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Purpose: Ductal carcinoma in situ (DCIS)-preinvasive breast cancer-with lymph node metastasis can clinically be treated as different stages: occult invasive cancer with true metastasis (T1N1) or pure DCIS with iatrogenic dissemination (TisN0). In this retrospective cohort study, we aimed to elucidate the prognostic impact and possible pathogenesis of nodal metastasis in DCIS to improve clinical management., Methods: Subjects were comprised of 427 patients with routine postoperative diagnosis of DCIS who underwent sentinel node (SN) biopsy using molecular whole-lymph-node analysis. Clinicopathological characteristics and prognosis were compared between SN-positive and -negative patients. Primary tumour tissues of SN-positive patients were exhaustively step-sectioned to detect occult invasions, and predictive factors for occult invasion were investigated. Median follow-up time was 73.6 months., Results: Of the 427 patients, 19 (4.4%) were SN-positive and 408 (95.6%) were SN-negative. More SN-positive patients received adjuvant systemic therapy than SN-negative patients (84.2% vs. 5.4%). Seven-year distant disease-free survivals were favourable for both cohorts (SN-positive, 100%; SN-negative, 99.7%). By examining 1421 slides, occult invasion was identified in 9 (47.4%) of the 19 SN-positive patients. Tumour burdens in SN and incidence of non-SN metastasis were similar between patients with and without occult invasion, and no predictive factor for occult invasion was found., Conclusions: Node-positive DCIS has favourable prognosis with adjuvant systemic therapy. Half of the cases may be occult invasive cancer with true metastasis. In practical settings, clinicians may have to treat these tumours as node-positive small invasive cancers because it is difficult to predict the pathogenesis without exhaustive primary tumour sectioning.

The effect of triamcinolone acetonide (TA) on the peripheral retinochoroidal thickness was determined after pars plana vitrectomy (PPV) with scatter photocoagulation in eyes with proliferative diabetic retinopathy. The peripheral retinochoroidal thickness was measured at 5 mm from the limbus in the four quadrants using anterior segment optical coherence tomography before, and 3 days, and 1 and 2 weeks after the surgery. The total peripheral thickness was significantly thicker than the baseline thickness after PPV alone (P < 0.001; 18 eyes), PPV combined with intravitreal TA injection (IVTA; P = 0.011; 19 eyes), and PPV combined with sub-tenon TA injection (STTA; P = 0001; 23 eyes). The total peripheral thickness in the PPV group at 3 days after surgery was significantly thicker than that of the PPV + IVTA (P = 0.015) and of the PPV + STTA groups (P = 0.016). Multiple linear regression analyses showed that the injection of TA by the two routes and the number of photocoagulation burns were significantly correlated with the total peripheral thicknesses at 3 days after the surgery. The results indicate that the PPV with large number of intraoperative scatter photocoagulation burns caused an increase in the total peripheral thickness and an administration of either IVTA and STTA can reduced the degree of thickening.

The time course of the changes in the optic nerve head (ONH) blood flow in response to changes in the ocular perfusion pressure (OPP) induced by an artificial elevation of the intraocular pressure (IOP) has not been determined. We measured the blood flow, represented by the mean blur rate (MBR), on the ONH determined by laser speckle flowgraphy. The MBR was determined before, during, and after the IOP was elevated by 20 or 30 mmHg by pressure applied on the eye by an ophthalmodynamometer in a total of 27 healthy eyes. For an IOP elevation of 20 mmHg, the percentage reduction in the MBR-vessel was -24.7%, and in the MBR-tissue was -16.0% (P < 0.001). For an IOP elevation of 30 mmHg, the percentage reduction of the MBR-vessel was -35.3% and the MBR-tissue was -24.7% (P < 0.001). During the 30 mmHg IOP elevation for 10 minutes, both the MBR-vessel and MBR-tissue began returning to the baseline level from 1 minute after the beginning of the IOP elevation (P < 0.01, P < 0.05, respectively) and continued returning during the 10 minutes IOP elevation (P < 0.001, P < 0.01, respectively). We conclude that the ONH can autoregulate its blood flow in response to experimental changes in OPP induced by IOP elevations.

Rationale: Earlier studies have shown that laser photocoagulation treatments are associated with good long-term visual acuity in most patients with severe nonproliferative diabetic retinopathy (S-NPDR). Histopathologic studies of autopsied eyes have demonstrated defects in the choriocapillaris beneath the retinal laser lesions secondary to photocoagulation for S-NPDR. These lesions have been observed to expand centrifugally over time especially in the posterior pole, and the atrophy of the retinal pigment epithelium (RPE) can be significantly enlarged. There are, however, limited studies detailing the in vivo changes that occur in the RPE and choriocapillaris following laser photocoagulation., Patient Concerns: A 46-year-old woman presented with visual disturbances in both eyes., Diagnoses: Fundus examinations showed many retinal hemorrhages and soft exudates in the four quadrants due to S-NPDR., Interventions: Laser photocoagulations with a 532-nm wavelength argon laser with power of 170 to 230 mW and spot size of 200 μm were performed to treat the S-NPDR. The changes in the choriocapillaris and retinal vasculature were followed by optical coherence tomography (OCT) angiography., Outcomes: The choriocapillaris beneath the laser spots was disrupted from 1 hour following the photocoagulation but it was restored at week 2. The choriocapillaris appeared almost normal at some laser spots, but they were still some spots that were altered at 1 year. The outer retina and RPE were disrupted beneath the laser spots at 1 year. On the contrary, there were no visible retinal vascular changes in the superficial and deep plexuses of retinal vasculature determined by OCT angiography with manual and automated segmentation., Lessons: The choriocapillaris in human eyes can recover after laser photocoagulation although the outer retina and RPE remain disrupted and do not recover.

