Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments.

AIM: The aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease. PATIENTS AND METHODS: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient. RESULTS: Median age was 62.9 years (range, 33.4-82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1-11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment. CONCLUSION: Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.

Gender difference of geographic distribution of physicians in Japan: three-point analysis of 1994, 2004 and 2014.

BACKGROUND: Japan's medical education system produces 9,000 graduates annually. Despite the government's implementation of several strategies, including increasing the number of doctors trained, the country still struggles with a shortage of physicians in rural areas. This study examined this issue, focusing on gender and considering years of physician experience, demographic and geographic factors. METHODS: We analyzed the Physician Census from 1994, 2004, and 2014, examining data on physicians' gender and the number of years since licensure. To correct the impact of municipal mergers, the analysis was aligned with the number of municipalities in 2014 (1741). We examined data from each physician (gender and years of medical experience) and analyzed the demographic and geographic distribution trend using Spearman correlation coefficients. We then used the Gini coefficient to evaluate the distribution change of physicians based on gender and years of experience. RESULTS: The number of physicians increased 1.29-fold over the 20-year observation period (1.23-fold for male physicians and 2.17-fold for female physicians), and the percentage of female physicians increased from 13.4% to 20.4%. We found that 87.7% of physicians were concentrated in the top 1/3 municipalities in terms of population. The number of female physicians was higher at 91.8% compared to 86.8% for male physicians. The Gini coefficients were lower for veteran physicians of both sexes than for younger physicians. The Gini coefficient for all physicians was 0.315-0.298-0.298 (male physicians: 0.311-0.289-0.283, female physicians: 0.394-0.385-0.395) The Gini coefficients for female compared to male physicians were higher in all age groups, showing that The distribution of female physicians is skewed toward urban areas. CONCLUSION: Female physicians are less distributed in rural areas than male physicians. In addition, despite the fact that the number of female physicians has increased more than male physicians over the past 20 years, the geographic ubiquity of female physicians has not improved. Since the trend of increasing the number of female physicians is expected to continue in the future, it is necessary to take some measures, such as providing a work-life balance suitable for female physicians.

Invasive lobular carcinoma of the breast detected with real-time virtual sonography: a case report.

BACKGROUND: Invasive lobular carcinoma (ILC) sometimes presents with unique clinical, pathologic, and radiographic features. In this case report, we describe a patient with ILC, whose initial presentation consisted with symptoms secondary to bone-marrow dissemination. In addition, the breast primary was revealed only by magnetic resonance imaging (MRI) followed by real-time virtual sonography (RVS). CASE PRESENTATION: A 51-year-old woman presented to our outpatient clinic with dyspnea on exertion. She had severe anemia (hemoglobin, 5.3 g/dL) and thrombocytopenia (platelet count, 31 × 103/mL). Bone-marrow biopsy was performed to evaluate hematopoietic function. The pathologic diagnosis was bone-marrow carcinomatosis due to metastatic breast cancer. Initial mammography followed by ultrasonography (US) failed to detect the primary tumor. On MRI, a non-mass-enhancement lesion was observed. While second-look US also did not detect the lesion, it was clearly visualized with RVS. We were finally able to biopsy the breast lesion. The pathologic diagnosis was ILC positive for both estrogen receptor and progesterone receptor, with 1 + immunohistochemical staining for human epidermal growth factor receptor 2. This case of ILC was characterized by bone-marrow metastasis. Due to decreased cell adhesion, the risk of bone-marrow metastasis is higher in ILC than in invasive ductal carcinoma, the most prevalent type of breast cancer. Biopsy of the primary lesion, which was initially only detected with MRI, was successfully performed with clear visualization during RVS, which is based on the fusion of MRI and US images. CONCLUSION: In this case report and literature review, we describe the unique clinical characteristics of ILC and a strategy for identifying primary lesions that are initially only visualized with MRI.

