Search

Background Tomosynthesis-guided vacuum assisted breast biopsy (3D-VAB) has been used increasingly and it is now replacing stereotactic vacuum assisted biopsy (2D-VAB). The aim of our study is to compare the clinical effectiveness of 3D-VAB and 2D-VAB on the number of tissue cores containing targeted calcifications and on the procedure time.Methods Consecutive 87 women who underwent biopsy at our hospital from April 2020 to March 2022 for calcifications mammographically suspicious of malignancy were included in this study: 57 patients with 3D-VAB and 30 patients with 2D-VAB. The procedure time was defined as the time between scout tomosynthesis for 3D-VAB and scout stereo images for 2D-VAB as a start and confirmation of targeted calcifications by specimen radiography as an end.Results Grouped or clustered calcified lesions were found in 39 and 21 patients among the 3D-VAB group and the 2D-VAB group, respectively. A mean long diameter and a mean area of the grouped or clustered calcified lesions of 39 patients were 9 mm and 50 mm2 from a MLO view. With the 21 cases of the 2D-VAB group, the corresponding figures were 10 mm and 78 mm2 from a MLO view. The mean number of tissue cores per biopsy containing targeted calcifications from the grouped or clustered calcified lesions was 3 and 2.3 specimens for 39 patients of the 3D-VAB group and for 21 patients of the 2D-VAB group, respectively. The mean procedure time for grouped or clustered calcifications was significantly shorter in the 3D-VAB group than in the 2D-VAB group (16.5 min vs. 27.4 min, P P Conclusion Our study demonstrated that the clinical performance of 3D-VAB is superior to that of 2D-VAB and that the significant reduction in examination time with 3D-VAB compared with 2D-VAB is expected to benefit patients.

Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer. Cancer Prev Res; 7(10); 1002–10. ©2014 AACR.

Correlation between colorectal lesions and BLF methylation

Supplementary Figure S1 Receiver operating characteristic curve analysis of the respective marker genes. Supplementary Figure S2 Ages of CRC patients (upper) and non-CRC individuals (lower) with the indicated M-scores. Each dot represents a single individual. Supplementary Figure S3 Comparison of the methylation results in paired BLF and biopsy specimens from primary tumors. The M-score and the Ct values of the endogenous control Alu repetitive element are indicated on the top. The methylation status of the three marker genes in the BLF and biopsy specimens is shown below. Supplementary Figure S4 CTC and colonoscopic views of the CRC of case 5 in Table 6 are shown. The polypoid adenoma portion is indicated by the red arrow and the flat adenocarcinoma portion is indicated by the yellow arrow.

Results of ROC curve analysis for detection of CRC using BLF methylation

Sequences of primers used in this study

MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. Additionally, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array-based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real-time polymerase chain reaction. We found that the expression of miRNA-5787 was correlated with reciprocal expression of 2 mRNAs, i.e., SRRM2 and POLR2J3, in SSL samples. In TSA samples, 2 pairs of miRNAs/mRNAs showing opposite expression patterns, i.e., miRNA-182-5p/ETF1 and miRNA-200b-3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA-222-3p/SLC26A3, miRNA-6753-3p/FABP1, and miRNA-222-3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR-222-3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR-222-3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype. This article is protected by copyright. All rights reserved.

Hyperplastic nodules (HNs) have been considered to be hyperplastic lesions among Japanese pathologists, although they have not been recognized worldwide. Here, we examined clinicopathological and molecular differences between goblet cell-rich variant hyperplastic polyp (GCHPs), microvesicular variant HPs (MVHPs), and HNs. Patients with hyperplastic lesions including 61 GCHPs, 62 MVHPs, and 19 HNs were enrolled in the present study. The clinicopathological and molecular features examined included the mucin phenotype expression, p53 overexpression, annexin A10, genetic mutations (BRAF and KRAS), and DNA methylation status (low, intermediate, and high methylation epigenotype). In addition, hierarchical cluster analysis was also performed to identify patterns among the histological features. The lesions were stratified into three subgroups and each lesion was assigned into a subgroup. While GCHP was associated with KRAS mutation, MVHP was closely associated with BRAF mutation; no mutation was found in HN. We list specific histological findings that corresponded to each lesion. Finally, there were no significant differences in the methylation status among lesions. The current result shows that both MVHPs and GCHPs have a neoplastic nature whereas HN is non-neoplastic. We suggest that HNs should be distinguished from HPs, in particular GCHPs, in terms of pathological and genetic features.