To study the properties of tracheal cilia beating under various conditions, we developed a method to monitor the movement of the ciliary tip. One end of a demembranated cilium was immobilized on the glass surface, while the other end was capped with a polystyrene bead and tracked in three dimensions. The cilium, when activated by ATP, stably repeated asymmetric beating as in vivo. The tip of a cilium in effective and recovery strokes moved in discrete trajectories that differed in height. The trajectory remained asymmetric in highly viscous solutions. Model calculation showed that cilia maintained a constant net flux during one beat cycle irrespective of the medium viscosity. When the bead attached to the end was trapped with optical tweezers, it came to display linear oscillation only in the longitudinal direction. Such a beating-mode transition may be an inherent nature of movement-restricted cilia.

The traditional classification of hypertensive retinopathy was based on the Keith-Wagener-Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

We prospectively investigated the changes in choroidal blood flow and morphology after panretinal photocoagulation (PRP) in 39 eyes with severe nonproliferative diabetic retinopathy (S-NPDR). Seventeen eyes underwent PRP by conventional laser and 22 eyes underwent pattern scan laser (PASCAL). The choroidal blood flow was assessed by laser speckle flowgraphy, and the subfoveal choroidal thickness (SFCT) was measured with optical coherence tomography before and 1, 4, 8, and 12 weeks after the two types of PRP treatments. The choroidal mean blur rate (MBR) at the macular region was significantly reduced to 86.4% of the baseline level in the conventional laser group and 85.7% in the PASCAL group at Week 12 (P = 0.001, P < 0.001, respectively). The SFCT was significantly increased at 1 week following PRP but it was significantly reduced at Week 8 (P = 0.001, P < 0.001, respectively) in both groups. The differences in the ratio of the MBR and the SFCT was not significant between the conventional laser and PASCAL groups at any time after PRP. The results suggest that appropriate PRP treatments even by the PASCAL method will reduce the choroidal blood flow and the choroidal morphological components.

A ready-made dry medium method for Staphylococcus aureus count, the Medi·Ca SA method incubated at 35 or 37°C, was compared with the Baird-Parker method (AOAC Official MethodSM 975.55) for 11 food matrices: raw beef, raw ground beef, raw lamb, cooked ham, raw salmon, frozen prawn, fresh chilled pasta, pasteurized milk, natural cheese, cream puff, and potato salad. The mean difference between the two methods at each contamination level for each matrix was <0.5 log10, and the 95% confidence intervals on the mean differences fell within the range of -0.50 to 0.50. Standard deviation of repeatability and RSDr values of the Medi·Ca SA method were generally the same level as those of the Baird-Parker method, and r2 ranged from 0.98 to 1.00. Product consistency and stability studies showed little variability between productions lots and a shelf-life of 16 months. Incubation time within the range of 22-26 h and variations to the sample volume did not adversely affect the results. These results showed that the Medi·Ca SA method is a reasonable alternative to the reference method for selected food matrices and makes it possible to simultaneously detect and enumerate S. aureus in only 24 h.

Objectives: Hypothermia (HT) improves the outcome of neonatal hypoxic-ischemic encephalopathy. Here, we investigated changes during HT in cortical electrical activity using amplitude-integrated electroencephalography (aEEG) and in cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation using near-infrared time-resolved spectroscopy (TRS) and compared the results with those obtained during normothermia (NT) after a hypoxic-ischemic (HI) insult in a piglet model of asphyxia. We previously reported that a greater increase in CBV can indicate greater pressure-passive cerebral perfusion due to more severe brain injury and correlates with prolonged neural suppression during NT. We hypothesized that when energy metabolism is suppressed during HT, the cerebral hemodynamics of brains with severe injury would be suppressed to a greater extent, resulting in a greater decrease in CBV during HT that would correlate with prolonged neural suppression after insult., Methods: Twenty-six piglets were divided into four groups: control with NT (C-NT, n = 3), control with HT (C-HT, n = 3), HI insult with NT (HI-NT, n = 10), and HI insult with HT (HI-HT, n = 10). TRS and aEEG were performed in all groups until 24 h after the insult. Piglets in the HI-HT group were maintained in a hypothermic state for 24 h after the insult., Results: There was a positive linear correlation between changes in CBV at 1, 3, 6, and 12 h after the insult and low-amplitude aEEG (<5 µV) duration after insult in the HI-NT group, but a negative linear correlation between these two parameters at 6 and 12 h after the insult in the HI-HT group. The aEEG background score and low-amplitude EEG duration after the insult did not differ between these two groups., Discussion and Conclusion: A longer low-amplitude EEG duration after insult was associated with a greater CBV decrease during HT in the HI-HT group, suggesting that brains with more severe neural suppression could be more prone to HT-induced suppression of cerebral metabolism and circulation., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: We hypothesized that an increase in BMI category during neoadjuvant chemotherapy (NAC) would be associated with pathological complete response (pCR) rate and worse survival outcomes in primary breast cancer patients., Methods: We reviewed the records of 4029 patients with stage I-III breast cancer who had undergone NAC and definitive surgery at our institution between May 1, 1990 and April 30, 2013. BMI values at baseline and after NAC were recorded, and the corresponding BMI category was assessed with the WHO classification. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and multivariate Cox regression models were used to estimate the effect of covariates of interest on OS and RFS., Results: The median follow-up period was 3.95 years. A change in BMI category from normal to obese during NAC was independently associated with shorter OS duration than was maintaining a normal weight [hazard ratio (HR) 1.637; 95%CI 1.066-2.514; p = 0.0242]. Kaplan-Meier curves among breast cancer subtypes showed differences, and a decrease in BMI led to better RFS and OS rates in obese patients with HR+/HER2- disease; those who maintained BMI also showed better prognosis for triple-negative breast cancer (TNBC). We saw no association between BMI change and pCR rate., Conclusion: Our data suggest that inability to maintain normal weight during NAC is a predictive marker of poor survival but not pCR. It may be important for patients to maintain a normal weight during NAC.

Purpose: To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs)., Methods: The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 μm thinner than the average thickness at 200 μm temporal and nasal to the central fovea. The characteristics of the two groups were compared., Results: Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units)., Conclusion: These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

Background: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling., Methods and results: Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01)., Conclusions: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Background: Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer., Methods: The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%, TILs2+ 30-50%, and TILs3+ > 50%., Results: Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04-23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30-25.44, P < 0.0001) were independent predictors for pCR., Conclusion: TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.

