLUSIONS: CFL view imaging enables better anatomical evaluation and improved sensitivity and accuracy of diagnosis of CFL injury. CFL view images should therefore be used to evaluate potential CFL injuries.

Evaluation of shoulder pathology: three-dimensional enhanced T1 high-resolution isotropic volume excitation MR vs two-dimensional fast spin echo T2 fat saturation MR.

OBJECTIVE: To evaluate the diagnostic accuracy of three-dimensional (3D) enhanced T1 high-resolution isotropic volume excitation (eTHRIVE) shoulder MR for the detection of rotator cuff tears, labral lesions and calcific tendonitis of the rotator cuff in comparison with two-dimensional (2D) fast spin echo T2 fat saturation (FS) MR. METHODS: This retrospective study included 73 patients who underwent shoulder MRI using the eTHRIVE technique. Shoulder MR images were interpreted separately by two radiologists. They evaluated anatomic identification and image quality of the shoulder joint on routine MRI sequences (axial and oblique coronal T2 FS images) and compared them with the reformatted eTHRIVE images. The images were scored on a four-point scale (0, poor; 1, questionable; 2, adequate; 3, excellent) according to the degree of homogeneous and sufficient fat saturation to penetrate bone and soft tissue, visualization of the glenoid labrum and distinction of the supraspinatus tendon (SST). The diagnostic accuracy of eTHRIVE images compared with routine MRI sequences was evaluated in the setting of rotator cuff tears, glenoid labral injuries and calcific tendonitis of the SST. RESULTS: Fat saturation scores for eTHRIVE were significantly higher than those of the T2 FS for both radiologists. The sensitivity and accuracy of the T2 FS in diagnosing rotor cuff tears were >90%, whereas sensitivity and accuracy of the eTHRIVE method were significantly lower. The sensitivity, specificity and accuracy of both images in diagnosing labral injuries and calcific tendonitis were similar and showed no significant differences. The specificity of both images for the diagnosis of labral injuries and calcific tendonitis was higher than the sensitivities. CONCLUSION: The accuracy of 3D eTHRIVE imaging was comparable to that of 2D FSE T2 FS for the diagnosis of glenoid labral injury and calcific tendonitis of SST. The 3D eTHRIVE technique was superior to 2D FSE T2 FS in terms of fat saturation. Overall, 3D eTHRIVE was inferior to T2 FS in the evaluation of rotator cuff tears because of poor contrast between joint fluid and tendons. ADVANCES IN KNOWLEDGE: The accuracy of 3D eTHRIVE imaging is comparable to that of 2D FSE T2 FS for the diagnosis of glenoid labral injury and calcific tendonitis of SST.

The purinergic P2Y14 receptor axis is a molecular determinant for organism survival under in utero radiation toxicity.

In utero exposure of the embryo and fetus to radiation has been implicated in malformations or fetal death, and often produces lifelong health consequences such as cancers and mental retardation. Here we demonstrate that deletion of a G-protein-coupled purinergic receptor, P2Y14, confers potent resistance to in utero radiation. Intriguingly, a putative P2Y14 receptor ligand, UDP-glucose, phenocopies the effect of P2Y14 deficiency. These data indicate that P2Y14 is a receptor governing in utero tolerance to genotoxic stress that may be pharmacologically targeted to mitigate radiation toxicity in pregnancy.

A practical MRI grading system for cervical foraminal stenosis based on oblique sagittal images.

OBJECTIVE: To propose a new and practical MRI grading method for cervical neural foraminal stenosis and to evaluate its reproducibility. METHODS: We evaluated 50 patients (37 males and 13 females, mean age 49 years) who visited our institution and underwent oblique sagittal MRI of the cervical spine. A total of 300 foramina and corresponding nerve roots in 50 patients were qualitatively analysed from C4-5 to C6-7. We assessed the grade of cervical foraminal stenosis at the maximal narrowing point according to the new grading system based on T2 weighted oblique sagittal images. The incidence of each of the neural foraminal stenosis grades according to the cervical level was analysed by χ(2) tests. Intra- and interobserver agreements between two radiologists were analysed using kappa statistics. Kappa value interpretations were poor (κ<0.1), slight (0.1≤κ≤0.2), fair (0.2<κ≤0.4), moderate (0.4<κ≤0.6), substantial (0.6<κ≤0.8) and almost perfect (0.8<κ≤1.0). RESULTS: Significant stenoses (Grades 2 and 3) were rarely found at the C4-5 level. The incidence of Grade 3 at the C5-6 level was higher than that at other levels, a difference that was statistically significant. The overall intra-observer agreement according to the cervical level was almost perfect. The agreement at each level was almost perfect, except for only substantial agreement at the right C6-7 by Reader 2. No statistically significant differences were seen according to the cervical level. Overall kappa values of interobserver agreement according to the cervical level were almost perfect. In addition, the agreement of each level was almost perfect. Overall intra- and interobserver agreement for the presence of foraminal stenosis (Grade 0 vs Grades 1, 2 and 3) and for significant stenosis (Grades 0 and 1 vs Grades 2 and 3) showed similar results and were almost perfect. However, only substantial agreement was seen in the right C6-7. CONCLUSION: A new grading system for cervical foraminal stenosis based on oblique sagittal MRI provides reliable assessment and good reproducibility. This new grading system is a useful and easy method for the objective evaluation of cervical neural foraminal stenosis by radiologists and clinicians. ADVANCES IN KNOWLEDGE: The use of the new grading system for cervical foraminal stenosis based on oblique sagittal MRI can be a useful method for evaluating cervical neural foraminal stenosis.