Effect of eribulin on epithelial-mesenchymal transition plasticity in metastatic breast cancer: An exploratory, prospective study.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer metastasis and treatment resistance, which worsens prognosis. In phase III trials, eribulin improved overall survival in metastatic breast cancer (MBC) patients. In preclinical studies, eribulin suppressed EMT. However, clinical data on the use of eribulin for MBC patients are limited. In this exploratory, prospective study, we examined the effect of eribulin on EMT in MBC patients. Twenty-two patients aged 44-82 years with recurrent breast cancer or MBC were treated with eribulin. Breast cancer tissue samples were obtained before treatment and on Day 15 ± 5 of the first cycle of eribulin treatment. EMT markers (E-cadherin, claudin-3, vimentin, and N-cadherin) were analyzed using western blotting. EMT changes were evaluated based on the ratio of epithelial to mesenchymal markers before and after treatment in individual tumors. E-cadherin/vimentin, claudin-3/vimentin, E-cadherin/N-cadherin, and claudin-3/N-cadherin ratios were significantly higher after treatment (p = .007, p = .005, p = .006, and p = .011, respectively). Based on E-cadherin/vimentin, 65.0% of tumors shifted to an epithelial phenotype, as compared to 66.7% based on claudin-3/vimentin, 84.6% based on E-cadherin/N-cadherin, and 71.4% based on claudin-3/N-cadherin ratios. Thus, our results showed that eribulin suppressed EMT in breast cancer tissues.

Clinical performance of digital breast tomosynthesis-guided vacuum-assisted biopsy: a single-institution experience in Japan.

BACKGROUND: The purpose of this study was to evaluate the clinical performance of Digital Breast Tomosynthesis guided vacuum-assisted biopsy (DBT-VAB) for microcalcifications in the breast. METHODS: Retrospective review of 131 mammography-guided VABs at our institution were performed. All of the targets were calcification lesion suspicious for cancer. 45 consecutive stereotactic vacuum-assisted biopsies (ST-VABs) and 86 consecutive DBT-VABs were compared. Written informed consent was obtained. Tissue sampling methods and materials were the same with both systems. Student's t-test was used to compare procedure time and the Fisher's exact test was used to compare success rate, complications, and histopathologic findings for the 2 methods. RESULTS: The tissue sampling success rate was 95.6% for ST-VAB (43/45) and 97.7% (84/86) for DBT-VAB. Time for positioning (10.6 ± 6.4 vs. 6.7 ± 5.3 min), time for biopsy (33.4 ± 13.1 vs. 22.5 ± 13.1 min), and overall procedure time (66.6 ± 16.6 min vs. 54.5 ± 13.0 min) were substantially shorter with DBT-VAB (P < 0.0001). There were no differences in the distribution of pathological findings between the 2 groups. CONCLUSION: Depth information and stable visibility of the target provided by DBT images led to quick decisions about target coordinates and improved the clinical performance of microcalcification biopsies.

Case report: surgical management of symptomatic pretracheal thyroid gland in a patient with dual ectopic thyroid.

BACKGROUND: Dual ectopic thyroid, a very rare condition, is defined as the simultaneous presence of ectopic thyroid tissue in two abnormal locations. Here, we report the surgical management of a patient with dual ectopic thyroid. CASE PRESENTATION: The patient was a 12-year-old boy with right para-midline swelling for 2 months. On physical examination of the upper anterior neck, there was a 4 cm × 3 cm mass that was soft, mobile, smooth, and painless. Blood examination showed euthyroidism. Neck ultrasonography showed a well-circumscribed multilocular cyst. We followed up by observation only because the patient had no local symptoms or malignancy. After 2 years, the mass gradually enlarged, so we performed surgery to improve cosmetic outcomes. Preoperative neck CT revealed both a high-density solid mass at the base of the tongue and a central low-density region surrounded by a high-density area at the pretracheal region below the hyoid. The infrahyoid mass was surgically removed, and the sublingual mass was left intact. Pathological findings showed the growth of multiple-size follicles, leading to a diagnosis of adenomatous goiter. Postoperative 123-I scintigraphy showed radioactive iodine uptake in the sublingual lesion, but none in the normal thyroid bed despite the extirpation of thyroid tissue. Postoperative thyroid hormone replacement was started for subclinical hypothyroidism. One year postoperatively, the patient became euthyroid. CONCLUSION: Surgical excision was used to manage a symptomatic cervical infrahyoid mass related to dual ectopic thyroid. Postoperatively, thyroid hormone replacement was required both to prevent enlargement of the remaining sublingual thyroid and to maintain adequate thyroid hormone levels.

Airway obstruction requiring tracheal intubation after fine-needle aspiration of the thyroid gland: a case report.

