bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Famciclovir, Valaciclovir, and Brivudine Treatments in Adult Immunocompetent Patients With Herpes Zoster
Authors: Yaldiz Mahizer , Solak Berna , Kara Rabia Oztas , Cosansu Nurcihan , Erdem Mustafa Teoman
Published: January 2016

Herpes zoster (HZ) is a common disease characterized by the recurrence of varicella zoster, that stays dormant in sensory ganglia. The primary goal of this study was to compare efficiencies of famciclovir, valaciclovir, and brivudine in terms of pain relief in HZ patients. Records of patients who were admitted to the Dermatology Clinic of our hospital due to acute HZ between the years 2012 and 2014 were retrospectively analyzed. Treatment decisions were at the discretion of caring physicians as valaciclovir (VACV), famciclovir (FCV), and brivudine (BRV) based on the clinical observations. BRV, FCV, and VACV were effective in treating pain in acute HZ. There was no significant difference between mild and moderate HZ patients. In severe cases, a significant reduction in intensity of pain was observed on day 3 in the BRV group, on day 7 in the FCV group, and at 2–3 weeks in the VACV group. There were no significant side effects observed in any of the groups. Results of this study indicate that brivudine may be the first choice in severe HZ cases as it controls pain earlier and is easier to use because of its once daily administration.
Validation of Molecular Pathology Codes for the Identification of Mutational Testing in Lung and Colon Cancer
Authors: Vachani Anil , Wong Yu-Ning , Israelite Jennifer , Mitra Nandita , Hin Sakhena , Yang Lin , Smith-McLallen Aaron , Armstrong Katrina , Groeneveld Peter W. , Epstein Andrew J.
Published: January 2016

Background:

Targeted therapy for patients with lung and colon cancer based on tumor molecular profiles is an important cancer treatment strategy, but the impact of gene mutation tests on cancer treatment and outcomes in large populations is not clear. In this study, we assessed the accuracy of an algorithm to identify tumor mutation testing in administrative claims data during a period before test-specific Current Procedural Terminology codes were available.

Materials and Methods:

We used Pennsylvania Cancer Registry data to select patients with lung or colon cancer diagnosed between 2007 and 2011 who were treated at the University of Pennsylvania Health System, and we obtained their administrative claims. A combination of Current Procedural Terminology laboratory codes (stacking codes) was used to identify potential tumor mutation testing in the claims data. Patients’ electronic medical records were then searched to determine whether tumor mutation testing actually had been performed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

Results:

An algorithm using stacking codes had moderate sensitivity (86% for lung cancer and 81% for colon cancer) and high specificity (98% for lung cancer and 96% for colon cancer). Sensitivity and specificity did not vary significantly during 2007–2011. In patients with lung cancer, PPV was 98% and NPV was 92%. In patients with colon cancer, PPV was 96% and NPV was 83%.

Conclusions:

An algorithm using stacking codes can identify tumor mutation testing in administrative claims data among patients with lung and colon cancer with a high degree of accuracy.
A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain
Authors: Bohnert Amy S. B. , Logan Joseph E. , Ganoczy Dara , Dowell Deborah
Published: January 2016

Background:

High opioid dosage has been associated with overdose, and clinical guidelines have cautioned against escalating dosages above 100 morphine-equivalent mg (MEM) based on the potential harm and the absence of evidence of benefit from high dosages. However, this 100 MEM threshold was chosen somewhat arbitrarily.

Objective:

To examine the association of prescribed opioid dosage as a continuous measure in relation to risk of unintentional opioid overdose to identify the range of dosages associated with risk of overdose at a detailed level.

Methods:

In this nested case-control study with risk-set sampling of controls, cases (opioid overdose decedents) and controls were identified from a population of patients of the Veterans Health Administration who were prescribed opioids and who have a chronic pain diagnosis. Unintentional fatal opioid analgesic overdose was measured from National Death Index records and prescribed opioid dosage from pharmacy records.

Results:

The average prescribed opioid dosage was higher (P<0.001) for cases (mean=98.1 MEM, SD=112.7; median=60, interquartile range, 30–120), than controls (mean=47.7 MEM, SD=65.2; median=25, interquartile range, 15–45). In a ROC analysis, dosage was a moderately good “predictor” of opioid overdose death, indicating that, on average, overdose cases had a prescribed opioid dosage higher than 71% of controls.

Conclusions:

A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MEM used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.
Complete and Repeated Response of a Metastatic ALK-rearranged Inflammatory Myofibroblastic Tumor to Crizotinib in a Teenage Girl
Authors: Gaudichon Jérémie , Jeanne-Pasquier Corinne , Deparis Marianna , Veyssière Alexis , Heyndrickx Maxime , Minckes Odile , Orbach Daniel
Published: January 2016

