Pembrolizumab response in stage IV luminal-type breast cancer with high microsatellite instability: a case report.

BACKGROUND: Pembrolizumab (PEM), an immune checkpoint inhibitor (ICI), is often used for triple-negative breast cancer, but can also be used to treat solid tumors that exhibit high microsatellite instability (MSI-High). However, patients with breast cancer rarely have MSI-High, the use of PEM in such cases in clinical practice is uncertain due to lack of sufficient supporting data. Here, we report the case of a premenopausal woman in who received PEM for MSI-High luminal-type breast cancer. CASE PRESENTATION: A 40-year-old premenopausal Asian woman was diagnosed with stage IIA (T2N0M0) breast cancer and had an Oncotype DX recurrence score of 38. After surgery, she received 4 courses of chemotherapy with docetaxel and cyclophosphamide. After 3 months of tamoxifen therapy, the patient complained of abdominal pain due to right iliac metastasis, and biopsy of the metastatic lesion showed of luminal type; she was sequentially treated with fulvestrant, a CDK4/6 inhibitor, and an anticancer drug (TS1), but over the next year, metastasis to the bone and para-aortic lymph nodes increased. Tumor was MSI-High; PEM was started, and after three courses, bone metastases were reduced, para-aortic lymph node metastases resolved, opioids were discontinued, and the patient returned to society; PEM was administered for 1 year with no worsening of bone metastases on imaging. Asymptomatic brain metastasis less than 1 cm was detected and gamma knife was performed. Six months after completion of PEM, the patient is working with no new lesions. CONCLUSION: We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response.

The role of cell-autonomous circadian oscillation of Cry transcription in circadian rhythm generation.

The current model of the mammalian circadian clock describes cell-autonomous and negative feedback-driven circadian oscillation of Cry and Per transcription as the core circadian rhythm generator. However, the actual contribution of this oscillation to circadian rhythm generation remains undefined. Here we perform targeted disruption of cis elements indispensable for cell-autonomous Cry oscillation. Mice lacking overt cell-autonomous Cry oscillation show robust circadian rhythms in locomotor activity. In addition, tissue-autonomous circadian rhythms are robust in the absence of overt Cry oscillation. Unexpectedly, although the absence of overt Cry oscillation leads to severe attenuation of Per oscillation at the cell-autonomous level, circadian rhythms in Per2 accumulation remain robust. As a mechanism to explain this counterintuitive result, Per2 half-life shows cell-autonomous circadian rhythms independent of Cry and Per oscillation. The cell-autonomous circadian clock may therefore remain partially functional even in the absence of overt Cry and Per oscillation because of circadian oscillation in Per2 degradation.

Usefulness of Denoising Process to Depict Myopic Choroidal Neovascularisation Using a Single Optical Coherence Tomography Angiography Image.

Quality of single optical coherence tomography angiography (OCTA) images of myopic choroidal neovascularisation (mCNV) is poorer than in averaged images, although obtaining averaged images takes much time. This study evaluated the clinical usefulness of novel denoising process for depicting mCNV. This study included 20 eyes of 20 patients with mCNV. Ten en face images taken in a 3 × 3 mm macular cube were obtained from outer-retina-to-choriocapillaris layer. Three image types were prepared for analysis; single images before and after the denoising process accomplished deep learning (single and denoising groups, respectively) and up to 10 images were averaged (averaging group). Pairwise comparisons showed vessel density, vessel length density, and fractal dimension (FD) were higher; whereas, vessel density index (VDI) was lower in single group than in denoising and averaging groups. Detectable CNV indices, contrast-to-nose ratio, and CNV diagnostic scores were higher in denoising and averaging groups than in single group. No significant differences were detected in VDI, FD, or CNV diagnostic scores between denoising and averaging groups. The denoising process can utilise single OCTA images to provide results comparable to averaged OCTA images, which is clinically useful for shortening examination times with quality similar to averaging.

In vivo evaluation of the effect of lithium on peripheral circadian clocks by real-time monitoring of clock gene expression in near-freely moving mice.

Lithium has been used as a mood stabilizer to treat human bipolar disorders for over half a century. Several studies have suggested the possibility that the efficacy of lithium treatment results in part from the amelioration of circadian dysfunction. However, the effect of lithium on clock gene expression has not yet been investigated in vivo because continuous measurement of gene expression in organs with high time resolution over a period of several days is difficult. To resolve this issue, we attached a small photo multiplier tube (PMT) tightly to the body surface of transgenic mice carrying a reporter gene such that the photon input window faced target organs such as the liver and kidney and succeeded in long-term continuous measurement of circadian gene expression in semi-freely moving mice over periods of several weeks. Using this simple method, we clearly showed that lithium causes circadian period elongation in peripheral clock gene expression rhythms in vivo. Further development of our detection system to maturity will aid a wide range of research fields in medicine and biology.

