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Sample records for somatic pathologies cancer

  1. Pathological narcissism and somatic symptoms among men and women attending an outpatient mental health clinic.

    Science.gov (United States)

    Kealy, David; Tsai, Michelle; Ogrodniczuk, John S

    2016-09-01

    To explore the relationship between types of pathological narcissism and somatic symptoms among psychiatric outpatients. Patients (N = 95) completed measures of somatic symptoms, narcissistic grandiosity and vulnerability, and psychiatric symptoms. Relationships among variables were analysed using t-tests and correlations, controlling for psychiatric distress. Somatic symptoms were positively associated with two types of narcissistic dysfunction. Among women there was a positive association between somatic symptoms and narcissistic vulnerability, but not grandiosity. Among men, somatic symptoms were positively associated with narcissistic grandiosity, but not vulnerability. The connection between narcissistic pathology and somatic symptom severity appears to differ based on gender. Further research is needed to confirm and extend this preliminary finding.

  2. Germinal and somatic mutations in cancer

    International Nuclear Information System (INIS)

    Knudson, A.G. Jr.

    1977-01-01

    The role of germinal and somatic mutations in carcinogenesis leads to the conclusion that environmental carcinogens probably exert their effects via somatic mutations. Susceptibility to this process may itself be genetically determined, so we may deduce that two groups, one genetic and one non-genetic, are included in the 'environmental' class. Other individuals seem to acquire cancer even in the absence of such environmental agents, and these too may be classified into a genetic and a non-genetic group. It has been estimated that in industrial countries, the environmental groups include 70-80% of all cancer cases, but we are only beginning to know how to separate the genetic and non-genetic subgroups. The genetic subgroup of the 'non-environmental' group is very small, probably of the order of magnitude of 1-2% for cancer as a whole. The remainder, about 25%, comprises a non-genetic, non-environmental subgroup that seems to arise as a consequence of 'spontaneous' somatic mutations. The incidence of these 'background' cancers is what we should combat with preventive and therapeutic measures

  3. POLE somatic mutations in advanced colorectal cancer.

    Science.gov (United States)

    Guerra, Joana; Pinto, Carla; Pinto, Diana; Pinheiro, Manuela; Silva, Romina; Peixoto, Ana; Rocha, Patrícia; Veiga, Isabel; Santos, Catarina; Santos, Rui; Cabreira, Verónica; Lopes, Paula; Henrique, Rui; Teixeira, Manuel R

    2017-12-01

    Despite all the knowledge already gathered, the picture of somatic genetic changes in colorectal tumorigenesis is far from complete. Recently, germline and somatic mutations in the exonuclease domain of polymerase epsilon, catalytic subunit (POLE) gene have been reported in a small subset of microsatellite-stable and hypermutated colorectal carcinomas (CRCs), affecting the proofreading activity of the enzyme and leading to misincorporation of bases during DNA replication. To evaluate the role of POLE mutations in colorectal carcinogenesis, namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in tumor DNA samples from 307 cases. Microsatellite instability and mutation analyses of a panel of oncogenes were performed in the tumors harboring POLE mutations. Three heterozygous mutations were found in two tumors, the c.857C>G, p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low microsatellite instability, whereas KRAS and PIK3CA mutations were found in one tumor each. We conclude that POLE somatic mutations exist but are rare in advanced CRC, with further larger studies being necessary to evaluate its biological and clinical implications. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Progression inference for somatic mutations in cancer

    Directory of Open Access Journals (Sweden)

    Leif E. Peterson

    2017-04-01

    Full Text Available Computational methods were employed to determine progression inference of genomic alterations in commonly occurring cancers. Using cross-sectional TCGA data, we computed evolutionary trajectories involving selectivity relationships among pairs of gene-specific genomic alterations such as somatic mutations, deletions, amplifications, downregulation, and upregulation among the top 20 driver genes associated with each cancer. Results indicate that the majority of hierarchies involved TP53, PIK3CA, ERBB2, APC, KRAS, EGFR, IDH1, VHL, etc. Research into the order and accumulation of genomic alterations among cancer driver genes will ever-increase as the costs of nextgen sequencing subside, and personalized/precision medicine incorporates whole-genome scans into the diagnosis and treatment of cancer. Keywords: Oncology, Cancer research, Genetics, Computational biology

  5. Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

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    Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

    2009-06-01

    The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

  6. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies.

    LENUS (Irish Health Repository)

    Toomey, Sinead

    2017-07-27

    The Cancer Genome Atlas analysis revealed that somatic EGFR, receptor tyrosine-protein kinase erbB-2 (ERBB2), Erb-B2 receptor tyrosine kinase 3 (ERBB3) and Erb-B2 receptor tyrosine kinase 4 (ERBB4) gene mutations (ERBB family mutations) occur alone or co-occur with somatic mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) in 19% of human epidermal growth factor receptor 2 (HER2)-positive breast cancers. Because ERBB family mutations can activate the PI3K\\/AKT pathway and likely have similar canonical signalling effects to PI3K pathway mutations, we investigated their combined impact on response to neoadjuvant HER2-targeted therapies.

  7. Somatic cancer variant curation and harmonization through consensus minimum variant level data

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    Deborah I. Ritter

    2016-11-01

    Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

  8. Molecular pathology of prostate cancer.

    Science.gov (United States)

    Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

    2010-01-01

    This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

  9. Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer

    Directory of Open Access Journals (Sweden)

    Wang Yu-Fen

    2006-04-01

    Full Text Available Abstract Background The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. Methods The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE, followed by direct DNA sequencing to identify the mutations. Results Fourteen somatic mtDNA mutations were identified in 55% (11/20 of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64% were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. Conclusion Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations.

  10. INFECTIOUS DISEASES IN CHILDREN: THE ROLE IN THE OCCURRENCE OF SOMATIC PATHOLOGY

    Directory of Open Access Journals (Sweden)

    L. N. Mazankova

    2013-01-01

    Full Text Available The article examines the relationship of infectious diseases, especially opportunistic and viral infections, with the formation of chronic and physical illness. Scientific meta-analysis of the effect of infections on the start of autoimmune disease, chronic diseases of broncho-pulmonary and cardiovascular system, gastrointestinal tract, urinary and other systems is carried out. Special attention is given to the role of fetal viral infection in the development of congenital malformations and intrauterine pathology. The article discusses the prevention measures taken for controlling certain somatic diseases.

  11. Golden rules in practice of cancer pathology

    African Journals Online (AJOL)

    M.N. El-Bolkainy

    2016-07-21

    Jul 21, 2016 ... Recent 5-year survival data of different cancer sites are presented with a .... Thanks to the break through discoveries of effective therapeutic modalities, ... The author of 111 scientific papers and 16 books on cancer pathology ...

  12. Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer

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    Adam Shlien

    2016-08-01

    Full Text Available Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.

  13. Pathological and Biological Aspects of Colorectal Cancer Treatment.

    NARCIS (Netherlands)

    Gosens, M.J.E.M.

    2008-01-01

    Pathological and biological aspects of colorectal cancer treatment. This thesis describes several pathological and biological aspects of colorectal cancer treatment. Different patient populations were investigated including patients with mobile rectal cancer enrolled in the Dutch TME trial, patients

  14. Biophysical pathology in cancer transformation

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Pokorný, Jan

    S1, Nov (2013), s. 1-9 ISSN 2324-9110 R&D Projects: GA ČR(CZ) GAP102/11/0649 Institutional support: RVO:68378271 ; RVO:67985882 Keywords : cancer biophysics * Warburg effect * reverse Warburg effect * biological electrodynamics * coherent states Subject RIV: BO - Biophysics

  15. Late somatic sequelae after treatment of childhood cancer in Slovenia

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    Erman Nuša

    2012-05-01

    Full Text Available Abstract Background This is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic. Methods The data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model. Results The incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis. Conclusions The change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment

  16. Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer

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    van Haaften, Gijs; Dalgliesh, Gillian L; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Chris; Edkins, Sarah; Hardy, Claire; O’Meara, Sarah; Teague, Jon; Butler, Adam; Hinton, Jonathan; Latimer, Calli; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J; Cole, Jennifer; Dunmore, Rebecca; Forbes, Simon; Jia, Mingming; Jones, David; Kok, Chai Yin; Leroy, Catherine; Lin, Meng-Lay; McBride, David J; Maddison, Mark; Maquire, Simon; McLay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Lee, Mulderrig; Mudie, Laura; Pleasance, Erin; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S; Turner, Rachel; Turrell, Kelly; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Collins, V Peter; Ichimura, Koichi; Law, Simon; Wong, John; Yuen, Siu Tsan; Leung, Suet Yi; Tonon, Giovanni; DePinho, Ronald A; Tai, Yu-Tzu; Anderson, Kenneth C; Kahnoski, Richard J.; Massie, Aaron; Khoo, Sok Kean; Teh, Bin Tean; Stratton, Michael R; Futreal, P Andrew

    2010-01-01

    Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase, UTX, pointing to histone H3 lysine methylation deregulation in multiple tumour types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene. PMID:19330029

  17. [Predictors of efficiency of autogenous melodeclamation training in patients with chronic somatic pathology].

    Science.gov (United States)

    Trdatian, N A

    2009-01-01

    This controlled study involving 99 patients with chronic somatic diseases (CSD) had the objective to identify psychological predictors of the efficiency of a new method of psychotherapy, namely autogenous melodeclamation training (AMDT). Dynamics of the psychological status of the patients in the course of therapy was assessed using SMOL test, Spilberger STAI test, overall health-physical activity-mood test, and Beck depression inventory. It was shown that moderately compromised psychological adaptation and minor depressive disorders were the most reliable predictors of marked improvement of the patients' psychological status under effect of autogenous melodeclamation training included in the combined rehabilitative therapy of chronic somatic diseases.

  18. Transcription factor Oct1 is a somatic and cancer stem cell determinant.

    Directory of Open Access Journals (Sweden)

    Jessica Maddox

    Full Text Available Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LOCD44(HI cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI and dye efflux(HI cells, and increasing Oct1 increases the proportion of ALDH(HI cells. Normal ALDH(HI cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.

  19. Cancer treatment in childhood and testicular function: the importance of the somatic environment

    Science.gov (United States)

    Stukenborg, Jan-Bernd; Jahnukainen, Kirsi; Hutka, Marsida

    2018-01-01

    Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment. PMID:29351905

  20. Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers.

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    Briggs, Sarah; Tomlinson, Ian

    2013-06-01

    Polymerases ε and δ are the main enzymes that replicate eukaryotic DNA. Accurate replication occurs through Watson-Crick base pairing and also through the action of the polymerases' exonuclease (proofreading) domains. We have recently shown that germline exonuclease domain mutations (EDMs) of POLE and POLD1 confer a high risk of multiple colorectal adenomas and carcinoma (CRC). POLD1 mutations also predispose to endometrial cancer (EC). These mutations are associated with high penetrance and dominant inheritance, although the phenotype can be variable. We have named the condition polymerase proofreading-associated polyposis (PPAP). Somatic POLE EDMs have also been found in sporadic CRCs and ECs, although very few somatic POLD1 EDMs have been detected. Both the germline and the somatic DNA polymerase EDMs cause an 'ultramutated', apparently microsatellite-stable, type of cancer, sometimes leading to over a million base substitutions per tumour. Here, we present the evidence for POLE and POLD1 as important contributors to the pathogenesis of CRC and EC, and highlight some of the key questions in this emerging field. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Population-based statistical inference for temporal sequence of somatic mutations in cancer genomes.

    Science.gov (United States)

    Rhee, Je-Keun; Kim, Tae-Min

    2018-04-20

    It is well recognized that accumulation of somatic mutations in cancer genomes plays a role in carcinogenesis; however, the temporal sequence and evolutionary relationship of somatic mutations remain largely unknown. In this study, we built a population-based statistical framework to infer the temporal sequence of acquisition of somatic mutations. Using the model, we analyzed the mutation profiles of 1954 tumor specimens across eight tumor types. As a result, we identified tumor type-specific directed networks composed of 2-15 cancer-related genes (nodes) and their mutational orders (edges). The most common ancestors identified in pairwise comparison of somatic mutations were TP53 mutations in breast, head/neck, and lung cancers. The known relationship of KRAS to TP53 mutations in colorectal cancers was identified, as well as potential ancestors of TP53 mutation such as NOTCH1, EGFR, and PTEN mutations in head/neck, lung and endometrial cancers, respectively. We also identified apoptosis-related genes enriched with ancestor mutations in lung cancers and a relationship between APC hotspot mutations and TP53 mutations in colorectal cancers. While evolutionary analysis of cancers has focused on clonal versus subclonal mutations identified in individual genomes, our analysis aims to further discriminate ancestor versus descendant mutations in population-scale mutation profiles that may help select cancer drivers with clinical relevance.

  2. Somatic mutations in breast and serous ovarian cancer young patients : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Encinas, Giselly; Maistro, Simone; Pasini, Fatima Solange; Hirata Katayama, Maria Lucia; Brentani, Maria Mitzi; de Bock, Geertruida Hendrika; Azevedo Koike Folgueira, Maria Aparecida

    2015-01-01

    Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of

  3. Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors.

    Science.gov (United States)

    Franke, F E; Pauls, K; Kerkman, L; Steger, K; Klonisch, T; Metzger, R; Alhenc-Gelas, F; Burkhardt, E; Bergmann, M; Danilov, S M

    2000-12-01

    Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P =.032 for sACE; P =.005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. HUM PATHOL 31:1466-1476. Copyright 2000 by W.B. Saunders Company

  4. Research into the biological effects of ionizing radiation somatic effects II: non-cancer

    International Nuclear Information System (INIS)

    Bond, V.P.

    1980-01-01

    Somatic effects of radiation can be considered in two categories: low and high level effects. In the low level exposure region (defined here arbitrarily as a single dose of the order of 10 rads or less, or higher doses at very low dose rates), the only somatic effects other than cancer known definitely at present to have health significance are those on fertiltiy and on the developing individual from conception to near birth. Knowledge of these effects is inadequate at present, and the bulk of this report will be devoted to discussing the types of additional investigations required. With respect to non-cancer somatic effects of radiation at intermediate to high doses and dose rates, enough is known to describe in general the course of early (over the first days to perhaps six weeks) effects, following different doses of external radiation. In particular, the non-cancer late effects of intermediate to high doses of internal and external radiation need better definition. The distinction between non-cancer and cancer-related somatic effects is blurred, at least at high dose levels

  5. Depression, anxiety, and somatic symptoms in older cancer patients: a comparison across age groups.

    Science.gov (United States)

    Cohen, Miri

    2014-02-01

    Previous studies have reported that older cancer patients experience lower psychological distress than younger patients, but most prior studies do not differentiate between age groups within the 'older' category. The aim of this study was to assess the intensity of the symptoms of depression, anxiety, and somatic symptoms among different age groups of older cancer patients. Participants were composed of 321 cancer patients 60 years and older, who were divided into three age groups: 60-69, 70-79, and 80+ years. The participants answered the Brief Symptom Inventory-18, which included subscales for depression, anxiety, and somatic symptoms and the cancer-related problem list, in addition to providing personal and cancer-related details. Depressive, anxiety, and somatic symptoms and cancer-related problems were lowest in the 70-79 years age group and highest in the 80+ years age group. Comparisons between pairs of groups showed significant differences between each of the groups in Brief Symptom Inventory total scores and between the 80+ years age group and the other two groups in regard to depressive symptoms and cancer-related problems. Differences, related to anxiety and somatic symptoms, were significant for the 70-79 year olds, in comparison with the youngest and oldest groups. Intensity of symptoms was explained by older age, higher number of cancer-related problems, female gender, and lower income. Nonlinear relations exist between age and psychological symptoms, which is in line with the postponement of age-related health and functional decline in the modern era. These results suggest that the study of psychological reactions to cancer should examine differences between age groups among older cancer patients. Copyright © 2013 John Wiley & Sons, Ltd.

  6. Measuring somatic symptoms with the CES-D to assess depression in cancer patients after treatment : Comparison among patients with oral/oropharyngeal, gynecological, colorectal, and breast cancer

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; Stewart, R.E.; Ranchor, A.V.; Roodenburg, J.L.N.

    2006-01-01

    There is a high prevalence of depression after cancer treatment. In the literature, several authors have raised questions about assessing somatic symptoms to explore depression after cancer treatment. These somatic sequelae are a consequence of cancer treatment and should cause higher depression

  7. Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs.

    Science.gov (United States)

    Christoforides, Alexis; Carpten, John D; Weiss, Glen J; Demeure, Michael J; Von Hoff, Daniel D; Craig, David W

    2013-05-04

    The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations--changes specific to a tumor and not within an individual's germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.

  8. [Pathogenetic associations of periodontal diseases with somatic therapeutic pathology, comorbid conditions in patients of advanced and senile age: state-of-the-art review. Part 1. Associations of periodontal diseases with somatic therapeutic pathology in patients of advanced and senile age].

    Science.gov (United States)

    Ar'eva, G T; Solov'ev, M M; Ar'ev, A L; Ryzhak, G A

    2014-01-01

    The state-of-the-art review of literature on existing views on the association of periodontal diseases with somatic therapeutic pathology (first part of the review) and comorbid conditions (second part of the review) is submitted. The conclusion about need of carrying out the further multicenter researches which purpose is development of new integrated indicators, in a complex and comprehensively characterizing not only the periodontal status, but also set of available somatic therapeutic pathology, especially at pa- tients of advanced and senile age is drawn.

  9. Somatic mutation analysis of MYH11 in breast and prostate cancer

    International Nuclear Information System (INIS)

    Alhopuro, Pia; Karhu, Auli; Winqvist, Robert; Waltering, Kati; Visakorpi, Tapio; Aaltonen, Lauri A

    2008-01-01

    MYH11 (also known as SMMHC) encodes the smooth-muscle myosin heavy chain, which has a key role in smooth muscle contraction. Inversion at the MYH11 locus is one of the most frequent chromosomal aberrations found in acute myeloid leukemia. We have previously shown that MYH11 mutations occur in human colorectal cancer, and may also be associated with Peutz-Jeghers syndrome. The mutations found in human intestinal neoplasia result in unregulated proteins with constitutive motor activity, similar to the mutant myh11 underlying the zebrafish meltdown phenotype characterized by disrupted intestinal architecture. Recently, MYH1 and MYH9 have been identified as candidate breast cancer genes in a systematic analysis of the breast cancer genome. The aim of this study was to investigate the role of somatic MYH11 mutations in two common tumor types; breast and prostate cancers. A total of 155 breast cancer and 71 prostate cancer samples were analyzed for those regions in MYH11 (altogether 8 exons out of 42 coding exons) that harboured mutations in colorectal cancer in our previous study. In breast cancer samples only germline alterations were observed. One prostate cancer sample harbored a frameshift mutation c.5798delC, which we have previously shown to result in a protein with unregulated motor activity. Little evidence for a role of somatic MYH11 mutations in the formation of breast or prostate cancers was obtained in this study

  10. The untapped potential of digital pathology in prostate cancer ...

    African Journals Online (AJOL)

    Xavier Farré

    2018-02-07

    Feb 7, 2018 ... prostate cancer diagnosis and medical education ... Discussion: Digital pathology platforms could offer new solutions to the diagnostic and ... Peer review under responsibility of Pan African Urological Surgeons' Association.

  11. Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis

    Directory of Open Access Journals (Sweden)

    Michael Castro

    2016-07-01

    Full Text Available Background: Synchronous cancers have occasionally been detected at initial diagnosis among patients with breast and ovarian cancer. However, simultaneous coexistence and diagnosis of breast and pancreas cancer has not previously been reported. Case Report: Paternal transmission of a germline BRCA2 mutation to a patient who was diagnosed at age 40 with locally advanced breast and pancreas cancer is presented. Somatic genomic analysis of both cancers with next-generation DNA sequencing confirmed the germline result and reported a variety of variants of unknown significance alterations, of which two were present in both the breast and pancreas cancers. Discussion: The possibility that genomic alterations could have been responsible for modulating the phenotypic or clinical expression of this rare presentation is considered. The authors call attention to the practice of privatizing the clinicogenetic information gained from genetic testing and call for health policy that will facilitate sharing in order to advance the outcomes of patients diagnosed with hereditary cancers.

  12. Scientific projection paper for somatic effects I - cancer

    International Nuclear Information System (INIS)

    Burns, F.J.

    1980-01-01

    Radiation-induced cancer is a research problem that bridges a wide spectrum of biophysical and biomedical scientific fields. The precise specification and integration of all of the events and interactions following the absorption of ionizing radiation by target tissues is not yet understood and is the subject of current and planned research. Most research on radiation carcinogenesis can be roughly categorized as being quantitative and/or qualitative in nature. Quantitative radiation carcinogenesis research generally assists in developing risk assessment values. Dose-response curves and models are generated, to provide a basis for extrapolation to low doses from high doses and rates, and assist in supporting risk assessment in the regulatory process. An independent research arena addresses the general question of basic mechanisms, interactions, and fundamental events that play a significant role in radiation-caused cancer. From these studies are evolved hypotheses and molecular, cellular, and tissue models. The development of the full field theory that completely explains why absorbed ionizing radiation causing cancer has the obvious promise of new approaches to cancer control and prevention, as well as potential to ameliorate radiation injury. This section attempts to highlight these areas from the molecular level of study to that of whole populations, from the basic mechanistic approach through the quantification of radiation cancer risk

  13. Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.

    Science.gov (United States)

    Iacovazzo, Donato; Caswell, Richard; Bunce, Benjamin; Jose, Sian; Yuan, Bo; Hernández-Ramírez, Laura C; Kapur, Sonal; Caimari, Francisca; Evanson, Jane; Ferraù, Francesco; Dang, Mary N; Gabrovska, Plamena; Larkin, Sarah J; Ansorge, Olaf; Rodd, Celia; Vance, Mary L; Ramírez-Renteria, Claudia; Mercado, Moisés; Goldstone, Anthony P; Buchfelder, Michael; Burren, Christine P; Gurlek, Alper; Dutta, Pinaki; Choong, Catherine S; Cheetham, Timothy; Trivellin, Giampaolo; Stratakis, Constantine A; Lopes, Maria-Beatriz; Grossman, Ashley B; Trouillas, Jacqueline; Lupski, James R; Ellard, Sian; Sampson, Julian R; Roncaroli, Federico; Korbonits, Márta

    2016-06-01

    Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101

  14. Detection of somatic mutations by high-resolution DNA melting (HRM) analysis in multiple cancers.

    Science.gov (United States)

    Gonzalez-Bosquet, Jesus; Calcei, Jacob; Wei, Jun S; Garcia-Closas, Montserrat; Sherman, Mark E; Hewitt, Stephen; Vockley, Joseph; Lissowska, Jolanta; Yang, Hannah P; Khan, Javed; Chanock, Stephen

    2011-01-17

    Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each). HRM analysis was performed in exons of the following candidate genes known to harbor established commonly observed mutations: PIK3CA, ERBB2, KRAS, TP53, EGFR, BRAF, GATA3, and FGFR3. Bi-directional sequencing analysis was used to determine the accuracy of the HRM analysis. For the 39 mutations observed in frozen samples, the sensitivity and specificity of HRM analysis were 97% and 87%, respectively. There were 67 mutation/variants in the paraffin-embedded samples, and the sensitivity and specificity for the HRM analysis were 88% and 80%, respectively. Paraffin-embedded samples require higher quantity of purified DNA for high performance. In summary, HRM analysis is a promising moderate-throughput screening test for mutations among known candidate genomic regions. Although the overall accuracy appears to be better in frozen specimens, somatic alterations were detected in DNA extracted from paraffin-embedded samples.

  15. Detection of somatic mutations by high-resolution DNA melting (HRM analysis in multiple cancers.

    Directory of Open Access Journals (Sweden)

    Jesus Gonzalez-Bosquet

    Full Text Available Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each. HRM analysis was performed in exons of the following candidate genes known to harbor established commonly observed mutations: PIK3CA, ERBB2, KRAS, TP53, EGFR, BRAF, GATA3, and FGFR3. Bi-directional sequencing analysis was used to determine the accuracy of the HRM analysis. For the 39 mutations observed in frozen samples, the sensitivity and specificity of HRM analysis were 97% and 87%, respectively. There were 67 mutation/variants in the paraffin-embedded samples, and the sensitivity and specificity for the HRM analysis were 88% and 80%, respectively. Paraffin-embedded samples require higher quantity of purified DNA for high performance. In summary, HRM analysis is a promising moderate-throughput screening test for mutations among known candidate genomic regions. Although the overall accuracy appears to be better in frozen specimens, somatic alterations were detected in DNA extracted from paraffin-embedded samples.

  16. Statistical method on nonrandom clustering with application to somatic mutations in cancer

    Directory of Open Access Journals (Sweden)

    Rejto Paul A

    2010-01-01

    Full Text Available Abstract Background Human cancer is caused by the accumulation of tumor-specific mutations in oncogenes and tumor suppressors that confer a selective growth advantage to cells. As a consequence of genomic instability and high levels of proliferation, many passenger mutations that do not contribute to the cancer phenotype arise alongside mutations that drive oncogenesis. While several approaches have been developed to separate driver mutations from passengers, few approaches can specifically identify activating driver mutations in oncogenes, which are more amenable for pharmacological intervention. Results We propose a new statistical method for detecting activating mutations in cancer by identifying nonrandom clusters of amino acid mutations in protein sequences. A probability model is derived using order statistics assuming that the location of amino acid mutations on a protein follows a uniform distribution. Our statistical measure is the differences between pair-wise order statistics, which is equivalent to the size of an amino acid mutation cluster, and the probabilities are derived from exact and approximate distributions of the statistical measure. Using data in the Catalog of Somatic Mutations in Cancer (COSMIC database, we have demonstrated that our method detects well-known clusters of activating mutations in KRAS, BRAF, PI3K, and β-catenin. The method can also identify new cancer targets as well as gain-of-function mutations in tumor suppressors. Conclusions Our proposed method is useful to discover activating driver mutations in cancer by identifying nonrandom clusters of somatic amino acid mutations in protein sequences.

  17. RELATIONSHIP OF SOME MARKERS OF PSYCHO-EMOTIONAL STATE AND DEVELOPMENT OF SOMATIC PATHOLOGY IN THE PATIENTS WITH OCCUPATIONAL DISEASES

    Directory of Open Access Journals (Sweden)

    Игорь Петрович Данилов

    2017-10-01

    Conclusions. The relationship between the emotional and personal attitude to health and a healthy lifestyle and the development of somatic diseases in the patients with occupational diseases has been revealed.

  18. Pathological study on preoperative concurrent chemoradiation for advanced hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Inoue, Toshiya; Nagata, Motoki; Yukawa, Hisaya

    2008-01-01

    Chemoradiotherapy is frequently applied as the first-line therapy for advanced hypopharyngeal cancer. However, organ-preserving therapy does not allow true pathological assessment of the effectiveness of the therapy. We therefore determined the following treatment modality for advanced hypopharyngeal cancer based on local findings upon the completion of radiotherapy at 40 Gy. Pathological assessments of 33 cases of advanced hypopharyngeal cancer who had undergone extended operation after chemoradiotherapy were performed. The pathological effects were 12 cases of Grade 1, 13 cases of Grade 2 and 8 cases of Grade 3. However, the rate of tumor-free cases was only 60% of the extended operation. In those cases, the local controlled lesions were well, however, distant metastases influenced the outcome; to control distant metastasis is a future issue. Additional studies to select a surgical approach will be needed. (author)

  19. Clinico pathological presentation of tongue cancers and early cancer treatment

    International Nuclear Information System (INIS)

    Najeeb, T.