BACKGROUND Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), has been implicated in the pathogenesis of skin disorders. However, the pathogenic role of IL-36Ra in cutaneous ischemia-reperfusion (I/R) injury remains unclear. OBJECTIVES We investigated the role of IL36Ra in cutaneous I/R injury. METHODS We examined I/R injury in Il36rn-/- mice. The area of wounds, numbers of infiltrated cells, apoptotic cells and neutrophil extracellular trap (NET) formation were assessed. The expression levels of various genes were analysed using real-time RT-PCR. The expression of high mobility group box 1 (HMGB1), an endogenous toll-like receptor (TLR) 4 ligand, was confirmed using immunohistology, and serum HMGB1 levels were measured by ELISA. Cytokine production by stimulated cultured J774A.1 and HaCaT cells was examined. RESULTS IL-36Ra deficiency resulted in significantly delayed wound healing and increased neutrophil and macrophage infiltration into the wound tissues. Il36rn-/- mice had increased mRNA expression levels of CXCL1, CXCL2, CCL4, TNF-α, TGF-β, IL-1β, IL-6 and IL-36γ relative to wild-type mice. Apoptosis was identified in keratinocytes by TUNEL assay. HMGB1 expression in the I/R site was decreased in both keratinocytes and adnexal cells, while serum HMGB1 levels were significantly elevated after reperfusion. The mRNA levels of various cytokines, including IL-1β, were elevated in J774A.1 cells through TLR4 signalling by HMGB1 stimulation. In addition, HaCaT cells stimulated with IL-1β showed significantly increased CXCL1, TNF-α, IL-6, IL-36β and IL-36γ mRNA expression. Furthermore, NET formation was increased by IL-36Ra deficiency. Finally, either the blockade of TLR4 signalling by TAK-242 or inhibition of NET formation by Cl-amidine normalized exacerbated I/R injury in Il36rn-/- mice. CONCLUSIONS This study indicated that IL-36Ra deficiency exacerbates cutaneous I/R injury due to excessive inflammatory cell recruitment, NET formation, and excessive cytokine and chemokine production via the TLR4 pathway by HMGB1 released from epidermal apoptotic cells.

AIMS Recent studies have shown that the microenvironment can include cancer cells and cancer-associated fibroblasts (CAFs), and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyse the expression patterns of cancer cell- and CAF-related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM). METHODS AND RESULTS Quantitative analysis was conducted for Ki-67, p53, β-catenin and matrix metalloproteinase-7 (MMP7) to assess cancer cell markers. In addition, we examined CAF markers, including smooth muscle alpha-actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP-1), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast-associated protein 1 (FAP-1), zinc finger E-box binding homeobox 1 (ZEB1) and TWIST-related protein 1 (TWIST1). In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell- and CAF- related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterised by high expression of Ki-67, p53, FAP-1, platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and TWIST1, was correlated with LNM (P

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in December 2019 in Wuhan, China. Coronavirus disease (COVID-19) mainly presents with lower respiratory tract symptoms. On the other hand, laryngotracheitis or croup shows barky cough and it is rare in adults. There were no reports of laryngotracheitis with COVID-19 in pregnant women. We report the case of a pregnant woman at 24 weeks of gestation presenting with acute laryngotracheitis and COVID-19 due to the R.1 variant of SARS-CoV-2. CASE REPORT A 29-year-old previously healthy woman at 24 weeks of gestation presented with hoarseness and sore throat without fever, of 1-day duration. Although she was treated by her primary care physician with nebulized epinephrine, her symptoms did not resolve. She came to our hospital the same day. On arrival at our department, she was tachypneic and had a 95% oxygen saturation. She had stridor and barking cough. Laryngeal endoscopy revealed edema under the vocal cords. She was hospitalized urgently. SARS-CoV-2 polymerase chain reaction (PCR) testing was positive and the E484K mutation was confirmed. She was treated with oral and inhaled corticosteroids. Two days after admission, her symptoms were improved. She was discharged 10 days after admission. Edema under the vocal cords was completely improved 24 days after discharge. There were no adverse effects on the pregnancy. CONCLUSIONS COVID-19 laryngotracheitis has a more severe disease course than other causes, especially in pregnancy. COVID-19 laryngotracheitis should be use corticosteroids to treatment. Prednisolone is recommended for laryngotracheitis with COVID-19 during pregnancy.

BACKGROUND Anosmia, which is loss of smell, is a recognized complication of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may persist after recovery from infection. Retronasal olfactory testing includes both subjective questionnaires and physiological tests that can be used to evaluate recovery of smell. This report presents the case of a 32-year-old man with persistent loss of smell following COVID-19 whose recovery was evaluated by retronasal olfactory testing. CASE REPORT The patient was a 32-year-old man with confirmed SARS-CoV-2 infection. He was aware of his olfactory dysfunction. Using the orthonasal test, a TT Olfactometer 2 months after disease onset showed an olfactory threshold score of 2.2 points (mild decrease) and olfactory identification result of 3.4 points (moderate decrease). However, the retronasal intravenous olfactory test showed no response, indicating severe olfactory dysfunction. After 3 months of olfactory training and therapy with steroidal nasal drops (Fluticasone Furoate, 27.5 µg/day) and oral vitamins (Mecobalamin, 1500 µg/day), the patient's orthonasal test olfactory threshold score improved to 0.6 points (normal), and his olfactory identification result improved to 1.2 points (mild decrease). Although the retronasal intravenous olfactory test showed a weak response, a reaction did occur. At this time, the patient did not report any improvement in his symptoms. CONCLUSIONS This report has shown that in cases of persistent anosmia following COVID-19, retronasal olfactory testing can be used to evaluate recovery of the sense of smell.