BACKGROUND: There have been no reports of tracheal intubation for airway obstruction after acute thyroid swelling following fine-needle aspiration (FNA) of the thyroid gland. CASE PRESENTATION: A 58-year-old woman with a 22 mm × 13 mm right hypervascular thyroid nodule underwent FNA once with a 22G needle under ultrasonographic guidance. Shortly after the aspiration, ultrasound revealed hypoechoic swelling with a crack-like pattern. The patient was observed under bed rest in the Fowler position and received intravenous steroids. A computed tomography (CT) scan showed swelling not only of the thyroid but also of the retropharyngeal space, and the patient complained of difficulty swallowing saliva. Laryngeal fiberscopy revealed protrusion of the posterior pharyngeal wall, edematous changes in the mucosa of the pharynx and epiglottis, and retention of saliva. The patient was intubated awake and hydrocortisone was administered every 8 h. She was extubated 3 days after FNA and discharged without any complications. CONCLUSIONS: When neck swelling is noticed after FNA, ultrasonographic findings are especially important to assess potential causes. If airway obstruction is suspected, CT findings and fiberscope observation of the pharynx provide particularly useful information.

Evaluation of an MRI/US fusion technique for the detection of non-mass enhancement of breast lesions detected by MRI yet occult on conventional B-mode second-look US.

PURPOSE: The aim of this study was to verify the utility of second-look ultrasound (US) using real-time virtual sonography (RVS), a magnetic resonance imaging (MRI)/US fusion technique, in identifying MRI-detected breast lesions with non-mass enhancement (NME). METHODS: Consecutive patients who had one or more NME lesions detected by MRI yet occult on the subsequent second-look US in conventional B (cB)-mode imaging were enrolled in the study between June 2015 and April 2020. Supine MRI of the lesions was performed and, using its data, second-look US using RVS was performed. RESULTS: Twenty patients with 21 NME lesions were included. The overall median lesion size on prone MRI was 23 mm (range, 5-63 mm). Supine MRI identified all the 21 NME lesions, and second-look US using RVS successfully detected 18 (86%) of them. RVS-guided biopsy was performed for histopathological evaluation, showing that nine of the 18 lesions were benign and the other nine malignant. Of the nine malignant lesions, two (22%) were invasive cancer and seven (78%) were ductal carcinoma in situ. In four of five patients who underwent prone MRI for preoperative evaluation, the diagnosis was benign and surgery was conducted as originally planned. In the other patient, the diagnosis was malignant and contralateral breast-conserving surgery was added. Three (14%) of the 21 NME lesions had no RVS correlates and were judged to be benign after 24-month follow-up. CONCLUSION: The results suggest that second-look US using RVS helps identify MRI-detected NME lesions that are occult on cB-mode second-look US.

Observational management of papillary microcarcinoma appearing in the remnant thyroid after hemithyroidectomy.

Active surveillance for papillary thyroid microcarcinomas (PTMCs) initiated in Japan is becoming adopted worldwide as a management option. However, it remains unclear how to manage newly appearing PTMCs in the remnant thyroid after hemithyroidectomy. We investigated the outcomes of similar observational management (OM) for PTMCs appearing in the remnant thyroid after hemithyroidectomy for papillary thyroid carcinoma (PTC) and benign thyroid nodules. Eighty-three patients were newly diagnosed with PTMC in the remnant thyroid between January 1998 and March 2017. Of these, 42 patients underwent OM with >3 times ultrasound examinations. Their initial diagnoses were PTC (initially malignant group) in 37 patients and benign nodule (initially benign group) in 5 patients. We calculated the tumor volume doubling rate (TV-DR) during OM for each PTMC. The TV-DR (/year) was <-0.1, -0.1-0.1, 0.1-0.5, and >0.5 in 12, 19, 5, and 6 patients, respectively. The TV-DRs in both groups did not statistically differ, but six patients (16%) in the initially malignant group showed moderate growth (TV-DR >0.5/year). They underwent conversion surgery and none of them had further recurrence. The remaining 36 patients retained OM without disease progression. The TV-DR in the initially malignant group was not significantly associated with patients' backgrounds or their initial clinicopathological features. None of the patients in this study showed distant metastases/recurrences or died of thyroid carcinoma. Although a portion of PTMCs appearing after hemithyroidectomy for thyroid malignancy are moderately progressive, OM may be acceptable as a management option for PTMCs appearing in the remnant thyroid after hemithyroidectomy.