    2006-01-01

    Objective: To analyze clinico pathological presentation of tongue cancers and to calculate survival rates (SR) with disease free survival rates (DFSR) and recurrence rates (RR) in different treatment modalities and to compare the results of surgery alone and radiotherapy alone in stage I and stage II disease and to calculate better option of treatment in early tongue cancers. Design: A longitudinal study. Place and Duration of Study: Department of Otolaryngology and Head and Neck Surgery, Pakistan Institute of Medical Sciences, Islamabad (PIMS) from January 1987 to June 1998. Patients and Methods: Case histories of 67 patients were collected from departmental record. Clinical data included age at diagnosis, gender of patient, location of tumor, presenting symptoms and their duration, biopsy report, predominant histological pattern of tumor, nodal status, stage of tumor, treatment modality employed, tumor recurrence, metastasis and survival rates with disease-free survival rates after 2 years' follow-up. Results: Among 67 patients there were 31 males and 36 females. Mean age was 50 years (range 20 - 80 years). Sixty seven patients with primary cancer of tongue constituted 38.8% of oral cavity cancers during period of 1987 - 1998 in PIMS. Smoking, poor oro dental hygiene (POOH) and betel nuts chewing were the main risk factors. Odynophagia and painful ulcers on lateral border of tongue were the main clinical symptoms with average duration of 7 months. Regional lymph nodes were palpable in 32.8%, 5.5% was in stage I, 35.8% in stage II, 29.8% in stage III, and 28.3% was in stage IV. No patient was found to have distant metastasis. Histopathology in 94% of cases was squamous cell carcinoma (SCC). Recurrence and survival rates were determined in 49 patients. Average time of recurrence was 12.5 months. Recurrence was 100% loco regional (LR). It was 85.7% in patients treated with radiotherapy (RT) alone, 42.1% in patients treated with surgery alone and 31.2% in patients

  20. Classification of breast cancer patients using somatic mutation profiles and machine learning approaches.

    Science.gov (United States)

    Vural, Suleyman; Wang, Xiaosheng; Guda, Chittibabu

    2016-08-26

    The high degree of heterogeneity observed in breast cancers makes it very difficult to classify the cancer patients into distinct clinical subgroups and consequently limits the ability to devise effective therapeutic strategies. Several classification strategies based on ER/PR/HER2 expression or the expression profiles of a panel of genes have helped, but such methods often produce misleading results due to their dynamic nature. In contrast, somatic DNA mutations are relatively stable and lead to initiation and progression of many sporadic cancers. Hence in this study, we explore the use of gene mutation profiles to classify, characterize and predict the subgroups of breast cancers. We analyzed the whole exome sequencing data from 358 ethnically similar breast cancer patients in The Cancer Genome Atlas (TCGA) project. Somatic and non-synonymous single nucleotide variants identified from each patient were assigned a quantitative score (C-score) that represents the extent of negative impact on the gene function. Using these scores with non-negative matrix factorization method, we clustered the patients into three subgroups. By comparing the clinical stage of patients, we identified an early-stage-enriched and a late-stage-enriched subgroup. Comparison of the mutation scores of early and late-stage-enriched subgroups identified 358 genes that carry significantly higher mutations rates in the late stage subgroup. Functional characterization of these genes revealed important functional gene families that carry a heavy mutational load in the late state rich subgroup of patients. Finally, using the identified subgroups, we also developed a supervised classification model to predict the stage of the patients. This study demonstrates that gene mutation profiles can be effectively used with unsupervised machine-learning methods to identify clinically distinguishable breast cancer subgroups. The classification model developed in this method could provide a reasonable

  1. Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Giselly Encinas

    2015-10-01

    Full Text Available Summary Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC or serous ovarian cancer (SOC. Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at ≤35 and ≤40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger and 16 studies (598, 41 younger, were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.

  2. The untapped potential of digital pathology in prostate cancer ...

    African Journals Online (AJOL)

    Discussion: Digital pathology platforms could offer new solutions to the diagnostic and educational challenges facing pathologists practicing in Africa. For prostate cancer, they could provide several advantages including the assessment of biopsy cores, measurement of tumor volumes and second opinion consultation of ...

  3. Quality of pathology reports for advanced ovarian cancer

    DEFF Research Database (Denmark)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant...

  4. Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

    Science.gov (United States)

    Ilie, M; Hofman, P

    2012-01-01

    New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

  5. Leptin and Pathological Indexes in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    B Noori Alavicheh

    2015-06-01

    Full Text Available Background & aim: Breast cancer is the most common cancer among women and one of the factors threatening the health of women worldwide. Leptin is a 16 kD glycoprotein hormone produced predominantly by white adipose tissue. Leptin binds to receptors in the hypothalamus and plays a key role in regulation of metabolism. Both leptin and leptin receptor have recently been implicated in processes and progress leading to breast cancer initiation. The aim of this study was to identify if there is association between leptin and pathological indexes in patients with breast cancer Methods: 45women with breast cancer were enrolled. Serum leptin levels of patients were measured by the ELISA method. Pathological information such as stage of the breast cancer, Hormonal receptor (ER, PR and Her2 status in these patients were determined. Result: Results revealed that the patients who were in stage one and two, the mean serum leptin level was (34.18±21.22 ng/ml And patients who were in stage three and four, the mean serum leptin level was (32.21±21/93 ng/ml. Also the mean serum leptin levels in patients whose receptor status of ER, PR and HER2 positive were (35.90±23.55, 35.74±23.91and 37.02±24.25ng/ml, respectively. The Patients whose receptor status of ER, PR and HER2 negative were 26.64±13.13, 28.17±14.26and31.32±19.9ng/ml respectively. No significant association was found between leptin leveland stage of the breast cancer, hormonal receptor (ER, PR and Her2 status in Patients with Breast cancer(p>0.05. Conclusions: In this study, no association was found between serum leptin level and pathological indices in women with Breast cancer in Yasuj, Iran.

  6. Survival pathological prognosis factors in breast cancer

    International Nuclear Information System (INIS)

    Gonzalez-Longoria Boada, Lourdes B.

    2012-01-01

    A descriptive and longitudinal study of 273 women with breast cancer belonging to Granma province was carried out from 2003 to 2004, in order to analyze the survival of this female population, reason why the method of Kaplan Meier was used for the calculation of the mentioned variable and the Log Rank test was used for the comparison of curves. Patients with higher survival at 5 years were those who had tumors of 2 cm or less (87.5%), histological grade I (90.3%), nuclear grade I (88.3%), as well as the absence of vascular, lymphatic or lymph node invasion (with 80.6; 74.9 and 6.1% respectively). Also, tumor size, histological and nuclear grade, nodal status, as well as lymphatic and vascular invasion constituted prognosis factors, which favored the individualization of therapeutic behaviors

  7. Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

    Science.gov (United States)

    Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

    2015-02-01

    Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  8. EMMPRIN in gynecologic cancers: pathologic and therapeutic aspects.

    Science.gov (United States)

    Liu, Dan-tong

    2015-07-01

    The highly glycosylated transmembrane protein extracellular matrix metalloproteinase inducer (EMMPRIN) is associated with several pathological conditions, including various types of cancers. In different gynecological malignancies, such as ovarian, cervical, and endometrial cancers, EMMPRIN plays significant roles in cell adhesion modulation, tumor growth, invasion, angiogenesis, and metastasis by inducing the production of various molecules, including matrix metalloproteinases and vascular endothelial growth factor. Because of its high level of expression, EMMPRIN can possibly be used as a diagnostic marker of gynecological cancers. Recent studies have showed that targeting EMMPRIN, especially by RNA interference (RNAi) technology, has promising therapeutic potential in basic research on gynecological cancer treatments, which make a platform for the future clinical success. This review study focused on the association of EMMPRIN in gynecological cancers in the perspectives of pathogenesis, diagnosis, and therapeutics.

  9. Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population

    Directory of Open Access Journals (Sweden)

    Alireza Torabi

    2016-08-01

    Full Text Available Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs, have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125, low grade dysplasia (cervical intraepithelial neoplasia (CIN-I, n = 4, high grade dysplasia (CIN-II and -III, n = 5 and invasive carcinoma (squamous cell carcinoma (SCC, n = 5 followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6% and pre-cancer and cancer (91.3% groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05 using Kyoto Encyclopedia of Genes and Genomes (KEGG. This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings.

  10. The dreams of a cancer patient: a "royal road" to understanding the somatic illness.

    Science.gov (United States)

    Calogeras, R C; Alston, T M

    2000-12-01

    In this paper we have presented the principal dreams of a 39-year-old female patient in order to demonstrate how closely the dreams were linked with the understanding of her cancerous condition. The analysis, lasting over a period of eight years, ended with the remission of the patient's cancerous condition to the point where she was without pain and symptom-free. The findings suggested that her dreams played a special role in her analysis by providing important landmarks regarding her treatment's progress and state of her cancerous condition. In a general sense, it was concluded that the patient's dreams did provide a "royal road" to understanding her somatic illness. Specifically, it was concluded that, first, the patient's dreams were able to represent quite reliably, in symbolic form, the state of her cancerous condition; second, that the cancer condition and transference-countertransference reactions were closely entwined; and third, that each of the patient's dreams seemed to be introduced by a crisis situation connected with a traumatic early memory.

  11. A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer. | Office of Cancer Genomics

    Science.gov (United States)

    Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kb centromeric to the AR. Systematic perturbation of this enhancer using genome editing decreased proliferation by suppressing AR levels. Insertion of an additional copy of this region sufficed to increase proliferation under low androgen conditions and to decrease sensitivity to enzalutamide.

  12. The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

    Science.gov (United States)

    Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

    2018-02-28

    Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

  13. Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

    Directory of Open Access Journals (Sweden)

    Michael Seiler

    2018-04-01

    Full Text Available Summary: Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA, and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like, or hotspot mutation profile (oncogene-like. Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. : Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration. Keywords: splicing, SF3B1, U2AF1, SRSF2, RBM10, FUBP1, cancer, mutation

  14. Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

    Science.gov (United States)

    Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

    2016-01-01

    Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

  15. The use of a proforma improves colorectal cancer pathology reporting.

    Science.gov (United States)

    Rigby, K.; Brown, S. R.; Lakin, G.; Balsitis, M.; Hosie, K. B.

    1999-01-01

    The detail and accuracy of pathological reporting for colorectal cancer is becoming increasingly recognised as important in the overall management of the patient. However, there is criticism of the variable standards of reporting. We assessed how the use of a proforma affected the completeness of reporting within one hospital. Data on all colorectal cancer patients attending one teaching hospital has been collected prospectively over a 15 month period from 1997 to 1998. The Royal College of Surgeons/Association of Coloproctology proforma lists all items considered to be essential for a complete pathological report of colorectal cancer. Its introduction in September 1997 allowed us to compare reporting before the proforma to that after. Of 54 patients, 46 (85%) had one or more items missing from their report before introduction of the proforma compared with only 8/44 (18%) patients after the proforma (P < 0.001). Circumferential resection margins and apical node status were the items most often absent, being significantly more frequently reported after the proforma (P < 0.05 and P < 0.001, respectively). There was no difference in the median number of lymph nodes harvested after proforma introduction. The introduction of the proforma has not only resulted in improvements in reporting, but has increased the dialogue between surgical oncologists and pathologists. These features should result in improved overall management of the colorectal cancer patient. PMID:10655894

  16. Colorectal Cancers: An Update on Their Molecular Pathology.

    Science.gov (United States)

    Inamura, Kentaro

    2018-01-20

    Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.

  17. Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.

    Directory of Open Access Journals (Sweden)

    Kay Dias

    Full Text Available Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified. Second, genes differentially expressed between claudin-low tumors and all other molecular subtypes of breast cancer were identified. Third, a number of these top differentially expressed genes were tested using immunohistochemistry for expression in a diverse panel of breast cancer cell lines to determine their specificity for claudin-low tumors. Finally, the immunohistochemical panel found to be most characteristic of claudin-low tumors was examined in a cohort of 942 formalin fixed paraffin embedded human breast cancers with >10 years clinical follow-up to evaluate the clinico-pathologic and survival characteristics of this tumor subtype. Using this approach we determined that claudin-low breast cancer is typically negative for ER, PR, HER2, claudin 3, claudin 4, claudin 7 and E-cadherin. Claudin-low tumors identified with this immunohistochemical panel, were associated with young age of onset, higher tumor grade, larger tumor size, extensive lymphocytic infiltrate and a circumscribed tumor margin. Patients with claudin-low tumors had a worse overall survival when compared to patients with luminal A type breast cancer. Interestingly, claudin-low tumors were associated with a low local recurrence rate following breast conserving therapy. In conclusion, a limited panel of antibodies can facilitate the identification of

  18. Resectable stage III lung cancer: CT, surgical, and pathologic correlation

    International Nuclear Information System (INIS)

    Scott, I.R.; Muller, N.L.; Miller, R.R.; Evans, K.G.; Nelems, B.

    1987-01-01

    Patients with stage IIIa lung cancer have improved survival following surgery. The authors reviewed the CT, surgical, and pathologic findings in 26 patients with completely resected stage IIIa lung cancer. These include examples of the different subsets of stage IIIa disease. CT correctly predicted chest-wall invasion in only two of ten patients, pericardial involvement in one of three, and tumor extension to within 2 cm of the carina in one of three patients. It detected mediastinal nodal disease in eight of 11 patients. CT is of limited value in assessing chest-wall or pericardial extension; however, such extension does not preclude complete resection. Ipsilateral nodal involvement also doses not preclude surgery

  19. Hashimoto's Thyroiditis Pathology and Risk for Thyroid Cancer

    Science.gov (United States)

    Paparodis, Rodis; Imam, Shahnawaz; Todorova-Koteva, Kristina; Staii, Anca

    2014-01-01

    Background: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC. Methods: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery. Patients with HT at final pathology were studied further. To estimate thyroid function, patients with preoperative hypothyroid HT (Hypo-HT) were divided into three equal groups based on their LT4 replacement: LT4-Low (1.43 μg/kg). A group of preoperatively euthyroid (Euth-HT) patients but with HT by pathology was also studied. All subjects were also grouped based on their TPO-Ab titer in TPO-high (titer >1:1000) or TPO-low/negative (titer thyroid glands (LT4-Low) but not in fully hypothyroid HT (LT4-Mid and LT4-High). High TPO-Ab titers appear to protect against DTC in patients with HT. PMID:24708347

  20. Guidance for laboratories performing molecular pathology for cancer patients

    Science.gov (United States)

    Cree, Ian A; Deans, Zandra; Ligtenberg, Marjolijn J L; Normanno, Nicola; Edsjö, Anders; Rouleau, Etienne; Solé, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J Han

    2014-01-01

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here. PMID:25012948

  1. Esophagographic findings of early esophageal cancer : comparison with pathologic results

    International Nuclear Information System (INIS)

    Chung, Jae Joon; Kim, Choong Bai; Kim, Ho Guen; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik

    1998-01-01

    The purpose of this study is to investigate the esophagographic findings of early esophageal cancer (EEC), and to compare these with the pathologic results, and to thus determine the most useful method of esophagography for detection of EEC. We examined 18 patients (M:F=16:2) with pathologically proven EEC; 17 cases were squamous cell carcinoma and one was adenocarcinoma. Tumor size, shape and location were evaluated by esophagography and the findings were compared with the pathologic results. The tumors were 0.5 - 7 cm in size; all except two were smaller than 4 cm. Twelve were located in the middle esophagus, five cases in the lower esophagus and one case in the upper esophagus; in ten cases, the margin was ill-defined. Esophagography showed that eight cases were of the superficial depressed type, seven were the superficial elevated type, and three were the tumorous type. All 18 cases were detected by double contrast study, but mucosal relief study and barium filling study revealed only ten and eight cases, respectively; for the detection of EEC double contrast study was thus the most useful. EEC was commonly demonstrated in the middle esophagus with an ill-defined margin; it was of the superficial depressed or elevated type. For the detection of EEC, double contrast study was the most useful. (author). 14 refs., 1 tab., 5 figs

  2. Endometrial cancer and somatic G>T KRAS transversion in patients with constitutional MUTYH biallelic mutations.

    Science.gov (United States)

    Tricarico, Rossella; Bet, Paola; Ciambotti, Benedetta; Di Gregorio, Carmela; Gatteschi, Beatrice; Gismondi, Viviana; Toschi, Benedetta; Tonelli, Francesco; Varesco, Liliana; Genuardi, Maurizio

    2009-02-18

    MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for PTEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis.

  3. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying Su

    2015-06-01

    Full Text Available Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

  4. [Quality of DNA from archival pathological samples of gallbladder cancer].

    Science.gov (United States)

    Roa, Iván; de Toro, Gonzalo; Sánchez, Tamara; Slater, Jeannie; Ziegler, Anne Marie; Game, Anakaren; Arellano, Leonardo; Schalper, Kurt; de Aretxabala, Xabier

    2013-12-01

    The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

  5. Molecular pathology and prostate cancer therapeutics: from biology to bedside.

    Science.gov (United States)

    Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

    2014-01-01

    Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Postoperative radiation for cervical cancer with pathologic risk factors

    International Nuclear Information System (INIS)

    Hart, Kimberly; Han, Ihn; Deppe, Gunter; Malviya, Vinay; Malone, John; Christensen, Carl; Chuba, Paul; Porter, Arthur

    1997-01-01

    Purpose: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. Methods and Materials: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidentally at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. Results: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced

  7. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  8. Stem Cell Interaction with Somatic Niche May Hold the Key to Fertility Restoration in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Deepa Bhartiya

    2012-01-01

    Full Text Available The spontaneous return of fertility after bone marrow transplantation or heterotopic grafting of cryopreserved ovarian cortical tissue has surprised many, and a possible link with stem cells has been proposed. We have reviewed the available literature on ovarian stem cells in adult mammalian ovaries and presented a model that proposes that the ovary harbors two distinct populations of stem cells, namely, pluripotent, quiescent, very small embryonic-like stem cells (VSELs, and slightly larger “progenitor” ovarian germ stem cells (OGSCs. Besides compromising the somatic niche, oncotherapy destroys OGSCs since, like tumor cells, they are actively dividing; however VSELs persist since they are relatively quiescent. BMT or transplanted ovarian cortical tissue may help rejuvenate the ovarian niche, which possibly supports differentiation of persisting VSELs resulting in neo-oogenesis and follicular development responsible for successful pregnancies. Postnatal oogenesis in mammalian ovary from VSELs may be exploited for fertility restoration in cancer survivors including those who were earlier deprived of gametes and/or gonadal tissue cryopreservation options.

  9. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

    2015-11-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

  10. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    International Nuclear Information System (INIS)

    Joo, Ijin; Kim, Haeryoung; Lee, Jeong Min

    2015-01-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients

  11. Clinical, mammographic, and pathologic concordance in breast cancer

    International Nuclear Information System (INIS)

    Rodriguez Cascaret, Argenis; Martin Rodriguez, Andres; Hernandez Castellanos, Kirenia

    2011-01-01

    An observational descriptive and cross-sectional study was carried out in 100 patients with breast cancer, who attended the Breast Care Department at 'Conrado Benitez' Teaching Oncology Hospital in Santiago de Cuba from August 2009 to July 2010, to characterize them according to imaging, pathological, clinical, and general variables. Percentage as summary measure to statically validate the results and Kappa index to determine diagnostic concordance were used. Women between 40-49 years with history of fibrocystic breast disease and palpable lesions, as well as lump in the right breast, upper outer quadrant and periphery of the breast, tumor greater than one centimeter in diameter and infiltrating ductal carcinoma in the stages III-b and IV prevailed in the case material.(author)

  12. Molecular Pathology: A Requirement for Precision Medicine in Cancer.

    Science.gov (United States)

    Dietel, Manfred

    2016-01-01

    The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's tissue as 'deeply' as possible and obtaining information on the morphological, genetic, proteomic and epigenetic background are the tasks of pathologists and molecular biologists and provide the clinicians with information relevant for precision medicine. Intensified cooperation between clinicians and pathologists will provide the basis of improved clinical drug selection and guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry. © 2016 S. Karger GmbH, Freiburg.

  13. [MRI findings and pathological features of occult breast cancer].

    Science.gov (United States)

    Zhang, J J; Yang, X T; Du, X S; Zhang, J X; Hou, L N; Niu, J L

    2018-01-23

    Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

  14. Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2017-07-01

    Full Text Available To explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients.

  15. 77 FR 59941 - Prospective Grant of Exclusive License: Terahertz Scanning Systems for Cancer Pathology

    Science.gov (United States)

    2012-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Terahertz Scanning Systems for Cancer Pathology AGENCY: National Institutes of Health... field of use limited to terahertz scanning systems for cancer pathology. Upon the expiration or...

  16. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  17. Effect of mindfulness-based stress reduction on somatic symptoms, distress, mindfulness and spiritual wellbeing in women with breast cancer

    DEFF Research Database (Denmark)

    Würtzen, Hanne; Dalton, Susanne Oksbjerg; Christensen, Jane

    2015-01-01

    Background. Women with breast cancer experience different symptoms related to surgical or adjuvant therapy. Previous findings and theoretical models of mind-body interactions suggest that psychological wellbeing, i.e. levels of distress, influence the subjective evaluation of symptoms, which...... influences or determines functioning. The eight-week mindfulness-based stress reduction (MBSR) program significantly reduced anxiety and depression in breast cancer patients in a randomized controlled trial (NCT00990977). In this study we tested the effect of MBSR on the burden of breast cancer related...... somatic symptoms, distress, mindfulness and spiritual wellbeing and evaluated possible effect modification by adjuvant therapy and baseline levels of, distress, mindfulness and spiritual wellbeing. Material and methods. A population-based sample of 336 women Danish women operated for breast cancer stages...

  18. Somatic mutation profiles of MSI and MSS colorectal cancer identified by whole exome next generation sequencing and bioinformatics analysis.

    Directory of Open Access Journals (Sweden)

    Bernd Timmermann

    Full Text Available BACKGROUND: Colorectal cancer (CRC is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS and microsatellite instable (MSI colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations.

  19. [Role of contemporary pathological diagnostics in the personalized treatment of cancer].

    Science.gov (United States)

    Tímár, József

    2013-03-01

    Due to the developments of pathology in the past decades (immunohistochemistry and molecular pathology) classification of cancers changed fundamentally, laying a ground for personalized management of cancer patients. Our picture of cancer is more complex today, identifying the genetic basis of the morphological variants. On the other hand, this picture has a much higher resolution enabling us to subclassify similar histological cancer types based on molecular markers. This redefined classification of cancers helps us to better predict the possible biological behavior of the disease and/or the therapeutic sensitivity, opening the way toward a more personalized treatment of this disease. The redefined molecular classification of cancer may affect the universal application of treatment protocols. To achieve this goal molecular diagnostics must be an integral and reimbursed part of the routine pathological diagnostics. On the other hand, it is time to extend the multidisciplinary team with molecular pathologist to improve the decision making process of the management of cancer patients.

  20. Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

    OpenAIRE

    Tao Liu; Jin Li; Dechun Li; Hongqiang Yang; Changhua Kou; Guijun Lei

    2017-01-01

    Abstract Objective To explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients. Methods An immunohistochemistry assay was used to test the expression levels of galectin-3 in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues adjacent to the cancer tissues of 23 cases. The associations between protein expression levels of gal...

  1. NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis.

    Science.gov (United States)

    Le Morvan, Marine; Zinovyev, Andrei; Vert, Jean-Philippe

    2017-06-01

    Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours, and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations.

  2. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    DEFF Research Database (Denmark)

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga

    2015-01-01

    Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrate...

  3. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

    Science.gov (United States)

    Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

    2017-07-01

    A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

  4. Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

    Directory of Open Access Journals (Sweden)

    Francisco J. Candido dos Reis

    2015-07-01

    Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.

  5. Pathology of ovarian cancers in BRCA1 and BRCA2 carriers

    NARCIS (Netherlands)

    Lakhani, Sunil R.; Manek, Sanjiv; Penault-Llorca, Frederique; Flanagan, Adrienne; Arnout, Laurent; Merrett, Samantha; McGuffog, Lesley; Steele, Dawn; Devilee, Peter; Klijn, Jan G. M.; Meijers-Heijboer, Hanne; Radice, Paolo; Pilotti, Silvana; Nevanlinna, Heli; Butzow, Ralf; Sobol, Hagay; Jacquemier, Jocylyne; Lyonet, Dominique Stoppa; Neuhausen, Susan L.; Weber, Barbara; Wagner, Teresa; Winqvist, Robert; Bignon, Yves-Jean; Monti, Franco; Schmitt, Fernando; Lenoir, Gilbert; Seitz, Susanne; Hamman, Ute; Pharoah, Paul; Lane, Geoff; Ponder, Bruce; Bishop, D. Timothy; Easton, Douglas F.

    2004-01-01

    Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the

  6. Interaction of pathology and molecular characterization of thyroid cancers

    International Nuclear Information System (INIS)

    Williams, E.D.; Cherstvoy, E.; Egloff, B.; Hoefler, H.; Vecchio, G.; Bogdanova, T.; Bragarnik, M.; Tronko, N.D.

    1996-01-01

    This paper presents the results of joint studies of thyroid cancer in children under 15 years of age between departments in Cambridge, Brussels, Naples and Munich in the European Union, and departments in Minsk, Kiev and Obninsk in the newly independent states of Eastern Europe. The pathology of 264 cases of childhood thyroid cancer out of 430 that have occurred since 1990 in the 3 countries in which high levels of fallout from the Chernobyl accident occurred has been restudied by NIS and EU pathologists. The overall level of agreement reached was about 97%. The diagnosis was supported by immunocytochemistry and ISH for the differentiation markers, thyroglobulin and calcitonin, and the tumors were classified according to the WHO, with papillary carcinomas being further subclassified. 99% of the 134 Belarussian cases were papillary carcinomas, as were 94% of the 114 Ukrainian tumors. All 9 of the Russian cases available for study were papillary in type. 76 of 154 cases of childhood thyroid cancer reviewed over a 30 year period in England and Wales and were also studied, 68% of these were papillary carcinoma. Histological study showed that a subtype of papillary carcinoma, rarely found in adults, with a solid/follicular architecture occurred in children. It was found in 72% of the Belarussian papillary carcinomas, 76% of the Ukrainian cases, but only 40% of the England and Wales cases. Molecular biological studies showed that the proportion of cases of papillary carcinoma expressing the ret gene was not significantly different in the exposed and the unexposed tumors, studies of the type of translocation leading to ret gene expression are not yet conclusive. Ras gene mutations were found as expected in follicular carcinoma, but were absent from any papillary carcinoma, whether from exposed or unexposed cases. TSH receptor mutations, normally found in follicular tumors were not found in any papillary carcinomas, nor were any p53 mutations identified. All these results

  7. Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors

    International Nuclear Information System (INIS)

    Pereira, Luísa; Soares, Pedro; Máximo, Valdemar; Samuels, David C

    2012-01-01

    The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level. Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO. The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors. Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype

  8. Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages.

    Science.gov (United States)

    Tüzün, Sefa; Yücel, Ahmet Fikret; Pergel, Ahmet; Kemik, Ahu Sarbay; Kemik, Ozgür

    2012-09-01

    High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects. HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001). Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05). These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

  9. Construction of a combinatorial pipeline using two somatic variant  calling  methods  for whole exome sequence data of gastric cancer.