Inflammatory myofibroblastic tumors (IMT) are rare tumors in children and young adults, considered by the World Health Organization to be intermediate malignancies and rarely metastasizing, with the presence of an anaplastic lymphoma kinase rearrangement in about 50% of the cases. We report the case of a teenager who presented with a metastatic aggressive IMT that was life-threatening despite multiple treatments, and which responded repeatedly to anaplastic lymphoma kinase–targeted crizotinib therapy. Crizotinib induced drastic primary tumor regression, which was sufficient to allow surgical resection and to control distant disease. This case shows that crizotinib is a promising therapy in IMT, even in adolescents and young adults.
A Severe Congenital Neutropenia Type 4 Case (G6PC3 Mutation) Presented With Large Platelets in the Peripheral Smear
Authors: Kaymak Cihan Meriç , Bolat Fatih , Onay Hüseyin , Sari Ahmet , Ünver Korğali Elif , Aslan Şükran , Cura Ceylan , İçağasioğlu Dilara
Published: January 2016

Severe congenital neutropenia type 4 is a disorder of the hematopoietic system associated with mutations in the glucose-6-phosphatase catabolic 3 (G6PC3) gene. This disorder is characterized by neutropenia, congenital heart defects, urogenital malformations, and prominent superficial veins. To our knowledge, although intermittent thrombocytopenia is observed in this mutation, the coexistence of large thrombocytes is rarely seen. Here we present a case of severe congenital neutropenia type 4 with G6PC3 mutation and large platelets in the peripheral smear.
Investigation of a Suicide Ideation Risk Profile in People With Co-occurring Depression and Substance Use Disorder
Authors: Handley Tonelle E. , Kay-Lambkin Frances J. , Baker Amanda L. , Lewin Terry J. , Kelly Brian J. , Inder Kerry J. , Attia John R. , Kavanagh David J.
Published: January 2016

Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial.
Clinicopathologic and Prognostic Significance of Metalloproteinase Tissue Inhibitor-2 Promoters in Tunisian Colorectal Cancer: A Case-Control Study
Authors: Ben Néjima Dalel , Ben Zarkouna Yosr , Pujol Pascal , Gammoudi Amor , Boussen Hamouda , Manai Mohamed
Published: January 2016

Tissue inhibitors of metalloproteinases (TIMPs) appear to affect many aspects of cancer biology, playing a crucial role in cell signaling by regulating cell growth, apoptosis, invasion, metastasis, angiogenesis, and genomic instability. In the present study, we investigate whether TIMP-2 SNP, TIMP-2 mRNAs, and TIMP-2 protein is associated with susceptibility to colorectal cancer (CRC) in Tunisian population. Taqman and DNA sequencing techniques were used for genotyping, TIMP-2 expression of each genotype was analyzed using semiquantitative RT-PCR and TIMP-2 protein expression was analyzed using immunohistochemistry staining. Our results showed that significantly elevated CRC risk was found in individuals with CC genotype (odds ratio 1.959; 95% confidence interval, 1.055-3.637). Moreover TIMP-2 mRNA expression in the colorectal cell carcinomas was significantly higher compared with the normal colorectal tissue (0.487±0.015 vs. 0.210±0.013) (P<0.05). In addition, serum levels of TIMP-2 were significantly lower in CRC patients than in adenoma patients (P=0.01) and healthy controls (P=0.003). Serum levels of TIMP-2 correlated significantly with tumor stage and TNM stage and were the lowest in CRC patients with stage D,T4,(N1,N2,N3),M(+). In conclusion, our study demonstrate for the first time the distribution and the clinical significance of TIMP-2 promoter polymorphisms, mRNA, protein expression, and serum level in CRC Tunisian patients suggesting that the genotyping and serum level of TIMP-2 as potential markers for susceptibility to CRC will allow a precise and early identification of individuals at high risk and will aid the design of therapeutic modalities and evaluation of treatment outcome.
Comprehensive Histologic Scoring to Maximize the Predictability of Pathology-generated Equation of Breast Cancer Oncotype DX Recurrence Score
Authors: Khoury Thaer , Huang Xiao , Chen Xiwei , Wang Dan , Liu Song , Opyrchal Mateusz
Published: January 2016

Background:

Pathology-generated equations have been introduced to predict Oncotype DX recurrence score (ORS) in breast cancer. The purpose of the study is to improve these equations.

Materials and Methods:

Slides from 416 (test set) consecutive breast cancers with available Oncotype DX were reviewed. A validation set (n=91) was prospectively scored using the generated formulas from the test set. The following histopathologic features were graded: Nottingham grade (designated as current Nottingham grade), necrosis, and degree of tumor-infiltrating lymphocytes. The following data were extracted from the pathology report: Nottingham grade (designated as reported Nottingham grade), tumor size, ER/PR Allred scores, HER2 status, and ORS. Equations were calculated, one included the reported Nottingham grade, one included the current Nottingham grade, and one included the current Nottingham grade with the other significant histopathologic variables.

Results:

In the equation that included the reported Nottingham grade, ER, PR, and HER2, the overall concordance with the ORS was 64.86%. After excluding the intermediate category detected by the formula, the concordance rate was 95.28%. When the current Nottingham grade was included, the concordance rate became 69.61% and 98.62%, respectively. When necrosis and the degree of tumor-infiltrating lymphocytes were added to the previous equation, these rates became 70.1% and 98.63%, respectively.

