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Brown tumor is a reactive osteolytic lesion associated with hyperparathyroidism and an extremely rare form of a single lesion in the maxilla. We report the case of a 57-year-old woman with renal dysfunction, nasal obstruction, and hypercalcemia. MRI and CT revealed a huge osteolytic lesion in the maxilla. 18F-FDG PET/CT demonstrated marked FDG uptake within the mass and the lower-left lobe of the thyroid gland. 99mTc-methoxy-isobutyl-isonitrile scintigraphy suggested that this accumulation was a parathyroid adenoma. Parathyroid adenoma resection was performed, and the maxillary tumor was diagnosed as brown tumor. FDG PET/CT was helpful in evaluating brown tumor and detecting parathyroid adenoma.

Objectives We sought to generate realistic synthetic breast ultrasound images and express virtual interpolation images of tumors using a deep convolutional generative adversarial network (DCGAN). Methods After retrospective selection of breast ultrasound images of 528 benign masses, 529 malignant masses, and 583 normal breasts, 20 synthesized images of each were generated by the DCGAN. Fifteen virtual interpolation images of tumors were generated by changing the value of the input vector. A total of 60 synthesized images and 20 virtual interpolation images were evaluated by 2 readers, who scored them on a 5-point scale (1, very good; to 5, very poor) and then answered whether the synthesized image was benign, malignant, or normal. Results The mean score of overall quality for synthesized images was 3.05, and that of the reality of virtual interpolation images was 2.53. The readers classified the generated images with a correct answer rate of 92.5%. Conclusions A DCGAN can generate high-quality synthetic breast ultrasound images of each pathologic tissue and has the potential to create realistic virtual interpolation images of tumor development.

Preoperatively diagnosed ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive cancer by postoperative pathological examination. Various preoperative factors associated with upstaging to invasive cancer have been reported; however, this subject remains to be clarified. DCIS takes various forms on imaging, but many cases show non-mass-type lesions. In non-mass-type DCIS, recognizing the presence of invasion is difficult. To investigate predictors associated with upstaging to invasive cancer more precisely, we examined only non-mass-type DCIS. The present study retrospectively analyzed 101 patients diagnosed with non-mass-type DCIS preoperatively on breast biopsy at our institution between 2007 and 2017. Data were analyzed using Fisher's exact probability test and two-sample t-tests. Multivariate analysis was performed using logistic regression. The results showed that 27 patients (27%) were finally diagnosed with invasive cancer. Univariate analysis revealed abnormal result of palpation on breast examination (P=0.05), comedo necrosis (P=0.05), and HER2 status (P=0.02) as significant predictors. Multivariate analysis revealed an abnormal result of palpation as an independent predictor of invasive cancer underestimation (odds ratio 4.76; confidence interval 1.44-15.7; P=0.01). In conclusion, preoperatively diagnosed non-mass-type DCIS represented an underestimation in approximately 27% of cases. In particular, the presence of a clinically abnormal palpation increases the chance of upstaging to invasive cancer.

To investigate the ability of deep learning (DL) using convolutional neural networks (CNNs) for distinguishing between normal and metastatic axillary lymph nodes on ultrasound images by comparing the diagnostic performance of radiologists.We retrospectively gathered 300 images of normal and 328 images of axillary lymph nodes with breast cancer metastases for training. A DL model using the CNN architecture Xception was developed to analyze test data of 50 normal and 50 metastatic lymph nodes. A board-certified radiologist with 12 years' experience. (Reader 1) and two residents with 3- and 1-year experience (Readers 2, 3), respectively, scored these test data with and without the assistance of the DL system for the possibility of metastasis. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated.Our DL model had a sensitivity of 94%, a specificity of 88%, and an AUC of 0.966. The AUC of the DL model was not significantly different from that of Reader 1 (0.969; p = 0.881) and higher than that of Reader 2 (0.913; p = 0.101) and Reader 3 (0.810; p 0.001). With the DL support, the AUCs of Readers 2 and 3 increased to 0.960 and 0.937, respectively, which were comparable to those of Reader 1 (p = 0.138 and 0.700, respectively).Our DL model demonstrated great diagnostic performance for differentiating benign from malignant axillary lymph nodes on breast ultrasound and for potentially providing effective diagnostic support to residents.

We used virtual navigator real-time ultrasound (US) fusion imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to identify a lesion that could not be detected on the US alone in a preoperative breast cancer patient. Of the patient’s two lesions of breast cancer, the calcified lesion could not be identified by US alone. By fusing US with 18F-FDG PET/CT, which had been performed in advance, the location of the lesion could be estimated and marked, which benefited planning an appropriate surgery. The fusion of US and 18F-FDG PET/CT was a simple and noninvasive method for identifying the lesions detected by 18F-FDG PET/CT.

Objective The aim of this study was to evaluate the performance of preoperative axillary lymph node assessment in breast cancer using time-of-flight 18F-fluorodeoxyglucose PET/computed tomography (TOF [F-18]FDG-PET/CT). Methods Eighty-two women with breast cancer (mean age, 59.3 years; range, 30-84 years) underwent TOF [F-18]FDG-PET/CT scanning before surgery between January 2016 and June 2018 at our hospital. Visual analysis of FDG uptake and the maximum standardized uptake value (SUVmax) of axillary lymph nodes were compared with the pathological diagnoses. Results There were 77 patients with invasive breast carcinoma (mean invasive long diameter, 18.5 mm; range, 2-90 mm) and five patients with noninvasive carcinoma. Axillary lymph node metastases were histologically confirmed in 13 of 82 patients (15.9%). SUVmax showed an area under a receiver operating characteristic curve of 0.916, and the cut-off value of 1.1 was appropriate. By visual assessment, there were 11 true positives, 15 false positives, 54 true negatives and two false negatives; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85%, 78%, 42%, 96% and 79%, respectively. SUVmax showed values of 69%, 99%, 90%, 94% and 94%, respectively. Conclusions The sensitivity of TOF [F-18]FDG-PET/CT was as high as 85% by visual analysis. SUVmax using TOF [F-18]FDG-PET/CT showed high diagnostic performance for N-staging in breast cancer patients, especially high negative predictive value. The specificity, positive predictive value and accuracy of SUVmax were higher than those of visual analysis.