    Science.gov (United States)

    Kohmoto, Tomohiro; Masuda, Kiyoshi; Naruto, Takuya; Tange, Shoichiro; Shoda, Katsutoshi; Hamada, Junichi; Saito, Masako; Ichikawa, Daisuke; Tajima, Atsushi; Otsuji, Eigo; Imoto, Issei

    2017-01-01

    High-throughput next-generation sequencing is a powerful tool to identify the genotypic landscapes of somatic variants and therapeutic targets in various cancers including gastric cancer, forming the basis for personalized medicine in the clinical setting. Although the advent of many computational algorithms leads to higher accuracy in somatic variant calling, no standard method exists due to the limitations of each method. Here, we constructed a new pipeline. We combined two different somatic variant callers with different algorithms, Strelka and VarScan 2, and evaluated performance using whole exome sequencing data obtained from 19 Japanese cases with gastric cancer (GC); then, we characterized these tumors based on identified driver molecular alterations. More single nucleotide variants (SNVs) and small insertions/deletions were detected by Strelka and VarScan 2, respectively. SNVs detected by both tools showed higher accuracy for estimating somatic variants compared with those detected by only one of the two tools and accurately showed the mutation signature and mutations of driver genes reported for GC. Our combinatorial pipeline may have an advantage in detection of somatic mutations in GC and may be useful for further genomic characterization of Japanese patients with GC to improve the efficacy of GC treatments. J. Med. Invest. 64: 233-240, August, 2017.

  10. Pathologically confirmed breast cancer in Malawi: a descriptive study

    African Journals Online (AJOL)

    2015-03-12

    Mar 12, 2015 ... Breast cancer is the most common female cancer in Africa, yet no published studies have ... receptor (HR) negative. However, HR ... to develop early diagnosis efforts to address high mortality rates. .... High Incidence of Triple-.

  11. Early experience after developing a pathology laboratory in Malawi, with emphasis on cancer diagnoses.

    Directory of Open Access Journals (Sweden)

    Satish Gopal

    Full Text Available BACKGROUND: Despite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses. METHODS AND FINDINGS: We performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99% with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%. Among cancers, cervical cancer was most common (n = 117, 14%, followed by lymphoma (n = 91, 11%, esophageal cancer (n = 86, 10%, sarcoma excluding Kaposi sarcoma (n = 75, 9%, and breast cancer (n = 61, 7%. HIV status was known for 95 (11% of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19-1.29 among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14-1.56 among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not. CONCLUSIONS: Despite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical information for

  12. Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships.

    Science.gov (United States)

    Sakr, Rita A; Schizas, Michail; Carniello, Jose V Scarpa; Ng, Charlotte K Y; Piscuoglio, Salvatore; Giri, Dilip; Andrade, Victor P; De Brot, Marina; Lim, Raymond S; Towers, Russell; Weigelt, Britta; Reis-Filho, Jorge S; King, Tari A

    2016-02-01

    Lobular carcinoma in situ (LCIS) has been proposed as a non-obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing. DNA samples extracted from microdissected LCIS, ILC and matched normal breast tissue or peripheral blood from 30 patients were subjected to massively parallel sequencing targeting all exons of 273 genes, including the genes most frequently mutated in breast cancer and DNA repair-related genes. Single nucleotide variants and insertions and deletions were identified using state-of-the-art bioinformatics approaches. The constellation of somatic mutations found in LCIS (n = 34) and ILC (n = 21) were similar, with the most frequently mutated genes being CDH1 (56% and 66%, respectively), PIK3CA (41% and 52%, respectively) and CBFB (12% and 19%, respectively). Among 19 LCIS and ILC synchronous pairs, 14 (74%) had at least one identical mutation in common, including identical PIK3CA and CDH1 mutations. Paired analysis of independent foci of LCIS from 3 breasts revealed at least one common mutation in each of the 3 pairs (CDH1, PIK3CA, CBFB and PKHD1L1). LCIS and ILC have a similar repertoire of somatic mutations, with PIK3CA and CDH1 being the most frequently mutated genes. The presence of identical mutations between LCIS-LCIS and LCIS-ILC pairs demonstrates that LCIS is a clonal neoplastic lesion, and provides additional evidence that at least some LCIS are non-obligate precursors of ILC. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Cancer and air pollution. Aspects of geographical pathology

    Energy Technology Data Exchange (ETDEWEB)

    Garbe, E; Brunet, M

    1970-01-01

    Data on deaths from all cancers in France (both sexes) for 1961-1963 (inclusive), 1966 and 1967 were compared with data relating to air pollution levels, including consumption of petroleum and petroleum products, per capita consumption of fossil fuels, population density and the urbanization coefficients for each of the departments of France, obtained at various times from 1951 through 1966. Significant correlations were found between cancer death rates and parameters of air pollution, including a highly significant correlation between the 1961-1963 data on cancer deaths and the 1951-1953 data per capita fossil fuel consumption. A comparison of crude cancer mortality rates/100,000 population (av for 1961-1963) and rates of petroleum consumption per unit surface area (1951-1953) showed significant correlations between petroleum consumption and cancer of the larynx, lung and oral cavity in males, breast cancer in females and leukemia in both sexes. When the 1961-1963 data on lung cancer in males (used as an index of urbanization) were compared with similar data for other tumor types in both sexes, the results suggested an urban predominance for cancer of the lung and the rural predominance for cancer of the prostate, stomach and upper g.i and respiratory tracts in males, breast and cervix cancer in females and leukemia in both sexes, and a esophagus in males. The results suggest that industrialization and air pollution are not the only factors of importance in the epidemiology of cancer in urban areas.

  14. Modern Soft Tissue Pathology | Center for Cancer Research

    Science.gov (United States)

    This book comprehensively covers modern soft tissue pathology and includes both tumors and non-neoplastic entities. Soft tissues make up a large bulk of the human body, and they are susceptible to a wide range of diseases. Many soft-tissue tumors are biologically very aggressive, and the chance of them metastasizing to vital organs is quite high. In recent years, the outlook

  15. Considerations for standardizing predictive molecular pathology for cancer prognosis.

    Science.gov (United States)

    Fiorentino, Michelangelo; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2017-01-01

    Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace. Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy. Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.

  16. Prognostic value of pathological response to chemo radiotherapy of locally advanced low rectal cancer

    International Nuclear Information System (INIS)

    Bannura C, Guillermo; Vargas N, Claudio; Barrera E, Alejandro; Melo L, Carlos; Illanes F, Felipe

    2013-01-01

    Background: Preoperative chemo radiotherapy improves the prognosis of locally advanced low rectal cancer and induces a pathological response in the tumor, which may have prognostic value. Aim: To assess the results of rectal cancer treatment according to the degree of pathological response of the tumor after chemo radiotherapy. Patients and Methods: All patients with a locally advanced rectal cancer located within 11 cm of the rectal margin, subjected to preoperative chemo radiotherapy followed by surgical treatment in a period of 13 years, were included. Pathological response was classified as complete, intermediate and poor. The tumor was staged according to TNM 2002 classification. Survival was analyzed with Kaplan Meier curves and Cox regression. Results: Patients were followed for a mean of 50 months (range 18-156). Exclusive and global local relapse was observed in 3 and 9.6% of patients, respectively. Pathological response was complete in 13 patients (none died), intermediate in 23 (three died) and poor in 68 (22 died). Global five years survival was 74%. There was a concordance of 0.64 between survival and pathological response. The concordance between survival and TNM classification was 0.69. Conclusions: The pathological response of the tumor to chemo radiotherapy has a good concordance with prognosis, although it is not superior to the final pathological status

  17. Clinico-pathological characteristics of cervical cancer in Ghanaian

    African Journals Online (AJOL)

    User

    This study found high prevalence of cervical cancer among female geni- tal tract cancers in Accra Ghana. ..... (serotypes 16, 18, 33, 35, 45) of human papilloma- virus (HPV), that are known to cause the condition and the high prevalence of HIV ...

  18. Improving Anatomic Pathology in Sub-Saharan Africa to Support Cancer Care.

    Science.gov (United States)

    Wilson, Michael L; Ayers, Stephanie; Berney, Daniel; Eslan, Alexia; Guarner, Jeannette; Lester, Susan; Masia, Ricard; Moloo, Zahir; Mutuku, Angela; Roberts, Drucilla; Stall, Jennifer; Sayed, Shahin

    2018-03-07

    Cancer care requires both accurate pathologic diagnosis as well as pathologic cancer staging. We evaluated three approaches to training pathologists in sub-Saharan Africa to perform pathologic cancer staging of breast, cervix, prostate, and colorectal cancers. One of three training methods was used at each workshop: didactic, case-based testing (CBT), or a blended approach. The project involved 52 participants from 16 pathology departments in 11 countries in East, Central, and Southern Africa. Evaluation of each method included pre- and postworkshop knowledge assessments, online pre- and postworkshop surveys of practice changes at the individual and institutional levels, and selected site visits. While CBT resulted in the highest overall average postassessment individual scores, both CBT and blended approaches resulted in 19% increases in average scores from pre- to postworkshop assessments. Institutions that participated in the blended workshop had increased changes in practice as indicated by the institutional survey. Both CBT and a blended approach are effective methods for training pathologists in pathologic cancer staging. Both are superior to traditional lectures alone.

  19. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Science.gov (United States)

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  20. Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

    Science.gov (United States)

    Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

    2018-01-01

    Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

  1. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  2. The untapped potential of digital pathology in prostate cancer ...

    African Journals Online (AJOL)

    Xavier Farré

    2018-02-07

    Feb 7, 2018 ... For prostate cancer, they could provide several advantages including the assessment of ... standardization purposes. Conclusion: A ... months or years. This kind of training is expensive and often competitive thus limiting the.

  3. Surgical and pathological outcomes of laparoscopic surgery for transverse colon cancer.

    Science.gov (United States)

    Lee, Y S; Lee, I K; Kang, W K; Cho, H M; Park, J K; Oh, S T; Kim, J G; Kim, Y H

    2008-07-01

    Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes of laparoscopic surgery for transverse colon cancer. Analysis of the medical records of patients who underwent laparoscopic colorectal resection from August 2004 to November 2007 was made. Computed tomography, barium enema, and colonoscopy were performed to localize the tumor preoperatively. Extended right hemicolectomy, transverse colectomy, and extended left hemicolectomy were performed for transverse colon cancer. Surgical outcomes and pathologic outcomes were compared between transverse colon cancer (TCC) and other site colon cancer (OSCC). Of the 312 colorectal cancer patients, 94 patients underwent laparoscopic surgery for OSCC, and 34 patients underwent laparoscopic surgery for TCC. Patients with TCC were similar to patients with OSCC in age, gender, body mass index, operating time, blood loss, time to pass flatus, start of diet, hospital stay, tumor size, distal resection margin, proximal resection margin, number of lymph nodes, and radial margin. One case in TCC and three cases in OSCC were converted to open surgery. Laparoscopic surgery for transverse colon cancer and OSCC had similar peri-operative clinical and acceptable pathological outcomes.

  4. Correlativity study on MRI morphologic features, pathology, and molecular biology of breast cancer

    International Nuclear Information System (INIS)

    Chen Rong; Gong Shuigen; Zhang Weiguo; Chen Jinhua; He Shuangwu; Liu Baohua; Li Zengpeng

    2004-01-01

    Objective: To investigate the correlation among MRI morphologic features, pathology, and molecular biology of breast cancer. Methods: MR scanning was performed in 78 patients with breast cancer before operation and MRI morphologic features of breast cancer were analyzed. The mastectomy specimens of the breast neoplasm were stained with immunohistochemistry, and the expression of estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, p53, and the distribution of microvessel density (MVD) was measured. The pathologic results were compared with MRI features. Results: Among the 80 breast cancers, ER positive expression was positively correlated with the spiculate margin of breast cancer (P 0.05). Among the 41 breast cancers with dynamic MR scans, there was positive correlation between the spatial distribution of contrast agent and MVD (P<0.01). Conclusion: There exists some correlation among MRI morphologic features, pathology, and molecular biology factors in breast cancer to certain extent. The biologic behavior and prognosis of the breast cancer can be assessed according to MRI features

  5. The effects of implementing synoptic pathology reporting in cancer diagnosis: a systematic review.

    Science.gov (United States)

    Sluijter, Caro E; van Lonkhuijzen, Luc R C W; van Slooten, Henk-Jan; Nagtegaal, Iris D; Overbeek, Lucy I H

    2016-06-01

    Pathology reporting is evolving from a traditional narrative report to a more structured synoptic report. Narrative reporting can cause misinterpretation due to lack of information and structure. In this systematic review, we evaluate the impact of synoptic reporting on completeness of pathology reports and quality of pathology evaluation for solid tumours. Pubmed, Embase and Cochrane databases were systematically searched to identify studies describing the effect of synoptic reporting implementation on completeness of reporting and quality of pathology evaluation of solid malignant tumours. Thirty-three studies met the inclusion criteria. All studies, except one, reported an increased overall completeness of pathology reports after introduction of synoptic reporting (SR). Most frequently studied cancers were breast (n = 9) and colorectal cancer (n = 16). For breast cancer, narrative reports adequately described 'tumour type' and 'nodal status'. Synoptic reporting resulted in improved description of 'resection margins', 'DCIS size', 'location' and 'presence of calcifications'. For colorectal cancer, narrative reports adequately reported 'tumour type', 'invasion depth', 'lymph node counts' and 'nodal status'. Synoptic reporting resulted in increased reporting of 'circumferential margin', 'resection margin', 'perineural invasion' and 'lymphovascular invasion'. In addition, increased numbers of reported lymph nodes were found in synoptic reports. Narrative reports of other cancer types described the traditional parameters adequately, whereas for 'resection margins' and '(lympho)vascular/perineural invasion', implementation of synoptic reporting was necessary. Synoptic reporting results in improved reporting of clinical relevant data. Demonstration of clinical impact of this improved method of pathology reporting is required for successful introduction and implementation in daily pathology practice.

  6. An analysis of the impact of pathology review in gynecological cancer

    International Nuclear Information System (INIS)

    Chafe, S.; Honore, L.; Pearcey, R.; Capstick, V.

    1996-01-01

    Objective: To analyze the impact of pathology review in gynecological malignancies. Materials and Methods: A retrospective chart review of all new gynecological patients seen between Dec. 2, 1993 and Jan. 4, 1996 was conducted to determine if a pathological review by the Institute's consultant pathologist altered the diagnosis, and if so whether the alteration changed patient management. A total of 528 patients were seen of which 124 had cervix cancer, 235 had endometrial cancer, 122 had a primary ovarian or peritoneal malignancy, 9 had a vaginal malignancy, 28 had vulvar cancer and 10 had a miscellaneous gynecological malignancy. Results: On pathology review the initial diagnosis was changed in 199 patients. This altered management of 63 patients. For patients with cervical cancer, the grade of tumor was the main alteration in pathological diagnosis, with occasional change in the presence of lymph vascular invasion. These did not translate into patient management changes. The occasional change in depth of invasion altered management in one patient. For endometrial primaries the changes in pathological diagnosis included grade, depth of invasion, and the presence of cervical involvement. This did change management in some cases. For the ovarian malignancies the main changes were grade, extent of disease or variation in histology, some of which resulted in changes in management. One patient with a vaginal lesion had the diagnosis changed which did change management. Of the patients diagnosed with vulvar cancer the pathological diagnosis changed in 8 patients. This included changes in grade and depth of invasion. This altered patient management in 2 patients. The remaining miscellaneous gynecological malignancies had only two diagnosis alterations which did alter management. Conclusion: Pathological reviews of gynecological malignancies are justified as it can alter patient management. In addition, the process facilitates the cooperation of the multidisciplinary team

  7. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Samm, Nicole; Werner, Kristin; Rückert, Felix; Saeger, Hans Detlev; Grützmann, Robert; Pilarsky, Christian

    2010-01-01

    Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-x L and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer

  8. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Hans Detlev Saeger

    2010-12-01

    Full Text Available Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

  9. The pathology of familial breast cancer: Morphological aspects

    International Nuclear Information System (INIS)

    Lakhani, Sunil R

    1999-01-01

    A small proportion of breast cancers are due to a heritable predisposition. Recently, two predisposition genes, BRCA1 and BRCA2, have been identified and cloned. The morphological features of tumours from patients harbouring mutations in the BRCA1 and BRCA2 genes differ from each other and from sporadic breast cancers. Both are of higher grade than are sporadic cases. An excess of medullary/atypical medullary carcinoma has been reported in patients with BRCA1 mutations. Multifactorial analysis, however, shows that the only features independently associated with BRCA1 mutations are a high mitotic count, pushing tumour margins and a lymphocytic infiltrate. For BRCA2 mutation, an association with tubular/lobular carcinoma has been suggested, but not substantiated in a larger Breast Cancer Linkage Consortium study. In multifactorial analysis, the independent features were a lack of tubule formation and pushing tumour margins only. The morphological analysis has implications for clinical management of patients

  10. [Pathological form in breast cancer: setting and evaluation of a professional pratice].

    Science.gov (United States)

    Barré, Maxime; Classe, Jean-Marc; Dravet, François; Dupré, Pierre-François; Loussouarn, Delphine; Toquet, Claire; Sagan, Christine

    2009-06-01

    According to national recommendations, the surgical oncologic specimens addressed to a pathology department must have the required clinical information. The objectives of this study are to evaluate the quality of filling out a pathology form used in breast pathology, to specify the nonconformity consequences on breast management, on histology report and to define modes of action in order to obtain an increase in the number of correct pathology forms. It is a prospective study on pathology forms transmitted with tumorectomy for cancers or microcalcifications filled out by three surgeons from the 1st October, 2004 to the 31st April, 2005. Two hundred and fifty-nine pathology forms were analyzed. There were not correctly filled out in a third of the cases. Nonconformity concerns only one preset information in 69% of pathology forms and is variable according to the surgeons (14 to 31%). The chapters least informed are "lesion" and "type of surgery". These nonconformities involve additional work for the pathologist either because the missing information must be found or because the specimen management must be modified. The prefilled pathology form is a guarantee of quality control. In our study, in 70% of cases, they are accurate. To improve this conformity rate, quality improvement plans must be implemented.

  11. A pathology atlas of the human cancer transcriptome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Zhang, Xi-Cheng; Lee, Sunjae

    2017-01-01

    Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes o...

  12. Guidance for laboratories performing molecular pathology for cancer patients

    NARCIS (Netherlands)

    Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

    2014-01-01

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

  13. CANCER-PAthological breakdown of coherent energy states

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří; Pokorný, Jan; Kobilková, J.; Jandová, Anna; Vrba, J.; Vrba, J. jr.

    2014-01-01

    Roč. 9, č. 1 (2014), s. 115-133 ISSN 1793-0480 Institutional support: RVO:67985882 ; RVO:68378271 Keywords : breakdown of coherent states * Cancer electrodynamics * Warburg effect Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering; BO - Biophysics (FZU-D)

  14. Pathological problems of cancer of the uterine cervix

    International Nuclear Information System (INIS)

    Ohmi, Kazuo

    1981-01-01

    Cancers of the uterine cervix were classified for prediction of radiosensitivity. They were classified into two types: radioresistant type (R-type), in which the cancer was predominated by the properties of adenocarcinoma and was radioresistant, and radiosensitive type (S-type) in all others. In preoperatively irradiated cases of stage IIb cancer of uterine cervix, 84% of R-type cases showed viable cancer cells, and 84% of S-type cases showed tumor disappearance. In cases of radiotherapy in a period 1965 - 70, 69% of stage II cases and 70% of stage III cases of R-type showed disease progress; for S-type, 88% of stage II and 77% of stage III cases had tumor control. In stage III cases given radiotherapy alone in 1971 and 1972 after the histological features were examined, 82% of R-type cases showed tumor recurrence and 77% of S-type cases had disease control. Problems in the classification and assessment were discussed. (Chiba, N.)

  15. Guidance for laboratories performing molecular pathology for cancer patients

    NARCIS (Netherlands)

    Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

  16. The first report of a 5-year period cancer registry in Greece (2009-2013): a pathology-based cancer registry.

    Science.gov (United States)

    Patsea, Eleni; Kaklamanis, Loukas; Batistatou, Anna

    2018-04-01

    Cancer registries are essential in health care, since they allow more accurate planning of necessary health services and evaluation of programs for cancer prevention and control. The Hellenic Society of Pathology (HSP) having recognized the lack of such information in Greece has undertaken the task of a 5-year pathology-based cancer registry in Greece (2009-2013). In this study, > 95% of all pathology laboratories in the national health system hospitals and 100% of pathology laboratories in private hospitals, as well as > 80% of private pathology laboratories have contributed their data. The most common cancer types overall were as follows: breast cancer (18.26%), colorectal cancer (15.49%), prostate cancer (13.49%), and lung cancer (10.24% of all registered cancers). In men, the most common neoplasms were as follows: prostate cancer, colorectal cancer, lung cancer, and gastric cancer. In women, the most common neoplasms were as follows: breast cancer, colorectal cancer, thyroid cancer, and lung cancer. The data on cancer burden in Greece, presented herein, fill the void of cancer information in Greece that affects health care not only nationally but Europe-wise.

  17. Useful radiologic sign in diagnosis of peripheral lung cancer: Nucleohalo sign and its pathologic basis

    International Nuclear Information System (INIS)

    Wang, H.; Shi, D.

    1994-01-01

    The authors investigated the x-ray findings of 117 patients with peripheral lung cancer proved by operation and pathology, of them 35(29.9%) cases were found to have the 'nucleohalo sign', 6(13.6%) in 44 cases of solitary metastatic lung cancers, but none in 167 cases of benign lung nodular lesions and 4 cases of primary lung sarcoma and lymphoma. Radiologic and pathologic correlative study of the nucleohalo sign with surgical specimens of 14 lung cancers suggested that the cancerous parenchymas in nuclear areas were more than the interstitices in 12 cases and the other 2 were equal in both parenchymas and interstitices. Instead, the cancerous parenchymas in halo areas were less than cancerous interstitices in all cases. Dynamic observation of the 'nucleohalo sign' showed that this sign was an appearance of a stage in cancer growth. It is considered a very important sign in x-ray diagnosis of peripheral lung cancer, especially in the early diagnosis of lung cancer under or equal to 3 cm in diameter

  18. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data

    Directory of Open Access Journals (Sweden)

    Tsang Percy CK

    2006-08-01

    Full Text Available Abstract Background Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management. Methods For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using χ2 or Fisher's exact test. Results APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2, endometrial cancer (CASP8, CDH13, hMLH1 and p73, and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1. The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer to the highest 56

  19. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data

    International Nuclear Information System (INIS)

    Yang, Hui-Juan; Liu, Vincent WS; Wang, Yue; Tsang, Percy CK; Ngan, Hextan YS

    2006-01-01

    Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management. For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers) was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using χ 2 or Fisher's exact test. APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2), endometrial cancer (CASP8, CDH13, hMLH1 and p73), and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1). The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers) were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Aberrant methylation

  20. The JAK2 V617F somatic mutation, mortality and cancer risk in the general population

    DEFF Research Database (Denmark)

    Nielsen, Camilla; Birgens, Henrik S; Nordestgaard, Børge G

    2011-01-01

    .1-1.1). Multifactorially adjusted hazard ratios for any cancer, hematologic cancer and myeloproliferative cancer were 3.7 (1.7-8.0), 58 (13-261) and 161 (12-2,197), respectively. Corresponding hazard ratios were 1.2 (0.8-2.0), 2.3 (0.2-25), 1.3 (0.3-5.4) for men versus women, and 1.0 (1.0-1.1), 1.1 (0.9-1.2), 0.9 (0......JAK2 V617F is present in the majority of patients with myeloproliferative cancer; however, its prevalence and clinical significance in the general population is unknown. We screened for presence of the mutation in 10,507 participants from the Copenhagen City Heart Study with up to 17.6 years...

  1. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

    OpenAIRE

    Chen, Victor E.; Gillespie, Erin F.; Zakeri, Kaveh; Murphy, James D.; Yashar, Catheryn M.; Lu, Sharon; Einck, John P.

    2017-01-01

    Purpose: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. Methods and materials: This was an institutional review board–approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservat...

  2. Surgical and pathological outcomes of laparoscopic surgery for transverse colon cancer

    OpenAIRE

    Lee, Y. S.; Lee, I. K.; Kang, W. K.; Cho, H. M.; Park, J. K.; Oh, S. T.; Kim, J. G.; Kim, Y. H.

    2008-01-01

    Purpose Several multi-institutional prospective randomized trials have demonstrated short-term benefits using laparoscopy. Now the laparoscopic approach is accepted as an alternative to open surgery for colon cancer. However, in prior trials, the transverse colon was excluded. Therefore, it has not been determined whether laparoscopy can be used in the setting of transverse colon cancer. This study evaluated the peri-operative clinical outcomes and oncological quality by pathologic outcomes o...

  3. HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer

    International Nuclear Information System (INIS)

    Urushibara, Masayasu; Kageyama, Yukio; Akashi, Takumi; Otsuka, Yukihiro; Takizawa, Touichiro; Koike, Morio; Kihara, Kazunori

    2007-01-01

    Heat shock proteins (HSPs) play crucial roles in cellular responses to stressful conditions. Expression of HSPs in invasive or high-risk superficial bladder cancer was investigated to identify whether HSPs predict pathological response to neoadjuvant chemoradiotherapy (CRT). Immunohistochemistry was used to assess expression levels of HSP27, HSP60, HSP70, HSP90 and p53 in 54 patients with invasive or high-risk superficial bladder cancer, prior to low-dose neoadjuvant CRT, followed by radical or partial cystectomy. Patients were classified into two groups (good or poor responders) depending on pathological response to CRT, which was defined as the proportion of morphological therapeutic changes in surgical specimens. Good responders showed morphological therapeutic changes in two-thirds or more of tumor tissues. In contrast, poor responders showed changes in less than two-thirds of tumor tissues. Using a multivariate analysis, positive HSP60 expression prior to CRT was found to be marginally associated with good pathological response to CRT (P=0.0564). None of clinicopathological factors was associated with HSP60 expression level. In the good pathological responders, the 5-year cause-specific survival was 88%, which was significantly better than survival in the poor responders (51%) (P=0.0373). Positive HSP60 expression prior to CRT may predict good pathological response to low-dose neoadjuvant CRT in invasive or high-risk superficial bladder cancer. (author)

  4. On endocytoscopy and posttherapy pathologic staging in esophageal cancers, and on evidence-based methodology.

    Science.gov (United States)

    Chao, Yin-Kai; Kawada, Kenro; Kumagai, Youichi; Takubo, Kaiyo; Wang, Helen H

    2014-09-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the value of endocytoscopy to replace biopsy histology for squamous cell carcinoma and the clinical significance of posttherapy pathologic stage in patients with esophageal adenocarcinoma following preoperative chemoradiation; a short discussion of evidence-based methodology is also included. © 2014 New York Academy of Sciences.

  5. MutSpec: a Galaxy toolbox for streamlined analyses of somatic mutation spectra in human and mouse cancer genomes.

    Science.gov (United States)

    Ardin, Maude; Cahais, Vincent; Castells, Xavier; Bouaoun, Liacine; Byrnes, Graham; Herceg, Zdenko; Zavadil, Jiri; Olivier, Magali

    2016-04-18

    The nature of somatic mutations observed in human tumors at single gene or genome-wide levels can reveal information on past carcinogenic exposures and mutational processes contributing to tumor development. While large amounts of sequencing data are being generated, the associated analysis and interpretation of mutation patterns that may reveal clues about the natural history of cancer present complex and challenging tasks that require advanced bioinformatics skills. To make such analyses accessible to a wider community of researchers with no programming expertise, we have developed within the web-based user-friendly platform Galaxy a first-of-its-kind package called MutSpec. MutSpec includes a set of tools that perform variant annotation and use advanced statistics for the identification of mutation signatures present in cancer genomes and for comparing the obtained signatures with those published in the COSMIC database and other sources. MutSpec offers an accessible framework for building reproducible analysis pipelines, integrating existing methods and scripts developed in-house with publicly available R packages. MutSpec may be used to analyse data from whole-exome, whole-genome or targeted sequencing experiments performed on human or mouse genomes. Results are provided in various formats including rich graphical outputs. An example is presented to illustrate the package functionalities, the straightforward workflow analysis and the richness of the statistics and publication-grade graphics produced by the tool. MutSpec offers an easy-to-use graphical interface embedded in the popular Galaxy platform that can be used by researchers with limited programming or bioinformatics expertise to analyse mutation signatures present in cancer genomes. MutSpec can thus effectively assist in the discovery of complex mutational processes resulting from exogenous and endogenous carcinogenic insults.

