Utility of CT texture analysis to differentiate olfactory neuroblastoma from sinonasal squamous cell carcinoma.

The purpose of this study was to examine differences in texture features between olfactory neuroblastoma (ONB) and sinonasal squamous cell carcinoma (SCC) on contrast-enhanced CT (CECT) images, and to evaluate the predictive accuracy of texture analysis compared to radiologists' interpretations. Forty-three patients with pathologically-diagnosed primary nasal and paranasal tumor (17 ONB and 26 SCC) were included. We extracted 42 texture features from tumor regions on CECT images obtained before treatment. In univariate analysis, each texture features were compared, with adjustment for multiple comparisons. In multivariate analysis, the elastic net was used to select useful texture features and to construct a texture-based prediction model with leave-one-out cross-validation. The prediction accuracy was compared with two radiologists' visual interpretations. In univariate analysis, significant differences were observed for 28 of 42 texture features between ONB and SCC, with areas under the receiver operating characteristic curve between 0.68 and 0.91 (median: 0.80). In multivariate analysis, the elastic net model selected 18 texture features that contributed to differentiation. It tended to show slightly higher predictive accuracy than radiologists' interpretations (86% and 74%, respectively; P = 0.096). In conclusion, several texture features contributed to differentiation of ONB from SCC, and the texture-based prediction model was considered useful.

Digital Mammographic Features of Breast Cancer Recurrences and Benign Lesions Mimicking Malignancy Following Breast-Conserving Surgery and Radiation Therapy.

Mammography after breast-conserving surgery and radiation therapy is an important tool for followup. Early diagnosis of local recurrence enables prompt treatment decisions, which may affect patient prognosis. For complicated post-treatment changes, radiologists sometimes have difficulties in interpreting follow-up mammography. Fat necrosis, dystrophic calcifications, suture calcification features, breast edema, seroma and distorted breast are benign changes related to treatment. These findings may mimic or hide tumor recurrence making it difficult to diagnose recurrences or prevent inappropriate biopsies. Recurrent tumors in follow-up mammography show several typical findings such as increasing asymmetric density, enlarging mass, reappearance of breast edema, and micro-calcifications. The purpose of this pictorial review is to demonstrate and discuss mammographic findings of recurrent tumors and important post-treatment changes that may mimic benign or malignant lesions, also using breast ultrasound images or breast magnetic resonance images. Recognizing post-treatment changes may help radiologists to more effectively identify candidates for suspected local recurrences.

Internal mammary lymph node metastases in breast cancer: what should radiologists know?

The internal mammary lymph node (IMLN) chain is a pathway through which breast lymphatic drainage flows. The internal mammary lymphatic vessel runs around the internal mammary artery and veins with IMLN in the parasternal intercostal spaces. IMLN metastasis, which forms a part of clinical TNM staging, may negatively affect the prognosis of primary breast cancer patients. IMLN metastasis is clinically detected using ultrasound, computed tomography, magnetic resonance imaging, and 18F-deoxyglucose positron emission tomography computed tomography. The uptake of radioactive tracers in IMLN with clinically negative axillary lymph nodes is often identified using sentinel lymph node mapping (SLNM) in primary breast cancer patients. The indication for IMLN biopsy or resection that is clinically detected or visualized using SLNM is controversial. The clinically suspicious IMLN may be considered for ultrasound-guided fine-needle aspiration. First IMLN recurrence needs to be biopsied. Irradiation of the breast, chest wall, and/or regional nodal irradiation, including IMLN, following lumpectomy or postmastectomy is recommended. Although radiation therapy for IMLN recurrence may improve clinical outcomes, it is also associated with pulmonary and cardiac toxicities. This review covers the local anatomy of IMLN, lymph drainage and image findings of IMLN with a discussion.

Diagnostic utility of a computer-aided diagnosis system for whole-body bone scintigraphy to detect bone metastasis in breast cancer patients.

OBJECTIVE: To compare the diagnostic ability of planar images (PI) and images obtained by a computer-aided diagnosis (CAD) system (Viewer for Standardized Bone Scintigraphies; VSBONE) of whole-body bone scintigraphy for detecting bone metastases in breast cancer patients. METHODS: 81 women (median: 56 years; range: 32-79) with a history of breast cancer were included in this study. They underwent whole-body bone scintigraphy after intravenous injection of 740 MBq technetium-99m hydroxymethylene diphosphonate. A total of 1066 bones (162 regions of the skull, 657 regions of the spine and pelvis, 223 regions of the sternum and rib, 18 regions of the upper extremities, and 6 regions of the lower extremities) were analyzed. The PI alone, VSBONE images alone, and both PI and VSBONE images (PI + VSBONE) were interpreted independently by two radiologists to diagnose bone metastases, which were then confirmed by magnetic resonance imaging. The sensitivity and specificity for each modality were analyzed using Fisher's exact and McNemar tests. Inter-reviewer agreement was evaluated using a kappa statistic. RESULTS: Bone metastases were confirmed in 43 patients with 442 positive lesions. The average sensitivity of PI, VSBONE images, and PI + VSBONE images was 40.8, 50.2, and 61.8 %, respectively. The average specificity was 97.8, 97.5, and 97.6 %, respectively. The kappa scores were 0.62 for PI, 0.69 for VSBONE, and 0.77 for PI + VSBONE. CONCLUSIONS: VSBONE was superior to PI in regard to sensitivity for detecting bone metastases in breast cancer patients. However, an improved CAD system is required to decrease the number of false-negative results.