Purpose: To determine whether the macula is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with an idiopathic macular hole., Design: A retrospective, observational case series., Methods: Optical coherence tomography angiography was used to obtain 3 mm × 3 mm en face images before and 2, 4, and 8 weeks after the vitrectomy with ILM peeling for 20 eyes of 20 patients with an idiopathic macular hole. The displacements of easily identifiable retinal vessel bifurcations were measured relative to the fovea and the optic disc., Results: The distance between the optic disc and vessel bifurcations was significantly shorter in all 4 quadrants throughout the postoperative period (P < .001). This distance was significantly greater in the temporal quadrant (P < .001). The distance of the bifurcations was significantly correlated with the preoperative distance from the optic disc (r = -0.579, P < .001). A significantly greater downward displacement was observed in the superior quadrant (P < .001). The change in the angle of bifurcations was significantly correlated with the preoperative angle to the optic disc (r = -0.632, P < .001). The change in the distance in the inner region was significantly greater than that in the outer region in all quadrants. A significant reduction was observed in the mean foveal avascular zone area during the follow-up period., Conclusions: The retina in the macular region was displaced nasally, probably owing to movement of the retina toward the optic disc because of a contraction after the ILM removal. There is also a possibility of a rotation downward by buoyancy from gas tamponade, and centripetal contraction during the process of hole closure., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD., Methods and results: A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EAT RCA ), the left anterior descending artery (EAT LAD ), and the left circumflex artery (EAT LCX ). Although EAT RCA and EAT LCX were similar between the 2 groups, EAT LAD was larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P<0.001). EAT LAD , after correcting for confounding factors, was strongly associated with CAD (r=0.276, P<0.001) and Gensini score (r=0.239, P<0.001). On multiple regression analysis, Framingham risk score combined with EAT LAD was a strong predictor of CAD (adjusted R 2 =0.121; P<0.001)., Conclusions: The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors.

Purpose: There are no randomized studies on the indication for postmastectomy radiation therapy (PMRT) in patients who receive neoadjuvant chemotherapy (NAC) followed by a mastectomy. The aim of this study was to determine clinical outcomes and identify reliable prognostic factors in patients with locally advanced breast cancer treated with NAC followed by a mastectomy and PMRT., Methods and Materials: We retrospectively evaluated the relationship between clinicopathological factors and outcomes in 351 patients with stage II or III breast cancer who underwent NAC followed by radical mastectomy and PMRT between March 2005 and December 2013., Results: The median follow-up duration was 81 months (Range, 12-156 months). For all patients, the 5-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 91.3 %, 69.8 %, and 83.4 %, respectively. On multivariate analysis, estrogen-receptor positivity, and complete response of cancer in axillary nodes (ypN0) were significant prognostic factors for better LRFS, while lympho-vascular invasion and clinical stage IIIC were independent prognostic factors for worse LRFS. The number of axillary node metastasesafter surgery was an independent prognostic factor of DMFS and OS. Patients with hormone receptor- and human epidermal growth factor receptor 2 positivity had significantly better 5-year LRFS rates., Conclusions: We identified several prognostic factors in our study. In particular, the number of axillary node metastases is significantly related to OS.

Regular health checkups for mothers of patients with Duchenne muscular dystrophy have been performed at National Hospital Organization Tokushima Hospital since 1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers were identified. Skeletal and cardiac muscle functions of these subjects were examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015. Cardiomyopathy was observed in 15 subjects (60.0%), including dilated cardiomyopathy-like damage that was more common in the left ventricular (LV) posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6 subjects, suggesting fibrotic cardiac muscle. In speckle tracking echocardiography performed seven years later, global longitudinal strain was decreased in these subjects, indicating LV myocardial contractile abnormality. These results suggest that female dystrophinopathy carriers should receive regular checkups for detection and treatment of cardiomyopathy, even if they have no cardiac symptoms., (Copyright © 2017. Published by Elsevier B.V.)

Biocompatibility of cinnamoyl-modified carbohydrate materials is not well-known, while they are attracting attention as a photoreactive material. In order to investigate biocompatible properties of cinnamoyl-modified carbohydrate, hydroxypropyl cellulose (HPC) was reacted with cinnamoyl chloride to yield cinnamoyl-modified HPC (HPC-C) for a cell proliferation test. HPC-Cs with three different degrees of substitution (DS) were prepared by changing a feed ratio of cinnamoyl chloride to HPC. The DS of the products ranged from 1.3 to 3.0 per one hydroxylpropyl anhydroglucose unit. Thermal analysis using DSC and TGA showed that the HPC-C with higher DS has a glass transition temperature and higher thermal stability. Ultraviolet (UV) light was irradiated on the HPC-C thin films, and changes in the UV-vis spectrum of the films were examined. In the course of UV irradiation, the absorbance at 280 nm was reduced. Fibroblast cells were cultured on the photocrosslinked HPC-C films, and cell growth was examined. The cell proliferation test revealed that the photocrosslinked HPC-C films have good compatibility with fibroblast cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Study Design: Animal experimental study with intervention., Objective: The purpose of this study was to elucidate whether local administration of an α-antagonist around the dorsal root ganglion (DRG) suppressed sympathetic nerve sprouting, from the acute to the chronic pain development phase, in a lumbar radiculopathy model using immunohistochemical methods., Summary of Background Data: The abnormal sympathetic-somatosensory interaction may underlie some forms of neuropathic pain. There were several reports suggesting α-antagonists are effective to treat neuropathic pain. However, its pathophysiological mechanisms remain obscure., Methods: We used 70 male Sprague-Dawley rats. After root constriction (RC), rats received a series of three local injections of the nonselective α-antagonist phentolamine around the DRG for 3 days. There were three groups of rats: those that were injected from the day of surgery and those injected from day 4 and third group injected from day 11. The control rats were subjected to RC but equal-volume normal saline injections, and the naïve rats were not subjected to any surgical procedures. At the 14th postoperative day, the left L5 DRG was removed, embedded in paraffin, and sectioned. Sections were then immunostained with antibodies to tyrosine hydroxylase (TH). To quantify the extent of the presence of sympathetic nerve fibers, we counted TH-immunoreactive fibers in the DRG using a light microscope equipped with a micrometer graticule. We counted the squares of the graticule, which contained TH-immunoreactive fibers for each of five randomly selected sections of the DRG., Results: In the naïve group, TH-immunoreactive fibers were scarce in the DRG. α-antagonist injections from postoperative day 0 and 4 suppressed sympathetic nerve sprouting compared with the control group. α-antagonist injections from postoperative day 11 had no suppressant effect compared with the control group., Conclusion: The α-antagonist administered around the DRG could suppress neural plastic changes in the early phase after nerve injury., Level of Evidence: N/A.