Identification of molecular alterations occurring in the adenomatous and carcinomatous components within the same tumor would greatly enhance understanding of the neoplastic progression of colorectal cancer. We examined somatic copy number alterations (SCNAs) and mRNA expression at the corresponding loci involved in the adenoma–carcinoma sequence in the isolated adenomatous and cancer glands of the same tumor in 15 cases of microsatellite‐stable “carcinoma in adenoma,” using genome‐wide SNP and global gene expression arrays. Multiple copy‐neutral loss of heterozygosity events were detected at 4q13.2, 15q15.1, and 14q24.3 in the adenomatous component and at 4q13.2, 15q15.1, and 14q24.3 in the carcinomatous component. There were significant differences in the copy number (CN) gain frequencies at 20q11.21–q13.33, 8q13.3, 8p23.1, and 8q21.2–q22.2 between the adenomatous and carcinomatous components. Finally, we found a high frequency of five genotypes involving CN gain with upregulated expression of the corresponding gene (RPS21, MIR3654, RSP20, SNORD54, or ASPH) in the carcinomatous component, whereas none of these genotypes were detected in the adenomatous component. This finding is interesting in that CN gain with upregulated gene expression may enhance gene function and play a crucial role in the progression of an adenoma into a carcinomatous lesion.

An undulator generating a magnetic field whose longitudinal profile is arbitrarily varied has been developed, which is one of the key components in a number of proposed new concepts in free-electron lasers. The undulator is composed of magnet modules, each of which corresponds to a single undulator period, and is driven by a linear actuator to change the magnetic gap independently. To relax the requirement on the actuator, the mechanical load on each module due to magnetic force acting from opponent and adjacent modules is reduced by means of two kinds of spring systems. The performance of the constructed undulator has been successfully demonstrated by magnetic measurement and characterization of synchrotron radiation.

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome‐wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22‐q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

Impetigo herpetiformis (IH) is a rare pustular dermatosis. It can be life-threatening for both the mother and fetus and often causes therapeutic problems. However, there is no specific guideline for the treatment of IH and the evidence regarding the efficacy of treatments for IH has not been established. Herein, we report two cases of IH, which were successfully treated with anti-tumor necrosis factor (TNF)-α drugs. The serum levels of the drugs in the infants and mothers were examined using enzyme-linked immunosorbent assay (ELISA). Case 1 was a 35-year-old, gravida 2, para 1, female patient in week 20 of pregnancy; she was treated with adalimumab (ADA) until delivery. Case 2 was a 26-year-old, gravida 1, para 0, female patient in week 30 of pregnancy; she was treated with certolizumab pegol (CZP) until delivery. In both cases, the skin lesions started regressing considerably after administration of the biologic agents. We examined the serum levels of the biologic agents in the mothers and infants using ELISA. In case 1, the ADA serum level in the infant was as high as that in the mother at birth; it then decreased below the lower limit of quantification at week 12 post-delivery. In case 2, the CZP serum level in the infant was below the lower limit of quantification at birth. In this report, we revealed that biologic agents could be an effective treatment for severe IH and that CZP treatment can be considered safe for the mothers and fetuses.

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.

Objective lenses are frequently employed in state-of-the-art ultrafast time-resolved microscopy techniques. While it enables tight spatial focusing, its dispersion causes a longer optical pulse duration. Since an objective lens is a combination of different lens materials, finding its correct dispersion can be challenging. In this paper, we propose a dispersion measurement method for an objective lens using white light interferometry. Our proposed method enables the experimental determination of the lens dispersion and improves the temporal resolution of ultrafast time-resolved microscopy techniques.

Precursor lesions that progress into colorectal cancer (CRC) could be largely classified into sessile serrated lesions (SSLs), traditional serrated adenoma (TSA), and tubular adenoma (TA). We aimed to determine whether high expression of trefoil factor 1 (TFF1) is closely associated with serrated lesions, particularly SSLs. The samples were divided into the first (12 SSLs, 5 TSAs, and 15 TAs) and second cohorts (15 SSLs, 9 TSAs, and 15 TAs). First, we investigated TFF1 expression in isolated gland samples using array-based and reverse-transcription PCR. Second, we performed immunohistochemical analysis of TFF1 expression in paraffin-embedded tissues obtained from SSL, TSA, TA, and hyperplastic polyp (HP) samples. In addition, we compared TFF1 mRNA levels between SSLs and HPs. TFF1 expression was significantly higher in SSLs than in TSA and TA in both cohorts. Additionally, immunohistochemical staining of TFF1 in the HP, SSL, TSA, and TA samples revealed significant differences in the immunohistochemical scores of TFF1 among the four types of lesions (higher expression in SSLs than in the other three lesions). Finally, there were significant differences in TFF1 mRNA expression levels between SSLs and HPs in paraffin-embedded tissues. However, there was considerable overlap in the immunohistochemical scores and expression levels of TFF1 transcripts between SSLs and HPs. The current findings may help elucidate the molecular mechanisms involved in serrated lesion development. In addition, we suggest that despite the limited practical application, upregulation of TFF1 transcripts may help differentiate SSLs from other lesions.