Atypical pseudoangiomatous stromal hyperplasia showing rapid growth of the breast: Report of a case.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign lesion manifesting as myofibroblastic proliferation and anastomosing slit-like spaces. Atypical PASH is an extremely rare lesion characterized by cytological alteration of myofibroblast, presenting as myofibroblastic sarcoma arising from PASH. To our knowledge, only one other case has been reported since the first report of Rosen. We present a case of atypical PASH. A 39-year-old female presented with a round, elastic hard, painless mass in the left breast. Mammography and ultrasonography revealed no definitive sign of malignancy. Core needle biopsy report was suggestive of atypical PASH. Five months later, the mass had grown rapidly with pain. Considering the clinicopathological features, excision was performed. Pathological examination revealed the spindle cells proliferation in collagenous stroma. The spindle cell involved the adipose tissue and lobules and lined peudoangiomatous spaces. These cells exhibited marked cytological atypia and mitotic activity. Immunohistochemically, these spindle cells were positive for SMA, CD10, and bcl-2, and negative for podoplanin, p63, CD31, ERG and cytokeratins. The final diagnosis was atypical PASH. She is tumor-free on 12 months follow-up. The nature of atypical PASH remains unknown. Further studies are required for a clear definition, a new histological entity and diagnostic criteria.

Accuracy assessment methods of tissue marker clip placement after 11-gauge vacuum-assisted stereotactic breast biopsy: comparison of measurements using direct and conventional methods.

BACKGROUND: The objective of the study was to compare direct measurement with a conventional method for evaluation of clip placement in stereotactic vacuum-assisted breast biopsy (ST-VAB) and to evaluate the accuracy of clip placement using the direct method. METHODS: Accuracy of clip placement was assessed by measuring the distance from a residual calcification of a targeted calcification clustered to a clip on a mammogram after ST-VAB. Distances in the craniocaudal (CC) and mediolateral oblique (MLO) views were measured in 28 subjects with mammograms recorded twice or more after ST-VAB. The difference in the distance between the first and second measurements was defined as the reproducibility and was compared with that from a conventional method using a mask system with overlap of transparent film on the mammogram. The 3D clip-to-calcification distance was measured using the direct method in 71 subjects. RESULTS: The reproducibility of the direct method was higher than that of the conventional method in CC and MLO views (P = 0.002, P < 0.001). The median 3D clip-to-calcification distance was 2.8 mm, with an interquartile range of 2.0-4.8 mm and a range of 1.1-36.3 mm. CONCLUSION: The direct method used in this study was more accurate than the conventional method, and gave a median 3D distance of 2.8 mm between the calcification and clip.

Axillary lymph node recurrence after sentinel lymph node biopsy performed using a combination of indocyanine green fluorescence and the blue dye method in early breast cancer.

BACKGROUND: There is limited information on indocyanine green (ICG) fluorescence and blue dye for detecting sentinel lymph node (SLN) in early breast cancer. A retrospective study was conducted to assess the feasibility of an SLN biopsy using the combination of ICG fluorescence and the blue dye method. METHODS: Seven hundred and fourteen patients with clinically node-negative breast cancer were included in this study. They underwent SLN biopsy using a combination of ICG fluorescence and the blue dye method from March 2007 to February 2014. The ICG (a fluorescence-emitting source) and patent blue (the blue dye) were injected into the patients' subareolar region. The removed lymph nodes that had ICG fluorescence and/or blue dye uptake were defined as SLNs. The results of the SLN biopsies and follow-up results of patients who underwent SLN biopsy alone were investigated. RESULTS: In 711 out of 714 patients, SLNs were identified by a combination of ICG fluorescence and the blue dye method (detection rate, 99.6 %). The average number of SLNs was 2.4 (range 1-7), and the average number of resected swollen para-SLNs was 0.4 (range 0-5). Ninety-nine patients with an SLN and/or para-SLN involvement during the intraoperative pathological diagnosis underwent axillary lymph node resection (ALND). In addition, two of three patients whose SLN was not identified also underwent ALND. In 46 of 101 patients with an ALND, non-SLN involvement was not found. Follow-up results were analyzed in 464 patients with invasive carcinoma excluding those with ductal carcinoma in situ (n = 148) and those who underwent ALND (n = 101). During the follow-up period (range 4.4-87.7 months; median, 38 months), two patients (0.4 %) developed axillary lymph node recurrence. They were successfully salvaged, and to date, no further locoregional recurrence has been observed. CONCLUSIONS: A high rate of SLN detection and low rate of axillary lymph node recurrence were confirmed by an SLN biopsy using a combination of ICG fluorescence and the blue dye method. Therefore, it is suggested that this method may replace the combination of dye and radioisotope methods.