Digital mammography versus digital breast tomosynthesis for detection of breast cancer in the intraoperative specimen during breast-conserving surgery.

PURPOSE: To compare the diagnostic ability of specimen radiography using digital mammography (DM) and digital breast tomosynthesis (DBT) for detecting breast cancer and evaluating its extension in the intraoperative specimen. METHODS: Sixty-five specimens from 65 women (median 62 years; range 34-86) obtained during breast-conserving surgery were prospectively investigated. Specimens underwent DM (25-40 kVp, 12-322 mA s) and DBT (25-34 kVp, 13-137 mA) in two orthogonal planes, anteroposterior (AP) and latero-lateral (LL). Images were interpreted by a radiologist to detect invasive lesions and their extensive intraductal components (EIC) or ductal carcinomas in situ (DCIS); afterwards, they were compared with histopathological findings. RESULTS: In AP views, 96 % of the invasive lesions were detected by both the methods. Of the EICs, 55 and 65 % were detected by DM and DBT, respectively (P = 0.61). Of the DICSs, 31 and 38 % were detected by DM and DBT, respectively (P > 0.99). In LL views, 71 and 13 % of the invasive lesions were detected by DBT and DM, respectively (P < 0.0001). Of the EICs, 42 and 10 % were detected by DBT and DM, respectively (P = 0.0078). Of the 13 DCISs, 42 and 8 % were detected by DBT and DM, respectively (P = 0.32). The whole lesion and contour could be delineated in 45 % by DBT and in 6.2 % by DM (P < 0.0001). CONCLUSIONS: DBT could detect breast cancer more accurately than DM in LL views, indicating its potential to more precisely diagnose vertical invasion.

Multi-detector row CT-guided marking technique for breast-conserving therapy of early breast cancer: margin positivity and local control rates.

BACKGROUND: In breast-conserving surgery (BCS), image-guided marking of the tumor border is important for preventing local recurrence and achieving a good cosmetic outcome. The purpose of this study was to evaluate the usefulness of multi-detector row computed tomography (MDCT)-guided marking technique before BCS in patients in whom ultrasound (US)-guided marking was not feasible. METHODS: Between 2004 and 2010, 94 lesions underwent contrast-enhanced MDCT-guided marking. Margin positivity and local control rates were compared with those of 149 lesions undergoing US-guided marking during the same period. RESULTS: In 21 lesions undergoing CT marking (22 %) and 20 lesions undergoing US marking (13 %), a negative resection margin could not be achieved, and hence the marking was judged as unsuccessful. Eighty-four lesions of the CT marking group and 119 of the US marking group received postoperative radiotherapy with 50 Gy in 25 fractions with or without an additional 10-Gy boost to the tumor bed. The remaining 10 and 30 patients, respectively, did not receive radiotherapy. The median follow-up period was 54 and 51 months for patients with CT marking and those with US marking, respectively. At 4 postoperative years, the local control rate was 96.5 % for patients with CT marking and 97.3 % for those with US marking (P = 0.89). CONCLUSIONS: The MDCT marking technique appears to be a valuable tool for determining the surgical margin for BCS in patients in whom ultrasound marking cannot be performed. Combining this technique with appropriate postoperative radiation therapy is expected to yield reasonably high local control rates.

Reproductive history and breast cancer risk.

The fact that reproductive factors have significant influence on the risk of breast cancer is well known. Early age of first full-term birth is highly protective against late-onset breast cancers, but each pregnancy, including the first one, increases the risk of early-onset breast cancer. Estradiol and progesterone induce receptor activator of NF-kappa B ligand (RANKL) in estrogen receptor (ER)- and progesterone receptor (PgR)-positive luminal cells. RANKL then acts in a paracrine fashion on the membranous RANK of ER/PgR-negative epithelial stem cells of the breast. This reaction cascade is triggered by chorionic gonadotropin during the first trimester of pregnancy and results in the morphological and functional development of breast tissue. On the other hand, the administration of non-steroidal anti-inflammatory drugs in the early steps of weaning protects against tumor growth through reduction of the acute inflammatory reaction of post lactation remodeling of breast tissue. This is experimental evidence that may explain the short-term tumor-promoting effect of pregnancy. The protective effect of prolonged breast feeding may also be explained, at least in a part, by a reduced inflammatory reaction due to gradual weaning. Delay of first birth together with low parity and short duration of breast feeding are increasing social trends in developed countries. Therefore, breast cancer risk as a result of reproductive factors will not decrease in these countries in the foreseeable future. In this review, the significance of reproductive history with regard to the risk of breast cancers will be discussed, focusing on the age of first full-term birth and post lactation involution of the breast.

Genetic and environmental predictors, endogenous hormones and growth factors, and risk of estrogen receptor-positive breast cancer in Japanese women.