Background We occasionally encounter increases in direct bilirubin value on reanalysis of the surplus serum collected in the past from a neonate with indirect hyperbilirubinemia. But the details of this phenomenon are unclear. We evaluated the change of direct bilirubin and the relation of bilirubin photoisomer of the serum exposed to room light. Methods Surplus serum samples from neonates with indirect hyperbilirubinemia were exposed to room light for 24 h. The bilirubin fraction assay of samples was performed by the bilirubin oxidase method (Nescauto and Aqua-auto Kainos reagent) and high-performance liquid chromatography. Results Direct bilirubin increased significantly from 0.61 to 2.36 mg/dL. The respective ratios of bilirubin photoisomers before and after exposure were as follows: cyclobilirubin (0.007 to 0.29) and (EZ)-bilirubin (0.018 to 0.041) increased significantly, (ZZ)-bilirubin decreased 0.84 to 0.55 significantly. The difference of the cyclobilirubin concentration was most closely associated with those of the direct bilirubin concentration. Conclusion Direct bilirubin value was increased after exposure to the room light, and increase in direct bilirubin was significantly correlated by cyclobilirubin increase in the serum samples from neonates with indirect hyperbilirubinemia.

The present study aimed to understand the biofilm formation mechanism of Propionibacterium acnes by analyzing the components and structure of the biofilms. P. acnes strains were isolated from the surface of explanted cardiac pacemaker devices that exhibited no clinical signs of infection. Culture tests using a simple stamp culture method (pressing pacemakers against the surface of agar plates) revealed frequent P. acnes colonization on the surface of cardiac pacemaker devices. P . acnes was isolated from 7/31 devices, and the isolates were categorized by multilocus sequence typing into five different sequence types (STs): ST4 (JK18.2), ST53 (JK17.1), ST69 (JK12.2 and JK13.1), ST124 (JK5.3), ST125 (JK6.2), and unknown ST (JK19.3). An in vitro biofilm formation assay using microtiter plates demonstrated that 5/7 isolates formed biofilms. Inhibitory effects of DNase I and proteinase K on biofilm formation varied among isolates. In contrast, dispersin B showed no inhibitory activity against all isolates. Three-dimensional live/dead imaging of P. acnes biofilms with different biochemical properties using confocal laser microscopy demonstrated different distributions and proportions of living and dead cells. Additionally, it was suggested that extracellular DNA (eDNA) plays a role in the formation of biofilms containing living cells. Ultrastructural analysis of P. acnes biofilms using a transmission electron microscope and atmospheric scanning electron microscope revealed leakage of cytoplasmic components along with cell lysis and fibrous structures of eDNA connecting cells. In conclusion, the biochemical properties and structures of the biofilms differed among P. acnes isolates. These findings may provide clues for establishing countermeasures against biofilm-associated infection by P. acnes .

Cellular glycogen levels reflect the activity of RpoS, an important stress-inducible bacterial sigma factor known to regulate several stress-resistance related genes, such as katE, encoding hydroperoxidase II (HPII), and the glg genes, encoding glycogen synthesis enzymes, in Escherichia coli. In this study, a straightforward assay for measuring glycogen levels and RpoS activity was developed combining the ease and simplicity of qualitative approaches. The assay reagent was a 2% iodine solution (2% iodine/1M NaOH), and the basic principle of this assay is the iodine-glycogen reaction, which produces a reddish brown color that can be measured using a spectrophotometer. A calibration plot using a known amount of glycogen yielded the best linear fit over a range of 10-300μg/assay (R 2 =0.994). The applicability of the assay for measuring the glycogen level of various samples was assessed using a wild type (WT) E. coli K-12 strain, glycogen- and RpoS-deficient isogenic mutants, and clinical bacterial isolates with or without RpoS activity; the assay generated reproducible results. Additionally, the assay was successfully applied for measuring glycogen levels in human cells. In conclusion, we developed a straightforward and cost-effective assay for measuring glycogen levels, which can be applied for measuring RpoS activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

Background: Although there are a large number of epidemiological studies investigating the etiological role of lifestyle factors in breast cancer, there are few studies on the association between lifestyle factors and breast cancer prognosis. To investigate the influence of lifestyle factors such as diet and physical activity, use of complementary and alternative medicine, and psychosocial factors on prognosis, we designed a large-scale cohort study of female breast cancer patients in Japan., Methods: The planned sample size is 7200. The cohort is being conducted in collaboration with several clinical trials, a cancer registry, and daily practice. Information on clinical factors, treatment, and follow-up will be obtained from the clinical trials and participating hospitals. A self-administered questionnaire is given to subjects before, immediately after, or 1 to 5 years after surgery. Blood and tissue samples are also collected. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and health-related quality of life. The follow-up period will be at least 5 years after the last participant is enrolled. Recruitment began in November 2007., Current Status: As of April 2017, there are 5852 patients enrolled in the study along with 1430 biological samples and the study is still ongoing. The number of subjects enrolled in the study is already the largest in the world., Conclusions: The ROK study will provide much important evidence for breast cancer survivorship.