Conclusions:

Our equation has better correlation with ORS than previously published results.
Breast Carcinoma–associated Fibroblasts Share Similar Biomarker Profiles in Matched Lymph Node Metastasis
Authors: Mundim Fiorita G.L. , Pasini Fatima S. , Nonogaki Suely , Rocha Rafael M. , Soares Fernando A. , Brentani Maria M. , Logullo Angela F.
Published: January 2016

This study sought to understand the role of breast carcinoma–associated fibroblasts in the progression of cancer cells into lymph nodes. We compared fibroblasts of primary tumors and matched the involved lymph nodes to select fibroblast activation markers, namely α-smooth muscle actin (α-SMA), S100A4, and vimentin, as well as to determine the frequency of transforming growth factor β1, a pleiotropic cytokine that induces the differentiation of fibroblasts to myofibroblasts, and its downstream effectors: CXCR4 and p-AKT. We disposed samples of 80 primary invasive ductal carcinomas and matched the involved lymph nodes from 43 cases into 3 tissue microarrays, and analyzed stromal and tumor epithelial cells separately by immunohistochemistry. Control uninvolved lymph nodes were analyzed by whole-tissue sections. Cancer-associated fibroblast in lymph nodes with macrometastasis expressed similar profiles of vimentin, α-SMA, and S100A4 as those found in primary tumors. Cancer-associated fibroblast were uniformly estrogen receptor, progesterone receptor, HER-2, Ki-67, and p53 negative, but expressions of transforming growth factor β1 (TGFβ1), CXCR4, and p-AKT staining (62.3%, 52.4%, 65%, respectively) were equivalent between primary and lymph node metastasis (LNM) fibroblasts. A significant coexpression of TGFβ1 with p-AKT and CXCR4 in LNMs suggested the involvement of these proteins with TGFβ1 signaling. These biomarkers, including α-SMA and S100A4, were negative in fibroblasts of cancer-free lymph nodes, with the exception of vimentin. Our finding that expressions of biological markers were similar in fibroblasts of the primary tumors and in matched LNMs, but were absent in cancer-free lymph nodes, supports the assumption that the lymph node stroma mimics the microenvironment observed in primary tumors.
Granuloma Faciale and Eosinophilic Angiocentric Fibrosis: Similar Entities in Different Anatomic Sites
Authors: Stelini Rafael F. , Moysés Mayara D. G. , Cintra Maria L. , Soares Tânia C. B. , Souza Elemir M. d. , Altemani Albina M. d. A. M. , Teixeira Fernanda
Published: January 2016

Background:

Eosinophilic angiocentric fibrosis (EAF) and granuloma faciale (GF) share several histopathologic features, including eosinophil-rich inflammation, microangiitis, and progressive fibrosis. Concurrent presentation of EAF and GF suggests a pathogenetic link between them.

Objectives:

To identify histologic findings that tell them apart and construe the pathogenetic mechanisms behind each morphologic variable, 14 immunohistochemical markers were used to study the cells subpopulations in 14 cases of GF and 3 cases of EAF.

Materials and Methods:

The lesions were classified according to their stage of development. The antibodies studied were: CD4, Foxp3, CD8, granzymes A and B, perforin, granulysin, CD20, CD56, CD68, ICAM-1, CD34, CD105, and 1A4.

Results:

The intensity of the sclerotic response and the density of 1A4-immunostained cells were significantly higher in EAF. In both diseases, CD68+ cells were the most numerous, followed by CD20+, CD8+, and CD4+ cells. About 30% of cells expressed ICAM-1. Among cells with cytotoxic granules, granulysin-positive cells were the most frequent.

Conclusions:

Differences between GF and EAF were found to be mostly like due to anatomic site (usually skin of the face vs. sinonasal cavity) and stage of the disease development (usually earlier in cutaneous lesions because of their visibility). Innate and adaptive immunity, including B cells, T cells, and cytotoxic granules have a role in their pathogenesis.
Napsin A Expression in Anaplastic Lymphoma Kinase-positive Diffuse Large B-Cell Lymphoma: A Diagnostic Pitfall
Authors: Jain Deepali , Mallick Saumya R. , Singh Varsha , Singh Geetika , Mathur Sandeep R. , Sharma Mehar C.
Published: January 2016

Background:

Napsin A is frequently used to classify a tumor of unknown origin as lung primary. Recent studies have shown that Napsin A positivity occurs in adenocarcinomas of nonpulmonary origin such as renal cell carcinomas, endometrial carcinomas, and clear cell carcinomas of ovary. Nonspecific reactivity has been reported with polyclonal Napsin A antibody. On the basis of an index case of anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) expressing Napsin A, which was misdiagnosed as poorly differentiated carcinoma of pulmonary origin, we studied Napsin A expression in our archived cases of ALK-DLBCL.

Materials and Methods:

A total of 3 cases of ALK-DLBCL were studied for Napsin A immunohistochemistry along with typical immunophenotypic profile of these cases. Archived paraffin-embedded tissue blocks and cytology aspiration smears were used for morphologic interpretation and immunohistochemistry. Rabbit monoclonal Napsin A antibody has been used.