The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We have recently shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype. It is necessary to establish risk factors capable of predicting the risk of ER-positive breast cancer that will enable the efficient selection of candidates for preventive therapy. We analyzed genetic factors, including 14 single nucleotide polymorphisms (SNPs), environmental risk factors (body mass index, age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake, and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 [IGF1] and IGF binding protein 3 [IGFBP3]), and mammographic density in 913 women with breast cancer and 278 disease-free controls. To identify important risk factors, risk prediction models for ER-positive breast cancer in both pre- and postmenopausal women were created by logistic regression analysis. In premenopausal women, one SNP (CYP19A1-rs10046), age, pregnancy, breastfeeding, alcohol intake, serum levels of prolactin, testosterone, and IGFBP3 were considered to be risk predictors. In postmenopausal women, one SNP (TP53-rs1042522), age, body mass index, age at menopause, serum levels of testosterone, and IGF1 were identified as risk predictors. Risk factors may differ between women of different menopausal status, and inclusion of common genetic variants and serum hormone measurements as well as environmental factors might improve risk assessment models. Further validation studies will clarify appropriate risk groups for preventive therapy.

Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging.

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.

[The frontiers of diagnostic radiology--PET/CT, 3DCT--].

Recently, positron-emission tomography (PET) systems have been introduced in many institutions around Japan and their clinical importance should increase in the management of many malignant diseases particularly systems using 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG). Since March 2004, we have been using the first PET/computed tomography (CT) scanner in Japan with 4-slice multidetector CT (MDCT) and now have introduced a second PET/CT scanner with 8-slice MDCT because of its excellent diagnostic capability and higher throughput capacity than that of the ordinal PET scanner. MDCT was a landmark in the history of CT in 1998. Subsequently, 8-, 16-, 32-, and 40-slice MDCT was developed in rapid succession. Finally, 64-slice MDCT became commercially available in 2005. In the future, 256-slice MDCT and flat-panel CT will appear in the clinical setting. Using these MDCT systems, we can now obtain multidimensional CT images very easily. These multidimensional images are less-invasive methods that are gradually phasing out the use of invasive angiography including digital subtraction angiography. In this article we describe the current features of PET/CT and multidimensional CT using MDCT.

A problem in diagnosing N3 disease using FDG-PET in patients with lung cancer--high false positive rate with visual assessment.

OBJECTIVE: To evaluate the accuracy of diagnosing N3 disease using positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in patients with pulmonary disease. SUBJECTS AND METHODS: Twenty patients diagnosed as FDG-PET N3 were enrolled. On FDG-PET, lymph nodes were considered to be positive when increased uptake as compared with that of the surrounding mediastinum was visually observed, or the mean standardized uptake ratio (SUR) was more than 2, 2.5, or 3. On CT, lymph nodes exceeding 1 cm in the shortest diameter were regarded as positive. RESULTS: The PET result was true positive (TP) in 2 patients and false positive (FP) in 18 with an overall accuracy (OA) of 10% using visual criteria. Using an SUR of more than 2.5, the result was TP in 2, FP in 3, and true negative (TN) in 15, the false negative (FN) in 0, with an OA of 85%. CT diagnosis was TP in 2, FP in 9, and TN in 9 with an OA of 55%. The accuracy using the SUR criteria of more than 2.5 was superior to that of CT. CONCLUSION: Of 20 patients with the diagnosis of PET N3, we found frequent over-diagnosis in nodal staging using the visual criteria.

False-positive and true-negative hilar and mediastinal lymph nodes on FDG-PET--radiological-pathological correlation.

OBJECTIVE: To compare histological findings of FDG-PET false-positive and true-negative hilar and mediastinal lymph nodes. METHODS: Sixty-seven lymphnode areas in 11 patients who were diagnosed to have N3 lymph nodes by FDG-PET and underwent surgery were histologically examined, and the histopathological findings in false-positive and true-negative lymph nodes were compared. Lymph nodes with higher accumulation of FDG than the surrounding mediastinum level were judged as positive. On histological sections, proportions of macrophages and lymphocytes, amount of coal dust deposit, presence of silicotic nodules, long- and short-axes of the largest node, and volume of macrophages and lymphocytes were evaluated. Correlations between the above-mentioned factors and FDG accumulation were evaluated. RESULTS: FDG uptake was not correlated with the proportion of macrophages and lymphocytes, coal dust amounts, or the presence of silicotic nodules. The long- and short-axes of the largest node in the false-positive areas were significantly longer than those in the true-negative areas (p = 0.01, and 0.001, respectively). Volumes of lymph nodes (mean +/- SD: 150 +/- 190 mm3) and macrophages (78 +/- 71 mm3) in false-positive areas were markedly larger than those in true-negative areas (68 +/- 87 mm3, p = 0.0009 and 34 +/- 54 mm3, p = 0.0001, respectively). The volume of lymphocytes was also larger in false-positive areas but less markedly. CONCLUSION: Our study suggested that false-positive results of FDG-PET in hilar and mediastinal lymph nodes were closely related to the size of lymph node and the volume of macrophages.