A 62-year-old woman received chemotherapy for breast cancer with bone metastasis and malignant pleural and pericardial effusion. She was examined by imaging for progressive cognitive impairment and headache. Enhanced MRI findings showed multiple solid tumors on brain surface, and brain perfusion scintigraphy showed blood flow decrease in both parietal lobes. She was diagnosed with secondary dementia due to leptomeningeal metastases of breast cancer, and whole brain external irradiation was performed(30 Gy/15 Fr). After treatment, multiple tumors were decreased in size and her cognitive impair- ment was improved.

Neoadjuvant chemotherapy (NAC) with anthracyclines followed by taxane chemotherapy has become the standard treatment for patients with locally advanced, operable breast cancer. Recently, the efficacy of nanoparticle albumin-bound paclitaxel (nab-PTX) for metastatic breast cancer was reported. However, there are still few studies of a neoadjuvant regimen including nab-PTX. Thus, the present phase II study evaluated the efficacy and safety of 5-fluorouracil, epirubicin and cyclophosphamide (FEC regimen) followed by nab-PTX as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Women with operable HER2-negative breast cancer (clinical stage T1a-4N1-3) received 4 cycles of FEC (5-fluorouracil 500 mg/m 2 , epirubicin 100 mg/m 2 and cyclophosphamide 500 mg/m 2 every 21 days), followed by 4 cycles of nab-PTX at 260 mg/m 2 every 21 days. The patients then underwent mastectomy or breast-conserving surgery (BCS). The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included clinical response rate, pathological response rate, BCS rate and safety. A total of 16 patients were evaluated and 3 patients (18%) achieved pCR (1 patient with estrogen receptor-positive cancer and 2 with estrogen receptor-negative cancer). The pCR rate was 12 and 25% in patients with estrogen receptor-positive and -negative cancers, respectively. The clinical response rate was 100% (clinical complete and partial response in 6 and 10 patients, respectively). The BCS rate was 31.25%. Three patients experienced grade 3 neutropenia during FEC therapy, and no grade 3/4 events occurred during nab-PTX therapy. Thus, neoadjuvant therapy with FEC followed by nab-PTX for operable HER2-negative breast cancer was found to be a safe and effective option.

Background: The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can detect metastasis in a whole lymph node based on cytokeratin 19 mRNA copy number. This cohort study aimed to establish an OSNA-based nodal staging (pN(mol)) classification for breast cancer., Methods: The cohort consisted of 1039 breast cancer patients who underwent sentinel node (SN) biopsy using the OSNA assay. Cutoff value of the SN tumour burden stratifying distant disease-free survival (DDFS) was determined, and predictive factors for DDFS and breast cancer-specific survival (BCSS) were investigated. pN(mol) classification of the SN status was defined as: pN0(mol)(sn), SN negative; pN1mi(mol)(sn), SN positive and tumour burden

To investigate the diurnal variation of the pulse waveform parameters determined by laser speckle flowgraphy (LSFG) on the optic nerve head (ONH) in healthy subjects.This prospective cross sectional study was conducted at Nagoya University Hospital. We studied 13 healthy volunteers whose mean age was 33.5 ± 7.6 years. Eight pulse waveform parameters on the ONH were determined by LSFG (LSFG-NAVI) every 3 hours from 6 AM to 12 PM. The intraocular pressure (IOP), systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) in the brachial artery were also recorded. We evaluated the diurnal variations of the parameters and compared the pulse waveform parameters to the other parameters using a linear mixed model.Of the 8 parameters, skew (P < .001), blow out score (BOS, P < .001), blow out time (BOT, P = .028), rising rate (P < .001), falling rate (P < .001), resistivity index (P < .001) had a significant diurnal fluctuation. In addition, IOP (P < .001), SBP (P = .005), DBP (P = .001), and HR (P < .001) had significant diurnal fluctuations. The BOS and resistivity index were significantly correlated with the HR (P = .009, P = .012, respectively), and the BOT were significantly correlated with the DBP and mean ocular perfusion pressure (P = .042, P = .041, respectively).We found that there was significant diurnal variation in 6 waveform parameters on the ONH in LSFG. We believe that our results highlighting diurnal variations in these waveform parameters need to be considered when interpreting pulse waveform parameter data and in understanding the precise underlying mechanism of ocular diseases such as diabetic retinopathy, retinal vein occlusion, and glaucoma.

Background: Cellular dynamics depend on cytoskeletal filaments and motor proteins. Collective movements of filaments driven by motor proteins are observed in the presence of dense filaments in in vitro systems. As multiple macromolecules exist within cells and the physiological ionic conditions affect their interactions, crowding might contribute to ordered cytoskeletal architecture because of collective behavior., Methods: Using an in vitro reconstituted system, we observed the emergence of stripe patterns resulting from collective actin filament streaming driven by myosin motors in the presence of the crowding agent, methylcellulose (MC)., Results: Although at high KCl concentrations (150mM), actin filaments tended to dissociate from a myosin-coated surface, 1% MC prevented this dissociation and enabled filament movement on myosin molecules. At concentrations of actin filaments above 0.2mg/mL, the moving filaments accumulated and progressively formed long, dense bands. The bands were spaced at about 10-μm intervals. Increasing the KCl concentration up to 300mM resulted in narrowing of the spacing between the aligned bands. On the other hand, low KCl concentrations (≤25mM) induced broad streams, where actin filaments exhibited bidirectional movement., Conclusions: These results suggest that crowded environments can promote spatial patterning of the actin cytoskeleton, depending on the intensity of the myosin driving force and filament velocity, both modulated by the ionic strength., General Significance: The mutual contribution of packing and driving forces provides insight into cytoskeleton organization in living cells, in which various macromolecules mingle., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In addition to BRCA1 and BRCA2, RAD51C, PALB2 and BRIP1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not yet been evaluated. To this end, we analyzed the exon sequence and genomic rearrangement of RAD51C, PALB2 and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. We detected a large deletion from exons 6 to 9 in RAD51C, 4 novel BRIP1 missense variants containing 3 novel non-synonymous variants, c.89A>C, c.736A>G and c.2131A>G, and a splice donor site variant c.918+2T>C. No deleterious variant of PALB2 was detected. The results of pedigree analysis showed that the proband with a large deletion on RAD51C had a family history of both breast and ovarian cancer, and the families of probands with novel BRIP1 missense variants included a male patient with breast cancer or many patients with breast cancer within the second-degree relatives. We showed that the mutation frequency of RAD51C in Japanese familial breast cancer cases was similar to that in Western countries and that the prevalence of deleterious mutation of PALB2 was possibly lower. Furthermore, our results suggested that BRIP1 mutation frequency in Japan might differ from that in Western countries., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Sex-related differences are present in the systemic and ocular blood flow. However, the cause of the sex-related differences has not been determined. We investigated the ocular blood flow, represented by the mean blur rate (MBR), on the optic nerve head (ONH) determined by laser speckle flowgraphy in 138 males (63.9 ± 8.9 years) and 194 females (63.5 ± 9.4 years). The correlations between the MBR on the ONH and the clinical data were determined. The overall ONH-MBR was significantly higher in females than males (P < 0.001). In addition, the levels of the hemoglobin and hematocrit were significantly lower in females than in males (P < 0.001). The ONH-MBR was negatively and significantly correlated with the levels of the hemoglobin and hematocrit (both, P < 0.001). Multiple regression analyses showed that the sex (β = 0.248, P < 0.001) was an independent factor correlated with the ONH-MBR when the clinical examination data were not included in the analyses. However, when the clinical examination data were included, the hemoglobin level (β = -0.295, P < 0.001) was an independent factor that contributed to the ONH-MBR but the sex was not. We conclude that the sex-related differences in the hemoglobin level and the negative correlation between hemoglobin and the ONH-MBR are the causes of the sex-related differences in the ONH-MBR.