  6. Development and validation of a surgical-pathologic staging and scoring system for cervical cancer.

    Science.gov (United States)

    Li, Shuang; Li, Xiong; Zhang, Yuan; Zhou, Hang; Tang, Fangxu; Jia, Yao; Hu, Ting; Sun, Haiying; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Zhou, Jin; Wang, Shaoshuai; Huang, Kecheng; Wang, Lin; Yao, Yuan; Yang, Qifeng; Yang, Xingsheng; Zhang, Qinghua; Han, Xiaobing; Lin, Zhongqiu; Xing, Hui; Qu, Pengpeng; Cai, Hongbing; Song, Xiaojie; Tian, Xiaoyu; Shen, Jian; Xi, Ling; Li, Kezhen; Deng, Dongrui; Wang, Hui; Wang, Changyu; Wu, Mingfu; Zhu, Tao; Chen, Gang; Gao, Qinglei; Wang, Shixuan; Hu, Junbo; Kong, Beihua; Xie, Xing; Ma, Ding

    2016-04-12

    Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.

  7. Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

    Science.gov (United States)

    Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

    2015-06-01

    Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  8. A computational approach to distinguish somatic vs. germline origin of genomic alterations from deep sequencing of cancer specimens without a matched normal.

    Directory of Open Access Journals (Sweden)

    James X Sun

    2018-02-01

    Full Text Available A key constraint in genomic testing in oncology is that matched normal specimens are not commonly obtained in clinical practice. Thus, while well-characterized genomic alterations do not require normal tissue for interpretation, a significant number of alterations will be unknown in whether they are germline or somatic, in the absence of a matched normal control. We introduce SGZ (somatic-germline-zygosity, a computational method for predicting somatic vs. germline origin and homozygous vs. heterozygous or sub-clonal state of variants identified from deep massively parallel sequencing (MPS of cancer specimens. The method does not require a patient matched normal control, enabling broad application in clinical research. SGZ predicts the somatic vs. germline status of each alteration identified by modeling the alteration's allele frequency (AF, taking into account the tumor content, tumor ploidy, and the local copy number. Accuracy of the prediction depends on the depth of sequencing and copy number model fit, which are achieved in our clinical assay by sequencing to high depth (>500x using MPS, covering 394 cancer-related genes and over 3,500 genome-wide single nucleotide polymorphisms (SNPs. Calls are made using a statistic based on read depth and local variability of SNP AF. To validate the method, we first evaluated performance on samples from 30 lung and colon cancer patients, where we sequenced tumors and matched normal tissue. We examined predictions for 17 somatic hotspot mutations and 20 common germline SNPs in 20,182 clinical cancer specimens. To assess the impact of stromal admixture, we examined three cell lines, which were titrated with their matched normal to six levels (10-75%. Overall, predictions were made in 85% of cases, with 95-99% of variants predicted correctly, a significantly superior performance compared to a basic approach based on AF alone. We then applied the SGZ method to the COSMIC database of known somatic variants

  9. Targeted pharmacotherapy after somatic cancer mutation screening [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Thomas M. Polasek

    2016-09-01

    Full Text Available Many patients with solid tumours are treated with targeted pharmacotherapy based on the results of genetic testing (‘precision medicine’. This study investigated the use of targeted drugs after OncoFOCUS™+KIT screening in patients with malignant melanoma, non-small cell lung cancer and metastatic colorectal cancer, and then audited the results against the National Comprehensive Cancer Network (NCCN guidelines. Patients who were not indicated for targeted pharmacotherapy did not receive such treatment (99%, 100/101. Of the patients indicated for targeted drugs, 79% (33/42 received treatment according to NCCN guidelines. In 48% (20/42 of these patients the results from OncoFOCUS™+KIT screening were required for targeted drug selection, with the remaining 52% (22/42 prescribed drugs independent of the screening results for various reasons. This study highlights the growing importance of precision medicine approaches in directing pharmacotherapy in medical oncology.

  10. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    Science.gov (United States)

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

  11. Estimation of T2 relaxation time of breast cancer: Correlation with clinical, imaging and pathological features

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Mirinae; Sohn, Yu Mee [Dept. of Radiology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Ryu, Jung Kyu; Jahng, Geon Ho; Rhee, Sun Jung; Oh, Jang Hoon; Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2017-01-15

    The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer.

  12. Somatic Cells Become Cancer’s “Starter Dough” | Center for Cancer Research

    Science.gov (United States)

    Cancer stem cells (CSCs) is a term that sparks animated differences of opinions among researchers in the oncology community.  Much of the disagreement comes from the difficulty involved in isolating these cells and manipulating them ex vivo. When putative CSCs are isolated from clinical samples, researchers are unable to retrospectively identify the cell type that suffered the

  13. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated

  14. Pathology of breast cancer in women irradiated for acute postpartum mastitis

    International Nuclear Information System (INIS)

    Dvoretsky, P.M.; Woodard, E.; Bonfiglio, T.A.; Hempelmann, L.H.; Morse, I.P.

    1980-01-01

    The gross and microscopic pathology of breast cancers in women irradiated for acute postpartum mastitis was compared to the breast cancers found in the sisters of the irradiated women. In considering the lesions in the two populations, the size, location, histologic type, histologic grade, inflammatory response, lymphatic and blood vascular invasion, nipple involvement, axillary lymph node metastases, and menopausal status at the time of diagnosis were statistically indistinguishable. The only parameter that was different in the two populations was the desmoplastic response to the malignant lesion. The control population had more marked fibrosis within the cancers compared with the irradiated women

  15. Lipid Peroxidation and Transforming Growth Factor-β1 Levels in Gastric Cancer at Pathologic Stages

    Directory of Open Access Journals (Sweden)

    Özgür Kemik

    2012-09-01

    Full Text Available Objective: High levels of TGF-β1 and enhanced TGF-β1 receptor signaling are related to the pathology of gastric cancer. This effect is caused by oxidative stress and lipid peroxidation products. The aim of this study was to investigate the levels of TGF-β1 and lipid peroxidation products in gastric cancer patients and their correlation with pathologic stage. Material and Methods: Lipid peroxidation products and TGF-β1 levels were studied in the serum samples of 50 gastric cancer patients and 18 control subjects.Results: HNE-protein adducts and TGF-β1 levels were significantly higher in T2, T3 and T4 gastric cancers than in either the T1 stage or controls (p<0.001. Pathologic stage was correlated with TGF-β1 levels (r=0.702, p<0.05.Conclusion: These markers production may contribute to tumor angiogenesis and aid in the prognosis of the gastric cancer.

  16. Intraoperative visualization, frozen section, and permanent pathology in endometrial cancer

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2014-12-01

    Conclusion: Although the sample size of the studied population was small but our study results support the previous data and suggest that in early stages and low grade tumors, gross examination and frozen section diagnosis are conveniently predictive of lymph node metastasis. These data might be useful for prediction of tumor invasion using frozen section and gross examination in low grade tumors and early stages and for doing complete surgical staging and lymph node sampling. However the im-portance of surgical staging always must be considered in patients who need systemat-ic lymphadenectomy. In overall these data might help to come up with new guidelines for surgical risk assessment in endometrial cancer.

  17. The relationship of radiological findings and pathological types of primary lung cancer

    International Nuclear Information System (INIS)

    Kang, Hye Jung; Baik, Dae Il; Han, Chang Yul; Park, Soo Sung

    1982-01-01

    The present study was intended to define the relationship of radiological findings and pathological types of primary lung cancer. The 85 cases was selected after confirmation of the cell types by bronchoscopic biopsy, cervical lymph node or thoracotomy biopsy and lung resection. Results of the study were presented below. 1. Primary lung cancer is frequently developed after 4th decade and males were affected more frequently than females with ratio of 2 to 1. 2. The frequencies of pathologic cell types of lung cancer were presented as follows. Squamous cell carcinoma 40% Adenocarcinoma 25% Undifferential cell carcinoma 30% Alveolar cell carcinoma 5% 3. The findings of plain chest radiography were presented as follows. In squamous cell carcinoma. hilar enlargement or hilar mass is the most frequent findings (53%) with atelectasis (26%) or obstructive pneumonitis (26%). In adenocarcinoma, pleural effusion is accompanied about half of cases (53%). In undifferential cell carcinoma, hilar mass with mediastinal widening and pleural effusion is frequent finding

  18. Casein kinase I epsilon somatic mutations found in breast cancer cause overgrowth in Drosophila

    Czech Academy of Sciences Publication Activity Database

    Doležal, Tomáš; Kučerová, K.; Neuhold, J.; Bryant, P. J.

    2010-01-01

    Roč. 54, č. 10 (2010), s. 1419-1424 ISSN 0214-6282 R&D Projects: GA ČR GA301/07/0814 Institutional research plan: CEZ:AV0Z50070508 Keywords : Drosophila * breast cancer * Dco Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.856, year: 2010 http://www.ijdb.ehu.es/web/paper.php?doi=093032td

  19. Evaluating the Genetic, Hormonal, and Exogenous Factors Affecting Somatic Copy Number Variation in Breast Cancer

    Science.gov (United States)

    2016-10-01

    assess genomic instability in different mammary epithelial populations in vivo and in vitro, 2) determine how mutations in heritable breast cancer genes...respectively, located on chromosome 6. When loci harboring the shRNAs are deleted by a spontaneous mutation event, affected cells become GFP and/or RFP...assay adapted from the yeast genetics literature, we will determine whether baseline deletion rates in normal human mammary epithelial cells (HMECs

  20. Colorectal cancer risk and patients' survival: influence of polymorphisms in genes somatically mutated in colorectal tumors

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Bevier, M.; Pardini, Barbara; Naccarati, Alessio; Vodičková, Ludmila; Novotný, J.; Vodička, Pavel; Hemminki, K.; Försti, A.

    2014-01-01

    Roč. 25, č. 6 (2014), s. 759-769 ISSN 0957-5243 R&D Projects: GA ČR(CZ) GAP304/12/1585; GA ČR GAP304/10/1286 Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1 Institutional support: RVO:68378041 Keywords : colorectal cancer * risk * survival Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.735, year: 2014

  1. Deep Learning for Automated Extraction of Primary Sites From Cancer Pathology Reports.

    Science.gov (United States)

    Qiu, John X; Yoon, Hong-Jun; Fearn, Paul A; Tourassi, Georgia D

    2018-01-01

    Pathology reports are a primary source of information for cancer registries which process high volumes of free-text reports annually. Information extraction and coding is a manual, labor-intensive process. In this study, we investigated deep learning and a convolutional neural network (CNN), for extracting ICD-O-3 topographic codes from a corpus of breast and lung cancer pathology reports. We performed two experiments, using a CNN and a more conventional term frequency vector approach, to assess the effects of class prevalence and inter-class transfer learning. The experiments were based on a set of 942 pathology reports with human expert annotations as the gold standard. CNN performance was compared against a more conventional term frequency vector space approach. We observed that the deep learning models consistently outperformed the conventional approaches in the class prevalence experiment, resulting in micro- and macro-F score increases of up to 0.132 and 0.226, respectively, when class labels were well populated. Specifically, the best performing CNN achieved a micro-F score of 0.722 over 12 ICD-O-3 topography codes. Transfer learning provided a consistent but modest performance boost for the deep learning methods but trends were contingent on the CNN method and cancer site. These encouraging results demonstrate the potential of deep learning for automated abstraction of pathology reports.

  2. Pathological Bases for a Robust Application of Cancer Molecular Classification

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2015-04-01

    Full Text Available Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes, and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors.

  3. A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events.

    Directory of Open Access Journals (Sweden)

    Angela N Brooks

    Full Text Available Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35 have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA. Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML, in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3' splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3' splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types.

  4. Eighteen cases of small breast cancer: a comparative study of mammography, CT scan and pathology

    International Nuclear Information System (INIS)

    Wu Yaopan; Lin Haogao; Cai Peiqiang; Ouyang Yi; Zhang Weizhang; Lu Bingui

    2003-01-01

    Objective: To improve the early diagnosis of breast cancer through a study of the mammography and CT findings of small breast cancer. Methods: The mammography and CT findings of 18 cases of small breast cancer (φ≤2.0 cm in diameter) were studied and compared with pathological results. Results: The diagnostic accuracy of CT and mammography was 83% and 61%, respectively. There was a statistical difference between both modalities (P<0.05), CT scan was superior to mammography. However, there was no difference between them when assessing the lesion arising in F-type breast. In detecting breast fine cluster of calcification, the sensitivity of mammography was better than CT scan. Conclusion: The patient suspected of small breast cancer should take mammography as the first evaluation. CT scan is reserved for the further investigation. The mammography combined with CT scan can improve the early diagnostic rate of breast cancer

  5. Somatic and genetic effects

    International Nuclear Information System (INIS)

    Broerse, J.J.; Barendsen, G.W.; Kal, H.B.; Kogel, A.J. van der

    1983-01-01

    This book contains the extended abstracts of the contributions of the poster workshop sessions on somatic and genetic effects of the 7th international congress of radiation research. They cover the following main topics: haematopoietic and immune systems, mechanisms of late effects in various tissues, endogenous and exogenous factors in radiation carcinogenesis, teratogenic effects, genetic effects, in vitro transformation, tumour induction in different tissues, carcinogenesis in incorporated tissues, cancer epidemology and risk assessment. refs.; figs.; tabs

  6. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006 and Mortality Rates (1997–2009

    Directory of Open Access Journals (Sweden)

    Chantal Babb

    2014-01-01

    Full Text Available Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA from the pathology based National Cancer Registry (1986–2006 and data on mortality (1997–2009 from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma. There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  7. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009).

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  8. 11C-Choline PET/pathology image coregistration in primary localized prostate cancer

    International Nuclear Information System (INIS)

    Grosu, Anca-Ligia; Prokic, Vesna; Weirich, Gregor; Wendl, Christina; Geinitz, Hans; Molls, Michael; Kirste, Simon; Souvatzoglou, Michael; Schwaiger, Markus; Gschwend, Juergen E.; Treiber, Uwe; Weber, Wolfgang A.; Krause, Bernd Joachim

    2014-01-01

    The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of 11 C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). In 28 PC patients, 11 C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71 % of patients, and complete overlap in 4 %. PET/pathology image coregistration can be used for evaluation of different imaging modalities. 11 C-Choline PET failed to distinguish tumour from nontumour tissue. (orig.)

  9. An analysis of the impact of pathology review in gynecologic cancer

    International Nuclear Information System (INIS)

    Chafe, Susan; Honore, Louis; Pearcey, Robert; Capstick, Valerie

    2000-01-01

    Purpose: To analyze the impact of pathology review in gynecologic malignancies. Methods and Materials: For all new gynecologic patients seen between December 2, 1993 and January 4, 1996, we conducted a retrospective chart review to determine if a pathology review by the institute's consultant pathologist changed the diagnosis, and if so whether the change altered patient management. A total of 514 patients were seen, of whom 120 had cervical cancer, 226 had endometrial cancer, 122 had a primary ovarian or peritoneal malignancy, 9 had a vaginal malignancy, 28 had vulvar cancer, and 9 had a miscellaneous gynecologic malignancy. Results: On pathology review the diagnosis changed for 200 of 599 specimens (33%). This altered management for 63 of 514 patients (12%). For patients with cervical cancer, the grade of tumor was the main change in pathologic diagnosis, with occasional change in the presence of lymph vascular invasion. These did not translate into patient management alterations. Eight patients (1.5%) had management alterations. The changes in depth of invasion and vascular invasion altered management for 3 patients. Changes in pap smears resulted in two management alterations, and changes in histologic diagnoses altered management for 3 cases. For endometrial primaries the changes in pathologic diagnosis included grade, depth of invasion, and the presence of cervical involvement. This did alter management in 40 cases (8%). For the ovarian malignancies, the main changes were grade, extent of disease, or histologic classification, some of which (10 patients, 2%) resulted in altered management. One patient with a vaginal lesion had the diagnosis changed, which did alter management. Of the patients diagnosed with vulvar cancer, the pathologic diagnosis changed for 11 patients. This included changes in grade and depth of invasion. This altered management of 2 patients. The remaining miscellaneous gynecologic malignancies had only two diagnosis changes that altered

  10. A wide variety of dynamic contrast-enhanced MR appearances of breast cancer: Pathologic correlation study

    International Nuclear Information System (INIS)

    Onishi, Masayuki; Furukawa, Akira; Takahashi, Masashi; Murata, Kiyoshi

    2008-01-01

    Purpose: The aim of this study was to elucidate the characteristic magnetic resonance (MR) appearance of breast cancers, as well as, its variations and to investigate the pathology providing different patterns of dynamic-MR appearances. Materials and methods: Fifty-two women with cancer underwent mastectomy (52 tumors resected) and had MR imaging at our institution between April 2001 and March 2004. MR images of T1WI, T2WI, dynamic-MRI and contrast-enhanced T1WI were obtained and evaluated. Dynamic-MR images were correlated with pathological findings. Results: Common MR appearance of breast cancer was a focal mass either with irregular or spiculated margins with similar signal intensity on T1WI as and similar to higher signal intensity on T2WI compared to the normal mammary gland. On static contrast-enhanced T1WI, apparent enhancement was typically observed. On dynamic MRI, tumor-rim-enhancement on an early phase image and washout enhancement pattern on dynamic images, both characteristic for breast cancer, were observed, however, the prevalence of them was relatively low, which could be explained by the variation of histopathology among breast cancer nodules. Conclusion: In diagnosing breast masses on MRI, as well as the common and characteristic findings of breast cancer, the variations of MR findings and their underlying histopathology should also be considered

  11. Image and pathological changes after microwave ablation of breast cancer: A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Wenbin [Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Jiang, Yanni [Department of Radiology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Chen, Lin; Ling, Lijun; Liang, Mengdi; Pan, Hong [Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Wang, Siqi [Department of Radiology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Ding, Qiang [Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Liu, Xiaoan, E-mail: liuxiaoan@126.com [Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China); Wang, Shui, E-mail: ws0801@hotmail.com [Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029 (China)

    2014-10-15

    Highlights: • We report successful experience of MWA in breast cancer under local anesthesia. • We report MR imaging evaluation of microwave ablation zone in breast cancer. • Pathological changes after microwave ablation in breast cancer was reported. • 2 min MWA caused an ablation zone with three diameters > 2 cm in breast cancer. - Abstract: Purpose: To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer. Materials and methods: Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area. Results: All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM. Conclusions: 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future.

  12. Comparison of MRI of liver cancer (preoperative and resected liver specimen) and pathological feature

    International Nuclear Information System (INIS)

    Tanaka, Toshihiko

    1990-01-01

    Twenty-one nodules of hepatocellular carcinoma (HCC) and eighteen nodules of liver metastasis, which were confirmed pathologically, were investigated by MRI before operation and MRI of resected liver specimen. Pre-operative MRI pointed out all HCCs and seventeen metastases. STIR method was most useful for detection of HCCs. T2WI and STIR method were most useful for detection of liver metastases. Pre-operative MRI also revealed 93% of capsule formation, 29% of septal formation, 75% of fatty metamorphosis of HCC and 75% of necrosis of liver metastasis, and post-operative MRI of resected specimens revealed 100% of capsule formation, 71% of septal formation, 75% of fatty metamorphosis of HCC and 88% of necrosis of liver metastasis. T1WI showed a high intensity halo surrounding metastasis. This characteristic peripheral halo was seen in 22% of metastases. These findings corresponded to pathological feature of liver cancer. MRI was thought to be useful diagnostic modality of liver cancer. (author)

  13. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    Science.gov (United States)

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Classical pathological variables recorded in the Danish Breast Cancer Cooperative Group's register 1978-2006

    DEFF Research Database (Denmark)

    Kiaer, Henrik W; Laenkholm, Anne-Vibeke; Nielsen, Bernt B

    2008-01-01

    >50mm from 7 to 4%. The distribution of the histological subtypes of malignant breast tumours has been almost unchanged. We found however a significant increase in the number of high grade tumours. A large increase in the number of removed axillary lymph nodes from 1989-2001 is related to improved......The Danish Breast Cancer Cooperative Group's register containing data from about 75 000 patients undergoing surgery for primary invasive breast cancer from 1978-2006 has been examined for classical pathological variables. During that period the diagnostic approach of malignant breast tumours...

  15. Influence of Body Mass Index on Tumor Pathology and Survival in Uterine Cancer

    DEFF Research Database (Denmark)

    Bjerrum Kristensen, Anne; Hare-Bruun, Helle; Høgdall, Claus Kim

    2017-01-01

    OBJECTIVE: To evaluate the influence of body mass index (BMI) on endometrial tumor pathology, stage and complication rate and to identify individual prognostic factors, such as BMI, in types I and II endometrial cancer. DESIGN: Register study included all Danish women who underwent surgery...... I and II endometrial cancer were retrieved. Kaplan-Meier plot was used to illustrate differences in survival in relation to BMI. Log-rank test was used to demonstrate difference between the curves. Cox regression hazard model was used to estimate hazard ratios (HR) of the effect of BMI on overall...

  16. Quantitative Imaging In Pathology (QUIP) | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    This site hosts web accessible applications, tools and data designed to support analysis, management, and exploration of whole slide tissue images for cancer research. The following tools are included: caMicroscope: A digital pathology data management and visualization plaform that enables interactive viewing of whole slide tissue images and segmentation results. caMicroscope can be also used independently of QUIP. FeatureExplorer: An interactive tool to allow patient-level feature exploration across multiple dimensions.

  17. Gastric wall shortening in early gastric cancer: upper gastrointestinal series and pathologic correlation

    International Nuclear Information System (INIS)

    Kim, In Jae; Choi, Chul Soon; Kim, Eun Ah; Kim, Kyu Sun; Yun, Ku Sub; Kim, Ho Chul; Bae, Sang Hun; Kang, Gu; Shin, Hyung Sik

    1995-01-01

    To investigate the causes of gastric wall shortening in early gastric cancer, upper gastrointestinal study was correlated with pathologic findings. We evaluated 41 cases (M:F = 1.7:1, average age = 49) of early gastric cancer, retrospectively. The gastric wall shortening were classified as Grade I; none, Grade II; intermediate, and Grade III; prominent. Pathologic findings such as size of lesions, depth of tumor invasion, degree of the submucosal fibrosis, degree of thickness of the submucosa and muscularis propria, and morphologic patterns of lesions including conversing mucosal folds were correlated with the degree of gastric wall shortening on upper gastrointestinal series. Submucosal fibrosis was present in 4 cases in Grade I (n = 21), 4 cases in Grade II (n = 6) and 8 cases in Grade III (n = 10). Positive conversing mucosal folds were seen in 5 cases in Grade I (n = 17), 0 case in Grade II (n = 2) and 9 cases in Grade III (n = 9). Gastric wall shortening was significantly associated with submucosal fibrosis and conversing mucosal folds of early gastric cancer. (ρ = 0.0001, and ρ = 0.02, respectively) Upper gastrointestinal finding of gastric wall protrusion in patients with early gastric cancer should not misinterprete as advanced gastric cancer since the finding could be a result of submucosal fibrosis

  18. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.

    Science.gov (United States)

    Vanderlaan, Paul A; Yamaguchi, Norihiro; Folch, Erik; Boucher, David H; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Goldstein, Michael A; Huberman, Mark S; Kocher, Olivier N; Costa, Daniel B

    2014-04-01

    Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special

  19. Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations

    Science.gov (United States)

    Quirke, Phil; Risio, Mauro; Lambert, René; von Karsa, Lawrence

    2010-01-01

    In Europe, colorectal cancer is the most common newly diagnosed cancer and the second most common cause of cancer deaths, accounting for approximately 436,000 incident cases and 212,000 deaths in 2008. The potential of high-quality screening to improve control of the disease has been recognized by the Council of the European Union who issued a recommendation on cancer screening in 2003. Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document consists of ten chapters and an extensive evidence base. The content of the chapter dealing with pathology in colorectal cancer screening and diagnosis is presented here in order to promote international discussion and collaboration leading to improvements in colorectal cancer screening and diagnosis by making the principles and standards recommended in the new EU Guidelines known to a wider scientific community. PMID:21061133

  20. The Microscope against Cell Theory: Cancer Research in Nineteenth-Century Parisian Anatomical Pathology.

    Science.gov (United States)

    Loison, Laurent

    2016-07-01

    This paper examines the reception of cell theory in the field of French anatomical pathology. This reception is studied under the lens of the concept of the cancer cell, which was developed in Paris in the 1840s. In the medical field, cell theory was quickly accessible, understood, and discussed. In the wake of research by Hermann Lebert, the cancer cell concept was supported by a wealth of high-quality microscopic observations. The concept was constructed in opposition to cell theory, which appears retrospectively paradoxical and surprising. Indeed, the biological atomism inherent in cell theory, according to which the cell is the elementary unit of all organs of living bodies, appeared at the time incompatible with the possible existence of pathological cells without equivalent in healthy tissues. Thus, the postulate of atomism was used as an argument by Parisian clinicians who denied the value of the cancer cell. This study shows that at least in the field of anatomical pathology, cell theory did not directly result from the use of the microscope but was actually hindered by it. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. CLINICORADIOLOGICAL AND PATHOLOGICAL CORRELATION OF LUNG CANCER PATIENTS PRESENTING TO A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Mehak Sawhney

    2017-04-01

    Full Text Available BACKGROUND Lung cancer is the most common cancer worldwide since 1985, both in terms of incidence and mortality. Globally, lung cancer is the largest contributor to new cancer diagnoses and cancer-related deaths. The aim of the study is to study the clinical, radiological and pathological features of patients diagnosed with lung carcinoma. MATERIALS AND METHODS This observational and cross-sectional study was conducted at Himalayan Institute of Medical Sciences (HIMS, which is a large tertiary centre of Uttarakhand on 77 patients of proven lung carcinoma diagnosed over a period of February 2015 to March 2016. The clinical history of the patients was recorded in detail along with the radiological and pathological findings. Ethical clearance certificate was obtained from the ethical committee. RESULTS The study included a total of 77 patients of proven lung carcinoma. Out of the total patients, 70 were males and 7 were females. Cough was the most common symptom. Smoking was the commonest addiction (89.61% in the patients. Non-small cell carcinoma was seen in 59 patients while small cell carcinoma was seen in 23.38% of the cases. Amongst the total patients of non-small cell carcinoma, the maximum number of patients had squamous cell carcinoma (56%. CONCLUSION This study showed that smoking is a principle risk factor in causation of lung carcinoma. Lung cancer should be suspected in an old person presenting with cough and other symptoms such as malaise, weight loss etc. Squamous cell carcinoma is still the most common histological type of lung cancer in India.