Results and Conclusions:

All 3 cases were positive for Napsin A exhibiting strong cytoplasmic positivity. To the best of our knowledge, expression of monoclonal Napsin A in lymphomas has never been reported. ALK-DLBCL should be considered in the differential diagnosis when evaluating a Napsin A-positive tumor of poorly differentiated morphology and of unknown primary. As Napsin A has not been described in the lymphoid tissue development, the significance of Napsin A positivity in hematolymphoid neoplasms is unknown and warrants further investigation.
Correlation of Classic and Molecular Cytogenetic Alterations in Soft-Tissue Sarcomas: Analysis of 46 Tumors With Emphasis on Adipocytic Tumors and Synovial Sarcoma
Authors: Rao Uma N.M. , Cieply Kathleen , Sherer Carol , Surti Urvashi , Gollin Susanne M.
Published: January 2016

Introduction:

Sarcomas are heterogeneous, and their treatment and prognosis are driven by the morphologic subtype and the clinical stage. Classic cytogenetics and fluorescence in situ hybridization (FISH) analysis play an important role in their diagnostic work up.

Materials and Methods:

Forty-six cases of soft-tissue sarcoma were reviewed that underwent karyotyping and simultaneous FISH analysis at initial diagnosis. They included 10 dedifferentiated liposarcomas, 10 myxoid liposarcomas, and 14 synovial sarcomas. Six tumors were investigated for EWSR1 rearrangement. Six high-grade miscellaneous sarcomas were also examined.

Results:

The dedifferentiated liposarcoma had complex karyotypes and MDM2 amplification by FISH, and of these, 5 tumors with myxoid changes also had complex signals for DDIT3. All but 4 myxoid liposarcomas had complex karyotypes, in addition to the characteristic translocation. FISH analysis displayed DD1T3 rearrangement. All synovial sarcomas except 1 recurrence had a t(X;18) translocation by karyotyping and FISH. The EWSR1 rearrangement was present in all extraskeletal myxoid chondrosarcomas, angiomatoid fibrous histiocytoma, atypical Ewing sarcoma, and a clear-cell sarcoma, all of which had characteristic karyotypes. Seven high-grade sarcomas had no specific karyotype or rearrangements for DDIT3, SS18, and EWSR1 by FISH.

Conclusions:

There is good correlation between karyotyping and FISH. Complex FISH signals found in dedifferentiated liposarcomas may be related to an increased chromosome 12 copy number and ploidy. Karyotyping is an important baseline standard for the quality assurance of newly developed FISH probes. It also provides a global view of chromosomal changes and the opportunity to investigate the role of other genetic alterations and potential therapeutic targets.
Two Cases of Chronic Intestinal Pseudo-obstruction: A Comparison of Staining Characteristics of Enteric Visceral Myopathy With Hirschsprung Disease
Authors: Chaffin Joanna , Lee Jeffrey R. , Rao Satish S.C. , Sharma Suash J.
Published: January 2016

Chronic intestinal pseudo-obstruction (CIPO), a rare, debilitating disorder of bowel motility dysfunction, is largely a clinical diagnosis, without any universally accepted diagnostic criteria. Three subgroups are generally acknowledged based on the cell-type affected: enteric visceral myopathy (the most common subgroup), neuropathy, and mesenchymopathy. A fourth subgroup includes abnormalities of neurohormonal peptides. Although immunohistochemical staining is reportedly useful for identifying the mesenchymopathic type, its role in diagnosing enteric visceral myopathy and neuropathy has been fraught with difficulties. We present two cases of chronic intestinal pseudo-obstruction that are clinically and histopathologically suggestive of type III visceral enteric myopathy, aiming to expound upon the diagnostic and pathogenic features. We found that the outer-longitudinal layer of the muscularis propria was more severely affected as compared with the inner circular layer. To investigate the value of this finding, we performed immunostains in the one case in which a paraffin block was available. We found increased peripherin and calretinin immunopositive nerve fibers in the outer layer as compared with inner, but without any significant increase in S-100 positivity or alteration in neuronal morphology of myenteric plexus, a novel finding. This differential staining pattern was completely different from Hirschsprung disease, in which we found rare to absent peripherin and calretinin staining. It is unclear if this increase in the outer layer in visceral myopathy reflects a reactive change or dysfunctional axons. In addition, the history of volvulus in one patient and transmural inflammatory changes in the second raise concerns about the higher propensity of clinical complications secondary to the attenuated outer muscular layer. This study suggests that enteric visceral myopathy has histologic and staining characteristics different from Hirschsprung disease, a finding of diagnostic significance in the differential diagnosis of bowel obstruction. Moreover, these features may have pathogenic value and need further confirmation.
Reduced E-Cadherin and Aberrant β-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas
Authors: Ma Yihong R. , Ren Zhiyong , Conner Michael G. , Siegal Gene P. , Wei Shi
Published: January 2016

Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and β-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant β-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered β-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant β-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant β-catenin expression were frequent events in SRCCs of various organs, and that the altered β-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/β-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.
A New Hitherto Unreported Histopathologic Manifestation of Mammary Analogue Secretory Carcinoma: “Masked MASC” Associated With Low-grade Mucinous Adenocarcinoma and Low-grade In Situ Carcinoma Components
Authors: Petersson Fredrik , Michal Michael , Kazakov Dmitry V. , Grossmann Petr , Michal Michal
Published: January 2016

