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.

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.

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.

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.

Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma.

BACKGROUND AND AIMS: Clinicians sometimes encounter papillary thyroid microcarcinoma (PMC) that is less than 10 mm, associated with lymph node metastasis. In this study, we assessed PMC clinicopathologically to clarify risk factors for poor prognosis. PATIENTS AND METHODS: Fifty-one patients who underwent thyroid surgery at Aichi Medical University from September 2009 to October 2016 were included. Patients were divided into two groups, pEX-positive (23 patients) and pEX-negative (28 patients), based on the pathological finding of thyroid capsule invasion. The former indicates that the tumor infiltrated the thyroid capsule and spread to the neighboring tissue, and the latter indicates no capsule invasion. We analyzed factors such as patient characteristics, pathological findings, and serum levels of thyroid hormones in the two groups. RESULTS: No statistical differences were observed between the two groups in gender distribution or age at surgery. Preoperative cancer diagnoses were established for more patients in the pEX-positive group than in the pEX-negative group (n = 21 and 14, respectively; P = 0.004). The mean (±SD) pathological tumor diameter was 5.42 ± 2.77 in the pEX-negative group and 8.32 ± 1.61 in the pEX-positive group (P < 0.001). No significant differences in preoperative serum levels of free T3, free T4, thyroid-stimulating hormone, or thyroglobulin were observed between the two groups. The odds ratio for node positivity in tumors invading thyroid capsules (pEX-positive) compared to those with no capsule invasion (pEX-negative) was 13.20 (95% confidence interval, 3.45-50.42). Immunohistological staining for phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Akt (protein kinase B) revealed the facilitation of PTEN and suppression of Akt, which might indicate downregulation of the phosphoinositide 3-kinase-Akt (PI3K-Akt) cascade. DISCUSSION: In general, the prognosis of PMC is favorable. However, the prognosis is less favorable in patients with nodal metastasis or extrathyroidal invasion. It is controversial whether resection is required for proven PMCs. For PMCs associated with extrathyroidal invasion, regional lymph node resection with lobectomy should be performed due to the high risk for lymphatic spread. There might be a possibility that the natural progression of PMC seems to be controlled by the facilitation of PTEN. However, a tumor in the lateral peripheral region of the thyroid parenchyma might be associated with capsule invasion followed by lymphatic spread.

Development of Erythema Nodosum After Olaparib Treatment in a Patient With Recurrent Breast Cancer and BRCA2 Mutation: A Case Report.

BRCA1 and 2 mutations are known to be associated with breast cancer, and olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, has been shown to be effective in cells carrying these mutations in some studies. Erythema nodosum (EN), which is one adverse event of olaparib and is discussed in this paper, is considered to be a very rare condition. A 69-year-old female patient underwent left breast conservative surgery with axillary lymph node dissection for left invasive ductal breast cancer (stage IIB). Her family history included a sister who developed ovarian cancer at age 63. Five years postoperatively, systemic metastases were discovered in the lung, bone, hilar, and poststernal lymph nodes. The surgically removed metastatic lung nodule was diagnosed as an estrogen receptor (ER)-positive, progesterone receptor (PgR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative metastatic adenocarcinoma of breast cancer origin. And germline mutations of BRCA1/2 were assessed using BRACAnalysis CDx® (Myriad Genetics, Salt Lake City, UT, USA), and BRCA2 1241 delC was identified as a deleterious mutation. Oral administration of olaparib was started. On day 4 of this treatment, numerous erythematous plaques characterized by intense tenderness and infiltration appeared on the extensor surfaces of the bilateral lower legs. On the basis of the clinical findings, the lesions were diagnosed as EN. Oral prednisolone was started at the same time as olaparib discontinuation, and the EN lesions disappeared in one week. EN is an inflammatory lesion characterized by tender subcutaneous induration with a flushed surface, predominantly on the bilateral lower legs. EN occurring after olaparib administration is considered to be very rare. This article describes such a case and reviews the relevant literature.

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.

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.

A case of estrogen receptor positive secretory carcinoma in a 9-Year-old girl with ETV6-NTRK3 fusion gene.

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

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.

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.

[Chemotherapy of a 2-week S-1 administration followed by 1-week rest for advanced and metastatic breast cancer].