To compare the addition of diagnostic strain elastography (SE) and shear wave elastography (SWE) values to the conventional B-mode ultrasonography in differentiating between benign and malignant breast masses by qualitative and quantitative assessments. B-mode ultrasound, SE, and SWE were simultaneously performed using one ultrasound system in 148 breast masses; 88 of them were malignant. The breast imaging reporting and data system category in the B-mode, Tsukuba score (SETsu), Fat-Lesion-Ratio (SEFLR) in SE, and five-point color assessment (SWEcol) and elasticity values (SWEela) in SWE were assessed. The results were compared using the area under the receiver-operating characteristic curve (AUC). The AUC for B-mode and each elastography were similar (B-mode, 0.889; SETsu, 0.885; SEFLR, 0.875; SWEcol, 0.881; SWEela, 0.885; P > 0.05). The combined sets between B-mode and either of the elastography technique showed good diagnostic performance (B-mode + SETsu, 0.903; B-mode + SEFLR, 0.909; B-mode + SWEcol, 0.919; B-mode + SWEela, 0.914). B-mode + SWEcol and B-mode + SWEela showed a higher AUC than B-mode alone (P = 0.026 and 0.029), and B-mode + SETsu and B-mode + SEFLR showed comparable AUC to B-mode alone (P = 0.196 and 0.085). There was no significant difference between qualitative and quantitative assessments for the combined sets of B-mode and elastography (P > 0.05). The addition of both SE and SWE to B-mode ultrasound improved the diagnostic performance with increased AUC, and especially SWE was more useful than SE, and no significant difference was found between qualitative and quantitative assessments.

We aimed to use deep learning with convolutional neural network (CNN) to discriminate between benign and malignant breast mass images from ultrasound. We retrospectively gathered 480 images of 96 benign masses and 467 images of 144 malignant masses for training data. Deep learning model was constructed using CNN architecture GoogLeNet and analyzed test data: 48 benign masses, 72 malignant masses. Three radiologists interpreted these test data. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. The CNN model and radiologists had a sensitivity of 0.958 and 0.583–0.917, specificity of 0.925 and 0.604–0.771, and accuracy of 0.925 and 0.658–0.792, respectively. The CNN model had equal or better diagnostic performance compared to radiologists (AUC = 0.913 and 0.728–0.845, p = 0.01–0.14). Deep learning with CNN shows high diagnostic performance to discriminate between benign and malignant breast masses on ultrasound.

This retrospective study examined the relationship between the standardized uptake value max (SUVmax) of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic stage of breast cancer. We examined 358 breast cancers in 334 patients who underwent 18F-FDG PET/CT for initial staging between January 2016 and December 2019. We extracted data including SUVmax of 18F-FDG PET and pathological biomarkers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and nuclear grade. Anatomical and prognostic stages were determined per the American Joint Committee on Cancer (eighth edition). We examined whether there were statistical differences in SUVmax between each prognostic stage. The mean SUVmax values for clinical prognostic stages were as follow: stage 0, 2.2 ± 1.4, stage IA, 2.6 ± 2.1, stage IB, 4.2 ± 3.5, stage IIA, 5.2 ± 2.8, stage IIB, 7.7 ± 6.7, and stage III + IV, 7.0 ± 4.5. The SUVmax values for pathological prognostic stages were as follows: stage 0, 2.2 ± 1.4, stage IA, 2.8 ± 2.2, stage IB, 5.4 ± 3.6, stage IIA, 6.3 ± 3.1, stage IIB, 9.2 ± 7.5, and stage III + IV, 6.2 ± 5.2. There were significant differences in mean SUVmax between clinical prognostic stage 0 and ≥II (p &lt, 0.001) and I and ≥II (p &lt, 0.001). There were also significant differences in mean SUVmax between pathological prognostic stage 0 and ≥II (p &lt, 0.001). In conclusion, mean SUVmax increased with all stages up to prognostic stage IIB, and there were significant differences between several stages. The SUVmax of 18F-FDG PET/CT may contribute to prognostic stage stratification, particularly in early cases of breast cancers.

A woman in her 60s presented to our hospital with a left breast mass that was diagnosed as breast cancer. 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) revealed intense, hot uptake in the cancerous mass and left axillary lymph node metastasis. After chemotherapy, another PET/CT scan was performed. Although the mass and left axillary lymph nodes shrank and FDG uptake decreased, enlarged lymph nodes with high FDG uptake appeared in the right axilla. The patient had a painful vesicular eruption on the front to the back of the right upper hemithorax, which was diagnosed as active herpes zoster. Active herpes zoster mimics a worsening axillary lymph node metastasis on the PET/CT scan.

Background and Objectives: It is necessary to properly diagnose and manage axillary lymphadenopathy caused by a variety of diseases. This study aimed to evaluate the utility of ultrasound (US)-guided sampling in patients with axillary lymphadenopathy. Materials and Methods: Patients with axillary lymphadenopathy (excluding patients with newly diagnosed breast cancer) who underwent US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at a single center between February 2016 and September 2020 were retrospectively examined. The association between US imaging findings and malignancy was investigated and the diagnostic performance of US-guided sampling was assessed. Results: Fifty-five patients (including eight males) were included in the study, of these, 34 patients (61.8%) were finally diagnosed with a malignant lymph node lesion. Twenty-two patients (40.0%) had undergone FNA and 33 (60.0%) had undergone CNB. Larger short and long axis diameters, thicker lymph node cortex, and the absence of fatty hilum on the US were significantly associated with malignancy (p &lt, 0.05). The diagnostic performance of FNA, CNB, and FNA + CNB was excellent (sensitivity, specificity, and accuracy of 0.909, 0.900, and 0.917 for FNA, 0.958, 1.000, and 0.970 for CNB, and 0.941, 0.952, and 0.945 for FNA + CNB, respectively). Conclusions: US-guided FNA and CNB play an important role in the diagnosis and management of patients with axillary lymphadenopathy

Background and purpose Bilateral T2 hyperintensities in the medial part of the globus pallidus (GP) are sometimes incidentally observed in patients without a known history of diseases that present with such lesions. The purpose of this study was to evaluate the frequency of this finding and the association between this finding and age, lifestyle diseases and GP calcification. Methods We retrospectively investigated the brain magnetic resonance imaging (MRI) of 742 patients, which included between 104 and 108 consecutive patients from each decade of life between the 20s and 80s. The signal intensity ratio of the medial part to the lateral part of the GP in T2-weighted images (T2 medial/lateral ratio) was evaluated. For cases in which brain computed tomography images were available ( N=437), GP calcifications were also evaluated. The associations between the T2 medial/lateral ratio and age, sex, history of lifestyle diseases and GP calcification were investigated. Results Bilateral T2 medial/lateral ratios >1.10, 1.30 and 1.50 were observed in 29.8%, 7.1% and 1.8% of all cases, respectively. A high bilateral T2 medial/lateral ratio was observed less frequently in young patients ( pConclusion Incidental bilateral T2 hyperintensities in the medial part of the GP on brain MRI are most likely an age-related physiological finding.

Background: Indocyanine green angiography enables real-time visualization of blood vessels at depths of up to 10 mm beneath the body surface, thereby aiding the evaluation of the viability of skin flaps and predicting necrosis in surgical fields requiring good tissue perfusion. Although skin-flap necrosis also occurs in mastectomy without reconstruction, most studies have focused on reconstructive plastic surgery. Several patients undergoing mastectomy are eligible for postoperative adjuvant therapy, but complications can lead to delays in treatment and thus require prevention. However, a lack of a standard protocol for evaluating skin-flap perfusion using indocyanine green necessitates the study of its characteristics to facilitate comparison of the perfusion rate among individuals. Methods: This retrospective study focused on the characteristics of indocyanine green and established a protocol for indocyanine green angiography using laser-assisted imaging (SPY system) to predict postoperative skin-flap necrosis from intraoperative images of 30 patients who underwent mastectomy without reconstruction. Results: Our protocol predicted postoperative skin-flap necrosis as follows. First, the intravenous dose and concentration were set at 2.5 mg/mL and 0.05 mg/kg, respectively. Second, the timing of measurement was set to 100 s after the entry of indocyanine green into the skin (plateau phase); the analysis pattern was set to single frame. Third, comparisons among individuals were made using relative values. Conclusions: We analyzed the area of postoperative flap necrosis using this protocol. We found that the intraoperative images showed decreased perfusion in that area, which was useful in predicting skin-flap necrosis, as reported by previous breast reconstruction studies.