Evaluation of the diagnostic utility of the aminotransferase/lactate dehydrogenase ratio for the suspension of tissue specimens during thyroid surgery for the identification of parathyroid tissue.

Identification of the parathyroid glands during surgery is crucial for preventing postoperative hypoparathyroidism. Kikumori et al. reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio for the saline suspension of a suspicious tissue can differentiate parathyroid tissue from other tissues. The aim of this study was to evaluate the utility of this method and investigate the appropriate time for measurement. We obtained 465 tissue specimens during thyroidectomy of 102 patients with papillary thyroid carcinoma (PTC), and 422 specimens (129 parathyroid, 92 PTC, and 201 other tissues) with measurable AST and LDH were analyzed. Small pieces of the tissues were immersed in saline and sent for measurement of AST and LDH. The assay was performed immediately after thyroidectomy for 245 specimens (the same-day group) and during the next morning for the remaining 177 specimens (the next-day group). The accuracy of diagnosing parathyroid tissue was significantly better in the same-day group than in the next-day group. A cut-off value of 0.18 gave the best diagnostic precision, with an area under the receiver operating characteristic curve of 0.95 and 88.7% sensitivity and specificity in the same-day group. When the cut-off value was set to 0.20, the specificity for excluding carcinomatous tissues was 100%. When measured on the day of the surgery, the AST/LDH ratio for the saline suspension of the surgical specimens is useful for discriminating parathyroid tissues from other tissues. This method can be utilized at most hospitals where intraoperative frozen sections or rapid parathyroid hormone assays are not available.

Mechanism of turnover or persistence of radiation-induced myofibroblast in vitro.

We recently made an important discovery that radiation induces myofibroblasts, which play a role in radiation-related carcinogenesis via tumor microenvironment formation. Here, we investigated the threshold dose and the mechanisms of myofibroblast induction to assess adverse radiation effects on normal cells. Single-dose of healthy human fibroblasts in vitro promotes myofibroblast induction at high doses (≥ 5 Gy). In contrast, repeated low dose of fractionated radiation is at least equivalent to high-dose single radiation regarding myofibroblast induction. ROS play a pivotal role in the process of myofibroblast induction in normal tissue injury. Antioxidants, such as epicatechin and ascorbic acid can prevent myofibroblast induction by scavenging ROS. We further investigated the role of DNA damage responses (DDR) on myofibroblast induction. Blocking the DDR using DNA-PK or AKT inhibitors enhanced cellular sensitivity to radiation and facilitated myofibroblast induction, whereas an ATM inhibitor also enhanced radiation sensitivity but abrogated ROS accumulation and myofibroblast induction. In contrast to standard culture conditions, myofibroblasts remained after low or moderate doses of radiation (below 2.5 Gy) under growth-restricted conditions. In conclusion, the recovery of damaged cells from radiation is essential for myofibroblast clearance, which restores stromal cell dormancy and prevents tumor microenvironment formation. However, residual ROS, by way of sustaining myofibroblast presence, can facilitate tumor microenvironment formation. Targeting ROS using antioxidants is effective in the mitigation of radiation-related adverse effects, such as growth retardation and myofibroblast induction, and helps protect normal tissues.

Pre-Operative Planning Using Real-Time Virtual Sonography, an MRI/Ultrasound Image Fusion Technique, for Breast-Conserving Surgery in Patients with Non-Mass Enhancement on Breast MRI: A Preliminary Study.