  2. Correlation between p53 expression and clinical-pathological characteristics of gastric cancer

    Directory of Open Access Journals (Sweden)

    Radovanović Dragče

    2011-01-01

    Full Text Available Backgraund/Aim. Gene p53, or “cell genome keeper”, has a preventive effect on the occurrence of genetic aberrations and prevents abnormal expansion of (tumor cells. In gastric cancer cells in most cases we register high expression of mutated p53 gene, which correlates with prognosis and specific clinicalpathological characteristics of gastric cancer. Methods. Using the imunohistochemical method we determined the level of expression of p53 protein in 62 gastric cancers and 30 precancerous conditions (intestinal metaplasia of the stomach. We analyzed the relationship of the level of p53 expression and clinical pathological characteristics of gastric cancer. Results. Expression of p53 was positive in 42 (67.7% tumor cases and in 7 (14.3% cases of intestinal metaplasia. Expression of P53 and stomach cancer were in direct correlation (p = 0.000. Sensitivity for p53 in stomach cancer cases was 67.7% (42/62, and specifility was 76.7% (23/30. Expression of mutated p53 protein was in direct correlation with the invasion of lymph nodes (p = 0.034 and with invasion of blood vessels by carcinoma cells (p = 0.042. Conclusion. There is a direct correlation between p53 expression and gastric cancer and it indicates the ability of carcinoma cells to invade blood vessels.

  3. Pseudocarcinomatous hyperplasia of the fallopian tube mimicking tubal cancer: a radiological and pathological diagnostic challenge.

    Science.gov (United States)

    Lee, Nam Kyung; Choi, Kyung Un; Han, Ga Jin; Kwon, Byung Su; Song, Yong Jung; Suh, Dong Soo; Kim, Ki Hyung

    2016-11-14

    Pseudocarcinomatous hyperplasia of the fallopian tube is a rare, benign disease characterized by florid epithelial hyperplasia. The authors present the history and details of a 22-year-old woman with bilateral pelvic masses and a highly elevated serum CA-125 level (1,056 U/ml). Ultrasonography and magnetic resonance imaging (MRI) of the pelvis showed bilateral adnexal complex cystic masses with a fusiform or sausage-like shape. Contrast-enhanced fat-suppressed T1-weighted images showed enhancement of papillary projections of the right adnexal mass and enhancement of an irregular thick wall on the left adnexal mass, suggestive of tubal cancer. Based on MRI and laboratory findings, laparotomy was performed under a putative preoperative diagnosis of tubal cancer. The final pathologic diagnosis was pseudocarcinomatous hyperplasia of tubal epithelium associated with acute and chronic salpingitis in both tubes. The authors report a rare case of pseudocarcinomatous hyperplasia of the fallopian tubes mimicking tubal cancer.

  4. Adenopathies in lung cancer: a comparison of pathology, Computed Tomography and endoscopic ultrasound findings

    International Nuclear Information System (INIS)

    Potepan, P.; Meroni, E.; Spinelli, P.

    1999-01-01

    A prospective comparative study with pathology was performed to assess the clinical value of Computed Tomography (CT) and endoscopic ultrasound (EUS) for nodal staging in lung cancer. A total of 329 nodal stations were dissected or sampled and 755 lymph nodes were examined at histology. On a pre-station basis, CT had greater sensitivity (74%) than EUS (56%), but EUS was more specific (83% versus 93%). The accuracy rates of the two techniques were similar. In conclusion, endoscopic ultrasound should be part of a routine preoperative diagnostic approach to non-small-cell lung cancer., because of its high specificity. Results can be improved when EUS and CT are combined., which suggests that these imaging modalities should be used together in selected patients for the noninvasive staging of non-small-cell lung cancer to identify local lymphatic spread [it

  5. [Clinical and pathological features of breast cancer in a population of Mexico].

    Science.gov (United States)

    Maffuz-Aziz, Antonio; Labastida-Almendaro, Sonia; Espejo-Fonseca, Aura; Rodríguez-Cuevas, Sergio

    Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  6. Breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-69. Pathologic features

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, D H [Veterans Administration Hospital, Kansas (USA); Land, C E; Choi, K; Tokuoka, S; Liu, P I

    1981-01-01

    The pathological features of 161 cases of breast cancer --7% noninfiltrating carcinoma, 47% nonspecific infiltrating duct carcinoma, 21% nonfiltrating papillary duct carcinoma, 7% comedo carcinoma, 6% medullary carcinoma, 6% colloid carcinoma, 4% lobular carcinoma, and 2% sarcoma-- were investigated and their relation to irradiation dosage due to the atomic bomb was studied. Irradiation dosage was estimated from T65 dosage, the total dosage of ..gamma..-rays and neutrons in unshielded tissue. However, there was no relation between the dosage and any specific tissue type. Breast cancers were classified as either type I, type II, or type III according to the histological grade, and each grade was divided according to the degree of differentiation, multiplicity, and mitiotic activity. The pathological characteristics, lymphatic infiltration, fibrosis, necrosis, localization, calcification, and vascular, perineurial, muscular, and dermal invasion were investigated in each case. The histological grade and the incidence of localized invasion, necrosis, localization, and calcification were lower in the patients who were irradiated with more than 50 rad than in those who were not irradiated. The absolute risk rate for breast cancer was estimated to increase by 1.9 cases/100,000 rad from 1950 to 1969. This increase was much smaller than that estimated from x-ray irradiation during medical treatment in North America. The dose response curves at Hiroshima and Nagasaki were similar and fitted well with a linear model, suggesting that the effect of ..gamma..-rays was analogous to that of neutrons in inducing cancer. The problems involved in the histological classification of breast cancer and the histological differences between cancer patients in Japan and in the U.S.A. were discussed.

  7. Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

    International Nuclear Information System (INIS)

    Patel, Samir; Portelance, Lorraine; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis

    2007-01-01

    Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients

  8. CT presentations of colorectal cancer with chronic schistosomiasis: A comparative study with pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei, E-mail: zhangwei976@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Wang, Pei-Jun, E-mail: peijunwang_tongji@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Shen, Xing, E-mail: shenxing1997@163.com [Department of Radiology, Traditional Chinese Hospital, No. 189, Chaoyangxi Road, Kun Shan 215300, Jiangsu Province (China); Wang, Guo-liang, E-mail: glwang1960@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Zhao, Xiao-hu, E-mail: tiger1968@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Seema, S.F., E-mail: saaaamaaaa@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Zheng, Shao-qiang, E-mail: shaoqiangzh@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China); Li, Ming-hua, E-mail: minghuali@163.com [Department of Radiology, Tongji Hospital, Tongji University, No. 389, Xincun Road, Putuo District, Shanghai 200065 (China)

    2012-08-15

    Objective: To clarify pathological basis of computed tomography (CT) presentations of colorectal cancer (CRC) with schistosomiasis for the purpose of improving the accuracy of CT diagnosis and differential diagnosis of the condition. Materials and methods: 130 patients (87 male and 43 female; age range 49-86 years, mean 71.1) were selected whose diagnoses were pathologically confirmed as CRC with schistosomiasis. All the patients underwent abdominal plain CT and contrast enhanced scanning. The location, morphology, size, calcification features and enhancement modalities (patterns) were evaluated and compared with the pathological findings by two radiologists in a blind way. Results: CT showed that in 130 patients, the tumors occurred in the large intestine, among which 109 (83.9%) were solitary and 21 (16.1%) were multifocal. The intestinal wall was irregularly thickened in 123 patients, with soft tissue masses in 7 patients. Linear, spotty and small patchy calcifications were seen in 104 (80.0%) patients, with unclear margins in 96 patients. The tumors were markedly unevenly enhanced in 92 patients. Pathological examination revealed adenocarcinoma in 114 patients and in 104 patients, calcified Shistosoma japonicum (S. japonicum) ova inside the tumors, 15 patients were mucinous adenocarcinoma, and one patient was that of adenosquamous carcinoma. Conclusion: Irregular thickening of the intestinal wall, soft tissue masses, multiple S. japonicum ova calcifications inside the tumor with obscured margins and multiple intestinal masses in some patients are important CT features of CRC with schistosomiasis.

  9. A controlled study of mental distress and somatic complaints after risk-reducing salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer.

    Science.gov (United States)

    Michelsen, Trond M; Dørum, Anne; Dahl, Alv A

    2009-04-01

    Risk-reducing salpingo-oophorectomy (RRSO) provides effective protection against ovarian cancer in BRCA mutation carriers and in women at risk for hereditary breast ovarian cancer, but little is known about non-oncologic morbidity after the procedure. We explored mental distress and somatic complaints in women after RRSO compared to controls from the general population. 503 women from hereditary breast ovarian cancer families who had undergone RRSO after genetic counseling received a mailed questionnaire. 361 (71%) responded and 338 (67%) delivered complete data (cases). Controls were five randomly allocated age-matched controls per case (N=1690) from the population-based Norwegian Nord-Trøndelag Health Study (HUNT-2). Mean age of cases and controls was 54.6 years at survey. Mean time since surgery was 5.3 years (median 6.0). Compared to controls, the RRSO group had more palpitations (p=0.02), constipation (p=0.01), pain and stiffness (p=0.02), osteoporosis (p=0.02) and musculoskeletal disease (p=0.01) even after adjustments for demographic factors including use of hormonal replacement therapy. The RRSO group had lower levels of depression (pdepression (p<0.001) and total mental distress (p=0.002). In this controlled observational study, we found more somatic morbidity such as osteoporosis, palpitations, constipation, musculoskeletal disease and pain and stiffness but lower levels of mental distress among women who had undergone RRSO compared to controls.

  10. Pathological diagnosis of bladder cancer by image analysis of hypericin induced fluorescence cystoscopic images

    Science.gov (United States)

    Kah, James C. Y.; Olivo, Malini C.; Lau, Weber K. O.; Sheppard, Colin J. R.

    2005-08-01

    Photodynamic diagnosis of bladder carcinoma based on hypericin fluorescence cystoscopy has shown to have a higher degree of sensitivity for the detection of flat bladder carcinoma compared to white light cystoscopy. The potential of the photosensitizer hypericin-induced fluorescence in performing non-invasive optical biopsy to grade bladder cancer in vivo using fluorescence cystoscopic image analysis without surgical resection for tissue biopsy is investigated in this study. The correlation between tissue fluorescence and histopathology of diseased tissue was explored and a diagnostic algorithm based on fluorescence image analysis was developed to classify the bladder cancer without surgical resection for tissue biopsy. Preliminary results suggest a correlation between tissue fluorescence and bladder cancer grade. By combining both the red-to-blue and red-to-green intensity ratios into a 2D scatter plot yields an average sensitivity and specificity of around 70% and 85% respectively for pathological cancer grading of the three different grades of bladder cancer. Therefore, the diagnostic algorithm based on colorimetric intensity ratio analysis of hypericin fluorescence cystoscopic images developed in this preliminary study shows promising potential to optically diagnose and grade bladder cancer in vivo.

  11. Altered JS-2 expression in colorectal cancers and its clinical pathological relevance.

    Science.gov (United States)

    Lam, Alfred King-Yin; Gopalan, Vinod; Nassiri, Mohammad Reza; Kasim, Kais; Dissanayake, Jayampathy; Tang, Johnny Chuek-On; Smith, Robert Anthony

    2011-10-01

    JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the clinicopathological features of the cancer patients. We evaluated the DNA copy number and mRNA expression of JS-2 in 176 colorectal tissues (116 adenocarcinomas, 30 adenomas and 30 non-neoplastic tissues) using real-time polymerase chain reaction. JS-2 expression was also evaluated in two colorectal cancer cell lines and a benign colorectal cell line. JS-2 amplification was noted in 35% of the colorectal adenocarcinomas. Significant differences in relative expression levels for JS-2 mRNA between different colorectal tissues were noted (p = 0.05). Distal colorectal adenocarcinoma had significantly higher copy number than proximal adenocarcinoma (p = 0.005). The relative expression level of JS-2 was different between colonic and rectal adenocarcinoma (p = 0.007). Mucinous adenocarcinoma showed higher JS-2 expression than non-mucinous adenocarcinoma (p = 0.02). Early T-stage cancers appear to have higher JS-2 copy number and lower expression of JS-2 mRNA than later stage cancers (p = 0.001 and 0.03 respectively). Colorectal cancer cell lines showed lower expression of JS-2 than the benign colorectal cell line. JS-2 copy number change and expression were shown for the first time to be altered in the carcinogenesis of colorectal cancer. In addition, genetic alteration of JS-2 was found to be related to location, pathological subtypes and staging of colorectal cancer. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

    Science.gov (United States)

    Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

    2013-01-01

    Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

  13. Determinants of anxiety in patients with advanced somatic disease: differences and similarities between patients undergoing renal replacement therapies and patients suffering from cancer.

    Science.gov (United States)

    Janiszewska, Justyna; Lichodziejewska-Niemierko, Monika; Gołębiewska, Justyna; Majkowicz, Mikołaj; Rutkowski, Bolesław

    2013-10-01

    Anxiety is the most frequent emotional reaction to the chronic somatic disease. However, little is known about anxiety and coping strategies in patients with end-stage renal disease (ESRD) undergoing renal replacement therapies (RRTs). The purpose of the study was to assess the intensity and determinants of anxiety in patients treated with different RRTs in comparison with end-stage breast cancer patients and healthy controls. The study involved (1) ESRD patients undergoing different RRTs: 32 renal transplant recipients, 31 maintenance haemodialysis and 21 chronic peritoneal dialysis patients, (2) women with end-stage breast cancer (n = 25) and (3) healthy persons (n = 55). We used State-Trait Anxiety Inventory, Scale of Personal Religiousness, Mental Adjustment to Cancer Scale, Rotterdam Symptom Checklist with reference to medical history. The data thus obtained were analysed using the analysis of variance, the Tukey's HSD post hoc test and Spearman's rank correlation coefficient. Both ESRD and breast cancer patients revealed higher level of anxiety state and trait than healthy controls; however, there was no statistically significant difference found between both findings. There was a tendency towards higher levels of anxiety state in breast cancer patients when compared to ESRD patients undergoing the RRT treatment and for both groups non-constructive coping strategies correlated with the levels of anxiety state. With ESRD patients undergoing RRTs, the intensity of anxiety state did not depend on the mode of treatment but on the correlation between the levels of anxiety and the general quality of their life, psychological condition and social activity. In patients with advanced somatic disease (ESRD and end-stage breast cancer), non-constructive strategies of coping with the disease require further evaluation and possibly psychological support.

  14. Time-Trend in Epidemiological and Pathological Features of Schistosoma-Associated Bladder Cancer

    International Nuclear Information System (INIS)

    ZAGHLOUL, M.S.; EL-BARADIE, M.; NAZMY, M.; NOUH, A.; MONEER, M.; YOUNIS, A.

    2008-01-01

    To investigate the different emerging trends in the features of bladder cancer along 17 years. Patients and Methods: During a 17-year period (1988- 2004), 5071 epithelial bladder cancer patients underwent radical cystectomy at the National Cancer Institute (NCI), Cairo University, Egypt. The time was divided into 3 time periods to detect changes of the clinico pathologic features of patients in these periods. Results: There was a significant progressive increase in the patients' age with time and decrease in squamous/ transitional ratio, with transient increase in male predominance during the 2nd time period. Moreover, there was a decrease in the well differentiated (grade 1) tumor (p<0.001) and an increase in the frequency of pelvic nodal involvement (p<0.001). Transitional cell carcinoma (TCC) patients were significantly older than those with squamous cell carcinoma (SCC) (p<0.001). Progressive increase of age with time was evident in TCC, SCC and adenocarcinoma patients. Male to female ratio changed significantly in TCC and SCC. Conclusion: Time trend was confirmed with relative decrease in frequency of SCC and increase of TCC with changes in their pathological details. The differences between their characteristics and that of the Western countries are decreasing.

  15. Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

    Science.gov (United States)

    Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

    2017-01-01

    The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

  16. Barium enema and CT volumetry for predicting pathologic response to preoperative chemoradiotherapy in rectal cancer patients.

    Science.gov (United States)

    Murono, Koji; Kawai, Kazushige; Tsuno, Nelson H; Ishihara, Soichiro; Yamaguchi, Hironori; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2014-06-01

    Preoperative chemoradiotherapy has been widely used for the prevention of local recurrence of locally advanced rectal cancer, and the effect of chemoradiotherapy is known to be associated with overall survival. We aimed to evaluate the association of the pathologic response grade with tumor recurrence rate after chemoradiotherapy, using radiographic analysis and the Response Evaluation Criteria in Solid Tumors as the parameters. This study was conducted at a single tertiary care institution in Japan. This was a retrospective cohort study of patients undergoing preoperative chemoradiotherapy. A total of 101 low rectal cancer patients receiving preoperative chemoradiotherapy from July 2004 to August 2012 were enrolled. The tumor reduction rate was measured with the use of traditional Response Evaluation Criteria in Solid Tumors, barium enema, and CT volumetry, and the correlation between the reduction rate and the pathologic response grade was examined. The tumor reduction rate assessed according to Response Evaluation Criteria in Solid Tumors showed no association with the pathologic response grade (p =0.61). In contrast, the radiographic response rate by both barium enema and CT volumetry strongly correlated with the pathologic response grade (p volumetry had a lower recurrence rate (p =0.03, p =0.03, p =0.0002, and p =0.001). The difference between high responders and low responders was especially prominent by barium enema and CT volumetry. The study is limited by its retrospective nature. Double-contrast barium enema and CT volumetry were superior to Response Evaluation Criteria in Solid Tumors in evaluating the effect of chemoradiotherapy and predicting the likelihood of tumor recurrence.

  17. Somatic symptom disorder

    Science.gov (United States)

    ... related disorders; Somatization disorder; Somatiform disorders; Briquet syndrome; Illness anxiety disorder References American Psychiatric Association. Somatic symptom disorder. Diagnostic and Statistical Manual of Mental Disorders . ...

  18. [Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

    Science.gov (United States)

    Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

    2017-02-01

    Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

  19. Occult inflammatory breast cancer: review of clinical, mammographic, US and pathologic signs

    International Nuclear Information System (INIS)

    Cumo, Francesca; Gaioni, Maria Berenice; Bonetti, Franco; Manfrin, Erminia; Remo, Andrea; Pattaro, Christian; Policlinico G.B. Rossi, Verona

    2005-01-01

    Purpose: To examine the clinical, radiologic and pathologic findings of occult inflammatory breast cancer (OIBC) in order to identify features useful for diagnosis. Materials and methods: We retrospectively reviewed the records of 19 women with OIBC observed at our Department between 1992 and 2001. We analysed the clinical history, mammographic, ultrasonographic, and pathologic findings and investigated overall survival (OS), prognostic variables and radio-pathologic correlations. Results: The most common mammographic findings were: diffusely density (52.63%), trabecular thickening (42.1%), mass (36.84%). The most common US findings were axillary lymphadenopathy (68,75%), skin thickening (43.75%) and mass (56.25%). At least one inflammatory sign was found in 14 women (74%) at mammography (subcutaneous thickening, trabecular thickening, diffuse increase of density) or at US (subcutaneous thickening, diffuse increase in echogenicity due to oedema, lymph vessel dilatation). Estrogen receptors (ER) were present in 63.2% and Progesterone receptors (PgR) in 36.8%. Significant prognostic variables were ER and Ki 67. Conclusions: The typical radiological pattern of clinical inflammatory breast carcinoma is less frequently present in OIBC; nevertheless the radiologist must pay attention because frequently OIBC presents just one radiological sign and this should be enough for a diagnostic suspicion. Moreover, the absence of clinical and radiological inflammatory signs does not exclude inflammatory breasts cancer because OIBC can manifest at imaging as a mass or isolated calcification. ER and PgR are positive in a high percentage of patients and confirm that OIBC has a better prognosis that clinical inflammatory breast cancer [it

  20. Prostate Cancer Diagnosed After Repeat Biopsies Have a Favorable Pathological Outcome but Similar Recurrence Rate

    Science.gov (United States)

    Lopez-Corona, Ernesto; Ohori, Makoto; Wheeler, Thomas M.; Reuter, Victor E.; Scardino, Peter T.; Kattan, Michael W.; Eastham, James A.

    2007-01-01

    Purpose We investigated whether repeat prostate biopsies are associated with more favorable prognoses, less extensive disease or higher rates of IC in patients who are ultimately diagnosed with prostate cancer and treated with RRP. Materials and Methods We examined standard clinical and pathological data on 1,357 patients treated with RRP from 1983 to 2001. In addition, we noted the rate of IC in a subgroup of 847 patients in whom tumor volume was measured. Results Cancer was found in 1,042 patients (77%) at the first biopsy, in 227 (17%) at the second biopsy, in 59 (4%) at the third biopsy and in 29 (2%) at the fourth or later biopsy. Patients with 2 or greater biopsies had a higher rate of clinical T1c stage cancer and larger prostates than patients with only 1 biopsy (each p <0.0001). After RRP patients with 1 biopsy had a lower rate of organ confined tumors (61% vs 75%, p <0.0001), and a higher rate of extracapsular extension, seminal vesicle invasion, lymph node metastases and Gleason sum 7 or greater than other patients. IC was found in 10% of patients with 1 biopsy and 18% of those with 2 or greater biopsies (p = 0.018). Despite these more favorable pathological outcomes there was no difference in biochemical recurrence rate. Conclusions Although we found that a greater number of biopsies was related to a better pathological outcome after RRP, the number of biopsies did not predict disease recurrence. The increasing number of biopsies currently being performed, especially in patients with larger prostates, likely results in higher rates of IC. PMID:16469581

  1. Key tumor suppressor genes inactivated by "greater promoter" methylation and somatic mutations in head and neck cancer

    NARCIS (Netherlands)

    Guerrero-Preston, Rafael; Michailidi, Christina; Marchionni, Luigi; Pickering, Curtis R.; Frederick, Mitchell J.; Myers, Jeffrey N.; Yegnasubramanian, Srinivasan; Hadar, Tal; Noordhuis, Maartje G.; Zizkova, Veronika; Fertig, Elana; Agrawal, Nishant; Westra, William; Koch, Wayne; Califano, Joseph; Velculescu, Victor E.; Sidransky, David

    Tumor suppressor genes (TSGs) are commonly inactivated by somatic mutation and/or promoter methylation; yet, recent high-throughput genomic studies have not identified key TSGs inactivated by both mechanisms. We pursued an integrated molecular analysis based on methylation binding domain sequencing

  2. Analysis of clinical factors for pathological complete response after preoperative neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Ayiguli Hare; Palida Apizi; Iskandar Abulimiti; Zhang Jinrong; Tian Hanhan

    2014-01-01

    Objective: To evaluate the clinical factors associated with pathological complete response (pCR) after preoperative neoadjuvant chemoradiotherapy for rectal cancer. Methods: A retrospective analysis was performed on the clinical data of 116 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy followed by radical surgery from January 2009 to December 2012. All patients received pelvic intensity-modulated radiotherapy (50 Gy/25 fractions) with concurrent fluorouracil based chemotherapy and then underwent radical surgery 4-8 weeks later. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Of the 116 patients, 20 (17.2%) achieved a pCR after neoadjuvant chemoradiotherapy. The univariate analysis showed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum carcinoembryonic antigen (CEA) level, T stage, N stage, distance from the anal verge, degree of tumor differentiation, and maximum tumor diameter were associated with pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. The multivariate analysis revealed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum CEA level,and T stage were predictive factors for pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. Conclusions: Non-circumferential tumor (percentage of circumference of the rectal tube invaded by the tumor <75 %), low CEA level, and early T stage before treatment may be associated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. (authors)

  3. Immunohistochemical expression of Fascin-1 in colorectal cancer in relation to clinical and pathological parameters.

    Science.gov (United States)

    Piskor, Barbara M; Pryczynicz, Anna; Lubowicka, Emilia; Miniewska, Katarzyna; Zinczuk, Justyna; Zareba, Konrad; Guzinska-Ustymowicz, Katarzyna

    2018-06-11

    Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 expression and clinical-pathological parameters. The study material included postoperative samples (tumor and unchanged colon tissue) obtained from 51 CRC patients. Fascin-1 expression was assessed in the paraffin sections by immunohistochemistry. A statistically significant correlation was found between the histological type of cancer and the expression of Fascin-1 (p = 0.012). Increased expression of Fascin-1 in CRC was more frequent in adenocarcinoma type without the mucosal component with a better prognosis and decreased expression of this protein correlated with infiltration of cancer cells to blood and lymphatic vessels (p = 0.038). Our findings indicate a potential role of Fascin-1 in the pathogenesis of colon cancer; however, further studies will show whether this protein plays a role in the infiltration of colorectal cancer cells.

  4. [S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology].

    Science.gov (United States)

    Horn, L-C; Beckmann, M W; Follmann, M; Koch, M C; Mallmann, P; Marnitz, S; Schmidt, D

    2015-11-01

    Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

  5. Associations between pathologic tumor features and preadjuvant therapy cognitive performance in women diagnosed with breast cancer.

    Science.gov (United States)

    Koleck, Theresa A; Bender, Catherine M; Sereika, Susan M; Ryan, Christopher M; Ghotkar, Puja; Brufsky, Adam M; Jankowitz, Rachel C; McAuliffe, Priscilla F; Clark, Beth Z; Conley, Yvette P

    2017-02-01

    Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early-stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2-positive tumor contributed to poorer verbal (b = -0.287, P = 0.018), visual (b = -0.270, P = 0.001), and visual working (b = -0.490, P Breast Cancer Assay Recurrence Score ® .) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow-up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Apparent diffusion coefficient ratio correlates significantly with prostate cancer gleason score at final pathology

    DEFF Research Database (Denmark)

    Boesen, Lars; Chabanova, Elizaveta; Løgager, Vibeke

    2015-01-01

    PURPOSE: To evaluate the correlation between apparent diffusion coefficient measurements (ADCtumor and ADCratio ) and the Gleason score from radical prostatectomy specimens. MATERIALS AND METHODS: Seventy-one patients with clinically localized prostate cancer scheduled for radical prostatectomy...... correlated with the Gleason score from the prostatectomy specimens. RESULTS: The association between ADC measurements and Gleason score showed a significant negative correlation (P ... ) and 0.90 (ADCratio ) when discriminating Gleason score ≤7(3+4) from Gleason score ≥7(4+3). CONCLUSION: ADC measurements showed a significant correlation with tumor Gleason score at final pathology. The ADCratio demonstrated the best correlation compared to the ADCtumor value and radically improved...

  7. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  8. MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

    Science.gov (United States)

    Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

    2015-03-01

    Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

  9. The prognostic value of dividing epithelial ovarian cancer into type I and type II tumors based on pathologic characteristics

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Karlsen, Mona Aarenstrup; Høgdall, Estrid

    2015-01-01

    OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information on histo......OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information...... for survival confirmed the increased overall survival for type I tumors after two years of follow-up (hazard ratio: 1.85, 95% confidence interval: 1.35-2.54, Pbased on pathologic variables was associated with an increased risk of death...

  10. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.

    Directory of Open Access Journals (Sweden)

    Georgina Cosma

    Full Text Available The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA level, the biopsy most common tumor pattern (Primary Gleason pattern and the second most common tumor pattern (Secondary Gleason pattern in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD or Extra-Prostatic Disease (ED using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC, with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812. The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR

  11. Pathology findings and validation of gastric and esophageal cancer cases in a European cohort (EPIC/EUR-GAST)

    DEFF Research Database (Denmark)

    Carneiro, F; Moutinho, C; Pera, G

    2007-01-01

    OBJECTIVE: Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological...... classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). MATERIAL AND METHODS: In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project......, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. RESULTS: The whole series encompassed 467 cancer cases (gastric and esophageal...