PURPOSE Synthetic MRI reconstructs multiple sequences in a single acquisition. In the present study, we aimed to compare the image quality and utility of synthetic MRI with that of conventional MRI in the breast. METHODS We retrospectively collected the imaging data of 37 women (mean age: 55.1 years; range: 20-78 years) who had undergone both synthetic and conventional MRI of T2-weighted, T1-weighted, and fat-suppressed (FS)-T2-weighted images. Two independent breast radiologists evaluated the overall image quality, anatomical sharpness, contrast between tissues, image homogeneity, and presence of artifacts of synthetic and conventional MRI on a 5-point scale (5 = very good to 1 = very poor). The interobserver agreement between the radiologists was evaluated using weighted kappa. RESULTS For synthetic MRI, the acquisition time was 3 min 28 s. On the 5-point scale evaluation of overall image quality, although the scores of synthetic FS-T2-weighted images (4.01 ± 0.56) were lower than that of conventional images (4.95 ± 0.23; P < 0.001), the scores of synthetic T1- and T2-weighted images (4.95 ± 0.23 and 4.97 ± 0.16) were comparable with those of conventional images (4.92 ± 0.27 and 4.97 ± 0.16; P = 0.484 and 1.000, respectively). The kappa coefficient of conventional MRI was fair (0.53; P < 0.001), and that of conventional MRI was fair (0.46; P < 0.001). CONCLUSION The image quality of synthetic T1- and T2-weighted images was similar to that of conventional images and diagnostically acceptable, whereas the quality of synthetic T2-weighted FS images was inferior to conventional images. Although synthetic MRI images of the breast have the potential to provide efficient image diagnosis, further validation and improvement are required for clinical application.

At our institution (Tokyo Medical and Dental University, Medical Hospital), latissimus dorsi flap (LD flap) reconstruction without a prosthetic implant is a popular surgical strategy following total mastectomy in patients with breast cancer. The LD flap, especially the extended LD flap, is usually rotated anteriorly through the axilla. However, if future additional surgery is required for axillary recurrence after LD flap reconstruction, the flap interferes with the visual field, making the surgical procedure more difficult. Because cases of axillary lymph node recurrence alone are rare, to the best of our knowledge, no paper has reported in detail on the technique and course of lymph node recurrence after LD flap reconstruction. The present study describes two cases of successful axillary lymph node dissection without sacrificing the flap for breast cancer recurrence after LD flap reconstruction. A brief analysis of immediate breast reconstruction with an LD flap performed in patients with breast cancer at our institution is also reported.

Breast cancer is the most frequently diagnosed cancer in women; it poses a serious threat to women’s health. Thus, early detection and proper treatment can improve patient prognosis. Breast ultrasound is one of the most commonly used modalities for diagnosing and detecting breast cancer in clinical practice. Deep learning technology has made significant progress in data extraction and analysis for medical images in recent years. Therefore, the use of deep learning for breast ultrasonic imaging in clinical practice is extremely important, as it saves time, reduces radiologist fatigue, and compensates for a lack of experience and skills in some cases. This review article discusses the basic technical knowledge and algorithms of deep learning for breast ultrasound and the application of deep learning technology in image classification, object detection, segmentation, and image synthesis. Finally, we discuss the current issues and future perspectives of deep learning technology in breast ultrasound.

Highlights • Patients with Stanford type A acute aortic dissection with perfused false lumen. • We created and randomized 10 cross-sectional images of each phase for 20 patients. • We scored these images depending on the degree of flap stoppage. • Image scores were significantly better in the 65 %–100 % R-R interval group., Objective To determine the phase that facilitates flap observation of the ascending aorta in Stanford type A acute aortic dissection with perfused false lumen. Methods We reconstructed retrospective Electrocardiogram-gated Computed Tomography Angiography images of the ascending aorta of all 20 patients to 20 phases of curved-multiplanar reconstruction in 5% increment. One radiologist created and randomized 10 cross-sectional images of each phase for every patient and two radiologists scored these images on a 5-point scale depending on the degree of flap stoppage. We calculated the average score for each phase of each case and compared them among the three groups. Results Image scores were significantly better in the 65 %–100 % R-R interval group than those in the 5%–30 % (p < 2e-16) and 35 %–60 % R-R interval groups(p = 7.2e-10). Similar scores were observed in the Heart Rate > 70 group (p = 0.00039, 2.2e-14). Moreover a similar tendency was observed in the arrhythmia group (p = 0.0035, 0.294). No difference was found in the degree of flap stoppage in the 65 %–100 % R-R interval group between the Heart Rate > 70 and Heart Rate ≤ 70 groups (p = 0.466) and between the arrhythmia and non-arrhythmia groups (p = 0.1240). Conclusion In observing the ascending aorta, We obtained a good image at 65 %–100 % R-R interval and similar tendency was observed in the patients with arrhythmia.

Background Adenomyoepithelioma (AME) is a rare type of benign breast tumor. Many AMEs have demonstrated benign behavior, but very few cases of malignant AME have been reported. Case presentation A 53-year-old woman visited our hospital with a 16-mm, palpable mass in the right breast. Core needle biopsy was performed. The pathological diagnosis was AME. Partial mastectomy was performed. Two years later, local recurrence developed, and the patient again underwent partial mastectomy. The pathology showed malignant AME, and the margin was negative. Eight months later, local recurrence developed again in the same location, and total mastectomy was performed. The pathological diagnosis was malignant AME. The patient has remained recurrence-free without adjuvant therapy.Conclusions A very rare case of AME with repeated local recurrences and malignant transformation was reported.

A 74 year old Japanese woman was diagnosed with invasive breast carcinoma. Her axillary lymph node was slightly swollen and had a short-axis diameter of 8 mm, but fine-needle aspiration did not lead to the diagnosis of metastasis. Subsequent 18F-fluorodeoxyglucose positron emission tomography/computed tomography showed no abnormal accumulation on the lymph node. Ultrafast dynamic magnetic resonance imaging yielded a very fast contrast enhancement like that of the primary lesion based on which we suspected lymph node metastasis. To our knowledge, this is the first report that shows that ultrafast imaging has contributed to the diagnosis of axillary lymph node metastasis.