[Evaluation of Pre-Therapeutic Ki-67 as a Predictive Marker for Histological Response to Neoadjuvant Therapy in Breast Cancer].

There is controversy as to whether the proliferative marker Ki-67 is useful as a predictive marker for response to neoadjuvant therapy in breast cancer. We evaluated Ki-67 levels in pre-therapeutic breast cancer core biopsies from 52 breast cancer patients. These patients underwent anthracycline and taxane-based chemotherapy (n=48) or endocrine therapy (n=4) followed by surgery between March 2010 and February 2015. Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67 were examined by immunohistochemistry in the core-needle biopsy specimens. Ki-67 levels were categorized into 3 groups: low (<20%), intermediate (20-50%), and high (≥50%). Pathological response rates were 29%, 15%, and 48% in the low, intermediate, and high-risk groups, respectively. In univariate analysis, pre-therapeutic high levels of Ki-67, as well as negative ER status were significantly associated with the responder group (p<0.05). However, neither Ki- 67 nor ER status were significantly associated with a response in multivariate analysis. Ki-67 appears to be a promising parameter for histological response to neoadjuvant therapy in breast cancer.

[Local control of advanced breast cancer with mohs'paste].

We report two cases of primary advanced breast cancer that was locally controlled by using Mohs'paste. CASE 1: A 70- year-old woman was suffering massive exudates and offensive smell from her right giant breast tumor. Histopathological examination showed an invasive ductal carcinoma. However, she didn't have distant metastases. The patient received chemotherapy and the breast tumor has been fixed using Mohs'paste, and dissected. The giant tumor became flat and dry, so we could perform a radical operation. Then, she had contra-lateral axillary lymph node metastases. We performed a resection of left axillary lymph node and radiation therapy. After two years, we have not found a new lesion. CASE 2: A 54-year- old woman with right local advanced breast cancer discharged massive exudates and oozed blood. Histopathologically, she had an invasive ductal carcinoma. Moreover, she had lung and contra-lateral axillary lymph node metastases. She received chemotherapy and the breast tumor has been fixed using Mohs'paste, and dissected. The bleeding and exudates stopped almost completely, and the breast tumor became flat and dry. Both patients had experienced a mild pain, but their QOL improved remarkably. It is suggested that the patient with local advanced breast cancer may be controlled by using Mohs' paste.

[A case of urinary incontinence due to hypoplastic kidney with an ectopic ureteral opening: successful treatment with transcatheter arterial embolization].

We report a 21-year-old woman,who presented with a major complaint of urinary incontinence without dry time. On the basis of computed tomographic examination and vaginography,she was diagnosed as having a hypoplastic left kidney with a solitary ectopic ureteral opening on the left. Transcatheter arterial embolization of the renal artery using anhydrous ethanol was conducted for renal ablation. No postoperative complications were noted,and the symptoms of urinary incontinence were eliminated. Embolization of the renal artery for ablation of a hypoplastic kidney with symptoms can be achieved without laparotomy while causing little stress and few complications,with an outcome comparable to surgical nephrectomy. This procedure is expected to be adopted as a standard therapeutic modality in the future.

[Developments in diagnostic imaging of breast cancer].

Recent developments in diagnostic imaging of breast cancer are briefly reviewed. Innovations of the imaging equipment and progress in treatment strategy against breast cancer have both achieved remarkable developments in diagnosis.

[A case of urachal xanthogranuloma suspected to be a urachal tumor].

A 47-year-old female consulted our hospital with the chief complaints of lower abdominal pain and fever. There was a palpable mass in the lower abdomen. The patient had undergone oophorectomy by lower abdominal median incision. Ultrasonography, computed tomography, and magnetic resonance imaging (MRI) demonstrated a cystic mass above the bladder dome extending to the umbilicus, which was strongly suspected to be a urachal tumor. Enhanced T1 weighted MRI showed a mass enhanced by contrast media. Partial cystectomy with urachal resection was performed by lower abdominal median incision. The histological diagnosis was xanthogranuloma. This is the thirteenth case report of xanthogranuloma of the urachus in the Japanese literature.