Clinical correlation of a new MR imaging method for assessing lumbar foraminal stenosis.

BACKGROUND AND PURPOSE: Recently, Lee et al reported a new grading system for the lumbar spinal foraminal stenosis. They considered the type of stenosis, the amount of fat obliteration, and the presence of nerve root compression. Our aim was to evaluate whether a new MR imaging grading system correlated with symptoms and neurologic signs and could replace the previous grading system. MATERIALS AND METHODS: We examined 91 patients (M/F = 49:42; mean age, 50 years) who visited our institution and underwent MR imaging of the L-spine and were evaluated by 2 musculoskeletal radiologists. The presence and grade of lumbar foraminal stenosis at the maximal narrowing point was assessed according to the new grading system suggested by Lee et al (Lee system) and the Wildermuth grading system (Wildermuth system). Results were correlated with clinical manifestations and neurologic physical examination. Statistical analysis was performed by using κ statistics, categoric regression analysis, and nonparametric correlation analysis (Spearman correlation). RESULTS: Interobserver agreement in the grading of foraminal stenosis between the 2 readers was substantially correlated (κ of Lee system = 0.767, κ of Wildermuth system = 0.734). The Rs for reader 1 and reader 2 between the Lee system and the Wildermuth system were 0.880 and 0.885, between Lee system and PNM were 0.715 and 0.604, and between the Wildermuth system and PNM were 0.800 and 0.680. For patients younger than 50 years of age, the R between the Lee and Wildermuth systems was higher than that for patients 50 years or older, but the Rs between the grading system and PNM were lower in the younger group than in the older group. The Rs of the Wildermuth system with PNM were higher in the older group than in the younger group; the differences between the Rs of the Lee system with PNM and the Wildermuth system with PNM were higher in the older group (0.016 [young] versus 0.130 [old] and 0.008 versus 0.107). CONCLUSIONS: Interobserver agreement of the Lee system was slightly higher than the Wildermuth system and substantially correlated. Both systems are good for evaluation of lumbar spinal foraminal stenosis, but the Lee system showed slightly better interobserver agreement and good clinical correlation in the younger group of patients.

Mechanical force augments the anti-osteoclastogenic potential of human gingival fibroblasts in vitro.

BACKGROUND AND OBJECTIVE: The cellular response of human gingival fibroblasts to a mechanical force is considered to be primarily anti-osteoclastic because they produce relatively high levels of osteoprotegerin. However, there is little information available on the effects of compression force on the production of osteoprotegerin and osteoclastic differentiation by these cells. In this study, we examined how mechanical force affects the nature of human gingival fibroblasts to produce osteoprotegerin and inhibit osteoclastogenesis. MATERIAL AND METHODS: Human gingival fibroblasts were exposed to mechanical force by centrifugation for 90 min at a magnitude of approximately 50 g/cm(2). The levels of osteoprotegerin, receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-1beta and tumor necrosis factor-alpha were measured at various time-points after applying the force. The effect of the centrifugal force on the formation of osteoclast-like cells was also determined using a co-culture system of human gingival fibroblasts and bone marrow cells. RESULTS: Centrifugal force stimulated the expression of osteoprotegerin, RANKL, interleukin-1beta and tumor necrosis factor-alpha by the cells, and produced a relatively high osteoprotegerin to RANKL ratio at the protein level. Both interleukin-1beta and tumor necrosis factor-alpha accelerated the force-induced production of osteoprotegerin, which was inhibited significantly by the addition of anti-(interleukin-1beta) immunoglobulin Ig isotype; IgG (rabbit polyclonal). However, the addition of anti-(tumor necrosis factor-alpha) immunoglobulin Ig isotype; IgG1 (mouse monoclonal) had no effect. Centrifugal force also had an inhibitory effect on osteoclast formation. CONCLUSION: Application of centrifugal force to human gingival fibroblasts accelerates osteoprotegerin production by these cells, which stimulates the potential of human gingival fibroblasts to suppress osteoclastogenesis. Overall, human gingival fibroblasts might have natural defensive mechanisms to inhibit bone resorption induced by a mechanical stress.