This study aimed to compare magnetic resonance enterocolonography (MREC) features among the endoscopic ulcer stages reclassified to include healing ulcers and to assess the prognoses in Crohn disease (CD). Altogether, 89 consecutive patients with CD who had undergone MREC and ileocolonoscopy or balloon-assisted enteroscopy were retrospectively studied. Patients were reclassified into 38 patients with no deep ulcer, seven with healing deep ulcer, and 44 with active deep ulcer stage. MREC score derived from a 5-point MR classification and MR index of activity (MaRIA) were evaluated, and patients were followed-up. The primary endpoint was hospitalization. Healing deep ulcers had higher values in MREC score and MaRIA than no deep ulcers (p

The accuracy of modern imaging techniques for the diagnosis of peritoneal carcinomatosis is poor. A breast cancer patient with a high serum CA15-3 level did not receive a definitive diagnosis of peritoneal dissemination by imaging examination and then underwent laparoscopy. Pathological examination showed peritoneal dissemination of breast cancer, but the biological markers were different from the primary lesion: ER(−), PgR(−), and Her2:3 +. T-DM1 therapy was very effective, and her systemic symptoms disappeared. Since biomarkers of metastatic lesions may sometimes change, laparoscopic biopsy is very important and useful.

We aimed to use deep learning with convolutional neural networks (CNNs) to discriminate images of benign and malignant breast masses on ultrasound shear wave elastography (SWE). We retrospectively gathered 158 images of benign masses and 146 images of malignant masses as training data for SWE. A deep learning model was constructed using several CNN architectures (Xception, InceptionV3, InceptionResNetV2, DenseNet121, DenseNet169, and NASNetMobile) with 50, 100, and 200 epochs. We analyzed SWE images of 38 benign masses and 35 malignant masses as test data. Two radiologists interpreted these test data through a consensus reading using a 5-point visual color assessment (SWEc) and the mean elasticity value (in kPa) (SWEe). Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. The best CNN model (which was DenseNet169 with 100 epochs), SWEc, and SWEe had a sensitivity of 0.857, 0.829, and 0.914 and a specificity of 0.789, 0.737, and 0.763 respectively. The CNNs exhibited a mean AUC of 0.870 (range, 0.844–0.898), and SWEc and SWEe had an AUC of 0.821 and 0.855. The CNNs had an equal or better diagnostic performance compared with radiologist readings. DenseNet169 with 100 epochs, Xception with 50 epochs, and Xception with 100 epochs had a better diagnostic performance compared with SWEc ( P = 0.018–0.037). Deep learning with CNNs exhibited equal or higher AUC compared with radiologists when discriminating benign from malignant breast masses on ultrasound SWE.

A 46-year-old woman visited our hospital with the chief complaint of left axillary mass enlargement, which she had been aware of for 8 years. Palpation revealed that the mass was 15mm in size. Redness and gathering of the skin were also observed. Mammographic imaging of the left axilla revealed an irregular mass with skin infiltration. Breast ultrasonography revealed a low echo mass in the left axilla, which was continuous from the skin. Core needle biopsy was used to diagnose the tumor as an invasive ductal carcinoma. No other lesions were observed in the breast, and primary lesions were not found in any other organs. The patient was diagnosed with axillary accessory breast cancer and underwent local extensive resection and axillary lymph node dissection. Because the skin defect was widespread, we performed axillary reconstruction using the latissimus dorsi musculocutaneous flap to prevent upper limb contracture. At present, she can move her upper limbs and lymphedema has not been observed. In cases of axillary accessory breast cancer with skin infiltration, reconstruction using the latissimus dorsi musculocutaneous flap can be a useful procedure.

We aimed to evaluate an artificial intelligence (AI) system that can detect and diagnose lesions of maximum intensity projection (MIP) in dynamic contrast-enhanced (DCE) breast magnetic resonance imaging (MRI). We retrospectively gathered MIPs of DCE breast MRI for training and validation data from 30 and 7 normal individuals, 49 and 20 benign cases, and 135 and 45 malignant cases, respectively. Breast lesions were indicated with a bounding box and labeled as benign or malignant by a radiologist, while the AI system was trained to detect and calculate possibilities of malignancy using RetinaNet. The AI system was analyzed using test sets of 13 normal, 20 benign, and 52 malignant cases. Four human readers also scored these test data with and without the assistance of the AI system for the possibility of a malignancy in each breast. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were 0.926, 0.828, and 0.925 for the AI system; 0.847, 0.841, and 0.884 for human readers without AI; and 0.889, 0.823, and 0.899 for human readers with AI using a cutoff value of 2%, respectively. The AI system showed better diagnostic performance compared to the human readers (p = 0.002), and because of the increased performance of human readers with the assistance of the AI system, the AUC of human readers was significantly higher with than without the AI system (p = 0.039). Our AI system showed a high performance ability in detecting and diagnosing lesions in MIPs of DCE breast MRI and increased the diagnostic performance of human readers.

The objectives of our study were to establish the efficacy of a 5-point MR enterocolonography classification for assessing Crohn disease (CD) activity, compare this classification with a validated MRI score (i.e., the MR index of activity [MaRIA]), and compare both with endoscopic findings, which were assessed using the Crohn disease endoscopic index of severity (CDEIS).Seventy (derivation cohort) and 50 (validation cohort) patients with CD were retrospectively enrolled in this study. We developed a 5-point MR enterocolonography classification that consists of visual assessments alone. MR enterocolonography results were evaluated for each bowel segment (rectum; sigmoid, descending, transverse, and ascending colon; terminal and proximal ileum; and jejunum) by one observer in the derivation phase and independently by three observers in the validation phase using the 5-point MR enterocolonography classification lexicon and MaRIA. Areas under the ROC curves (AUCs) in discriminating endoscopic deep ulcers were compared between the MR enterocolonography classification and MaRIA. Interobserver reproducibility was assessed using weighted kappa coefficients.The AUCs of the MR enterocolonography classification were 89.0% in the derivation phase and 88.5%, 81.0%, and 77.3% for the three observers in the validation phase. The AUCs of the MR enterocolonography classification were statistically noninferior to those of MaRIA (p0.001). The cross-validation accuracy was 81.9% in the derivation phase and 81.5% in the validation phase. The MR enterocolonography classification showed good reproducibility.The 5-point MR enterocolonography classification was shown to be effective for evaluating CD activity in the large and small bowel.

Purpose We aimed to evaluate deep learning approach with convolutional neural networks (CNNs) to discriminate between benign and malignant lesions on maximum intensity projections of dynamic contrast-enhanced breast magnetic resonance imaging (MRI). Methods We retrospectively gathered maximum intensity projections of dynamic contrast-enhanced breast MRI of 106 benign (including 22 normal) and 180 malignant cases for training and validation data. CNN models were constructed to calculate the probability of malignancy using CNN architectures (DenseNet121, DenseNet169, InceptionResNetV2, InceptionV3, NasNetMobile, and Xception) with 500 epochs and analyzed that of 25 benign (including 12 normal) and 47 malignant cases for test data. Two human readers also interpreted these test data and scored the probability of malignancy for each case using Breast Imaging Reporting and Data System. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. Results The CNN models showed a mean AUC of 0.830 (range, 0.750–0.895). The best model was InceptionResNetV2. This model, Reader 1, and Reader 2 had sensitivities of 74.5%, 72.3%, and 78.7%; specificities of 96.0%, 88.0%, and 80.0%; and AUCs of 0.895, 0.823, and 0.849, respectively. No significant difference arose between the CNN models and human readers (p > 0.125). Conclusion Our CNN models showed comparable diagnostic performance in differentiating between benign and malignant lesions to human readers on maximum intensity projection of dynamic contrast-enhanced breast MRI.