  12. The roles of pathology in targeted therapy of women with gynecologic cancers.

    Science.gov (United States)

    Murali, Rajmohan; Grisham, Rachel N; Soslow, Robert A

    2018-01-01

    The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor. Therefore, expanding the arsenal of available systemic therapies with targeted therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the treatment of advanced gynecologic cancer, and many more are under investigation. Pathologists remain important in the clinical management of patients with targeted therapy, by identifying potentially targetable tumors on the basis of their pathologic phenotype, by assessing biomarkers that are predictive of response to targeted therapy (e.g. microsatellite instability, PD1/PDL1 expression), and by monitoring treatment response and resistance. Pathologists are also vital to research efforts exploring novel targeted therapies by identifying homogenous subsets of tumors for more reliable and meaningful analyses, and by confirming expression in tumor tissues of novel targets identified in genomic, epigenetic or other screening studies. In the era of precision gynecologic oncology, the roles of pathologists in the discovery, development and implementation of targeted therapeutic strategies remain as central as they are for traditional (surgery-chemotherapy-radiotherapy) management of women with gynecologic cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Perfusion of prostate cancer: correlation between p-CT and whole-mount pathology - case report

    International Nuclear Information System (INIS)

    Luczynska, E.; Aniol, J.; Szczudlo, J.; Stelmach, A.; Jaszczynski, J.; Hartel, M.; Konopka, M.

    2006-01-01

    Prostate cancer is the second most common form of cancer among malignant neoplasm for men in Poland, next to lung cancer, as far as frequency is concerned. Incidence of this kind of neoplasm increases by about 3 % annually. In the last decade a growing number of this type of diseases has been observed and its detections are closely related to the development of biochemical (PSA - prostate-specific antigen) and diagnostic imaging technologies. A 60-year-old patient was diagnosed in the Oncology Institute because of an increasing level of PSA in his blood. The PSA level in March 2005 was 10,4 ng/ml. There was a slight increase of PSA during the year, up to 1,5 ng/ml (this is less than 25% / year). The patient came for the following check up to repeat the core-needle sextant biopsy, to exclude neoplasmatic process. Before operation the patient's prostate was tested by p-CT. The parametric maps revealed some disturbances of blood flow parameters. Blood flow - BF, blood volume - BV, mean transit time - MTT and permeability surface - PS were noted in the form of their asymmetry within peripheral zone in the right lobe. A pathological focus with increased BF, BV, PS and decreased MTT was revealed on the right side. This examination suggested that neoplasmatic process might be localized in this area. Core needle biopsy taken from the suspicious region revealed prostate cancer. That was also confirmed in histopathology examination after radical prostatectomy. P-CT examination can be performed during classical CT exam and it leads to obtaining morphological and functional data at the same time. P-CT examination allowed us to localize pathological process and helped to continue its verification by other diagnostic methods. (author)

  14. Clinical–Pathologic Stage Discrepancy in Bladder Cancer Patients Treated With Radical Cystectomy: Results From the National Cancer Data Base

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Phillip J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Lin, Chun Chieh; Jemal, Ahmedin [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Fedewa, Stacey A. [Surveillance and Health Services Research Program, American Cancer Society, Atlanta, Georgia (United States); Kibel, Adam S. [Division of Urology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Rosenberg, Jonathan E. [Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kamat, Ashish M. [Division of Surgery, Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Virgo, Katherine S. [Department of Health Policy and Management, Emory University, Atlanta, Georgia (United States); Blute, Michael L. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A., E-mail: jefstathiou@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-04-01

    Purpose: To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database. Methods and Materials: A total of 16,953 patients with BC without distant metastases treated with RC from 1998 to 2009 were analyzed. Factors associated with clinical–pathologic stage discrepancy were assessed by multivariate generalized estimating equation models. Survival analysis was conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan-Meier method and Cox proportional hazards models. Results: At RC 41.9% of patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common in females, the elderly, and in patients who underwent a more extensive lymphadenectomy. Downstaging was less common in patients treated at community centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy was highly associated with downstaging. Five-year overall survival rates for patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%, 36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were 70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis, upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80, P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In contrast, more extensive lymphadenectomy was associated with decreased 5-year mortality (HR 0.76 for ≥10 lymph nodes examined, P<.001), as was treatment at an National Cancer Institute–designated cancer center (HR 0.90, P=.042). Conclusions: Clinical–pathologic stage discrepancy in BC patients is remarkably common across the United States. These findings should be considered when selecting patients for preoperative or nonoperative management strategies and when comparing the outcomes of bladder sparing approaches to RC.

  15. Surgical and Pathological Characteristics of Papillary Thyroid Cancer in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Davor Dzepina

    2012-01-01

    Full Text Available Background. Thyroid carcinoma is a relatively rare pediatric pathology, comprising around 3% of all childhood tumors. We investigated parameters of tumor aggressiveness, multicentricity, and locoregional metastatic spread patterns in patients up to 18 years of age and made comparison with the older group. All patients were operated upon with total thyroidectomy, with or without lymph-node neck dissection. Results. Patients with papillary carcinoma present with more advanced stage, larger primary tumor, and more commonly present with palpable thyroid and/or neck node. Overall, papillary cancer demonstrated pathological aggressiveness as defined by our criteria in 60%, multicentricity in 40%, and locoregional metastatic foci in 77% of cases. Multicentric tumor foci in both thyroid lobes and tumor aggressiveness were identified as a risk factor for metastatic development. Conclusion. By observing clinicopathological parameters, we demonstrated that papillary thyroid cancer behaves more aggressively in the younger group. We recommend total thyroidectomy with careful intraoperative exploration of thyroid bed and lateral neck in search for possible metastatic spread. In case of positive findings, it is obligatory to perform a standard neck dissection, keeping in mind that neck lymphonodes are primary site of locoregional recurrence. With meticulous attention to technical aspects of operation, perioperative morbidity should be minimal.

  16. Human Papillomavirus Subtype 16 and the Pathologic Characteristics of Laryngeal Cancer

    Directory of Open Access Journals (Sweden)

    Mohammed Abdel Motaal Gomaa MD

    2017-05-01

    Full Text Available Objective Laryngeal cancer is the most common type of cancer in the head and neck. Human papillomavirus (HPV represents a group of >150 related viruses. Infection with certain types of HPV can cause some types of cancer. This study aimed to evaluate the sociodemographic and histopathologic characters of squamous cell carcinoma of the larynx and its relationship to HPV subtype 16 (HPV-16. Study design Cross-sectional. Setting Tertiary university hospitals at 5 districts in Egypt (Minia, Cairo, Giza, Qaluobia, and Bani Seuif. Subjects and Methods This cross-sectional study was conducted on 50 adult patients with laryngeal cancer who were admitted at 5 tertiary care hospitals in Egypt from January 2014 through December 2014. All patients were subjected to a comprehensive preoperative assessment, histopathologic assessments of tumor biopsies, and immunohistochemical staining for HPV-16. Results HPV-16 immunostaining was positive in 9 patients (18%. A significant correlation between HPV-16 immunoreactivity and tumor grade ( P < .001 was detected, with no significant correlation between HPV-16 immunoreactivity and other clinical and pathologic variables. Conclusion The frequency of HPV-16 in laryngeal carcinoma is 18%, and there is significant correlation between HPV-16 and tumor grade.

  17. Perineural Invasion is a Marker for Pathologically Advanced Disease in Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Lee, Irwin H.; Roberts, Rebecca; Shah, Rajal B.; Wojno, Kirk J.; Wei, John T.; Sandler, Howard M.

    2007-01-01

    Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy

  18. Value of Specialist Pathology Review in a Single Statewide Gynecologic Cancer Service.

    Science.gov (United States)

    Melon, Jerome; Leung, Yee; Salfinger, Stuart G; Tan, Jason; Mohan, Ganendra; Cohen, Paul A

    2017-01-01

    A case review by specialist diagnostic pathologists as part of a Gynecologic Oncology Multi-disciplinary Tumor group has the potential to influence the management of patients with cancer. The primary aim of this study was to determine the frequency of diagnostic discrepancies between the initial (nonspecialist) and final pathological diagnoses in cases referred to the Gynecologic Oncology Tumor Conference (TC) in Western Australia and the impact of such revised diagnosis on clinical management. A secondary aim was to assess the evolving workload encountered by the TC during a 5-year interval. The records of the weekly TC for the 2 calendar years 2008 and 2013 were examined, and histological and cytological specimens that had been initially assessed by "outside" (nonspecialist) pathology departments, and subsequently reviewed by specialist pathologists, were assessed. The initial and final diagnoses were compared, and where the pathological findings were amended upon review, it was determined whether the change affected clinical management. Diagnostic discrepancies that resulted in a change in patient management were classified as major, whereas discrepancies that did not affect patient management were classified as minor. A total of 481 outside cases were included among 2387 cases presented for histological review at the TC during the 2 years. For outside cases alone, the incidence of major diagnostic discrepancies was 3.4% in 2008, 5.5% in 2013 (no significant difference, P = 0.3787), and 4.6% for the 2 years combined. A recommendation for surgery was the most common change in clinical management as a result of major discrepancy. The minor discrepancy rate was 4.4% of outside cases for both years combined. Pathological discrepancies (major and minor) of the uterine corpus and cervix were most frequent, followed by those of the vulva and ovary. There was a 48.4% increase in total case discussions at the TC during the interval period with a significant rise in

  19. Loss of Maspin Expression in Bladder Cancer: Its Relationship with p53 and Clinico pathological Parameters

    International Nuclear Information System (INIS)

    Abd El-Maqsoud, N.M.R.; Tawfiek, E.R.

    2010-01-01

    Maspin (mammary serine protease inhibitor) is a member of the serpin super family of protease inhibitors and is known to have tumor-suppressor function in breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of Maspin in squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of urinary bladder. Patients and Methods: We have evaluated the immunohistochemical expression of Maspin and p53 in a series of 134 bladder cancer patients (56 SCC and 78 TCC) and the interrelationship between Clinico pathological features and Maspin and p53 expression. Results: There was positive Maspin expression in 53.7% in all cases. In TCC, expression was found in 48/78 cases (61.5%). High Maspin expression was found in low grade (p<0.001) and advanced stage (p=0.02). In SCC, expression was found in 24/56 (42.8%). There was a statistically significant association between lost Maspin expression and grading (p=0.001). No correlation was found between Maspin expression and other Clinico pathological parameters including gender, clinical stage and Bilharzial infestation. These results indicated that Maspin expression might predict a better prognosis for bladder carcinoma. Also Maspin probably could play a role in tumor progression. p53 was positive in 70 cases (52.2%) of all patients evaluated. In TCC, it was positive in 36/78 cases (46.1%) and correlated with high grade (p=0.01) and advanced stage (p=0.01). In SCC, it was positive in 34/56 cases (60.7%). There was a statistically significant association between p53 expression and high grade (p=0.01) and advanced stage (p=0.01). There was an inverse correlation between the Maspin and p53 expression in TCC and SCC of bladder cancer. We found no significant association between both Maspin and p53 expression and bilharziasis in TCC and SCC; this indicated that Maspin and p53 expression could be prognostic factors in both bilharzial and non

  20. Sextant localization of prostate cancer in peripheral zone by MRI: correlation with systemic biopsy pathology

    International Nuclear Information System (INIS)

    Huang Rong; Wang Xiaoying; Li Feiyu; Xu Yufeng; Jiang Xuexiang; He Yunfeng; Liu Pengcheng

    2006-01-01

    Objective: To determine the efficacy of sextant localization of prostate cancer (PCa) in PZ (peripheral zone) by MR Imaging. Methods: Fifty-one cases of PCa and 29 cases of benign prostate diseases were enrolled in the study. Each peripheral zone was divided into 6 sections (left/right bottom, middle and tip ) in the same fashion for biopsy and the characteristics of each sextant was evaluated separately. Being blinded to clinical data, 2 radiologists with different subspeciahy experience analyzed MR images of the 480 sections of these 80 cases retrospectively. Each sextant region impression of likelihood for cancer was estimated by the rank of a five-point rating scale (1=definite PCa, 2=probable PCa, 3=possible PCa, 4=probably not PCa, 5=definitely not PCa). If definite PCa was considered, then it was staged furthermore. Each diagnosis of sextant region was compared with the pathological result of corresponding biopsy site. Result: (1) Four hundred and seventy sections (205 cancerous and 265 benign) were proved by biopsy. The diagnosis efficacy was best when cutoff point was 2. There was moderate consistency between the results of MRI and pathology with the kappa value of 0.549-0.560. The total accuracy was 78.1%-78.3% with the sensitivity of 69.3%-76.1% and the specificity of 84.9%-80.0%. The positive predictive value was 78.0%-74.6% and the negative predictive value was 78.1%-81.2%. (2) The ROC analysis demonstrated that Az with total impression recorded by two readers had not significant difference(0.829±0.020 vs. 0.840±0.019, U=-0.3988, P>0.05). Conclusion: MRI may be an elementary way to localize PCa in PZ, but the diagnosis efficacy need to be improved furthermore. (authors)

  1. Clinical and pathological implications of miRNA in bladder cancer

    Directory of Open Access Journals (Sweden)

    Braicu C

    2015-01-01

    Full Text Available Cornelia Braicu,1 Roxana Cojocneanu-Petric,1,2 Sergiu Chira,1 Anamaria Truta,1,3 Alexandru Floares,4 Bogdan Petrut,5,6 Patriciu Achimas-Cadariu,7,8,* Ioana Berindan-Neagoe1,9–11,*1Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; 3Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Solutions of Artificial Intelligence Applications, Cluj-Napoca, Romania; 5Department of Urology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 6Department of Urology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 7Department of Surgery, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 8Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 9Department of Immunology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 10Department of Functional Genomics and Experimental Pathology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 11Department of Experimental Therapeutics M.D. Anderson Cancer Center Houston, TX, USAAbstract: MicroRNAs (miRNAs are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with

  2. Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.

    Science.gov (United States)

    Shafiee, Mohammad Javad; Chung, Audrey G; Khalvati, Farzad; Haider, Masoom A; Wong, Alexander

    2017-10-01

    While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.

  3. Mamma cancer behavior at the Provincial Consultation of Mammary Pathologies. 2009

    International Nuclear Information System (INIS)

    Rodriguez Gonzalez, Jose Antonio; Martinez Sanchez, Yariana; Estorino Escaig, Nereida; Vidal Jimenez, Eligio

    2010-01-01

    We developed a retrospective, interventionist, transversal study, with the objective of identifying the most frequently diagnosed Mamma Cancers in the Provincial Consultation of Mamma Cancer at the Hospital 'Jose Ramon Lopez Tabranes' of Matanzas, during 2009. The universe was 305 women assisting the consultation with possible mammary pathologies. Data were collected from the records of the Statistic Department of the hospital. They were grouped by age. The ultrasound diagnosis was compared with the mammographic and histological ones. Our sample were 114 women with nodules suspected of mamma cancer diagnosed using the before mentioned studies. We decided surgical treatment in patients with positive cytologies and metastasis found in CT. The highest percent of studied patients were in the age group from 31 to 49 years old. There was a predominance of hypoechoic nodules in ultrasound studies, and spiculated nodules with axillary adenopathies in mammographic studies. The most frequent diagnosis of mammographic studies was duct infiltrating carcinomas. The highest percent was subject for mastectomy. Axillary ganglion and bone metastasis were observed more frequently in CT made in operated patients

  4. [The clinical and pathological research of complete mesocolic excision on the treatment of right colon cancer].

    Science.gov (United States)

    Yang, Yingchi; Wang, Jin; Jin, Lan; Zhao, Xiaomu; Wu, Guocong; Wang, Kangli; Zhang, Zhongtao

    2016-01-01

    To verify the clinical safety of complete mesocolic excision (CME) and manufacture pathological large slices. A prospective analysis clinical data of 85 right colon cancer in patients by the same group of surgeons at the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2012 to December 2013 which were divided into two groups: CME group (n=39) and traditional radical operation group (n=46) by surgical approach. CME group and control group were compared the differences of clinic and pathologic variables, precise tissues morphometry, lymph nodes harvest, mesocolic area and so on. By comparison to operation time, blood loss, postoperative complications, flatus restoring time, drainage removal time and length of stay, the security of CME was analyzed. Statistical methods included independent sample t-test, Wilcoxon rank sum test and χ(2) test. In order to manufacture pathological large slices, the CME operation specimens were fixed. The large slices were stained by routine HE staining to detection of circumferential resection margin. Mean number of total lymph nodes was increased obviously in CME group (26.8±1.9 vs. 23.2±3.4, t=4.261, P=0.000). Mean number of lymph nodes of stage Ⅰ, Ⅱ were different between two groups (25.8±3.6 vs. 18.2±4.5, 26.8±7.7 vs. 24.9±6.2, t=8.776, 2.802, P=0.000). The positive lymph nodes of CME group was higher than control group (4(7) vs. 1.5(2), P=0.032), above all with statistically significant difference. Comparing CME group with the control group, there were the larger area of mesentery ((15 555±1 263) mm(2) vs. (12 493±1 002) mm(2,) t=12.456, P=0.000), the greater distance between the tumor and the high vascular tie ((116±22) mm vs. (82±11) mm, t=9.295, P=0.000), the greater distance between the normal bowel and the high vascular tie ((92±17) mm vs. (74±10) mm, t=8.132, P=0.000) of CME, with statistically significant difference. There were no statistically significant

  5. Indicators of breast cancer in patients undergoing microdochectomy for a pathological nipple discharge in a middle-income country.

    Science.gov (United States)

    Lesetedi, Chiapo; Rayne, Sarah; Kruger, Deirdre; Benn, Carol-Ann

    2017-12-01

    The management of a pathological nipple discharge often involves surgery for the exclusion of a malignant etiology. This study aimed to determine the prevalence of cancer in patients who had microdochectomy for pathological nipple discharge in a population in South Africa and to evaluate patients' demographics and clinical characteristics as indicators of underlying cancer and make recommendations for their management in resource-limited settings. Clinical, radiological, and histological data from 153 patients who underwent a microdochectomy for a pathological nipple discharge at two South African breast clinics was collected. Invasive or in situ cancer was found in 12 patients (7.84%), and in all patients, cancer was associated with a bloody nipple discharge. Bloody discharge had a sensitivity of 100% in indicating cancer, specificity of 55.32%, positive predictive value of 16%, and negative predictive value of 100%. Patients with breast cancer were also more likely to be aged 55 y or older (P = 0.04). Preoperative mammogram and ultrasound were poor in detecting cancer (0/12). In our population, a bloody discharge in women aged 55 years or older should mandate a microdochectomy, with selective surgery for younger women and those with nonbloody discharges. Thorough clinical examination to determine the true color and nature of the discharge is vital in the initial assessment of these patients. Preoperative radiology is not helpful in determining the presence of cancer (in an isolated pathological nipple discharge), and microdochectomy still remains the gold standard in diagnosing cancer in these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

    Science.gov (United States)

    Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

    2014-11-01

    The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

  7. Two cases of pathological complete response to neoadjuvant chemoradiation therapy in pancreatic cancer

    International Nuclear Information System (INIS)

    Fujii-Nishimura, Yoko; Nishiyama, Ryo; Kitago, Minoru

    2015-01-01

    Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years. (author)

  8. Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting.

    Science.gov (United States)

    Dougherty, Brian A; Lai, Zhongwu; Hodgson, Darren R; Orr, Maria C M; Hawryluk, Matthew; Sun, James; Yelensky, Roman; Spencer, Stuart K; Robertson, Jane D; Ho, Tony W; Fielding, Anitra; Ledermann, Jonathan A; Barrett, J Carl

    2017-07-04

    To gain a better understanding of the role of somatic mutations in olaparib response, next-generation sequencing (NGS) of BRCA1 and BRCA2 was performed as part of a planned retrospective analysis of tumors from a randomized, double-blind, Phase II trial (Study 19; D0810C00019; NCT00753545) in 265 patients with platinum-sensitive high-grade serous ovarian cancer. BRCA1/2 loss-of-function mutations were found in 55% (114/209) of tumors, were mutually exclusive, and demonstrated high concordance with Sanger-sequenced germline mutations in matched blood samples, confirming the accuracy (97%) of tumor BRCA1/2 NGS testing. Additionally, NGS identified somatic mutations absent from germline testing in 10% (20/209) of the patients. Somatic mutations had >80% biallelic inactivation frequency and were predominantly clonal, suggesting that BRCA1/2 loss occurs early in the development of these cancers. Clinical outcomes between placebo- and olaparib-treated patients with somatic BRCA1/2 mutations were similar to those with germline BRCA1/2 mutations, indicating that patients with somatic BRCA1/2 mutations benefit from treatment with olaparib.

  9. Nomogram for predicting pathologically complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

    International Nuclear Information System (INIS)

    Toxopeus, Eelke Lucie Anne; Nieboer, Daan; Shapiro, Joel; Biermann, Katharina; Gaast, Ate van der; Rij, Carolien M. van; Steyerberg, Ewout Willem; Lanschot, Joseph Jan Baptiste van; Wijnhoven, Bas Peter Louis

    2015-01-01

    Background: A pathologically complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) is seen in 30% of the patients with oesophageal cancer. The aim is to identify patient and tumour characteristics associated with a pCR and to develop a nomogram for the prediction of pCR. Patients and methods: Patients who underwent nCRT followed by surgery were identified and response to nCRT was assessed according to a modified Mandard classification in the resection specimen. A model was developed with age, gender, histology and location of the tumour, differentiation grade, alcohol use, smoking, percentage weight loss, Charlson Comorbidity Index (CCI), cT-stage and cN-stage as potential predictors for pCR. Probability of pCR was studied via logistic regression. Performance of the prediction nomogram was quantified using the concordance statistic (c-statistic) and corrected for optimism. Results: A total of 381 patients were included. After surgery, 27.6% of the tumours showed a pCR. Female sex, squamous cell histology, poor differentiation grade, and low cT-stage were predictive for a pCR with a c-statistic of 0.64 (corrected for optimism). Conclusion: A nomogram for the prediction of pathologically complete response after neoadjuvant chemoradiotherapy was developed, with a reasonable predictive power. This nomogram needs external validation before it can be used for individualised clinical decision-making

  10. [Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

    Science.gov (United States)

    Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

    2015-01-01

    To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  11. Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts.

    Science.gov (United States)

    Wang, Zhenfei; Ma, Daguang; Wang, Changshan; Zhu, Zhe; Yang, Yongyan; Zeng, Fenfang; Yuan, Jianlong; Liu, Xia; Gao, Yue; Chen, Yongxia; Jia, Yongfeng

    2017-12-01

    Direct attacks on tumour cells with chemotherapeutic drugs have the drawbacks of accelerating tumour metastasis and inducing tumour stem cell phenotypes. Inhibition of tumour-associated fibroblasts, which provide nourishment and support to tumour cells, is a novel and promising anti-tumour strategy. However, effective drugs against tumour-associated fibroblasts are currently lacking. In the present study, we explored the possibility of inhibiting the pathological functions of tumour-associated fibroblasts with triptonide. Paired gastric normal fibroblasts (GNFs) and gastric cancer-associated fibroblasts (GCAFs) were obtained from resected tissues. GCAFs showed higher capacities to induce colony formation, migration, and invasion of gastric cancer cells than GNFs. Triptonide treatment strongly inhibited the colony formation-, migration-, and invasion-promoting capacities of GCAFs. The expression of microRNA-301a was higher and that of microRNA-149 was lower in GCAFs than in GNFs. Triptonide treatment significantly down-regulated microRNA-301a expression and up-regulated microRNA-149 expression in GCAFs. Re-establishment of microRNA expression balance increased the production and secretion of tissue inhibitor of metalloproteinase 2, a tumour suppressive factor, and suppressed the production and secretion of IL-6, an oncogenic factor, in GCAFs. Moreover, triptonide treatment abolished the ability of GCAFs to induce epithelial-mesenchymal transition in gastric cancer cells. These results indicate that triptonide inhibits the malignancy-promoting capacity of GCAFs by correcting abnormalities in microRNA expression. Thus, triptonide is a promisingly therapeutic agent for gastric cancer treatment, and traditional herbs may be a valuable source for developing new drugs that can regulate the tumour microenvironment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: A single center experience

    International Nuclear Information System (INIS)

    Choi, Eun Cheol; Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu

    2016-01-01

    To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results

  13. Predictors of pathologic complete response after preoperative concurrent chemoradiotherapy of rectal cancer: A single center experience

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Cheol [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of); Kim, Jin Hee; Kim, Ok Bae; Kim, Mi Young; Oh, Young Ki; Baek, Sung Gyu [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2016-06-15

    To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ≥7 weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ≥7 weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results.

  14. Clinical, pathologic, and biologic features associated with BRAF mutations in non-small cell lung cancer.

    Science.gov (United States)

    Cardarella, Stephanie; Ogino, Atsuko; Nishino, Mizuki; Butaney, Mohit; Shen, Jeanne; Lydon, Christine; Yeap, Beow Y; Sholl, Lynette M; Johnson, Bruce E; Jänne, Pasi A

    2013-08-15

    BRAF mutations are found in a subset of non-small cell lung cancers (NSCLC). We examined the clinical characteristics and treatment outcomes of patients with NSCLC harboring BRAF mutations. Using DNA sequencing, we successfully screened 883 patients with NSCLC for BRAF mutations between July 1, 2009 and July 16, 2012. Baseline characteristics and treatment outcomes were compared between patients with and without BRAF mutations. Wild-type controls consisted of patients with NSCLC without a somatic alteration in BRAF, KRAS, EGFR, and ALK. In vitro studies assessed the biologic properties of selected non-V600E BRAF mutations identified from patients with NSCLC. Of 883 tumors screened, 36 (4%) harbored BRAF mutations (V600E, 18; non-V600E, 18) and 257 were wild-type for BRAF, EGFR, KRAS, and ALK negative. Twenty-nine of 36 patients with BRAF mutations were smokers. There were no distinguishing clinical features between BRAF-mutant and wild-type patients. Patients with advanced NSCLC with BRAF mutations and wild-type tumors showed similar response rates and progression-free survival (PFS) to platinum-based combination chemotherapy and no difference in overall survival. Within the BRAF cohort, patients with V600E-mutated tumors had a shorter PFS to platinum-based chemotherapy compared with those with non-V600E mutations, although this did not reach statistical significance (4.1 vs. 8.9 months; P = 0.297). We identified five BRAF mutations not previously reported in NSCLC; two of five were associated with increased BRAF kinase activity. BRAF mutations occur in 4% of NSCLCs and half are non-V600E. Prospective trials are ongoing to validate BRAF as a therapeutic target in NSCLC. ©2013 AACR.

  15. Clinico-pathology of lung cancer in a regional cancer center in Northeastern India.

    Science.gov (United States)

    Mandal, Sanjeet Kumar; Singh, Thaudem Tomcha; Sharma, Takhenchangbam Dhaneshor; Amrithalingam, Venkatesan

    2013-01-01

    Globally, there have been important changes in trends amongst gender, histology and smoking patterns of lung cancer cases. This retrospective study was conducted on 466 patients with lung cancer who were registered in Regional Cancer Center, Regional Institute of Medical Sciences, Manipur from January 2008 to December 2012. Most were more than 60 years of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in 16.3% of patients. The most frequent symptom was coughing (36.6%) and most common radiological presentation was a mass lesion (70%). Most of the patients had primary lung cancer in the right lung (60.3%). The most common histological subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%). As many as 91.9% of squamous cell carcinoma patients had a history of smoking. About 32.5% of patients had distant metastasis at presentation with brain (23.8%) and positive malignant cells in pleural effusions (23.1%) as common sites. The majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II (30.2%). Our analysis suggests that the gender gap has been narrowed such that about half of the patients diagnosed with lung cancer are women in this part of India. This alarming rise in female incidence is mainly attributed to an increased smoking pattern. Squamous cell carcinoma still remains the commonest histological subtype. Most of the patients were elderly aged and presented at locally or distantly advanced stages.

  16. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D

    2008-01-15

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  17. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    International Nuclear Information System (INIS)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D.

    2008-01-01

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  18. Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository.

    Science.gov (United States)

    Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

    2016-01-01

    The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports.