Schwannoma of the breast showing massive exophytic growth: a case report.

Schwannoma is a slow-growing tumor that frequently occurs in the extremities, the trunk and the head region. Its occurrence in the breast is rare with only a few cases being reported. We present here the case of breast schwannoma in a 41-year-old woman who presented with a palpable mass in her right breast. This is the first report of breast schwannoma that showed massive exophytic growth with invasion of the skin, and it was initially presumed to be a breast cancer on preoperative mammography, ultrasonography and breast MRI examinations. Complete excision of the mass was done and pathology revealed a plexiform schwannoma.

The most useful findings for diagnosing acute appendicitis on contrast-enhanced helical CT.

PURPOSE: To evaluate the most useful findings to look for in diagnosing acute appendicitis on contrast-enhanced helical CT. MATERIAL AND METHODS: Appendiceal helical CT scans with intravenous contrast administration (abdomen, 7-mm collimation; abdominopelvic junction, 5-mm collimation) of 71 patients with surgically proven acute appendicitis and 167 patients with alternative diagnoses were reviewed retrospectively. Three radiologists analyzed the following parameters: enlarged appendix (>6 mm in diameter), appendiceal wall thickening, appendiceal wall enhancement, no identification of the appendix, appendicolith(s), appendiceal intraluminal air, intramural air, extraluminal air, periappendiceal fat stranding, extraluminal fluid, phlegmon, abscess, lymphadenopathy, segmental terminal ileal wall thickening, focal cecal apical thickening, focal colonic wall thickening, and segmental colonic wall thickening. The features that best distinguished appendicitis from alternative diagnoses were selected with stepwise logistic regression analysis. RESULTS: Nine CT findings distinguished acute appendicitis from alternative diagnoses (P < 0.05): enlarged appendix (R = 0.739), appendiceal wall thickening (R = 0.525), periappendiceal fat stranding (R = 0.414), appendiceal wall enhancement (R = 0.404), focal cecal apical thickening (R = 0.171), appendicolith(s) (R = 0.157), extraluminal air (R = 0.050), intramural air (R = 0.043), and phlegmon (R = 0.030). Enlarged appendix (sensitivity, 93%; specificity, 92%), appendiceal wall thickening (sensitivity, 66%; specificity, 96%), periappendiceal fat stranding (sensitivity, 87%; specificity, 74%), and appendiceal wall enhancement (sensitivity, 75%; specificity, 85%) showed the statistically most significant association with acute appendicitis. CONCLUSION: On 5-mm-section contrast-enhanced helical CT examinations, enlarged appendix, appendiceal wall thickening, periappendiceal fat stranding, and appendiceal wall enhancement were the most useful findings for diagnosing acute appendicitis.

Proximal gastrectomy and jejunal pouch interposition: radiographic evaluation of postoperative findings.

BACKGROUND: We assessed the postoperative findings of proximal gastrectomy and jejunal pouch interposition with contrast radiography. METHODS: Eleven patients with proximal gastrectomy and jejunal pouch interposition for proximal gastric carcinoma underwent contrast radiography. We evaluated the radiographic findings of the remnant stomach and interposed jejunal pouch. RESULTS: The interposed jejunal pouch showed good expansion, and the motility of the remnant gastric antrum was normal in all patients. One patient had significant lumenal narrowing of the esophageal pouch anastomotic site. Leak at the anastomotic site was not found. Reflux into the esophagus from the pouch was observed in two patients. Gastric emptying time was considerably delayed in two patients. CONCLUSION: Follow-up upper gastrointestinal series of the proximal gastrectomy and jejunal pouch interposition showed different postoperative findings. Awareness of the normal and abnormal findings is essential in the accurate postoperative evaluation of these patients.

Metastatic tumors to the breast: mammographic and ultrasonographic findings.