The purpose of this retrospective study was to evaluate the effect of pre-operative planning using real-time virtual sonography (RVS), a magnetic resonance imaging (MRI)/ultrasound (US) image fusion technique on breast-conserving surgery (BCS) in patients with non-mass enhancement (NME) on breast MRI. Between 2011 and 2015, we enrolled 12 consecutive patients who had lesions with NME that exceeded the US hypo-echoic area, in which it was particularly difficult to evaluate the tumor margin. During pre-operative planning before breast-conserving surgery, RVS was used to delineate the enhancing area on the breast surface after additional supine breast MRI was performed. We analyzed both the surgical margin positivity rate and the re-operation rate. All NME lesions corresponded to the index cancer. In all patients, the diameter of the NME lesion was greater than that of the hypo-echoic lesion. The median diameters of the NME and hypo-echoic lesions were 24 mm (range: 12-39 mm) and 8.0 mm (range: 4.9-18 mm), respectively (p = 0.0002). After RVS-derived skin marking was performed on the surface of the affected breast, lumpectomy and quadrantectomy were conducted in 7 and 5 patients, respectively. The surgical margins were negative in 10 (83%) patients. Two patients with positive margins were found to have ductal carcinoma in situ in 1 duct each, 2.4 and 3.2 mm from the resection margin, respectively. None of the patients required additional resection. Although further prospective studies are required, the findings of our preliminary study suggest that it is very well possible that the use of RVS-derived skin marking during pre-operative planning for BCS in patients with NME would have resulted in surgical outcomes similar to or better than those obtained without the use of such marking.

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions.

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

Second-look US Using Real-time Virtual Sonography, a Coordinated Breast US and MRI System with Electromagnetic Tracking Technology: A Pilot Study.

Our aim was to retrospectively evaluate the utility of second-look ultrasound (US) using real-time virtual sonography (RVS) for detection of conventional B-mode (cB-mode) occult magnetic resonance imaging (MRI)-detected breast lesions. Between July 2011 and May 2015, 53 consecutive patients who underwent second-look US to identify lesions detected by prone MRI were enrolled in this study. Second-look US using RVS was performed for cB-mode occult MRI-detected breast lesions after an additional supine MRI. In the 53 patients, 59 lesions were initially detected by prone MRI, followed by second-look US. Of the 59 lesions, 20 (34%) were identified by second-look US using cB-mode. Of the 39 (66%) cB-mode occult lesions, 38 (97%) were detected in supine MRI and 33 (85%) were detected by second-look US using RVS. MRI morphology types of the 33 lesions were as follows: mass, 16; non-mass enhancement, 5; and focus, 12. US-guided biopsy under RVS or excisional biopsy demonstrated that of the 33 lesions, 8 (24%) were malignant and the remaining 25 (76%) were benign. A total of 53 (90%) MRI-detected lesions were sonographically identified using both cB-mode and RVS (p < 0.001). All five remaining US-occult lesions could be followed up under RVS after the enhancing area was marked on the breast surface using RVS. Although further prospective studies are required, the findings of our pilot study suggest that second-look US using RVS with additional supine MRI may improve the sonographic and histopathologic detection rate of cB-mode occult MRI-detected breast lesions.

Development and Clinical Evaluation of New Topical Anesthetic Formulations for Dental Care.

To provide safe dental care, it is important to minimize the pain associated with the initial injection of the local anesthetic. For this purpose, a topical anesthetic is preliminarily applied to the area where a needle will be inserted in a clinical setting. In this study, we prepared new topical anesthetic formulations with favorable intra-oral retentivity and an excellent anesthetic effect, and clinically evaluated their efficacy. We used 4% lidocaine solution as an anesthetic drug and gelatin, agar, and a food thickener as a base to prepare new topical anesthetic formulations. The subjects rested in a supine position on a chair for dental practice prior to the following experiments. Firstly, about 0.2 g of the sample was applied at a test site. One minute later, the sample was removed, and a 30 G dental injection needle was inserted into the test site. The agar/gelatin-based formulation containing gelatin of 2% and agar of 1% had a moderate solidity at 25°C and a moderate fluidity at 37°C. This formulation showed a significantly greater depth than any of the commercially available topical anesthetics. The results of the present study demonstrated that the agar/gelatin-based formulation showed an excellent analgesic effect against pain associated with needle insertion.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

BACKGROUND: Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. METHODS: We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. RESULTS: With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p < 0.0001). Seventy-one patients (72.4 %) had TM data at the time of CTC testing. To study the relationship between CTCs and TMs, we divided patients into normal TM and high TM groups. In the normal TM group, the CTC-negative patients had statistically significant survival than the CTC-positive patients (p = 0.005). The data suggested that CTC count could provide additional prognostic information beyond TMs for advanced/metastatic breast cancer. In multivariate analysis, the only significant predictor of overall survival was CTC ≥ 1 (hazard ratio, 3.026; 95 % confidence interval 1.350-6.784). CONCLUSION: We found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

Targeted sonography using an image fusion technique for evaluation of incidentally detected breast lesions on chest CT: a pilot study.