  19. Cortisol and somatization.

    Science.gov (United States)

    Rief, W; Auer, C

    2000-05-01

    Somatization symptoms are frequently associated with depression, anxiety, and feelings of distress. These features interact with the activity of the HPA-axis. Therefore we investigated relationships between somatization symptoms and cortisol. Seventy-seven participants were classified into three groups: somatization syndrome (at least eight physical symptoms from the DSM-IV somatization disorder list), somatization syndrome combined with major depression, and healthy controls. The following data were collected: salivary cortisol at three time points (morning, afternoon, evening), nighttime urinary cortisol, serum cortisol after the dexamethasone suppression test (DST), and psychological variables such as depression, anxiety, somatization, and hypochondriasis. Salivary cortisol showed typical diurnal variations. However, the groups did not differ on any of the cortisol variables. A possible explanation may be counteracting effects of somatization and depression. Exploratory correlational analyses revealed that associations between cortisol and psychopathological variables were time-dependent. DST results correlated with psychological aspects of somatization, but not with the number of somatoform symptoms per se.

  20. Clinical and pathologic factors affecting lymph node yields in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Ta-Wen Hsu

    Full Text Available OBJECTIVE: Lymph node yield is recommended as a benchmark of quality care in colorectal cancer. The objective of this study was to evaluate the impact of various factors upon lymph node yield and to identify independent factors associated with lymph node harvest. MATERIALS AND METHODS: The records of 162 patients with Stage I to Stage III colorectal cancers seen in one institution were reviewed. These patients underwent radical surgery as definitive therapy; high-risk patients then received adjuvant treatment. Pathologic and demographic data were recorded and analyzed. The subgroup analysis of lymph node yields was determined using a t-test and analysis of variants. Linear regression model and multivariable analysis were used to perform potential confounding and predicting variables. RESULTS: Five variables had significant association with lymph node yield after adjustment for other factors in a multiple linear regression model. These variables were: tumor size, surgical method, specimen length, and individual surgeon and pathologist. The model with these five significant variables interpreted 44.4% of the variation. CONCLUSIONS: Patients, tumor characteristics and surgical variables all influence the number of lymph nodes retrieved. Physicians are the main gatekeepers. Adequate training and optimized guidelines could greatly improve the quality of lymph node yields.

  1. Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

    Science.gov (United States)

    Vermeulen, Marijn A; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H; Tryfonidis, Konstantinos; van Diest, Paul J; Dijkstra, Nizet H; Schröder, Carolien P; van Asperen, Christi J; Linderholm, Barbro; Benstead, Kim; Foekens, Renee; Martens, John W M; Bartlett, John M S; van Deurzen, Carolien H M

    2017-09-01

    Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed. Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus. Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts.

    Science.gov (United States)

    Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen

    2017-12-28

    To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs ( P GNFs, GCAFs expressed a lower level of microRNA-214 ( P < 0.01) and a higher level of microRNA-301a ( P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression ( P < 0.01) and down-regulated microRNA-301a expression ( P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production ( P < 0.01) and secretion ( P < 0.05), and elevated TIMP2 production ( P < 0.01) and secretion ( P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is

  3. Urothelial cancer of bladder in young versus older adults: clinical and pathological characteristics and outcomes.

    Science.gov (United States)

    Telli, Onur; Sarici, Hasmet; Ozgur, Berat Cem; Doluoglu, Omer Gokhan; Sunay, Mehmet Melih; Bozkurt, Selen; Eroglu, Muzaffer

    2014-09-01

    Bladder urothelial carcinoma is rare in young adults and occurs more commonly in older individuals. The aim of this study was to compare the clinical behavior, pathologic characteristics, and prognosis of urothelial carcinoma of urinary bladder in young versus older adults. A retrospective review of our records between 2007 and 2013 identified 56 patients (42 males and 14 females) with transitional cell carcinoma of the bladder who were less than 40 years old. Clinical and pathological parameters of patients who were less than 40 years of age were compared with those of a series of patients older than 40 years of age (the control group) during the same period. A survival analysis was performed using the Kaplan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinical outcomes. The mean age was 29.21 years (range, 5-40 years) for patients less than 40 years old and 61.66 years (range, 41-75) for those older than 40 years. The mean follow-up was 40.26 months (range, 12-65 months) for young patients and 42.57 months (range, 12-72 months) for the older patients. Young bladder cancer patients had smaller-sized tumors (less than 3 cm), less high-grade cancers, higher papillary urothelial neoplasms of low malignant potential, and low-grade tumors than patients older than 40 years. Multivariate logistic regression analysis predicted tumor recurrence in young patients with high-grade tumors [odds ratio (OR), 1.959; 95% confidence interval (CI), 1.235-2.965; p = 0.046] and tumors larger than 3 cm (OR, 1.772; 95% CI, 1.416-1.942; p = 0.032). The 5-year overall survival rate was 100% for young patients and 88.1% for older patients. No difference was observed in the recurrence-free (p = 0.321) and progression-free (p = 0.422) survival rates between the two groups. We concluded that although the clinical stage distribution, natural history, and outcomes of bladder urothelial cancer in young adults are

  4. Development of a Natural Language Processing Engine to Generate Bladder Cancer Pathology Data for Health Services Research.

    Science.gov (United States)

    Schroeck, Florian R; Patterson, Olga V; Alba, Patrick R; Pattison, Erik A; Seigne, John D; DuVall, Scott L; Robertson, Douglas J; Sirovich, Brenda; Goodney, Philip P

    2017-12-01

    To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports. Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer. When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer. NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data. Published by Elsevier Inc.

  5. MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

    2017-06-01

    Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  7. Management of somatic symptoms

    DEFF Research Database (Denmark)

    Schröder, Andreas; Dimsdale, Joel

    2014-01-01

    on the recognition and effective management of patients with excessive and disabling somatic symptoms. The clinical presentation of somatic symptoms is categorized into three groups of patients: those with multiple somatic symptoms, those with health anxiety, and those with conversion disorder. The chapter provides...

  8. MRI and pathological features of different molecular subtypes of breast cancers

    International Nuclear Information System (INIS)

    Yu Yang; Huo Tianlong; Lai Yunyao; Hong Nan

    2014-01-01

    Objective: To investigate the MRI and pathological features of different molecular subtypes of breast cancer. Methods: The data of 202 patients who underwent primary breast cancer resection were retrospectively reviewed. All of the patients had MRI preoperatively. The molecular subtypes of breast cancer defined by immunohistochemistry were classified as basal-like, luminal and HER-2 overexpression. Morphology (including mass or non-mass like enhancement, shape and margin of masses, unifocal or multifocal masses) and enhancement characteristics on MRI, histologic types and grades of tumors were analyzed with Chi-square test, exact test, Fisher exact test, Kruskal-Wallis H test, and Wilcoxon test. Results: Among the 202 patients, 34 were basal-like, 144 were luminal and 24 were HER-2 overexpression. The number of mass cases in each subtype was 29, 133 and 19 respectively,making no significant difference (χ 2 =4.136, P=0.126). As for the shape of basal-like lesions,8 were round,19 were lobular and 2 were irregular, while this distribution was 23, 58, 52 in luminal subtype and 1, 11, 7 in HER-2 overexpression subtype (χ 2 =13.391, P<0.05). The margin was also strikingly different among three groups (smooth, spiculate, irregular): 20, 5, 4 respectively in basal-like, 27, 53, 53 respectively in luminal, and 4, 7, 8 respectively in HER-2 overexpression (χ 2 =28.515, P<0.01). 52.6% (10/19) of HER-2 overexpression cases were multifocal, while only 6.9% (2/29) of luminal and 8.0% (24/133) of basal-like ones were multifocal (χ 2 =16.140, P<0.01). Characteristics in dynamic contrast-enhanced MRI were statistically different, with homogeneous, heterogeneous, and rim enhancement 0, 13, 16 respectively in basal-like cases, 28, 93, 11 respectively in luminal cases and 2, 11, 6 respectively in HER-2 overexpression cases (P<0.01). However, the difference for enhancement curve did not reach significance (P =0.457). Histologic types were significantly different among molecular

  9. Pathologic complete response in patients with neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Espinola M, Daniela; Espinola M, Daniela; Bellolio R, Felipe; Gellona V, Jose; Bustos C, Mariza; Zuniga D, Alvaro

    2013-01-01

    Background: The standard treatment of locally advanced rectal cancer (RC) of the middle and lower third of the rectum is neoadjuvant chemoradiotherapy (XRQT) follow by oncologic resection. After this treatment in 15-25% of the cases, the pathologist reports complete pathological response (pCR). Aim: To describe demographic, clinical and survival data of patients with pCR undergoing chemoradiotherapy and radical resection for RC. Material and Methods: Historic cohort study. In a prospectively maintained database between 2000 and 2010, we identified patients with RC, who underwent neoadjuvant chemoradiotherapy according to protocol, followed by radical resection. The preoperative staging was obtained by clinical examination, endoscopy, rectal ultrasound, CT scan of chest, abdomen and pelvis and pelvic MRI. Demographic data, tumor location, time between the end of XRTQ and surgery, postoperative staging (according AJCC) and survival, were collected. Results: 119 patients received preoperative XRTQ, 65% male, with a mean age of 58 years. The most frequent tumor site was the lower third (63%). Surgery was performed 8 weeks after the end of XRTQ. Of 119 patients with XRTQ, 15.1% had a pCR. Overall survival was 75%, and cancer-specific survival was 80.4% at 5 years in patients without pCR. For patients with pCR, the 5 year survival estimates for overall and cancer specific survival was 100%. We did not identify factors associated with pCR. Conclusions: In this study, pCR was comparable to other larger series reported elsewhere. No factors associated with pCR were identified

  10. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics.

    Directory of Open Access Journals (Sweden)

    Montserrat Garcia-Closas

    2008-04-01

    Full Text Available A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs in five loci (fibroblast growth receptor 2 (FGFR2, trinucleotide repeat containing 9 (TNRC9, mitogen-activated protein kinase 3 K1 (MAP3K1, 8q24, and lymphocyte-specific protein 1 (LSP1 associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI = 1.31 (1.27-1.36 than ER-negative (1.08 (1.03-1.14 disease (P for heterogeneity = 10(-13. This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5, 10(-8, 0.013, respectively. The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4, respectively. The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312 showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21. rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97. The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding

  11. Pathological features of Breast Cancer seen in Northwestern Tanzania: a nine years retrospective study

    Directory of Open Access Journals (Sweden)

    Manyama Mange M

    2011-06-01

    Full Text Available Abstract Background Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania. Methods This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score, and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15. Findings There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1. About half of the patients (52.4% were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012. The tumor size ranged from 1 cm to 18 cm in diameter with average (mean of 5.5 cm (+/- 2.5, and median size of 6 cm. Size of the tumor (above 6 cm in diameter and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000. Of all patients, 64% were at clinical stage III (specifically IIIB and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5% followed by mucinous carcinoma (5.2%, Invasive lobular carcinoma (3% and in situ ductal carcinoma (0.3%. In all patients, 185 (56.4% had tumor with histological grade 3. Conclusion Breast cancer

  12. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-01-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  13. Serum LAG-3 and DKK-1 levels in patients with gastric cancer and their correlation with clinical pathological characteristics

    Directory of Open Access Journals (Sweden)

    Yu-Fang Liu

    2017-04-01

    Full Text Available Objective: To study the correlation of serum LAG-3 and DKK-1 levels with cancer cell proliferation, invasion, angiogenesis and other clinical pathological characteristics in patients with gastric cancer. Methods: 48 patients who were diagnosed with early gastric cancer in our hospital between June 2014 and October 2016 were selected as the gastric cancer group of the research, 50 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the research, serum was collected to determine the levels of lymphocyte activation gene-3 (LAG-3, Dickkopf-1 (DKK-1 and angiogenesis molecules, and the gastric cancer tissue and the tissue adjacent to carcinoma were collected to determine the expression of proliferation and invasion-related molecules. Results: Serum LAG-1, DKK-1, angiogenin-1 (Ang-1, Ang-2, vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF levels of gastric cancer group were significantly higher than those of control group (P<0.05, and EPHA2, LOXL2, PCNA, Akt, CyclinD1, MYH-9, CXCR7, KDM1A and CatB mRNA expression in gastric cancer tissue were significantly higher than those in the tissue adjacent to carcinoma (P<0.05; serum Ang-1, Ang-2, VEGF and bFGF levels as well as EPHA2, LOXL2, PCNA, Akt, CyclinD1, MYH-9, CXCR7, KDM1A and CatB mRNA expression in gastric cancer tissue of patients with gastric cancer were positively correlated with serum LAG-3 and DKK-1 levels. Conclusion: Serum LAG-3 and DKK-1 levels are valuable to diagnose early gastric cancer and can assess the cancer cell proliferation, invasion, angiogenesis and other clinical pathological characteristics in gastric cancer tissue.

  14. Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Rominger, M.; Frauenfelder, T. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Berg, D. [Urbankrankenhaus Berlin, Anesthesiology, Berlin (Germany); Ramaswamy, A. [University Hospital Marburg, Pathology, Marburg (Germany); Timmesfeld, N. [Philipps University Marburg, Institute for Medical Biometry and Epidemiology, Marburg (Germany)

    2016-05-15

    To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86 % (97/113), overestimation 9 % (10/113) and underestimation 5 % (6/113); BI-RADS mass lesions were overestimated in 7 % (6/81) versus 41 % (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3 %) ILC did not enhance. Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance. (orig.)

  15. Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chopra, Supriya [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Princess Margaret Hospital, University Health Network, Toronto (Canada); Toi, Ants [Princess Margaret Hospital, University Health Network, Toronto (Canada); Department of Medical Imaging, University of Toronto, Toronto (Canada); Taback, Nathan [Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto (Canada); Evans, Andrew [Princess Margaret Hospital, University Health Network, Toronto (Canada); Department of Pathology, University of Toronto, Toronto (Canada); Haider, Masoom A. [Princess Margaret Hospital, University Health Network, Toronto (Canada); Department of Medical Imaging, University of Toronto, Toronto (Canada); Sunnybrook Health Sciences Center, Toronto (Canada); Milosevic, Michael; Bristow, Robert G.; Chung, Peter; Bayley, Andrew [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Princess Margaret Hospital, University Health Network, Toronto (Canada); Morton, Gerard; Vesprini, Danny [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto (Canada); Warde, Padraig; Catton, Charles [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Princess Margaret Hospital, University Health Network, Toronto (Canada); Menard, Cynthia, E-mail: Cynthia.Menard@rmp.uhn.on.ca [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Princess Margaret Hospital, University Health Network, Toronto (Canada)

    2012-03-01

    Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.

  16. Low levels of serum testosterone in middle-aged men impact pathological features of prostate cancer.

    Science.gov (United States)

    Llukani, Elton; Katz, Benjamin F; Agalliu, Ilir; Lightfoot, Andrew; Yu, Sue-Jean S; Kathrins, Martin; Lee, Ziho; Su, Yu-Kai; Monahan Agnew, Kelly; McGill, Alice; Eun, Daniel D; Lee, David I

    2017-03-01

    Serum testosterone deficiency increases with aging. Age is also a major risk factor for prostate cancer (PrCa) and PCa tumors are more frequently diagnosed among men >65 years old. We evaluated the relationship between preoperative serum testosterone and clinical/ pathological features of PrCa in middle-aged and elderly patients. A total of 605 PrCa patients who underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania, and who had serum testosterone levels measured using Elecsys Testosterone II Immunoassay were included in this IRB-approved protocol. Androgen deficiency was determined as serum free testosterone (FT) men with low vs. normal TT or FT were compared using t-test or chi-square tests. Logistic regression was used to determine associations of clinical and pathological variables with FT or TT levels. Among middle-aged men (45-64 years; n = 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4, P men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1 P = 0.019) and greater tumor volume (7.9 ml vs. 6.1 ml, P = 0.045) compared to those with normal FT. Among men ≥65 years ( n = 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT. Among men aged 45-64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters.

  17. Comparison of FDG Uptake with Pathological Parameters in the Well-differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Woo Hee; Chung, Yong An; Kim, Ki Jun; Park, Chang Suk; Jung, Hyun Suk; Sohn, Hyung Sun; Chung, Soo Kyo; Yoo, Chang Young [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2009-02-15

    Differentiated thyroid cancer (DTC) has variable degree of F-18 FDG avidity. The purpose of this study was to evaluate the relationship between F-18 FDG uptake and pathological or immunohistochemical features of DTC. DTC patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included in the study. Maximum standardized uptake values (SUVmax) of primary tumor were calculated. If the primary tumor showed no perceptibly increased F-18 FDG uptake, region of interest was drawn based on finding of CT portion of the PET/CT images. Pathological and immunohistochemical markers such as presence of lymph node (LN) metastasis and underlying thyroiditis, tumor size, Ki-67 labeling index, expressions of EGFR, COX-2, and Galectin-3 were evaluated. Total of 106 patients was included (102 papillary carcinomas, 4 follicular carcinomas). The mean SUVmax of the large tumors (above 1 cm) was significantly higher than the mean SUVmax of small (equal to or less than 1 cm) ones (7.8{+-}8.5 vs. 3.6{+-}3.1, p=0.004). No significant difference in F-18 FDG uptake was found according to the presence or absence of LN metastasis and underlying thyroiditis, or the degree of Ki-67 labeling index, expression of EGFR, COX-2 and Galectin-3. In conclusion, the degree of F-18 FDG uptake in DTC was associated with the size of primary tumor. But there seem to be no relationship between F-18 FDG uptake of DTC and expression of Ki-67, EGFR, COX-2 and Galectin-3.

  18. Comparison of FDG Uptake with Pathological Parameters in the Well-differentiated Thyroid Cancer

    International Nuclear Information System (INIS)

    Choi, Woo Hee; Chung, Yong An; Kim, Ki Jun; Park, Chang Suk; Jung, Hyun Suk; Sohn, Hyung Sun; Chung, Soo Kyo; Yoo, Chang Young

    2009-01-01

    Differentiated thyroid cancer (DTC) has variable degree of F-18 FDG avidity. The purpose of this study was to evaluate the relationship between F-18 FDG uptake and pathological or immunohistochemical features of DTC. DTC patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included in the study. Maximum standardized uptake values (SUVmax) of primary tumor were calculated. If the primary tumor showed no perceptibly increased F-18 FDG uptake, region of interest was drawn based on finding of CT portion of the PET/CT images. Pathological and immunohistochemical markers such as presence of lymph node (LN) metastasis and underlying thyroiditis, tumor size, Ki-67 labeling index, expressions of EGFR, COX-2, and Galectin-3 were evaluated. Total of 106 patients was included (102 papillary carcinomas, 4 follicular carcinomas). The mean SUVmax of the large tumors (above 1 cm) was significantly higher than the mean SUVmax of small (equal to or less than 1 cm) ones (7.8±8.5 vs. 3.6±3.1, p=0.004). No significant difference in F-18 FDG uptake was found according to the presence or absence of LN metastasis and underlying thyroiditis, or the degree of Ki-67 labeling index, expression of EGFR, COX-2 and Galectin-3. In conclusion, the degree of F-18 FDG uptake in DTC was associated with the size of primary tumor. But there seem to be no relationship between F-18 FDG uptake of DTC and expression of Ki-67, EGFR, COX-2 and Galectin-3

  19. A Site Specific Model And Analysis Of The Neutral Somatic Mutation Rate In Whole-Genome Cancer Data

    DEFF Research Database (Denmark)

    Bertl, Johanna; Guo, Qianyun; Rasmussen, Malene Juul

    2017-01-01

    Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation ra...

  20. The detection rates and tumor clinical/pathological stages of whole-body FDG-PET cancer screening

    International Nuclear Information System (INIS)

    Ono, Ken; Omagari, Junichi; Ochiai, Reiji; Yoshida, Tsuyoshi; Kitagawa, Mami; Kobayashi, Hisashi; Yamashita, Yasuyuki

    2007-01-01

    Fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been used for cancer screening, mainly in East-Asia, and cancers are found not infrequently. However, their stages have not been clarified. We examined the detection rates of various cancers using whole-body PET for the screening of cancers in asymptomatic individuals, focusing on their clinical and pathological stages. Whole-body PET was obtained as a part of our cancer screening program among 3,426 healthy subjects. All subjects participated in a course of PET examination in conjunction with conventional examinations including a medical questionnaire, tumor markers, immunological fecal occult blood test, neck and abdominal ultrasonography and whole body computed tomography. A diagnosis and staging was obtained by an analysis of the pathological findings or by an analysis of the clinical follow-up data. Malignant tumors were discovered in 65 lesions found in 3,426 participants (1.90%). The PET findings were true-positive in 46 of the 65 cancer cases. The cancers were found in the following organs: the colon 14; thyroid gland 10; stomach 7; lung 5; liver 3; breast 2; and one each in the kidney, gallbladder, esophagus, pancreas and retroperitoneum. The stages were as follows: stage 0 5, stage I 17, stage II 10, stage III 7, and stage IV 6. One was an unknown primary. There were 19 false-negative findings (0.6%) on PET. Six cancers (0.18%) were missed in our screening program. PET imaging has the potential to detect a wide variety of cancers at potentially curative stages. Most PET-negative cancers are early stage cancers, and thus can be detected using other conventional examinations such as endoscopy. (author)

  1. The value of external beam radiation in pathologic node positive prostate cancer: a multivariate analysis

    International Nuclear Information System (INIS)

    Morris, Astrid D.; Zietman, Anthony L.; Althausen, Alex F.; Heney, Niall M.; Kaufman, Donald S.; Shipley, William U.

    1997-01-01

    Purpose: The goal of this study was to evaluate the effect of local/regional treatment, particularly external beam radiation alone versus radical prostatectomy and radiation therapy in patients with pathologic node positive prostate cancer on survival. The effect of delayed vs. immediate endocrine therapy on patients treated with radiation alone was also examined. Methods: Medical records of all 116 patients who received their initial treatment at the Massachusetts General Hospital between 1980 and 1996 for adenocarcinoma of the prostate with pathologic confirmed nodal metastasis and no distant disease were reviewed. The mean follow up was 5.5 years. Disease specific survival, time to PSA failure on endocrine therapy, and time to first intervention were evaluated. PSA failure was defined as two consecutive post-nadir rises following the first use of endocrine therapy. Intervention was defined as any surgical or radiotherapeutic procedure required for relief of symptoms related to local/regional recurrence. Survival comparisons were made between any local/regional treatment vs. none, radiation therapy alone vs. prostatectomy with radiation therapy, and immediate vs. delayed endocrine therapy. The effect of the different treatment options on survival were compared using multivariate Cox proportional hazard models to simultaneously adjust for patient and tumor characteristics (tumor stage, Gleason grade, number of positive nodes) that might influence survival. Results: The combined patient population had a 5 year disease specific survival of 74% and a 10 year disease specific survival of 48%. The comparison groups for local/regional treatment had the following adjusted outcomes. In a subgroup analysis of patients with clinical T1-T2 and clinical T3-T4 disease, local/regional treatment continued to confer a disease specific survival advantage over no local regional treatment in both subgroups (p=0.05 and p=0.02, respectively). PSA failure on endocrine therapy was

  2. Management of somatic pain induced by treatment of head and neck cancer: Postoperative pain. Guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL).

    Science.gov (United States)

    Espitalier, F; Testelin, S; Blanchard, D; Binczak, M; Bollet, M; Calmels, P; Couturaud, C; Dreyer, C; Navez, M; Perrichon, C; Morinière, S; Albert, S

    2014-09-01

    To present the guidelines of the French Oto-Rhino-Laryngology--Head and Neck Surgery Society (SFORL) concerning the management of somatic pain induced by the treatment of head and neck cancer, and in particular the management of early and late post-surgical pain. A multidisciplinary work group conducted a review of the scientific literature on the study topic. An editorial group subsequently read the resulting guidelines before validation. It is recommended to prevent onset of pain caused by malpositioning on the operating table, as well as pain related to postoperative care. During surgery, it is recommended to spare nerve and muscle structures as far as possible to limit painful sequelae. Management of early postoperative pain upon tumor resection and flap harvesting sites requires patient-controlled analgesia by morphine pump. Physical therapy is recommended after flap harvesting to minimize painful sequelae. Preventive and curative measures should be undertaken for appropriate management of post-surgical pain in the treatment of head and neck cancers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  4. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim Lütken; Dubash, Taronish; Drainas, Alexandros P

    2017-01-01

    overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate...... intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. Our framework enables systematic inference of CRE rearrangements mediating dysregulation in cancer....

  5. Low cost continuous femoral nerve block for relief of acute severe cancer related pain due to pathological fracture femur

    Directory of Open Access Journals (Sweden)

    Rachel Cherian Koshy

    2010-01-01

    Full Text Available Pathological fractures in cancer patient cause severe pain that is difficult to control pharmacologically. Even with good pain relief at rest, breakthrough and incident pain can be unmanageable. Continuous regional nerve blocks have a definite role in controlling such intractable pain. We describe two such cases where severe pain was adequately relieved in the acute phase. Continuous femoral nerve block was used as an efficient, cheap and safe method of pain relief for two of our patients with pathological fracture femur. This method was proved to be quite efficient in decreasing the fracture-related pain and improving the level of well being.

  6. Prognosis of Esophageal Cancer Patients With Pathologic Complete Response After Preoperative Concurrent Chemoradiotherapy

    International Nuclear Information System (INIS)

    Park, Jae Won; Kim, Jong Hoon; Choi, Eun Kyung; Lee, Sang-wook; Yoon, Sang Min; Song, Si Yeol; Lee, Yu Sun; Kim, Sung Bae; Park, Seung il; Ahn, Seung Do

    2011-01-01

    Purpose: To define failure patterns and predictive factors in esophageal cancer patients who had a pathologic complete response (pCR) after preoperative concurrent chemoradiotherapy (PCRT). Methods and Materials: We performed a retrospective analysis of 61 esophageal cancer patients who were enrolled in prospective studies and showed pCR after PCRT. All of the patients had squamous cell carcinoma. Of the patients, 40 were treated with hyperfractionated radiotherapy (4,560 cGy in 28 fractions) with 5-fluorouracil (5-FU) and cisplatin (FP), and 21 patients received conventional fractionation radiotherapy with capecitabine and cisplatin (XP). Results: The median follow-up time was 45.2 months (range, 6.5-162.3 months). The 5-year overall survival (OS) and disease-free survival rates (DFS) were 60.2% and 80.4%, respectively. In univariate analysis, age and lymph node (LN) metastasis were poor prognostic factors for OS, and pretreatment weight loss (>2 kg) was a poor prognostic factor for DFS. In multivariate analysis, lymph node metastasis and pretreatment weight loss were independent prognostic factors for OS and DFS. Nine patients (15%) had disease recurrence. Of the nine patients, 5 patients had locoregional failure, 1 patients had distant metastasis, and 3 patients had distant and locoregional failure. In-field failure occurred in 5 patients; out-of-field failure occurred in 1 patient; both in-field and out-of-field failure occurred in 2 patients; and both marginal and out-of-field failure occurred in 1 patient. Conclusions: Even in pCR patients, the most common failure site was within the radiation field, which suggests that more efficient local treatment is needed. Tumor recurrence was more common in patients with older age and with pretreatment weight loss.