We present a salivary gland tumor of the parotid gland in a 54-year-old woman, which contained a minor mammary analogue secretory carcinoma (MASC) component (20%) intermixed with a morphologically entirely different mucinous adenocarcinomatous component that comprised 80% of the tumor mass and a morphologically nondescript low-grade intraductal carcinoma (in situ) component. On fluorescence in situ hybridization, a break in the ETV6 gene was documented in the mucinous adenocarcinomatous, the conventional MASC, and the intraductal (in situ) components. RT-PCR failed to reveal an ETV6-NTRK3 fusion. The entire conventional MASC and only rare mucinous adenocarcinoma tumor cells were mammaglobin positive, whereas the low-grade intraductal carcinoma (in-situ) component was negative. S-100 protein stained only the MASC component.
D2-40 Antibody is a Specific Marker for B2 Thymomas
Authors: Szolkowska Malgorzata , Langfort Renata , Winiarski Sebastian , Rudzinski Piotr , Giedronowicz Dorota , Szczepulska-Wojcik Ewa , Ronduda Piotr , Maksymiuk Beata , Orlowski Tadeusz
Published: January 2016

The correlation between the worse outcome of thymomas and expression of podoplanin (D2-40 antibody) in neoplastic cells has been proved in recent studies. We investigated the expression of podoplanin in thymic epithelial tumors of different histologic types and stages resected in our institution. The presence and type of reaction (membranous or cytoplasmic) with D2-40 antibody were assessed. Analyzed group consisted of 72 tumors: 3 type A, 19 type AB, 5 type B1, 24 type B2, 4 type B3, 2 micronodular, 1 metaplastic, and 9 combined B2B3 thymomas and 5 thymic carcinomas. Positive reaction with D2-40 was detected in 7 cases (37%) of AB type, 2 (40%) of B1, 28 (85%) of B2, 3 (23%) of B3, and 1 case (100%) of metaplastic thymoma. All positive B2 and 2 cases of B3 thymomas revealed membranous type of reaction, whereas other subtypes showed less conspicuous cytoplasmic reactivity. A correlation between B2 thymoma and membranous type of reaction was statistically significant (P<0.0001). There was also a slight relationship between cytoplasmic type of reaction and AB or B1 thymomas (P=0.0256). No correlation was detected between D2-40-reactivity and stage (P=0.4) or myasthenic symptoms (P=0.21). In conclusion, membranous type of reaction with D2-40 antibody in thymomas is highly specific for B2 subtype, but antipodoplanin immunoreactivity has no relationship with the tumor stage.
Application of Targeted Next-generation Sequencing, TruSeq Custom Amplicon Assay for Molecular Pathology Diagnostics on Formalin-fixed and Paraffin-embedded Samples
Authors: Csernák Erzsébet , Molnár János , Tusnády Gábor E. , Tóth Erika
Published: January 2016

The implementation of targeted therapies revolutionized oncology. As the number of new oncogenic driver mutations, which provide molecular targets for prediction of effective and selective therapies, is increasing, the implementation of fast and reliable methods by molecular pathology labs is very important. Here we report our results with TruSeq Custom Amplicon assay performed on formalin-fixed and paraffin-embedded material. The oligo capture probes targeted the hotspot regions of 10 well-known oncogenes linked to clinical diagnosis and treatment of lung and colorectal adenocarcinomas, melanomas, and gastrointestinal stromal tumors. Fifteen previously genotyped formalin-fixed and paraffin-embedded DNA samples from different tumor types were selected for massively parallel sequencing. A bioinformatics pipeline was developed to identify high-quality variants and remove sequence artifacts. With the exception of 1 sample, which was of lower quality than the others, relevant mutations corresponding to tumor types could be reliable detected by the developed bioinformatical pipeline. This study indicates that the application of TruSeq Custom Amplicon assay is a promising tool in molecular pathology diagnostics, but it is important to standardize sample processing (including fixation, isolation procedure, sample selection based on quality assessment, and rigorous variant calling) to achieve the highest success rate and avoid false results.
Comparison of Diffusion-Weighted Imaging in the Human Brain Using Readout-Segmented EPI and PROPELLER Turbo Spin Echo With Single-Shot EPI at 7 T MRI
Authors: Kida Ikuhiro , Ueguchi Takashi , Matsuoka Yuichiro , Zhou Kun , Stemmer Alto , Porter David
Published: January 2016

Objectives

The purpose of the present study was to compare periodically rotated overlapping parallel lines with enhanced reconstruction–type turbo spin echo diffusion-weighted imaging (pTSE-DWI) and readout-segmented echo planar imaging (rsEPI-DWI) with single-shot echo planar imaging (ssEPI-DWI) in a 7 T human MR system. We evaluated the signal-to-noise ratio (SNR), image distortion, and apparent diffusion coefficient values in the human brain.

Materials and Methods

Six healthy volunteers were included in this study. The study protocol was approved by our institutional review board. All measurements were performed at 7 T using pTSE-DWI, rsEPI-DWI, and ssEPI-DWI sequences. The spatial resolution was 1.2 × 1.2 mm2 in-plane with a 3-mm slice thickness. Signal-to-noise ratio was measured using 2 scans.