BACKGROUND: With increasing use of computed tomography (CT), incidentally detected breast lesions are being encountered more frequently. The aim of our study was to verify the utility of targeted sonography using an image fusion technique, real-time virtual sonography (RVS) that coordinates real-time sonography images with previously obtained CT images using a magnetic position tracking system, for evaluation of incidentally detected breast lesions on chest CT. METHODS: Eleven lesions in 11 women with no history of breast cancer who were referred to our unit for assessment of breast lesions incidentally detected on CT were enrolled in this study. To assess the efficacy of targeted sonography using RVS, we analyzed the frequency of sonographic detection of incidentally detected breast lesions and the difference between sonography- and CT-determined diameters. RESULTS: Using RVS guidance, all 11 lesions were sonographically detected. Ten (91 %) of 11 lesions underwent sonography-guided biopsy, yielding a success rate of 90 % (9/10). The remaining sonography-guided biopsy failure lesion required surgical biopsy for definitive diagnosis; this was performed after RVS was used to mark CT imaging information onto the breast surface. Four (36 %) lesions subsequently proved to be malignant. The mean diameters provided by RVS were 14.9 ± 6.7 mm for sonography and 16.8 ± 7.5 mm for CT (p = 0.538). CONCLUSION: Using RVS, a sonographic probe was precisely guided to the lesions. Our results suggest that targeted sonography using RVS is a useful technique for identifying incidentally detected breast lesions on chest CT.

Reproducible surveillance breast ultrasound using an image fusion technique in a short-interval follow-up for BI-RADS 3 lesions: a pilot study.

The aim of our study was to verify the utility of surveillance ultrasound (US) using real-time virtual sonography (RVS)--to coordinate present US images with past US images reconstructed from previously acquired US volume data using an image fusion technique--for short-interval follow-up of Breast Imaging-Reporting and Data System (BI-RADS) category 3 mass lesions. We enrolled 20 women (23 lesions) with more than 24 mo of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 mo. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit. RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 mo were 8.2 ± 4.2, 8.4 ± 4.5, 8.1 ± 4.5 and 8.3 ± 5.0 mm, respectively (p = 0.785). Our results suggest that RVS is a reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points.

Impact of real-time virtual sonography, a coordinated sonography and MRI system that uses an image fusion technique, on the sonographic evaluation of MRI-detected lesions of the breast in second-look sonography.

The aim of this study was to verify the utility of second-look sonography using real-time virtual sonography (RVS)-a coordinated sonography with an MRI system that uses an image fusion technique with magnetic navigation-on the sonographic evaluation of MRI-detected lesions of the breast. Of the 196 consecutive patients who were examined with breast MRI in our hospital from 2006 to 2009, those patients who underwent second-look sonography to identify MRI-detected lesions were enrolled in this study. MRI was performed using a 1.5-T imager with the patient in a supine position. To assess the efficacy benefits of RVS, the correlations between lesion detection rates, MRI features, distribution, and histopathological classification on second-look sonography using conventional B-mode or RVS were analyzed. Of the 196 patients, 55 (28 %) demonstrated 67 lesions initially detected by MRI, followed by second-look sonography. Of the 67 MRI-detected lesions, 18 (30 %) were identified with second-look sonography using conventional B-mode alone, whereas 60 (90 %) lesions were detected with second-look sonography using RVS (p < 0.001). The detection rates of 16 focal lesions, 46 mass lesions, 16 lesions sized <5 mm, 45 lesions sized 5-10 mm, 26 lesions situated within the mammary gland, 41 lesions situated around mammary fascia, 24 malignant lesions, and 43 benign lesions were, respectively, 25, 26, 25, 24, 42, 17, 33, and 23 % by conventional B-mode, and were significantly higher, respectively, at 94, 89, 94, 89, 88, 90, 92, and 88 % by RVS. Of the seven lesions with no sonographic correlates, five could be biopsied by marking MRI information onto the body surface using RVS. Overall, 65 of 67 (97 %) MRI-detected lesions were confirmed by histopathological results. Our results suggest that the additional use of RVS on second-look sonography significantly increases the sonographic detection rate of MRI-detected lesions without operator dependence.