We evaluated the mammographic (n = 16) and ultrasonographic (n = 15) findings of 18 patients with metastatic breast carcinoma. Fifteen patients showed multiple or diffuse lesions and three patients showed single lesions. Ten patients (55.6%) had bilateral lesions. Mammography revealed high density (15 cases, 93.8%), round to oval (11 cases, 68.8%) lesions with poorly defined or obscured margins (12 cases, 75.0%). No associated calcification was found in any lesion. Ultrasonographically, poorly defined (8 cases, 53.3%), irregularly shaped (8 cases, 53.3%), hypoechoic (14 cases, 93.3%), heterogeneous (8 cases, 53.3%) lesions were predominantly distributed superficially (11 cases, 73.3%). Axillary lymphadenopathy was detected in six patients (33.3%). The longest diameter of most of the lesions was less than 2.0 cm (13 cases, 81.3%). We conclude that metastatic tumors to the breast appear as relatively small, superficially located, poorly defined, irregular nodules without calcification on mammography and ultrasonography. However, when the metastatic lesion is diffuse, the appearance is indistinguishable from that of inflammatory breast carcinoma.

Evaluation of solid breast lesions with power Doppler sonography.

PURPOSE: We compared the abilities of power and conventional color Doppler sonography to depict the vascularity of solid breast lesions and evaluated the usefulness of power Doppler sonography in differentiating between benign and malignant breast lesions. METHODS: One hundred two solid breast lesions (59 benign and 43 malignant lesions) were studied with power and color Doppler sonography. Power and color Doppler sonograms were retrospectively compared for the depiction of blood flow signals. Power Doppler images were also reviewed for the amount of Doppler signals, pattern of vascularity, and morphology of vessels. The sensitivity, specificity, and accuracy of the 2 techniques were calculated. RESULTS: Compared with color Doppler sonography, power Doppler sonography depicted flow superiorly in 61 cases (60%) and equally in 41 cases (40%). On power Doppler sonography, the incidence of marked blood flow in malignant lesions (65%) was higher than that in benign lesions (39%). The pattern of vascularity was predominantly central (86%) and/or penetrating (65%) more often in malignant lesions than in benign lesions (51% and 34%, respectively). Branching (56%) and disordered vessels (42%) were seen more often in malignant lesions than in benign lesions (22% and 8%, respectively). The sensitivity, specificity, and accuracy in diagnosing malignancy were 64%, 76%, and 71%, respectively, for power Doppler sonography and 77%, 76%, and 76% for color Doppler sonography. CONCLUSIONS: Power Doppler sonography was more sensitive than color Doppler sonography in the detection of flow in solid breast lesions. Although power Doppler sonography was not more effective in diagnosing malignant lesions, central and penetrating vascularity patterns and branching and disordered vessels seem to be helpful findings in predicting malignancy.

Imaging of tuberculous disease involving breast.

The aim of our study was to evaluate radiologic findings of the tuberculosis involving breast. We evaluated the radiologic features of 17 patients (18 lesions) with tuberculous disease involving the breast. The radiologic examinations, including mammography (16 patients), ultrasonography (12 patients), and Gd-DTPA-enhanced dynamic MRI (6 patients), were analyzed. Mammographic findings included mass (12 of 17 lesions), calcification (3 of 17 lesions), asymmetric density with spiculated margin (5 of 17 lesions), and axillary lymph node enlargement (8 of 17 lesions). On ultrasonography, a smooth bordered mass (7 of 13 lesions) with thin boundary (7 of 13 lesions) and heterogeneous, intermediate internal echoes (9 of 13 lesions) were most commonly demonstrated. On Gd-DTPA-enhanced dynamic MRI, 3 lesions showed significant enhancement at the first minute after injection (3 of 7 lesions). The maximum enhancing amount was greater than 500 normalized units, and the enhancing pattern was smooth or irregular ring appearance. Breast involvement with tuberculosis is rare but should be considered in the differential diagnosis of a woman living in an endemic area or when extramammary foci of tuberculosis are present. A multimodality imaging approach with clinical evaluation will help to establish the diagnosis of tuberculosis involving breast.

Increased expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in Caco-2 cells infected by Salmonella typhimurium.

Salmonella penetrates the basement membrane of intestinal epithelial cells into deeper tissues, in which process extracellular matrix proteases should be required. Hypothesizing that the proteases might be provided by host cells, we investigated the changes of expression of urokinase type plasminogen activator(u-PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in epithelial cells(Caco-2) infected with Salmonella typhimurium. The change of mRNA levels, amount of the enzyme secretion and functional activity were analyzed by Northern blot, ELISA, and Zymography. The mRNA level of u-PA was elevated by Salmonella infection itself without any exogenous transcription regulators. u-PA was actively secreted into the medium and was enzymatically active. The synthesis and secretion of PAI-1 was increased over time from 2 hrs post infection(pi) to 8 hrs pi. Zymographic assay revealed that the secretion of collagenases (type IV, type V and interstitial collagenase) were also increased. Taken together, S. typhimurium infection might induce accumulation of pericellular proteolytic activity and consequently degrade the extracellular matrix surrounding the infected cells. These in turn might enable Salmonella to invade into deeper tissues.