Purpose: The purpose of this study was to determine the effects of an elevation in IOP on the choroidal blood flow and morphology., Methods: We studied 27 healthy subjects. The mean blur rate (MBR) determined by laser speckle flowgraphy was used to measure the choroidal blood flow. The subfoveal choroidal thickness (SFCT) was measured in the optical coherence tomographic images of the macular region. The luminal and stromal areas of the choroid were determined by the binarization method before, during, and after the IOP was elevated 20 and 30 mm Hg with pressure using an ophthalmodynamometer., Results: The ocular perfusion pressure (OPP) was significantly reduced by the elevation of the IOP by 20 (-52.0%, P < 0.001) and 30 mm Hg (-77.9%, P < 0.001). The percentage reduction in the macular choroidal MBR was -32.5% at an IOP elevation of 20 mm Hg (P < 0.001) and -46.6% at an IOP elevation of 30 mm Hg (P < 0.001). The SFCT was reduced by -3.8% (P = 0.014) and -7.7%, (P < 0.001) during an elevation of IOP of 20 and 30 mm Hg, respectively. The luminal area of the choroid was reduced during an elevation of the IOP of 20 (P = 0.001) and 30 mm Hg (P < 0.001). However, the stromal area did not change significantly. There was no significant correlation between the reduction ratio of OPP and other factors during the elevation of 20 mm Hg, but the correlation between the reduction ratio of OPP and the choroidal MBR during the elevation of 30 mm Hg was significant. The choroidal MBR had recovered significantly at 7 (P = 0.037) and 10 minutes (P = 0.022) compared with that immediately after the IOP elevation of 30 mm Hg., Conclusions: The choroid can autoregulate its blood flow in response to experimental changes in the OPP induced by IOP elevations.

Technical selection for surgical repair of complete atrioventricular septal defect (CAVSD) still remains controversial. This meta-analysis aimed to compare the modified single-patch (MP) technique with the two-patch (TP) technique for patients with CAVSD. Relevant studies comparing the MP technique with the TP technique were identified through a literature search using MEDLINE, EMBASE, Google Scholar, Cochrane Library, and the China National Knowledge Infrastructure databases. The variables were ventricular septal defect (VSD) size, cardiopulmonary bypass (CBP) time, aortic cross-clamp (ACC) time, intensive care unit stay, hospital stay, and other outcomes involving mortality, left ventricular outflow tract obstruction, atrioventricular valve regurgitation, residual septal shunt, atrioventricular block, and reoperation. A random-effect/fixed-effect model was used to summarize the estimates of mean difference/odds ratio with 95% confidence interval. Subgroup analysis stratified by region was performed. Fifteen publications involving 1034 patients were included. This meta-analysis demonstrated that (1) VSD size in the MP group was significantly smaller; (2) CBP time, ACC time, and hospital stay in the MP group experienced improvement; (3) Other postoperative outcomes showed no significant differences between two groups; and (4) The trends in China and other countries were close. The MP and TP techniques had comparable outcomes; however, the MP technique was performed with significantly shorter CBP and ACC times in patients with smaller VSDs. Given this limitation of data, the results of comparison of the two techniques in patients with larger VSDs remain unknown. Further studies are needed.

Purpose: To determine the perioperative factors that are significantly correlated with the final visual acuity following reattachment of a macula-off rhegmatogenous retinal detachment (RRD) by vitrectomy., Methods: Twenty-nine eyes of 29 patients with a successfully reattached RRD by vitrectomy were retrospectively analyzed. Spectral-domain optical coherence tomographic images of the macular regions were used to measure the thicknesses of the retinal layers and the integrity of the microstructures of the photoreceptors at 2 weeks, 1, 2, 3, 6, 9, and 12 months following the vitrectomy. The best-corrected visual acuities (BCVA) were evaluated at the same times., Results: The improvement of the BCVA from the preoperative BCVA to that at postoperative Week 2 (-0.67 ± 0.69 logMAR units) was the largest change between adjacent observation periods for the entire study duration. It was significantly greater than the improvement between Week 2 and Month 12 (-0.32 ± 0.22 logMAR units; P<0.001). The thickness of the ellipsoid zone (EZ)-retinal pigment epithelium (RPE) increased significantly with time (P<0.001). The final BCVA was significantly correlated with the BCVA at Week 2 (r = 0.61, P<0.001), the EZ-RPE thickness at Week 2 (r = -0.40, P = 0.035), the integrity of the external limiting membrane (ELM) (r = -0.61, P = 0.003), and an intact EZ (r = -0.66, P = 0.001) at Week 2. Multiple stepwise regression analyses of the final BCVA showed that the BCVA at Week 2 (P = 0.017) and the integrity of the EZ at Week 2 (P = 0.006) were independent predictors of the final BCVA., Conclusions: The significantly better BCVA and presence of an intact EZ at 2 weeks following vitrectomy and their significant correlations with the BCVA at Month 12 indicate that these perioperative values can be used to predict the BCVA at Month 12 after a reattachment of macula-off RRD following vitrectomy.