Results

The ssEPI-DWI sequence showed significant image blurring, whereas pTSE-DWI and rsEPI-DWI sequences demonstrated high image quality with low geometrical distortion compared with reference T2-weighted, turbo spin echo images. Signal loss in ventral regions near the air-filled paranasal sinus/nasal cavity was found in ssEPI-DWI and rsEPI-DWI but not pTSE-DWI. The apparent diffusion coefficient values for ssEPI-DWI were 824 ± 17 × 10−6 and 749 ± 25 × 10−6 mm2/s in the gray matter and white matter, respectively; the values obtained for pTSE-DWI were 798 ± 21 × 10−6 and 865 ± 40 × 10−6 mm2/s; and the values obtained for rsEPI-DWI were 730 ± 12 × 10−6 and 722 ± 25 × 10−6 mm2/s. The pTSE-DWI images showed no additional distortion comparison to the T2-weighted images, but had a lower SNR than ssEPI-DWI and rsEPI-DWI. The rsEPI-DWI sequence provided high-quality images with minor distortion and a similar SNR to ssEPI-DWI.

Conclusions

Our results suggest that the benefits of the rsEPI-DWI and pTSE-DWI sequences, in terms of SNR, image quality, and image distortion, appear to outweigh those of ssEPI-DWI. Thus, pTSE-DWI and rsEPI-DWI at 7 T have great potential use for clinical diagnoses. However, it is noteworthy that both sequences are limited by the scan time required. In addition, pTSE-DWI has limitations on the number of slices due to specific absorption rate. Overall, rsEPI-DWI is a favorable imaging sequence, taking into account the SNR and image quality at 7 T.
The Short Breath-Hold Technique, Controlled Aliasing in Parallel Imaging Results in Higher Acceleration, Can Be the First Step to Overcoming a Degraded Hepatic Arterial Phase in Liver Magnetic Resonance Imaging
Authors: Yoo Jung Lim , Lee Chang Hee , Park Yang Shin , Kim Jeong Woo , Lee Jongmee , Kim Kyeong Ah , Seol Hae Young , Park Cheol Min
Published: January 2016

Objective

The aim of this study was to assess whether a short breath-hold technique can improve hepatic arterial phase (HAP) image quality in gadoxetic acid–enhanced magnetic resonance (MR) imaging compared with a conventional long breath-hold technique.

Materials and Methods

Institutional review board approval and patient consent were obtained for this prospective randomized control study. One hundred nineteen patients undergoing gadoxetic acid–enhanced MR imaging were randomly assigned to groups A or B. Group A patients underwent an 18-second long breath-hold MR technique (conventional VIBE [volumetric interpolated breath-hold examination] technique with GRAPPA [generalized autocalibrating partially parallel acquisition]), and group B patients underwent a 13-second short breath-hold MR technique (VIBE technique with CAIPIRINHA [controlled aliasing in parallel imaging results in higher acceleration]). Respiratory-related graphs of the precontrast and HAP were acquired. The breath-hold degree was graded based on the standard deviation (SD) value of respiratory waveforms. Gadoxetic acid–related dyspnea was defined as when the SD value of the HAP was 200 greater than that of the precontrast phase without degraded image quality in the portal and transitional phases (SD value of the HAP − SD value of the precontrast phase). The overall image quality and motion artifacts of the precontrast and HAP images were evaluated. The groups were compared using the Student t or Fisher exact test, as appropriate.

Results

The incidence of breath-holding difficulty (breath-hold grades 3 and 4) during the HAP was 43.6% (27/62) and 36.8% (21/57) for group A and B, respectively. The SD value during the precontrast phase and the SD value difference between the precontrast and HAP were both significantly higher in group A than in group B (P = 0.047 and P = 0.023, respectively). Gadoxetic acid–related dyspnea was seen in 19.4% (12/62) of group A and 7.0% (4/57) of group B. Group B showed better precontrast and HAP image quality than group A (P < 0.001). Degraded HAP (overall image quality ≥4) was observed in 9.7% (6/62) and 3.5% (2/57) of group A and B, respectively.

Conclusions

The short breath-hold MR technique, CAIPIRINHA, showed better HAP image quality with less degraded HAP and a lower incidence of breath-hold difficulty and gadoxetic acid–related dyspnea than the conventional long breath-hold technique.
Human Imaging With Photon Counting–Based Computed Tomography at Clinical Dose Levels
Authors: Gutjahr Ralf , Halaweish Ahmed F. , Yu Zhicong , Leng Shuai , Yu Lifeng , Li Zhoubo , Jorgensen Steven M. , Ritman Erik L. , Kappler Steffen , McCollough Cynthia H.
Published: January 2016

Objectives

The purpose of this work was to measure and compare the iodine contrast-to-noise ratio (CNR) between a commercial energy-integrating detector (EID) computed tomography (CT) system and a photon-counting detector (PCD) CT scanner capable of human imaging at clinical dose rates, as well as to determine clinical feasibility using human cadavers.

Materials and Methods

A research dual-source PCD-CT scanner was used, where the “A” tube/detector subsystem used an EID and the “B” tube/detector subsystem used a PCD. Iodine CNR was measured in 4 anthropomorphic phantoms, simulating 4 patient sizes, at 4 tube potential settings. After biospecimen committee approval, PCD scans were performed on a fresh-frozen human head and a whole-body cadaver using clinical dose rates. Scans were repeated using the EID and identical parameters, and qualitative side-by-side comparisons were performed.