The patient was a 57-year-old woman with Castleman's disease. The follow-up CT scans obtained during the treatment of Castleman's disease, detected a 15mm nodule in the right breast AC area, and the patient was diagnosed with breast cancer. Lymphadenopathy was noted on both sides of the axilla; however, it was considered to be due to Catsleman's disease. Mastectomy and sentinel lymph node biopsy were performed with preoperative diagnosis of cT1cN0M0, cStage Ⅰ. Rapid diagnosis of the sentinel lymph node during the operation showed a metastatic tumor measuring 3mm and axillary dissection was performed. However, no metastasis was found in the dissected lymph node, which was, therefore, considered as an enlargement due to Castleman's disease.

Small bowel (SB) endoscopic healing has not been well studied in patients with Crohn's disease (CD). This study aims to evaluate the utility of magnetic resonance (MR) enterography (MRE) for SB lesions in comparison with balloon-assisted enteroscopy (BAE) findings.In total, 139 patients with CD in clinical-serological remission were prospectively followed after BAE and MRE procedures. We applied a modified version of the Simple Endoscopic Score for CD (SES-CD) for an endoscopic evaluation of the SB, called the Simple Endoscopic Active Score for CD (SES-CDa). We also used the MR index of activity (MaRIA) for MR evaluations. The primary end points were time to clinical relapse (CD activity index of150 with an increase of70 points) and serological relapse (abnormal elevation of C-reactive protein).Clinical and serological relapses occurred in 30 (21.6%) and 62 (44.6%) patients, respectively. SB endoscopic healing (SES-CDa5) was observed in 76 (54.7%) patients. A multiple regression analysis showed that the lack of SB endoscopic healing was an independent risk factor for clinical relapses (hazard ratio (HR): 5.34; 95% confidence interval (CI): 2.06-13.81) and serological relapses (HR: 3.02; 95% CI: 1.65-5.51), respectively. MR ulcer healing (MaRIA score11) demonstrated a high diagnostic accuracy (90.9%; 95% CI: 87.9-93.2%) for endoscopic healing. The kappa coefficient between BAE and MRE for longitudinal responsiveness was 0.754 (95% CI: 0.658-0.850) for clinical relapse and 0.783 (95% CI: 0.701-0.865) for serological relapse.SB inflammation was associated with a poor prognosis in patients with clinical-serological remission. MRE is a valid and reliable examination for SB inflammatory activity both for cross-sectional evaluations and prognostic prediction.

The oncological safety of immediate breast reconstruction (IBR) in lymph node-positive patients is unclear. In the present study, the impact of IBR on recurrence based on data of patients with axillary lymph node metastases only was examined. The subjects were 232 patients who underwent breast surgery. The patients were grouped into 2 cohorts: non-IBR patients who underwent mastectomy with axillary lymph node dissection; and IBR patients with tissue expander or flap transfer and axillary lymph node dissection. The Non-IBR group included 165 patients, and the IBR group included 67 patients. For the comparison of oncological outcomes between the 2 groups, propensity score matching was performed. The propensity scores were calculated by logistic regression analysis, including age, tumor staging, human epidermal growth factor receptor 2 status, and estrogen receptor status. There was no difference in locoregional recurrence-free survival (LRRFS) between the non-IBR and IBR groups. The 5-year LRRFS rate was 78.9% in the non-IBR group and 85.1% in the IBR group. There was no difference in recurrence-free survival (RFS) between the non-IBR and IBR groups. The 5-year RFS rate was 75.6% in the non-IBR group and 78.8% in the IBR group. In all patients, the 5-year LRRFS rate was 77.3%, and the RFS rate was 70.5%. Multivariate Cox regression analysis to identify factors affecting RFS in all patients showed that estrogen receptor status and high nuclear grade were significant prognostic factors; IBR was irrelevant. This is the first report of an analysis using propensity score matching limited to node-positive breast cancer patients, and it showed that IBR is relatively safe in such patients.

Preoperatively diagnosed ductal carcinoma in situ (DCIS) is sometimes upstaged to invasive cancer by postoperative pathological examination. Various preoperative factors associated with upstaging to invasive cancer have been reported; however, this subject remains to be clarified. DCIS takes various forms on imaging, but many cases show non-mass-type lesions. In non-mass-type DCIS, recognizing the presence of invasion is difficult. To investigate predictors associated with upstaging to invasive cancer more precisely, we examined only non-mass-type DCIS. The present study retrospectively analyzed 101 patients diagnosed with non-mass-type DCIS preoperatively on breast biopsy at our institution between 2007 and 2017. Data were analyzed using Fisher's exact probability test and two-sample t-tests. Multivariate analysis was performed using logistic regression. The results showed that 27 patients (27%) were finally diagnosed with invasive cancer. Univariate analysis revealed abnormal result of palpation on breast examination (P=0.05), comedo necrosis (P=0.05), and HER2 status (P=0.02) as significant predictors. Multivariate analysis revealed an abnormal result of palpation as an independent predictor of invasive cancer underestimation (odds ratio 4.76; confidence interval 1.44-15.7; P=0.01). In conclusion, preoperatively diagnosed non-mass-type DCIS represented an underestimation in approximately 27% of cases. In particular, the presence of a clinically abnormal palpation increases the chance of upstaging to invasive cancer.

Purpose This study evaluated whether high b-value computed diffusion-weighted imaging (cDWI) can improve detection and differentiation of bowel inflammation in patients with Crohn's disease (CD). Methods Fifty-four consecutive CD patients who had undergone magnetic resonance enterography (MRE) and ileocolonoscopy (ICS) or balloon-assisted enteroscopy (BAE) were retrospectively studied; cDWI with a b-value = 1500s/mm2 (cDWI1500) was generated using DWI acquired with b-values of 0 and 800 s/mm2 (aDWI800). Overall, 366 bowel segments were evaluated. The signal intensities (SIs) of the bowel lumina were visually assessed on DWI. Bowel wall-to-iliopsoas muscle SI ratios on aDWI800 and cDWI1500 images and apparent diffusion coefficient (ADC) values were measured; visual assessments for lesion detection were performed using a 5-point Likert-like scale on plain MRE with aDWI800, plain MRE with cDWI1500, and contrast-enhanced (CE)-MRE without DWI. The area under the receiver-operating characteristic curve (AUC) was calculated to compare quantitative and qualitative assessments. Results SIs of the intraluminal fluid were shown as comparable to, or lower than background SIs on 157 (44.7 %) and 345 (98.3 %) of 351 segments on aDWI800 and cDWI1500, respectively. AUCs of SI ratios on cDWI1500 images (82.0 %, [95 % confidence interval: 76.6–87.3 %]) were greater than on aDWI800 (75.2 %, [68.2–82.3 %]; p Conclusions As it suppresses the SIs of intraluminal fluid and improves contrast between severe and non-severe inflammation, cDWI1500 helps with CD evaluation.