When treating advanced and metastatic breast cancer patients with chemotherapy, it is mandatory to maintain the patients quality of life while keeping an acceptable level of antitumor activity. For these purposes, oral administration of S-1, fluorinated pyrimidine, is a good choice of treatment. Conventionally, a 4-week administration followed by a 2-week rest has been the treatment of choice with S-1. However, we applied a new regimen for 16 patients with advanced and metastatic breast cancer, in which one course consisted of a 2 week-administration followed by a week of rest, repeated twice. The median age of the patients who received this treatment was 59 years old(range 46. 8-80. 6). The response rate was 31. 2%, and the median values of time to progression and overall survival were 5. 1 and 17. 9 months, respectively. One case of thrombocytopenia as an adverse event was recognized. Our new S-1 regimen is likely to show an acceptable anti-tumor effect with minimal adverse events. The fidings suggest that this new regimen is clinically applicable for advanced and metastatic breast cancer patients.

Fusion of MRI and sonography image for breast cancer evaluation using real-time virtual sonography with magnetic navigation: first experience.

OBJECTIVE: We recently developed a real-time virtual sonography (RVS) system that enables simultaneous display of both sonography and magnetic resonance imaging (MRI) cutaway images of the same site in real time. The aim of this study was to evaluate the role of RVS in the management of enhancing lesions visualized with MRI. METHODS: Between June 2006 and April 2007, 65 patients underwent MRI for staging of known breast cancer at our hospital. All patients were examined using mammography, sonography, MRI and RVS before surgical resection. Results were correlated with histopathologic findings. MRI was obtained on a 1.5 T imager, with the patient in the supine position using a flexible body surface coil. Detection rate was determined for index tumors and incidental enhancing lesions (IELs), with or without RVS. RESULTS: Overall sensitivity for detecting index tumors was 85% (55/65) for mammography, 91% (59/65) for sonography, 97% (63/65) for MRI and 98% (64/65) for RVS. Notably, in one instance in which the cancer was not seen on MRI, RVS detected it with the supplementation of sonography. IELs were found in 26% (17/65) of the patients. Of 23 IELs that were detected by MRI, 30% (7/23) of IELs could be identified on repeated sonography alone, but 83% (19/23) of them were identified using the RVS system (P = 0.001). The RVS system was able to correctly project enhanced MRI information onto a body surface, as we checked sonography form images. CONCLUSIONS: Our results suggest that the RVS system can identify enhancing breast lesions with excellent accuracy.

Measurement and Analysis of Complex Permittivity of Breast Cancer in Microwave Band.

In order to obtain the basic data of breast cancer detection by microwave imaging, the complex permittivity of tissue excised from a breast cancer surgery was measured and analyzed. The relative permittivity and the conductivity of each tissue have strong linearity. In 80% of cases the relative dielectric constant and conductivity of the cancer tissue were higher than those in the breast tissue. However, in the remaining 20% case (scirrhous carcinoma) the dielectric constant and conductivity of the mammary gland were higher in those of cancer. We found that it is necessary to examine diagnostic approach of the reconstructed image by microwave imaging.

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.

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.

Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver.

Cystathionine gamma-lyase (CSE) is an enzyme catalyzing cystathionine and cysteine to yield cysteine and hydrogen sulfide (H(2)S), respectively. This study aimed to examine if H(2)S generated from the enzyme could serve as an endogenous regulator of hepatobiliary function. Gas chromatographic analyses indicated that, among rat organs herein examined, liver constituted one of the greatest components of H(2)S generation in the body, at 100 mumol/g of tissue, comparable to that in kidney and 1.5-fold greater than that in brain, where roles of the gas in the regulation of neurotransmission were reported previously. At least half of the gas amount in the liver appeared to be derived from CSE, because blockade of the enzyme by propargylglycine suppressed it by 50%. Immunohistochemistry revealed that CSE occurs not only in hepatocytes, but also in bile duct. In livers in vivo, as well as in those perfused ex vivo, treatment with the CSE inhibitor induced choleresis by stimulating the basal excretion of bicarbonate in bile samples. Transportal supplementation of NaHS at 30 mumol/L, but not that of N-acetylcysteine as a cysteine donor, abolished these changes elicited by the CSE inhibitor in the perfused liver. The changes elicited by the CSE blockade did not coincide with alterations in hepatic vascular resistance, showing little involvement of vasodilatory effects of the gas in these events, if any. These results first provided evidence that H(2)S generated through CSE modulates biliary bicarbonate excretion and is thus a determinant of bile salt-independent bile formation in the rat liver.