Results

For the same photon fluence, phantom measurements demonstrated a mean increase in CNR of 11%, 23%, 31%, 38% for the PCD system, relative to the EID system, at 80, 100, 120, and 140 kV, respectively. Photon-counting detector CT additionally provided energy-selective imaging, where low- and high-energy images reflected the energy dependence of the iodine signal. Photon-counting detector images of cadaveric anatomy demonstrated decreased beam hardening and calcium blooming in the high-energy bin images and increased contrast in the low-energy bins images relative to the EID images. Threshold-based PCD images were qualitatively deemed equivalent in other aspects.

Conclusions

The evaluated research PCD-CT system was capable of clinical levels of image quality at clinical dose rates. It further provided improved CNR relative to state-of-the-art EID-CT. The energy-selective bin images provide further opportunity for dual-energy and multienergy analyses.
Bioeffects of Diagnostic Dynamic 3-Dimensional (4-Dimensional) Ultrasound on Ultrastructure of Cerebral Cells of Fetal Mice in Late Pregnancy
Authors: Li Jianhui , Zhang Lei
Published: January 2016

The aim of this study was to study the bioeffects of diagnostic dynamic 3-dimensional ultrasound (4D) on ultrastructure of cerebral cells of fetal mice in late pregnancy. Thirty pregnant mice carrying 18th embryonic day fetuses were randomly allocated into 6 groups, namely, control group, sham-exposed group, 5 minute–exposed group, 10 minute–exposed group, 20 minute–exposed group, and 30 minute–exposed groups (5 in each group). In exposure groups, mice were put under the dynamic 3D ultrasound system's probe for 5 to 30 minutes. Mice in sham-exposed group did not receive ultrasound wave. At 24th hour after birth, 10 pups of each group were randomly selected (2 in each litter) and euthanized by decapitation, and the brains were immediately removed. Right parietal lobes were taken as specimen. The specimens were firstly fixed with glutaraldehyde and secondly with osmic acid, then sections were made and observed under the transmission electron microscope. There were no obvious abnormal ultrastructure changes in control group, sham-exposed group, and 5 minute–exposed group under transmission electron microscope. Ten minute–exposed group showed some enlarged mitochondria, broken crista, vacuolated endoplasmic resticulums, and a few apoptosis cells. More abnormal organelles and apoptosis cells were observed in 20 minute–exposed and 30 minute–exposed groups (P < 0.05). Dynamic 3D (4D) ultrasound exposure for more than 10 minutes may result in abnormal neuronal ultrastructure changes and apoptosis cells in fetal mouse cerebrum.
Point Shear Wave Elastography in Assessment of Hepatic Fibrosis
Authors: Perry Michael T. , Savjani Neal , Bluth Edward I. , Dornelles Adriana , Therapondos George
Published: January 2016

The objective of this study was to prospectively evaluate the use of point shear wave elastography for the assessment of liver fibrosis and to determine the usefulness and optimal location for obtaining elastography measurements in native and transplanted livers. Point shear wave elastography measurements were obtained from 100 consecutive patients presenting for percutaneous liver biopsy. Measurements were acquired within both the superior right hepatic lobe (segments VII/VIII) via an intercostal approach and the inferior right hepatic lobe (segments V/VI) via a subcostal approach. Analysis of variance was used to assess statistical differences between the degree of fibrosis on percutaneous liver biopsy and elastography measurements. No statistical difference was present when comparing elastography measurements in patients with hepatic steatosis compared with patients without steatosis (P = 0.2759). There was no difference in the accuracy of elastography measurements in native livers versus transplanted livers (P = 0.221). Point shear wave elastography can accurately differentiate between patients with no-to-mild hepatic fibrosis (F0–F1) and moderate-to-severe hepatic fibrosis (≥F2) with sensitivity of 72% and specificity of 69%. Point shear wave elastography can be used as a noninvasive method to assess fibrosis in patients with native or transplanted livers. In addition, measurements can be combined or taken separately from either the superior or inferior right hepatic lobe. The presence of hepatic steatosis does not affect the accuracy of point shear wave elastography. However, shear wave elastography values in patients with body mass index greater than 40 should be interpreted with caution.
Primary Overcorrection of the Unilateral Cleft Nasal Deformity
Authors: Lonic Daniel , Morris David E. , Lo Lun-Jou
Published: January 2016

Background

Because primary nasal correction by the time of lip repair has been incorporated into the treatment approach, many patients have benefitted from this combined procedure. However, primary nasal correction cannot guarantee an excellent result. Although overcorrection has been mentioned as a treatment rationale of the unilateral cleft lip nasal deformity, a detailed approach and quantitative evidence of the rationale are rare. This study evaluates whether overcorrection in the primary repair results in a quantitative improvement in nasal appearance.

Patients and Methods

In this retrospective study, the inclusion criteria were patients with complete unilateral cleft lip and palate who underwent primary lip and nose repair by the age of 3 to 4 months. Primary nasal overcorrection was achieved by application of muscle to septal base suture, alar cinching suture and Tajima reversed U incision method. Patients were further divided into an overcorrected (n = 19) and nonovercorrected group (n = 19). The following parameters were identified on basilar photos of all patients taken at least 12 months after repair, ratios of cleft to noncleft side in each patient were taken and the mean for each parameter calculated: Ac angle (ACA/ACA′), alar height (AH/AH′), alar width (AW/AW′), nostril height (NH/NH`), nostril width (NW/NW′), and columellar deviation from the midline (CD/NW). The means of the overcorrected and nonovercorrected groups were then compared using the t test.