In a 69-year-old woman with a history of Mikulicz's disease, a hypoechoic solitary renal mass was identified on routine ultrasound examination. Based on the findings of computed tomography (CT) and magnetic resonance imaging (MRI), renal cell carcinoma was a possible diagnosis. Subsequent partial nephrectomy revealed a mass characterized by an increased number of blood vessels, internal hemorrhage, and a thick fibrous capsule. Immunohistochemically, the mass comprised of tubulointerstitial nephritis with increased immunoglobulin (Ig)G4-positive plasma cells and fibrosis. Generally, diagnosis of IgG4-related kidney disease (IgG4-RKD) is not difficult when the kidney is involved together with other systemic involvements. However, diagnosis becomes harder when a solitary renal mass appears as a single-organ involvement. On precise review of our imaging findings, MRI signals were markedly affected by hemorrhage, so the mass showed hypointensity on both T1- and T2-weighted imaging, and the signal of in-phase images decreased. Dynamic MRI showed no apparent enhancement of the mass, while CT showed an apparent enhancement effect. Capsule formation was another key finding for IgG4-RKD and was recognized as a gradually enhancing boundary zone surrounding the mass on both CT and MRI. When a solitary renal mass is associated with hemorrhage and thick capsule formation, inflammatory pseudotumor should be considered as differential diagnosis.

Purpose This study investigated the correlation between fluorine-18-fluorodeoxyglucose (F-FDG)-PET/computed tomography (CT) and clinicopathological factors in patients with mucinous breast carcinoma and assessed the feasibility of using F-FDG-PET/CT in evaluating tumors. Patients and methods We retrospectively examined 42 consecutive patients with pathologically proven mucinous breast carcinoma who preoperatively underwent F-FDG-PET/CT. In addition, we compared F-FDG uptake with clinicopathological characteristics. Results F-FDG uptake was observed in 39 (92.9%) lesions. The maximum standardized uptake value (SUVmax) (mean±SD) of all mucinous carcinoma, pure type, and mixed type was 2.3±1.3 (range: 1.0-5.1), 1.9±0.9 (range: 1.0-3.5), and 3.2±1.3 (range: 1.4-5.1), respectively. The mixed type had a significantly higher F-FDG uptake than the pure type (P=0.006). In addition, the sensitivity, specificity, accuracy, and area under the curve for distinguishing the pure type from the mixed type were 61.5, 89.7, 81.0, and 0.76, respectively (cutoff value: SUVmax>3.0). Furthermore, SUVmax correlated significantly with the high nuclear grade (P=0.010) and the presence of axillary lymph node metastasis (P=0.017). Conclusion F-FDG uptake efficiently distinguishes the pure type from the mixed type and may play a potential role in predicting the aggressiveness of mucinous breast carcinoma.

Our objective was to evaluate the clinical usefulness of positron emission tomography/computed tomography using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG-PET/CT) for staging cancer of the external auditory canal (EAC).Retrospective case review.Tertiary referral center.Twenty-three patients (seven men, 16 women, mean age of 59.6-year-old) who underwent FDG-PET/CT and high-resolution CT within 1 month for staging cancer of the EAC between July 2006 and December 2014 were enrolled in this study.FDG-PET/CT, high-resolution CT.Sensitivity, specificity, and accuracy for diagnosing nodal metastases.Most primary tumors were FDG-avid and maximum standardized uptake values were 7.72 ± 3.04 and 9.06 ± 3.94 for the early (60 min) and delayed (120 min) phases of FDG-PET/CT, respectively. FDG-PET/CT was capable of detecting small nodal metastases (short axis10 mm), and patient-based sensitivity, specificity, and accuracy of FDG-PET/CT for the N staging were 71.4, 81.3, and 78.3%, respectively. There were no patients with distant metastases in our cohort. Compared with the combination of clinical examination and conventional imaging methods, additional FDG-PET/CT resulted in a change in the surgical strategy in five patients (21.7%).Most primary cancers of the EAC are FDG-avid, and FDG-PET/CT is useful for detecting small nodal metastases, followed by the change in the surgical strategy.

The patient was a 61-year-old woman with a history of treatment for breast cancer. She had undergone left breast-conserving surgery and axillary lymph node dissection followed by radiation therapy for left breast cancer when she was 43 years old and later presented to our hospital with a chief complaint of a left breast ulcer with a messy exudate. Core needle biopsy (CNB)from the ulcer showed no malignancy. PET-CT showed low FDG uptake at the left breast and high FDG uptake at a contralateral axillary lymph node. CNB of a contralateral axillary lymph node showed metastasis of breast cancer. She underwent left mastectomy and right axillary lymph node dissection for local control. Ipsilateral breast tumor recurrence in the left breast and contralateral axillary metastases were identified in the final pathological findings. The patient was treated with FEC 100 and tri-weekly docetaxel and has been recurrence-free for 2 years after surgery.

Background Positron emission tomography with 2-deoxy-2-[18F] fluoro-d-glucose integrated with computed tomography (FDG-PET/CT) is a useful method to evaluate patients with oral squamous cell carcinoma (OSCC). However, the prognostic significance of FDG-PET/CT for assessing early OSCC remains unclear. Methods Pretreatment FDG-PET/CT of 205 consecutive patients (125 men, 80 women, mean age 59.7 year old) with early OSCC (cT1-2N0M0) between June 2010 and December 2014 were retrospectively analyzed. FDG avidity in primary lesions was assessed by visual interpretation. Thereafter, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in primary lesions. The relationship between each parameter and recurrence free survival (RFS) was assessed using the log-rank test. The performance of FDG-PET/CT for diagnosing metastatic lesions and synchronous cancer was also assessed. Results During the follow-up period (mean 32.9 months), 43 patients developed recurrences (21.0%). Patients with visually positive FDG uptake in primary lesions showed significantly shorter RFS than the others (63.0 months vs. 52.9 months, P = 0.005). In those patients, greater SUVmax, MTV, and TLG did not significantly predict shorter RFS. The sensitivity and specificity of FDG-PET/CT for cervical nodal metastases detection were 32.3% and 77.6%, respectively. FDG-PET/CT detected eight synchronous cancers (3.9%) and overlooked six synchronous cancers (2.9%). Conclusions Although its utility for detecting cervical nodal metastases and synchronous cancers is limited, FDG-PET/CT is a potentially prognostic indicator in early OSCC.