Background: Paclitaxel plays a central role in chemotherapy for breast cancer. Peripheral neuropathy, a well-known toxicity with paclitaxel, may be of interest in predicting the efficacy of paclitaxel therapy for patients with metastatic breast cancer. We performed a retrospective analysis assessing whether the early occurrence of peripheral neuropathy (EPN) was a predictive marker for better efficacy in patients with metastatic breast cancer receiving chemotherapy containing paclitaxel., Patients and Methods: Between January 2000 and August 2008, we examined the records of 168 patients with metastatic breast cancer treated with paclitaxel in our hospital. EPN was defined as a symptom of Grade 2 or more during first three months of treatment. The overall response rate (ORR) and time to treatment failure (TTF) in each group were analyzed retrospectively., Results: Of 168 patients with metastatic breast cancer who were treated with paclitaxel, EPN was documented in 101 patients (60.1%). The clinical benefit rate (CR, PR, and SD ≥ 6 months) was 72.3% in the EPN group and 49.3% in the non-EPN group (p = 0.002). The TTF of the EPN group (median 11.2 months, 95% CI: 9.5-12.9) was significantly longer than that of the non-EPN group (5.7 months, 95% CI: 4.6-6.8) (p<0.001). Multivariate analysis demonstrated that EPN (p<0.001), dose intensity of less than 70% (p<0.001), and the history of microtubule agents (p = 0.001) were the significant favorable prognostic factors for TTF., Conclusion: The early onset of peripheral neuropathy might be a robust predictor for TTF in patients with metastatic breast cancer treated with paclitaxel.

Although scleral buckling is a well-established surgical treatment for rhegmatogenous retinal detachment (RRD), the procedure can reportedly cause problems in the ocular circulation. Segmental scleral bucking without a concomitant encircling procedure was performed on 46 eyes with successfully reattached macula-on RRD. Choroidal blood flow was assessed using laser speckle flowgraphy. Spectral-domain optical coherence tomography was used to image macular regions, to measure the subfoveal choroidal thickness (SFCT), and to calculate the luminal and the stromal areas by the binarization method preoperatively and 1, 4, 8 and 12 weeks postoperatively. Choroidal mean blur rate at the macula did not significantly change, while that at the buckle and unbuckle side significantly reduced at 8 weeks postoperatively in the operated eye (P = 0.007 and P = 0.017, respectively). The SFCT and the luminal area increased temporarily 1 week following surgery in the operated eye (P < 0.001). The trend of SFCT with time coincided with that of the luminal area (P < 0.001). Venous drainage obstruction induced by compression force of scleral buckling leads to SFCT thickening in the acute postoperative phase. The macular choroidal blood flow might be less susceptible because the blood flow at the macula, in contrast to the other areas, does not change following segmental scleral buckling.

The present case is the first report in Japan in which a breast cancer was discovered as a result of prospective magnetic resonance imaging (MRI) screening study for BRCA1/2 mutation carriers who were free of breast or ovarian cancer. This case is significant and it verifies the importance of MRI screening in breast or ovarian cancer-free BRCA1/2 mutation carriers who do not exhibit positive mammographic or ultrasonographic findings.

Background: The definition of complete resection of ductal carcinoma in situ (DCIS) is difficult to standardize because of the high variety of surgical breast conserving procedures, specimen handling, and pathological examinations. Using strictly controlled criteria in a single institute, the present study aimed to determine the ipsilateral breast cancer rate when radiotherapy is omitted following complete resection of DCIS., Methods: We retrospectively examined 363 consecutive DCIS patients who underwent breast-conserving surgery, and of these, 125 (34.4%) had complete resection according to the criteria. We finally included 103 patients who omitted radiotherapy. Ipsilateral and contralateral breast cancer events were assessed., Results: The median follow-up period was 118 months. The incidences of ipsilateral and contralateral breast cancer and ipsilateral invasive breast cancer at 10 years were 10.8%, 9.1%, and 3.6%, respectively. No patient died of breast cancer., Conclusion: If complete resection of DCIS can be ensured, the annual incidence of ipsilateral breast cancer, even without irradiation, can be limited to approximately 1%, which equals the incidence of contralateral breast cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The goal of this study is to establish a method for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients after surgical operation. The gene expression profiles of cancer tissues from the patients, who underwent complete surgical resection of breast cancer and were subsequently monitored for postoperative survival, were analyzed using cDNA microarrays. We detected seven and three probes/genes associated with the postoperative OS and DFS, respectively, from our discovery cohort data. By incorporating these genes associated with the postoperative survival into MammaPrint genes, often used to predict prognosis of patients with early-stage breast cancer, we constructed postoperative OS and DFS prediction models from the discovery cohort data using a Cox proportional hazard model. The predictive ability of the models was evaluated in another independent cohort using Kaplan-Meier (KM) curves and the area under the receiver operating characteristic curve (AUC). The KM curves showed a statistically significant difference between the predicted high- and low-risk groups in both OS (log-rank trend test P = 0.0033) and DFS (log-rank trend test P = 0.00030). The models also achieved high AUC scores of 0.71 in OS and of 0.60 in DFS. Furthermore, our models had improved KM curves when compared to the models using MammaPrint genes (OS: P = 0.0058, DFS: P = 0.00054). Similar results were observed when our model was tested in publicly available datasets. These observations indicate that there is still room for improvement in the current methods of predicting postoperative OS and DFS in breast cancer., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Natriuretic peptides have been proposed as biomarkers of cardiovascular disease, especially heart failure. Brain natriuretic peptide (BNP) has also been shown to be upregulated at the transcriptional and translational levels by pro-inflammatory cytokines in cardiac myocytes. Although we often measure plasma BNP levels in cancer patients, it remains unknown whether cancer-related inflammation affects the plasma BNP levels. We investigated the relationship between the BNP and human cancers., Methods: We retrospectively studied 2,923 patients in whom the plasma BNP levels and serum C-reactive protein (CRP) were measured and echocardiography was performed. Patients with clinically evident heart failure (NYHA II or higher), heart disease requiring medical treatment or surgery, renal dysfunction, and inflammatory disease were excluded. There were 234 patients in the final analysis. Blood sampling was performed before surgery and chemotherapy. In addition, we evaluated the relationship between the inflammation and plasma BNP levels in mouse models of colon cancer., Results: Of the 234 patients, 80 were diagnosed with cancer. Both the plasma BNP and serum CRP levels were significantly higher in cancer patients than those without. There were no significant differences in the echocardiographic parameters. There was a significant positive correlation between the plasma BNP and serum CRP levels in cancer patients (r = 0.360, P<0.01) but not in those without. In cancer patients, only the CRP correlated with the BNP independent of the age, creatinine level, hypertension, and body mass index. In addition, in nude mice with subcutaneous colon cancer, the plasma BNP level was elevated compared with that in non-cancer mice, and there was a significant relationship between the plasma BNP and serum levels of the inflammatory markers., Conclusions: In cancer patients, as well as colon cancer model mice, the plasma BNP levels were elevated, possibly due to cancer-related inflammation. The effect of cancer on the BNP levels should be considered when using BNP as an indicator of heart failure in cancer patients.