Results

From all investigated measuremens, Alar height (AH/AH': overcorrected, 0.983 to nonovercorrected, 0.941; P = 0.03) and nostril height ratio (NH/NH') (NH/NH': covercorrected, 0.897 to nonovercorrected, 0.680; P = 0.003) showed statistically significant differences favoring the overcorrected group at least 12 months after surgery.

Conclusions

Primary nasal overcorrection including muscle to columella base suture, alar cinch suture, and Tajima method resulted in quantitatively more long-term symmetric alae and nostril height compared to nonovercorrected patients.
On Beyond Lidocaine
Authors: Hsia Henry C.
Published: January 2016

The use of tumescent solution in liposuction is now considered standard of care; however, much debate still exists regarding its ideal components, especially surrounding the inclusion of local anesthetics. This article reviews the discussion regarding the use of local anesthetics in tumescent liposuction and how it may evolve in the future. The need for local anesthetic additives in tumescent liposuction has been questioned, and the use of longer-acting agents discouraged; however, increasing number of reports in recent years have described the increasingly widespread use of tumescent anesthesia where a wetting solution is infiltrated to achieve anesthesia in an operative field for procedures other than liposuction. More high-level evidence, such as randomized controlled clinical trials, will be required; however, it should be possible to develop a useful standardized algorithm that can guide surgeons to optimize patient safety as well as patient experience.
Is the Target of 1 Day of Stay per 1% Total Body Surface Area Burned Achieved in Chemical Burns?
Authors: Tan Teresa , Wong David S. Y.
Published: January 2016

The length of hospital stay (LOS) is a standard parameter used to reflect quality and evaluate outcomes in acute burn care. This study aims to assess whether the target of 1 day of stay per 1% total body surface area (TBSA) burned was achieved in acute chemical burns management and factors affecting the LOS. A retrospective analysis of the records of patients who suffered from chemical burn injuries admitted to a university burn center over a continuous 14-year period was performed.

A total of 118 patients were admitted over the period for chemical burns. Only 14% of cases achieved the target stated. Factors associated with lengthening of the hospital stay included TBSA, ocular involvement, the cause of injury, and the need for surgery during the same admission.

The LOS in chemical burns frequently exceeds 1 day of stay per 1% TBSA burned. Many factors can contribute to a patient’s LOS and are worth exploring in order to see if the impact of these factors could be minimized. Early surgical intervention should help to reduce the LOS if reliable methods of burn wound depth assessment are available.
Tissue Dynamics
Authors: Yu Jack C. , Cai Lei , Wang Tien-Hsiang , Berdel Henrik O. , Lee Jung-Hoon , Lam Poh-Sang , Hershman John , Baban Babak
Published: January 2016

Introduction

Why are cranial sutures the way they are? How do cancers grow? Merging physics and mathematics with biology, we develop equations describing these complex adaptive systems, to which all biological entities belong, calling them laws of tissue dynamics:

see full text for equations

Where t is time, E is energy, M is body mass, X is the biological characteristic of interest, C is a constant, a is an exponent.

(1) is based on conservation of matter: for any given tissue, materials in must equal to materials out +/− assimilated or degraded. (2) is based on energy conservation. All living systems require energy, without which life becomes impossible. Equation (2) is a power spectrum.

Objectives

This study aimed to introduce the laws of tissue dynamics and to illustrate them using observations from craniofacial and cancer growth.

Methods

We use cranial sutures as a model system to test Equation (1), we also measure the in vitro growth rate of normal murine liver and spleen cells, comparing them to B16F10 melanoma cells. We show the increase in compound growth rate and energetic requirement of malignant versus normal cells as partial proof of Equation (2).

Results

The constant width and wavy form of cranial sutures are the inevitable results of repeated iteration from coupling of growth and stress. The compound growth rate of B10F16 melanoma cells exceeds that of normal cells by 1.0 to 1.5%, whereas their glucose uptake is equal to 3.6 billion glucose molecules/cell per minute.

Living things are complex adaptive systems, thus a different way of thinking and investigating, going beyond the current reductive approach, is required.
Mechanisms of Fat Graft Survival
Authors: Pu Lee L.Q.
Published: January 2016

Although more fat grafting procedures have been performed by plastic surgeons with the primary goal to restore soft tissue loss, the actual mechanism on how fat graft survives remains less completely understood. An established old theory on fat graft survival is still based on the cell survival theory proposed by Peer in the early 1950s. On the basis of his preliminary experimental study, he proposed that the mechanism of fat graft survival is based on established early blood circulation through anastomosis of the fat graft and host blood vessels. Recently, several investigators have demonstrated new concepts of the fat graft survival: One further advanced the old Peer cell survival theory and another based on new discovery and understanding of adipose-derived stem cells. This article serves as a scientific review on how fat graft survives after in vivo transplantation based on a number of well-conducted experimental studies. Both the graft survival and graft replacement theories on how fat graft survives are true based on the previously mentioned well-conducted experimental studies. Each theory may play a role in fat graft survival. It is possible that graft survival may be more dominant in some patients but the graft replacement may be more dominant in other patients.