Magnetic resonance (MR) imaging is the recommended technique for detection of small bowel lesions in Crohn’s disease. We aimed to evaluate the impact of stricture findings obtained by MR imaging on patient outcomes using balloon-assisted enteroscopy (BAE) as a reference. Two hundred Crohn’s disease patients undergoing both MR enterocolonography and BAE were prospectively followed up for at least 1 year. The presence of strictures detected by MR enterocolonography was compared with endoscopic findings. Moreover, the relationship between MR findings and surgery was evaluated. The accuracy of MR imaging for detection of small bowel strictures was defined by a sensitivity of 60.6% and a specificity of 93.4%. Major strictures (diameter less than 10 mm or with internal fistula), long strictures (length 10 mm or greater), and prestenotic dilatation were predictors of stricture detection by MR imaging (P = 0.001, 0.017, and 0.002 respectively). Surgery was performed in 31.6% of patients (18 of 57) in the MR-positive–BAE-positive stricture group and in 10.8% of patients (4 of 37) in the MR-negative–BAE-positive stricture group. Multiple regression analysis showed MR-positive–BAE-positive strictures were an independent risk factor for surgery (P = 0.002 at 6 months and P

Enhancer of zests homologous (EZH)1 and its close homolog EZH2 are component of polycomb repressive complex (PRC) 2 protein complex, and play redundant and crucial role for the maintenance of transcriptional repression by tri-methylating histone H3 lysine 27 (H3K27). Hyper tri-methylation of H3K27 has been associated with lymphoma and myeloma progression, suggesting that PRC2 is a therapeutic target for hematological malignancies. Selective EZH2 inhibitors induce compensatory activation of EZH1 which in turn re-activates PRC2 function. We hypothesized that dual inhibition of EZH1 and EZH2 is more effective than selective EZH2 inhibition as anti-tumor therapy. We have developed a novel EZH1 and EZH2 dual inhibitor DS-3201, which simultaneously inhibited the enzymatic activity of EZH1 and EZH2 in nano-molar concentration. DS-3201 showed anti-proliferative effect against various NHL cells, such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and peripheral T-cell lymphoma, with GI50 values less than 100 nM regardless of EZH2 gain-of-function mutations. DS-3201 also induced differentiation of undifferentiated NHL cells with increment of cell lineage specific markers and which induced cell death in vitro. DS-3201 also showed synergistic effect with the standard of care agents for NHL in vitro and in vivo. An open-label phase 1 clinical study was initiated to examine the safety and pharmacokinetics of multiple-dose monotherapy of DS-3201b which is the salt form of DS-3201 in patients with NHL (ClinicalTrials.gov Identifier: NCT02732275). Eighteen patients with relapsed or refractory NHL were enrolled. The patients received oral administration of DS-3201b once daily in a 28-day cycle at dose of 150, 200 and 300 mg. Preliminary efficacy results (D. Maruyama, et al. ASH 2017), showed that the overall response rate was 58.8% (10/17) with 1 complete response and 9 partial responses (PR). Thirteen NHL patients including five follicular lymphoma (FL) and one DLBCL were analyzed for gene mutation status by targeted gene sequencing. EZH2 mutation was detected only in one FL patient, who achieved PR. It was suggested that DS-3201b has clinical activity against NHL, regardless of the mutation status of EZH2. Disclosures Honma: Daiichi Sankyo: Employment. Nosaka:Daiichi Sankyo: Employment. Shiroishi:Daiichi Sankyo: Employment. Takata:Daiichi Sankyo: Employment. Hama:Daiichi Sankyo: Employment. Yamamoto:Daiichi Sankyo RD Novare: Employment. Adachi:Daiichi Sankyo: Employment. Maruyama:Mundipharma International: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Bristol-Myers Squibb: Honoraria; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Amgen Astellas BioPharma: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; GlaxoSmithKline: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding. Tobinai:Chugai Pharma: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Eisai: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SERVIER: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Zenyaku Kogyo: Consultancy, Honoraria; HUYA Bioscience International: Consultancy, Honoraria. Ishida:Kyowa Hakko Kirin Co.Ltd: Honoraria, Research Funding; Celgene K.K: Honoraria, Research Funding; Bayer AG: Research Funding; Mundiparma K: Honoraria. Kusumoto:Bristol-Myers Squibb: Honoraria, Research Funding; Chugai Pharmaceutical Co. Ltd: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Tsukasaki:Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fujioka:Daiichi Sankyo: Employment. Watanabe:Daiichi Sankyo: Employment. Kanno:Daiichi Sankyo: Employment. Kumazawa:Daiichi Sankyo RD Novare: Employment. Fujitani:Daiichi Sankyo: Employment. Araki:Daiichi Sankyo: Employment. Fujiwara:Daiichi Sankyo: Employment.

Neoadjuvant chemotherapy (NAC) has become a standard therapy for patients with advanced breast cancer. Pathological complete response (pCR) after NAC is an important prognostic indicator, but some patients with pCR continue to experience recurrence. So new predictive and prognostic markers in addition to pCR are needed following NAC for breast cancer. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can evaluate metastases in the entire body simultaneously, and has several potential advantages over conventional imaging modalities. The purpose of this study was to evaluate whether FDG-PET/CT can determine NAC response and whether FDG-PET/CT can be a new prognostic marker. We imaged 83 breast cancer tumors with FDG-PET/CT, ultrasound (US), and magnetic resonance imaging (MRI) to evaluate NAC efficacy. As we previously analyzed 110 breast cancers with FDG PET/CT, we defined a threshold of >1.7 maximum standardized uptake value (SUVmax) as abnormal fluorodeoxyglucose (FDG) uptake. After NAC, 16 (19.3 %) tumors had a complete response, 54 (65.1 %) had a partial response, 11 (13.3 %) showed stable disease, and 2 (2.4 %) showed progressive disease. One of the two patients with progressive disease had bone metastasis detected by FDG-PET/CT and was not operated on. Remote metastases were evident in 2.4 % of patients after NAC as determined by FDG-PET/CT. Overall, 17 patients had pathological complete response (pCR). The sensitivity of abnormal FDG uptake after NAC for non-pCR was 20.3 % and the specificity was 94.7 %. Patients with abnormal FDG uptake after NAC experienced significantly more recurrences (P = 0.004) and more of them died (P = 0.010). Moreover, the difference in disease-free survival was more significant in the estrogen receptor (ER)-negative group. FDG-PET after NAC may be more effective for predicting prognosis than for evaluating treatment response. This tendency was particularly remarkable in ER-negative breast cancer tumors. FDG-PET/CT is useful for reevaluating surgical applicability after NAC.