Ductal carcinoma in situ (DCIS) of the breast has no potential to metastasize, but over 20% of cases preoperatively diagnosed as DCIS are upstaged on final pathology. The rates of upstaging and the predictors for invasion on final pathology were evaluated. For 240 primary breast cancers, radiological findings on mammography, ultrasonography, and magnetic resonance imaging were investigated along with pathological and clinical information. Univariate and multivariate analyses were performed to identify predictors of potential invasion. Of the 240 breast cancers, 68 (28.3%) showed invasion on final pathology, and 5 (2.5%) had sentinel node metastasis. The multivariate analysis identified five independent predictors: non-mass lesions >2.4 cm on ultrasonography (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.02-7.95, p=0.047), comedo-type histology (OR 6.89, 95% CI 1.89-25.08, p<0.01), solid-type histology (OR 7.97, 95% CI 2.08-30.49, p<0.01), palpable mass (OR 2.63, 95% CI 1.05-6.64, p=0.04), and bloody nipple discharge (OR 4.61, 95% CI 1.20-17.66, p=0.02). These five predictors were associated with invasion on final pathology and may help select candidates for sentinel node biopsy., Competing Interests: No potential conflict of interest relevant to this article was reported.

Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the "sub-silicone oil fluid (SOF)", enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

Purpose: To evaluate the long-term results of limited macular translocation (LMT) surgery with radial chorioscleral outfolding in patients with wet age-related macular degeneration (AMD) and subfoveal choroidal neovascularization (CNV). In addition, to identify the factors associated with the final best-corrected visual acuity (BCVA)., Methods: The medical records of 20 eyes of 20 consecutive patients (65.2±9.8 years) who had undergone LMT for the treatment of wet AMD and were followed for at least 5 years, were reviewed. The surgical outcomes including the BCVA, degree of foveal displacement, and complications were recorded., Results: The mean foveal displacement was 1332 ± 393 μm after the LMT. The CNV was removed in 16 eyes and photocoagulated in 4 eyes. The mean preoperative VA was 0.83 ± 0.33 logMAR units which significantly improved to 0.59 ± 0.37 logMAR units at 1 year after the surgery (P = 0.015). This BCVA was maintained at 0.59 ± 0.41 logMAR units on the final examination. The final BCVA was significantly correlated with that at 1 year after the surgery (r = 0.83, P<0.001). Multiple linear regression analysis showed that the final BCVA was significantly correlated with the BCVA at 1 year after the surgery (P<0.001), a recurrence of a CNV (P = 0.001), and the age (P = 0.022)., Conclusions: LMT improves the BCVA significantly at 1 year, and the improved BCVA lasted for at least 5 years. These results indicate that the impaired function of the sensory retina at the fovea can recover on the new RPE after the displacement for at least 5 years. The ability to maintain good retinal function on the new RPE for a long period is important for future treatments of CNVs such as the transplantation of RPE cells and stem cells.

Purpose: To investigate the regeneration of the cone outer segments in eyes after surgery for fovea-off rhegmatogenous retinal detachment with an adaptive optics (AO) fundus camera and to correlate these findings with the findings of optical coherence tomography (OCT)., Design: Retrospective, observational case series., Methods: Medical charts of 21 eyes of 21 patients who had undergone surgery for fovea-off rhegmatogenous retinal detachment were retrospectively studied. Cone mosaic images were obtained with an AO fundus camera. Cone packing density at 2 degrees from the fovea within the previously detached area was measured 6 and 12 months after surgery. Retinal thicknesses between the interdigitation zone and the retinal pigment epithelium (IZ-RPE) and between the ellipsoid zone and the retinal pigment epithelium (EZ-RPE) were measured in OCT images., Results: Cone density 12 months after surgery was significantly increased from that at 6 months (P = .001), but was still significantly lower than that of normal fellow eyes (P < .001). IZ-RPE and EZ-RPE thickness significantly increased from 6 to 12 months (P = .045, P = .033, respectively), and these values were not significantly different from those of normal fellow eyes. Multivariate analysis showed that cone density at 12 months was significantly associated with IZ-RPE thickness (P = .002), and increases in cone packing density were significantly associated with increases in IZ-RPE thickness (P = .001)., Conclusions: Recovery of cone packing density measured by AO was associated with structural recovery of the outer retina observed in OCT, suggesting regeneration of the photoreceptor outer segment after surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)