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation.

OBJECTIVE: To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. DESIGN AND PATIENTS: Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. RESULTS: CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. CONCLUSION: All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.

3D imaging of intraductal spread of breast cancer and its clinical application for navigation surgery.

BACKGROUND: To perform optimal tumor resection of breast cancer, preoperative information concerning intraductal spread of cancer (ISC) is very important. METHODS: To detect ISC, three-dimensional (3D) imaging methods including helical CT, MRI, and ultrasound were examined in patients with primary breast cancer by comparison with multi-sliced pathological specimens. RESULTS: The sensitivity of each modality for detecting ISC was 64.7%, 90.2% and 78.6%, and the specificity was 97.1%, 62.9% and 100%, respectively. Subsequently, the potential of each modality for navigation in breast conserving surgery was assessed. Three-dimensional helical CT navigation could reduce the positive rate of the specimen margins, and 3D MRI navigation using a special mapping sheet enabled removal of non-palpable breast cancer without positive margins in 66.7% of patients preliminarily. Real-time 3D ultrasound images correlated with the resected tumor size, with the difference between the two less than 2 cm in 72.7 % of the patients with ISC. CONCLUSION: Three-dimensional images from each modality were reliable enough for diagnosis of tumor spread, and surgical navigation using these images seemed to have potential clinical application for breast conserving surgery. Prospective studies for navigation surgery with more patients are needed.

Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer.

Several recent trials have demonstrated that neoadjuvant chemotherapy can allow more patients to successfully undergo breast-conserving treatment (BCT), and does not confer a survival disadvantage compared with standard adjuvant chemotherapy. In addition, the pathological response of primary breast tumors to neoadjuvant chemotherapy appears to be a surrogate marker for patient outcome. In our series, during the period from May 1995 to December 2000, 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. The margin positive rate was 14.1%(9/64), similar to the rate after BCT for early-stage breast cancers, the largest diameter of which was smaller than 3 cm. At a median follow-up of 30 months, only 3 patients in the BCT group have developed local recurrence; the local recurrence rate appears to be comparable to that after BCT for early stage breast cancers. Long term follow-up is required, however, to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.

Renal angiomyolipoma with minimal fat.

We report here two patients with angiomyolipoma with minimal fat, who were treated by radical nephrectomy, with a diagnosis of renal cell carcinoma. The tumors in these two patients were hyperattenuated on unenhanced computed tomography (CT) images, but did not show fat components, and were moderately enhanced on contrast-enhanced CT images. The tumor in one patient was homogeneously hypointense on T2-weighted magnetic resonance (MR) images, enhanced during the early phase on dynamic MR images, and, further, showed abundant pulsatile blood vessels on color Doppler examination. These imaging findings of renal tumors suggested the possibility of angiomyolipoma with minimal fat; accordingly, when imaging results suggest this possibility, further careful sampling to identify minimal fat components must be performed by thin-section unenhanced CT.

Ipsilateral adrenal involvement from renal cell carcinoma: retrospective study of the predictive value of computed tomography.

OBJECTIVES: To compare the radiologic evidence of adrenal involvement on computed tomography (CT) with pathologic reports and to assess the accuracy of CT in the diagnosis of adrenal involvement with renal cell carcinoma. METHODS: Between January 1992 and June 2000, we treated 229 patients with renal cell carcinoma. In this study, we retrospectively analyzed 73 patients who had been examined by CT before surgery and had undergone radical nephrectomy, including removal of the ipsilateral adrenal gland. The abnormal integrity of the adrenal glands on CT and the pathologic adrenal involvement of renal cell carcinoma were demonstrated by a radiologist and pathologist, respectively. RESULTS: The blinded review by a radiologist of the CT results of 73 patients with renal cell carcinoma identified a normal appearance of the ipsilateral adrenal gland in 54 patients (74%), none of whom had pathologic evidence of malignant involvement. The adrenal gland was diagnosed as abnormal on CT in 19 patients (26%), including enlargement in 7 patients, nodule formation in 7, and an irregular surface in 8. Two of these 19 patients had adrenal involvement. Both were staged at T3M1, and their primary tumors were large, measuring more than 10 cm. In this study, CT demonstrated 100% sensitivity, 76% specificity, 11% positive predictive value, and 100% negative predictive value for ipsilateral adrenal involvement of renal cell carcinoma. CONCLUSIONS: Normal adrenal images on CT could exclude adrenal involvement by renal cell carcinoma. However, radical nephrectomy, including removal of the ipsilateral adrenal gland, should be performed in patients with large tumors.