BACKGROUND There are no widely accepted endoscopic or magnetic resonance scoring systems to evaluate deep small intestinal lesions in Crohn's disease (CD). This study aimed to determine whether the simplified endoscopic activity score for Crohn's disease (SES-CD) and the Magnetic Resonance Index of Activity (MaRIA) could be adapted for assessing CD lesions in the deep small intestine. METHODS Magnetic resonance enterocolonography and single-balloon enteroscopy were prospectively performed in 125 patients with CD. SES-CD and MaRIA were applied to the deep small intestine. The correlation between the SES-CD and MaRIA was evaluated. RESULTS Endoscopic and magnetic resonance active lesions were detected in the terminal and proximal ileal segments at a similar rate. The total MaRIA scores correlated well with the total SES-CD scores (R = 0.808, P < 0.001). A MaRIA score of ≥11 had a high sensitivity, specificity, and diagnostic accuracy for ulcerative lesions that were defined by enteroscopy (sensitivity: 78.3%; specificity: 98.0%). Similarly, an MaRIA score of ≥7 had a high sensitivity, specificity, and diagnostic accuracy for all mucosal lesions defined by enteroscopy (sensitivity: 87.0%; specificity: 86.0%). CONCLUSIONS The MaRIA closely correlates with the SES-CD in the deep small intestine, indicating these scoring systems can be used to assess deep small intestinal lesions. We also showed the validity of MaRIA to evaluate the active lesions in the deep small intestine.

Pactimibe sulfate, [7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octylindolin-5-yl]acetic acid hemisulfate, a novel Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, was investigated in vitro and in vivo to characterize its potential. Pactimibe exhibited dual inhibition for ACAT1 and ACAT2 (concentrations inhibiting 50% [IC50s] at micromolar levels) more potently than avasimibe. Kinetic analysis revealed pactimibe is a noncompetitive inhibitor of oleoyl-CoA (Ki value: 5.6 microM). Furthermore, pactimibe markedly inhibited cholesteryl ester formation (IC50: 6.7 microM) in human monocyte-derived macrophages, and inhibited copper-induced oxidation of low density lipoprotein more potently than probucol. Pactimibe exerted potent lipid-lowering and anti-atherosclerotic effects in atherogenic diet-fed hamsters. At doses of 3 and 10 mg/kg for 90 days, pactimibe decreased serum total cholesterol by 70% and 72%, and aortic fatty streak area by 79% and 95%, respectively. Despite similar cholesterol lowering, fatty streak area reduction was greater by 10 mg/kg. These results suggest that ACAT1/2 dual inhibitor pactimibe has anti-atherosclerotic potential beyond its plasma cholesterol-lowering activity.

Purpose The present study evaluated the usefulness of postoperative fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in the management of olfactory neuroblastoma (ONB). Materials and methods Ten patients (eight men and two women; mean age, 48.5 years) with histologically confirmed ONB who underwent craniofacial resection were retrospectively included in this study. A total of 42 whole-body F-FDG PET/CT scans for postoperative surveillance or restaging were reviewed. The mean time from operation until the PET/CT scan was 42.1 months. We evaluated the F-FDG uptake and the presence of recurrent lesions during the follow-up period and compared the PET/CT results with the results of MRI and clinical examination (endoscopy). Results Seven of the 10 patients had 24 recurrent lesions, and 18 of these recurrent lesions (seven local recurrences, eight cervical lymph node metastases, one intracranial metastasis, and two distant metastases) were F-FDG positive (75.0%). Three local recurrences and three intracranial metastases were false negative and were detected by endoscopy and MRI, respectively. The mean time from operation until recurrence was 51.4 months, and 17 lesions (70.8%) occurred more than 2 years after the initial operation. Conclusion Although F-FDG PET/CT is useful for the detection of postoperative recurrences of ONB, long-term follow-up combined with endoscopy and MRI is mandatory.

A conformational analysis and docking study of potent factor XIIIa inhibitors having a cyclopropenone ring were carried out in an attempt to obtain structural insight into the inhibition mechanism. First, stable conformers of the inhibitors alone were obtained from the conformational analysis by systematic search and molecular dynamics. Next, a binding form model of factor XIIIa was built based on an X-ray crystal structure of the enzyme. Finally, the docking study of the inhibitors into the model's binding site was performed. From the resulting stable complex structures, it was found that the cyclopropenone ring fits the active site located at the base of the binding cavity with high complementarity. The carbonyl oxygen of the cyclopropenone ring formed a hydrogen bond to the indole NH group of Trp279 and the terminal carbon atom of the reactive C=C double bond was in close proximity to the sulfur atom of the catalytic residue, Cys314. This binding mode suggests a possible inhibition mechanism, whereby the cysteine residue reacts with the cyclopropenone ring of the inhibitor, forming an enzyme-ligand adduct. In addition, the higher interaction energies between factor XIIIa and the inhibitors alluded to the probable binding sites of the ligand side chain.

We examined the cholesterol metabolism of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model deficient in low-density lipoprotein (LDL) receptors, to clarify the mechanism of the age-associated decrease of plasma total cholesterol, one of the properties of WHHL rabbits. The rabbits were examined at several ages: after weaning at 3 months, at sexual maturation at 6 months, at 12 months, and at 24 months, equivalent to about 35 years of age in humans. Plasma total cholesterol, triglyceride, and phospholipid levels decreased with aging by about 45%. These reductions were mainly dependent on a decrease in the LDL fraction. In the liver microsomal fraction, although there were no age-related changes in the cholesterol concentration and cholesterol 7alpha-hydroxylase (C7H) activity, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity increased and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity decreased with aging. The lipolytic activity varied with aging. The secretion rate of very-low-density lipoprotein (VLDL) cholesterol as determined by injection of Triton WR-1339 decreased significantly with aging, while the catabolic rate of VLDL cholesterol was about 2-fold higher in the oldest group versus the young groups. From these results, we conclude that the age-associated decrease in plasma cholesterol in WHHL rabbits is related not only to a decrease in the secretion rate of VLDL cholesterol but also to an increase in the catabolic rate.

We examined the effect of pravastatin sodium (pravastatin), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastatin to rats at 250 mg/kg for 7 days led to a 2.8-fold increase in fatty acid synthesis in the liver. The diurnal change of fatty acid synthesis was not affected by the treatment. Hepatic fatty acid synthase activity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepatocytes, the incubation with 2 microg/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase activity 2.8-fold. These results suggest that HMG-CoA reductase inhibitors might increase fatty acid synthesis in vivo through the induction of hepatic fatty acid synthase.

1)Repeated administration of pravastatin significantly increased serum and liver cholesterol in rats. Hepatic LDL receptor activity was not changed and VLDL cholesterol secretion from the liver was increased. Net cholesterol synthesis in rat liver was increased after 7 days of repeated pravastatin administration. These results suggest that for rats, unlike other animals for which serum cholesterol is decreased, induced HMG-CoA reductase activity due to pravastatin treatment might overcome the inhibitory capability of pravastatin. 2) In the course of screening for squalene synthase inhibitors, novel zaragozic acids -F10863A, B, C and D-containing zaragozic acid D3 were isolated. F10863A was most potent and selectively inhibited cholesterol synthesis in freshly isolated rat hepatocytes among several cultured and isolated cells. It also showed in vivo serum cholestrerol-lowering effects in hamsters and marmosets. However, the inhibition for squalene synthase proved to cause acidosis due to the accumulation of farnesol-derived dicarboxylic acids in urines. 3) A novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A, a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent, was isolated from the fermentation broth of Stachybotrys bisbyi. It inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.