  7. Non small cell lung cancer – Comparison between clinical and pathological staging

    Directory of Open Access Journals (Sweden)

    G. Fernandes

    2006-07-01

    Full Text Available Lung cancer (LC staging remains a clinical challenge as it determines the disease's prognosis and treatment. Surgery is the best option for controlling non-small cell lung cancer (NSCLC and the only potential cure. In this setting, lung cancer staging helps select patients who will benefit from surgery, excluding inoperable patients and including patients with resectable lesions. The aim of this study is to compare clinical staging (TNMc with pathological staging (TNMp and to evaluate diagnosis, complementary treatment and survival of these patients.This is a retrospective study that included patients with non-small cell lung cancer or with highly sus- picious lesions who had undergone surgery and were followed up in the Hospital de São João lung cancer unit between January 1999 and December 2003. It is based on clinical files and pathology reports.73.3% of this group of 60 patients were male, with median age 59.2 years. The most frequent TNMc stages were 41.7% T1N0M0 and 36.7% T2N0M0. Thoracotomy for therapeutic purpose was performed in 80% and thoracotomy for diagnostic purpose also in the remaining 20%. In 6.7% the resection was incomplete. The most frequent TNMp stages were T2N0p in 33.3%, T2N1p in 15.0% and T2N2p in 13.3%. There was a significant difference between the two staging types, with upstaging in 65.0%, down staging in 67% and only 28.3% keeping the same stage. The most frequent differences were from T1N0c to T2N0p and from T2N0c to T2N1p. The global agreement between both staging methods was 21.7%. Median global survival was 43 months.In conclusion, while clinical staging was less accurate, it did not determine important changes in therapeutic strategy and survival. For the future, we should consider using other diagnostic tools and other biological factors to complement the anatomical information that we currently use. Resumo: O estadiamento do cancro do pulmão (CP permanece um desafio clínico, sendo fundamental para

  8. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    International Nuclear Information System (INIS)

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-01-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  9. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.

    Directory of Open Access Journals (Sweden)

    Yuichi Shiraishi

    Full Text Available Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs and their matched controls. Comparison of whole genome sequence (WGS and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3, and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.

  10. Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility.

    Science.gov (United States)

    van Soest, Johan; Meldolesi, Elisa; van Stiphout, Ruud; Gatta, Roberto; Damiani, Andrea; Valentini, Vincenzo; Lambin, Philippe; Dekker, Andre

    2017-09-01

    Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences). © 2017 American Association of Physicists in Medicine.

  11. MicroRNA genes and their target 3'-untranslated regions are infrequently somatically mutated in ovarian cancers.

    Directory of Open Access Journals (Sweden)

    Georgina L Ryland

    Full Text Available MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3'-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3'-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3'-untranslated regions are thus uncommon in ovarian cancer.

  12. A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data.

    Science.gov (United States)

    Bertl, Johanna; Guo, Qianyun; Juul, Malene; Besenbacher, Søren; Nielsen, Morten Muhlig; Hornshøj, Henrik; Pedersen, Jakob Skou; Hobolth, Asger

    2018-04-19

    Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration. To take into account the fine scale of the explanatory variables, we model the probabilities of different types of mutations for each position in the genome by multinomial logistic regression. We analyse 505 cancer genomes from 14 different cancer types and compare the performance in predicting mutation rate for both regional based models and site-specific models. We show that for 1000 randomly selected genomic positions, the site-specific model predicts the mutation rate much better than regional based models. We use a forward selection procedure to identify the most important explanatory variables. The procedure identifies site-specific conservation (phyloP), replication timing, and expression level as the best predictors for the mutation rate. Finally, our model confirms and quantifies certain well-known mutational signatures. We find that our site-specific multinomial regression model outperforms the regional based models. The possibility of including genomic variables on different scales and patient specific variables makes it a versatile framework for studying different mutational mechanisms. Our model can serve as the neutral null model

  13. The correlation study of radiological findings with pathological classification of superficial depressed (IIc type) early gastric cancer

    International Nuclear Information System (INIS)

    Liu Linxiang; Deng Bingxing; Liu Yujin; Iinuma, G.; Moriyama, N.

    2007-01-01

    Objective: To investigate the relations between radiological findings and pathological classification of superficial depressed (II c type) early gastric cancer. Methods: Radiological features in subtonic double contrast barium examination and the endoscopic pictures of early gastric cancer compared with the global pathological specimens and micro-pathological features were prospectively studied. Combined with the gastric endoscopic pictures, the sharpness of margin of the lesions, the changes of converging mucosal folds and the changes of the depressed surface on the film of double contrast barium examination were analyzed. The correlation between the radiological features and histological classification of gastric cancer including well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por) and signet-ring cell carcinoma (sig) were studied. Results: In 102 cases of II c type early gastric cancer, there were tub1 27 cases, tub2 11, por 26 and sig 38 cases histologically. The margin of the depressed lesions of tubl (24 cases) and tub2 (9 cases) cancers were mostly unsharply demarcated or with fine spicular border, while the margin of lesions of por(15 cases) and sig(31 cases) were mostly clearly and sharply demarcated, with statistical significance (P<0.01). The depressed surface of tub1 and tub2 lesions (17 cases) revealed little unevenness, sometimes with evenly granulations, single nodule and scar-like depression, while that of por and sig lesions (41 cases) manifested as nodules of varying sizes, with statistical significance (P<0.01). Conclusion: The radiological findings of superficial depressed early gastric cancer in different histological types were different, the possible histological type could be speculated according to the radiological findings of the lesions. (authors)

  14. A nomogram for predicting pathological complete response in patients with human epidermal growth factor receptor 2 negative breast cancer

    International Nuclear Information System (INIS)

    Jin, Xi; Jiang, Yi-Zhou; Chen, Sheng; Yu, Ke-Da; Ma, Ding; Sun, Wei; Shao, Zhi-Min; Di, Gen-Hong

    2016-01-01

    The response to neoadjuvant chemotherapy has been proven to predict long-term clinical benefits for patients. Our research is to construct a nomogram to predict pathological complete response of human epidermal growth factor receptor 2 negative breast cancer patients. We enrolled 815 patients who received neoadjuvant chemotherapy from 2003 to 2015 and divided them into a training set and a validation set. Univariate logistic regression was performed to screen for predictors and construct the nomogram; multivariate logistic regression was performed to identify independent predictors. After performing the univariate logistic regression analysis in the training set, tumor size, hormone receptor status, regimens of neoadjuvant chemotherapy and cycles of neoadjuvant chemotherapy were the final predictors for the construction of the nomogram. The multivariate logistic regression analysis demonstrated that T4 status, hormone receptor status and receiving regimen of paclitaxel and carboplatin were independent predictors of pathological complete response. The area under the receiver operating characteristic curve of the training set and the validation set was 0.779 and 0.701, respectively. We constructed and validated a nomogram to predict pathological complete response in human epidermal growth factor receptor 2 negative breast cancer patients. We also identified tumor size, hormone receptor status and paclitaxel and carboplatin regimen as independent predictors of pathological complete response. The online version of this article (doi:10.1186/s12885-016-2652-z) contains supplementary material, which is available to authorized users

  15. The possibility of using x-ray diffraction with hair to screen for pathologic conditions such as breast cancer

    International Nuclear Information System (INIS)

    James, Veronica; Cookson, David

    2000-01-01

    Mammalian hair exhibits a complex structure on length scales ranging from a few to hundreds of Angstroms. High-quality synchrotron x-ray images have yielded new insight about the structure and packing of the intermediate keratinous filaments that represent the bulk of a hair's volume. When comparing human hair diffraction patterns from healthy individuals and breast cancer patients significant differences have been seen, raising the possibility that fiber diffraction may be useful as a screening technique for certain pathologic conditions

  16. A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

    Science.gov (United States)

    Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

    2017-01-01

    Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

  17. Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer.

    Science.gov (United States)

    Candido Dos Reis, Francisco J; Lynn, Stuart; Ali, H Raza; Eccles, Diana; Hanby, Andrew; Provenzano, Elena; Caldas, Carlos; Howat, William J; McDuffus, Leigh-Anne; Liu, Bin; Daley, Frances; Coulson, Penny; Vyas, Rupesh J; Harris, Leslie M; Owens, Joanna M; Carton, Amy F M; McQuillan, Janette P; Paterson, Andy M; Hirji, Zohra; Christie, Sarah K; Holmes, Amber R; Schmidt, Marjanka K; Garcia-Closas, Montserrat; Easton, Douglas F; Bolla, Manjeet K; Wang, Qin; Benitez, Javier; Milne, Roger L; Mannermaa, Arto; Couch, Fergus; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Cox, Angela; Cross, Simon S; Blows, Fiona M; Sanders, Joyce; de Groot, Renate; Figueroa, Jonine; Sherman, Mark; Hooning, Maartje; Brenner, Hermann; Holleczek, Bernd; Stegmaier, Christa; Lintott, Chris; Pharoah, Paul D P

    2015-07-01

    Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.

  18. The results of radical retropubic prostatectomy and adjuvant therapy for pathologic stage C prostate cancer

    International Nuclear Information System (INIS)

    Schild, Steven E.; Wong, William W.; Grado, Gordon L.; Halyard, Michele Y.; Novicki, Donald E.; Swanson, Scott K.; Larson, Thayne R.; Ferrigni, Robert G.

    1996-01-01

    Purpose: The results of therapy in 288 men with pathologic Stage C prostate cancer who underwent radical retropubic prostatectomy (RRP) were analyzed to determine the effects of adjuvant therapy. Methods and Materials: Twenty-seven of the 288 patients received preoperative neoadjuvant hormonal therapy (leuprolide acetate). Postoperatively, 60 patients received adjuvant radiotherapy (RT) to the prostate bed. Follow-up ranged from 3 to 83 months (median = 32 months). Freedom from failure (FFF) was defined as maintaining a serum PSA level of ≤ 0.3 ng/ml. Results: The FFF was 61% at 3 years and 45% at 5 years for the entire group. The FFF following RRP plus RT was 75% at 3 years and 57% at 5 years as compared to 56% at 3 years and 40% at 5 years for RRP without RT (p = 0.049). The FFF following RRP plus neoadjuvant hormonal therapy was 58% at 3 years and 40% at 5 years as compared to 60% at 3 years and 45% at 5 years following RRP without hormonal therapy (p = 0.3). In patients without seminal vesicle (SV) invasion, the FFF was 81% at 3 and 5 years for RRP plus RT as compared to 61% at 3 years and 50% at 5 years for RRP without RT (p = 0.01). In patients with SV invasion, the FFF was 61% at 3 years and 36% at 5 years for RRP plus RT as compared to 44% at 3 years and 23% at 5 years for RRP without RT (p = 0.23). The projected local control rate was 83% at 5 years for those with RRP alone as compared to 100% for RRP plus RT (p = 0.02). Survival at 5 years was projected to be 92% and was not significantly altered by the administration of adjuvant therapies. Conclusions: Postoperative RT was associated with significantly improved local control and FFF rates, especially in patients with tumors which did not involve the seminal vesicles

  19. Impact of Somatic Mutations in the D-Loop of Mitochondrial DNA on the Survival of Oral Squamous Cell Carcinoma Patients

    Science.gov (United States)

    Lin, Jin-Ching; Wang, Chen-Chi; Jiang, Rong-San; Wang, Wen-Yi; Liu, Shih-An

    2015-01-01

    Objectives The aim of this study was to investigate somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in oral squamous cell carcinoma patients. Materials and Methods Surgical specimen confirmed by pathological examination and corresponding non-cancerous tissues were collected from 120 oral squamous cell carcinoma patients. The sequence in the D-loop of mtDNA from non-cancerous tissues was compared with that from paired cancer samples and any sequence differences were recognized as somatic mutations. Results Somatic mutations in the D-loop of mtDNA were identified in 75 (62.5%) oral squamous cell carcinoma patients and most of them occurred in the poly-C tract. Although there were no significant differences in demographic and tumor-related features between participants with and without somatic mutation, the mutation group had a better survival rate (5 year disease-specific survival rate: 64.0% vs. 43.0%, P = 0.0266). Conclusion Somatic mutation in D-loop of mtDNA was associated with a better survival in oral squamous cell carcinoma patients. PMID:25906372

  20. Cancer Digital Slide Archive: an informatics resource to support integrated in silico analysis of TCGA pathology data

    Science.gov (United States)

    Gutman, David A; Cobb, Jake; Somanna, Dhananjaya; Park, Yuna; Wang, Fusheng; Kurc, Tahsin; Saltz, Joel H; Brat, Daniel J; Cooper, Lee A D

    2013-01-01

    Background The integration and visualization of multimodal datasets is a common challenge in biomedical informatics. Several recent studies of The Cancer Genome Atlas (TCGA) data have illustrated important relationships between morphology observed in whole-slide images, outcome, and genetic events. The pairing of genomics and rich clinical descriptions with whole-slide imaging provided by TCGA presents a unique opportunity to perform these correlative studies. However, better tools are needed to integrate the vast and disparate data types. Objective To build an integrated web-based platform supporting whole-slide pathology image visualization and data integration. Materials and methods All images and genomic data were directly obtained from the TCGA and National Cancer Institute (NCI) websites. Results The Cancer Digital Slide Archive (CDSA) produced is accessible to the public (http://cancer.digitalslidearchive.net) and currently hosts more than 20 000 whole-slide images from 22 cancer types. Discussion The capabilities of CDSA are demonstrated using TCGA datasets to integrate pathology imaging with associated clinical, genomic and MRI measurements in glioblastomas and can be extended to other tumor types. CDSA also allows URL-based sharing of whole-slide images, and has preliminary support for directly sharing regions of interest and other annotations. Images can also be selected on the basis of other metadata, such as mutational profile, patient age, and other relevant characteristics. Conclusions With the increasing availability of whole-slide scanners, analysis of digitized pathology images will become increasingly important in linking morphologic observations with genomic and clinical endpoints. PMID:23893318

  1. 18F-Fluorodeoxyglucose Positron Emission Tomography for Primary Thyroid Cancer: Correlation with the Clinical, Pathologic and Sonographic Findings

    International Nuclear Information System (INIS)

    Kim, Kyung Eun; Kim, Eun Kyung; Moon, Hee Jung; Kwak, Jin Young

    2011-01-01

    We wanted to investigate the incidence and the clinicopathologic and sonographic characteristics of thyroid cancers that exhibit positive PET scans. From January 2007 to February 2008, 156 patients with thyroid cancer underwent both sonography and FDG-PET for the purpose of staging the cancer. We conducted a retrospective review of their clinical, radiologic and pathologic records and we evaluated the incidence of PET-positive thyroid cancer, as well as the associated clinicopathologic aggressiveness and the sonographic features. The incidence of PET-positive thyroid carcinoma was 78.2% (122/156). On univariate analysis, PET-positive thyroid cancer was significantly associated with tumor size, extracapsular invasion and central lymph node metastasis, but there was no association between the sonographic features of the thyroid cancer or the sonographic features of the 2 groups of tumor (1. probably benign and 2. suspicious for malignancy) and the FDG uptake. Multivariate logistic regression analysis showed a significant association between PET positivity and both extrathyroidal extension and a higher cancer stage (III/IV) (p < 0.05). The incidence of PET positive thyroid carcinoma is high (78.2%) and PET positivity is significantly associated with tumor size, extracapsular extension and a higher stage. However, there is no significant association between PET positivity and the sonographic features of thyroid carcinoma

  2. Your Pathology Report

    Science.gov (United States)

    ... Pathology Tests Breast Cancer News February 20, 2013 Star-gazing software helps fight breast cancer See More ... Phone: (855) 807-6386 email Facebook Twitter Instagram YouTube Contact Us Privacy Policy Site Credits Terms of ...

  3. Validation of natural language processing to extract breast cancer pathology procedures and results

    Directory of Open Access Journals (Sweden)

    Arika E Wieneke

    2015-01-01

    Full Text Available Background: Pathology reports typically require manual review to abstract research data. We developed a natural language processing (NLP system to automatically interpret free-text breast pathology reports with limited assistance from manual abstraction. Methods: We used an iterative approach of machine learning algorithms and constructed groups of related findings to identify breast-related procedures and results from free-text pathology reports. We evaluated the NLP system using an all-or-nothing approach to determine which reports could be processed entirely using NLP and which reports needed manual review beyond NLP. We divided 3234 reports for development (2910, 90%, and evaluation (324, 10% purposes using manually reviewed pathology data as our gold standard. Results: NLP correctly coded 12.7% of the evaluation set, flagged 49.1% of reports for manual review, incorrectly coded 30.8%, and correctly omitted 7.4% from the evaluation set due to irrelevancy (i.e. not breast-related. Common procedures and results were identified correctly (e.g. invasive ductal with 95.5% precision and 94.0% sensitivity, but entire reports were flagged for manual review because of rare findings and substantial variation in pathology report text. Conclusions: The NLP system we developed did not perform sufficiently for abstracting entire breast pathology reports. The all-or-nothing approach resulted in too broad of a scope of work and limited our flexibility to identify breast pathology procedures and results. Our NLP system was also limited by the lack of the gold standard data on rare findings and wide variation in pathology text. Focusing on individual, common elements and improving pathology text report standardization may improve performance.

  4. Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

    Directory of Open Access Journals (Sweden)

    Anne Bruun Krøigård

    Full Text Available Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

  5. Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

    Science.gov (United States)

    Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A; Larsen, Martin Jakob

    2016-01-01

    Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

  6. Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

    Science.gov (United States)

    Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

    2014-01-17

    Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

  7. Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

    Science.gov (United States)

    Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

    2016-11-01

    Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

  8. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-01-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  9. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L.; Gonen, M.; Kuk, D.; Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L.; Saltz, L.; Schrag, D.; Goodman, K.; Shia, J.; Schwartz, L.H.

    2012-01-01

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K trans , k ep , v e , AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K trans (mean 0.5 min -1 vs. 0.2 min -1 , P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  10. Clinical Outcome of Patients with Complete Pathological Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancers: The Indian Scenario

    Directory of Open Access Journals (Sweden)

    Snita Sinukumar

    2014-01-01

    Full Text Available Introduction. Neoadjuvant chemoradiotherapy and total mesorectal excision are considered the standard treatment for locally advanced rectal cancer. Various studies have reported pathological downstaging and a complete pathological response rate of 15%–27% following neoadjuvant chemoradiotherapy which has translated into improved survival. We endeavour to determine the clinical outcome of patients attaining a complete pathological tumor response following neoadjuvant chemoradiotherapy in the Indian setting where most of our patient population is younger and presents with aggressive tumor biology. Materials and Methods. Clinicopathological and treatment details were recorded for 64 patients achieving pathological complete response from 2010 to 2013. Disease-free survival (DFS, overall survival (OS, and locoregional and systemic recurrence rates were evaluated for these patients. Results. After a median follow-up of 30.5 months (range 11–59 months, the 3-year overall survival (OS was 94.6% and the 3-year disease-free survival (DFS was 88.5%. The locoregional and systemic recurrence rates were 4.7% and 3.1%, respectively. Conclusion. In the Indian subcontinent, despite younger patients with aggressive tumor biology, outcome in complete responders is good.

  11. SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of Cancer Evolutionary Trees from Multi-region Next Generation Sequencing.

    Directory of Open Access Journals (Sweden)

    Noushin Niknafs

    2015-10-01

    Full Text Available Recent improvements in next-generation sequencing of tumor samples and the ability to identify somatic mutations at low allelic fractions have opened the way for new approaches to model the evolution of individual cancers. The power and utility of these models is increased when tumor samples from multiple sites are sequenced. Temporal ordering of the samples may provide insight into the etiology of both primary and metastatic lesions and rationalizations for tumor recurrence and therapeutic failures. Additional insights may be provided by temporal ordering of evolving subclones--cellular subpopulations with unique mutational profiles. Current methods for subclone hierarchy inference tightly couple the problem of temporal ordering with that of estimating the fraction of cancer cells harboring each mutation. We present a new framework that includes a rigorous statistical hypothesis test and a collection of tools that make it possible to decouple these problems, which we believe will enable substantial progress in the field of subclone hierarchy inference. The methods presented here can be flexibly combined with methods developed by others addressing either of these problems. We provide tools to interpret hypothesis test results, which inform phylogenetic tree construction, and we introduce the first genetic algorithm designed for this purpose. The utility of our framework is systematically demonstrated in simulations. For most tested combinations of tumor purity, sequencing coverage, and tree complexity, good power (≥ 0.8 can be achieved and Type 1 error is well controlled when at least three tumor samples are available from a patient. Using data from three published multi-region tumor sequencing studies of (murine small cell lung cancer, acute myeloid leukemia, and chronic lymphocytic leukemia, in which the authors reconstructed subclonal phylogenetic trees by manual expert curation, we show how different configurations of our tools can

  12. SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of Cancer Evolutionary Trees from Multi-region Next Generation Sequencing.

    Science.gov (United States)

    Niknafs, Noushin; Beleva-Guthrie, Violeta; Naiman, Daniel Q; Karchin, Rachel

    2015-10-01

    Recent improvements in next-generation sequencing of tumor samples and the ability to identify somatic mutations at low allelic fractions have opened the way for new approaches to model the evolution of individual cancers. The power and utility of these models is increased when tumor samples from multiple sites are sequenced. Temporal ordering of the samples may provide insight into the etiology of both primary and metastatic lesions and rationalizations for tumor recurrence and therapeutic failures. Additional insights may be provided by temporal ordering of evolving subclones--cellular subpopulations with unique mutational profiles. Current methods for subclone hierarchy inference tightly couple the problem of temporal ordering with that of estimating the fraction of cancer cells harboring each mutation. We present a new framework that includes a rigorous statistical hypothesis test and a collection of tools that make it possible to decouple these problems, which we believe will enable substantial progress in the field of subclone hierarchy inference. The methods presented here can be flexibly combined with methods developed by others addressing either of these problems. We provide tools to interpret hypothesis test results, which inform phylogenetic tree construction, and we introduce the first genetic algorithm designed for this purpose. The utility of our framework is systematically demonstrated in simulations. For most tested combinations of tumor purity, sequencing coverage, and tree complexity, good power (≥ 0.8) can be achieved and Type 1 error is well controlled when at least three tumor samples are available from a patient. Using data from three published multi-region tumor sequencing studies of (murine) small cell lung cancer, acute myeloid leukemia, and chronic lymphocytic leukemia, in which the authors reconstructed subclonal phylogenetic trees by manual expert curation, we show how different configurations of our tools can identify either a single

  13. [A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

    Science.gov (United States)

    Ichinohe, Daichi; Morohashi, Hajime; Umetsu, Satoko; Yoshida, Tatsuya; Wakasa, Yusuke; Odagiri, Tadashi; Kimura, Toshirou; Suto, Akiko; Saito, Takeshi; Yoshida, Eri; Akasaka, Harue; Jin, Hiroyuki; Miura, Takuya; Sakamoto, Yoshiyuki; Hakamada, Kenichi

    2016-11-01

    We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

  14. Skin Cancer: ClinicoPathological Study of 204 Patients in Southern Governorates of Yemen.

    Science.gov (United States)

    AlZou, Amer Bin; Thabit, Mazen Abood Bin; AlSakkaf, Khalid Abdulla; Basaleem, Huda Omer

    2016-01-01

    Skin cancer is a group of heterogeneous malignancies, in general classified into nonmelanoma skin cancer (NMSC) and melanoma skin cancer (MSC). Incidences are high in many parts in the world with considerable geographical and racial variation. In the Yemen, there has been scarce information about skin cancer. The aim of this study was to evaluate the demographic characteristics and histological trend of skin cancer in Southern Governorates of Yemen. This retrospective study covered 204 cases of skin cancer at the Modern Histopathology Laboratory and Aden Cancer Registry and Research Center, Faculty of Medicine and Health Sciences, University of Aden, for the period 20062013. Data were classified regarding different demographic and tumor related variables and analyzed using CanReg4 for cancer registry and SPSS (version 21). The commonest encountered skin cancer was NMSC (93.1%). Generally, skin cancer appears slightly more frequently in females than males with a 1:1.06 male: female ratio, with a mean age of 62.9 years. Slightly higher than onethird (36.3%) were from Aden governorate. The head and neck proved to be the most common site in both males and females (58%). Basal cell carcinoma (BCC) is the most common histological type of skin cancer (50.5%). Skin cancer is a common cancer in patients living in southern governorates of Yemen. The pattern appears nearly similar to the international figures with a low incidence of MSC.

  15. Whole pelvis radiotherapy for pathological node-positive prostate cancer. Oncological outcome and prognostic factors

    Energy Technology Data Exchange (ETDEWEB)

    Poelaert, Filip; Decaestecker, Karel; Claeys, Tom; Dhondt, Bert; Lumen, Nicolaas [Ghent University Hospital, Department of Urology, Ghent (Belgium); Fonteyne, Valerie; Ost, Piet [Ghent University Hospital, Department of Radiation Oncology, Ghent (Belgium); Troyer, Bart de [AZ Nikolaas, Department of Urology, Sint-Niklaas (Belgium); Meerleer, Gert de [University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Visschere, Pieter de [Ghent University Hospital, Department of Radiology, Ghent (Belgium)

    2017-06-15

    The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors. All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2-3 years of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors. Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25-87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17-1.54) and OS (HR 1.22, 95% confidence interval 1.10-1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%). Patients with pN1 PCa treated with wpRT and 2-3 years ADT have an encouraging 5-year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment. (orig.) [German] Das Ziel dieser Studie war es, das onkologische Outcome der Bestrahlung des gesamten Beckens (wpRT) beim histologisch gesicherten nodal metastasierten Prostatakarzinom zu untersuchen, die Lokalisation eines eventuellen Rezidivs zu charakterisieren und moegliche prognostische Faktoren zu identifizieren. Alle Patienten, bei denen seit dem Jahr 2000 eine pelvine Lymphknotendissektion (PLND) durchgefuehrt worden war

  16. Quality of pathology reporting is crucial for cancer care and registration: a baseline assessment for breast cancers diagnosed in Belgium in 2008.

    Science.gov (United States)

    De Schutter, H; Van Damme, N; Colpaert, C; Galant, C; Lambein, K; Cornelis, A; Neven, P; Van Eycken, E

    2015-04-01

    Given the crucial role of pathology reporting in the management of breast cancers, we aimed to investigate the quality and variability of breast cancer pathology reporting in Belgium. Detailed information on non-molecular and molecular parameters was retrieved from the pathology protocols available at the Belgian Cancer Registry for 10,007 breast cancers diagnosed in Belgium in 2008. Substantial underreporting was shown for several clinically relevant non-molecular parameters, such as lymphovascular invasion. High-volume laboratories performed only slightly better than others, and analyses at the individual laboratory level showed clear inter-laboratory variability in reporting for all volume categories. Information on ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for HER2 IHC. For cases with different specimens analysed, discordance between these specimens was highest for HER2, followed by PR. For HER2, results obtained from different laboratories were even less concordant. In addition, inter-laboratory differences were noted in the used ER/PR scoring systems, the proportion of ER-/PR+ cases, and the relation between histological grade and ER/PR positivity. Data on Ki67 were only available for 43.8% of the investigated cases, and showed inconsistent use of cut-off values. Breast pathology reporting in Belgium in 2008 was suboptimal and showed considerable inter-laboratory variability. Synoptic reporting has been proposed as a facilitator towards increased reporting quality and harmonization, but the lack of aligned informatics remains a major hurdle in its concrete implementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne Vibeke

    2016-01-01

    a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2...

  18. Somatization: a perspective from self psychology.

    Science.gov (United States)

    Rodin, G M

    1991-01-01

    Somatization is a complex phenomenon that occurs in many forms and diverse settings. It is not necessarily pathological and may be found in a variety of psychiatric disorders. Much of the psychiatric literature has focused on patients with conversion disorders and hypochondriasis. Psychoanalytic theories regarding such conditions were largely based upon concepts of drive, conflict, and defense. The perspective from self psychology, with its emphasis on subjective experience and the sense of self, may further enhance the psychoanalytic understanding of somatization. Individuals with disturbances in the stability and organization of the self may present with somatic symptoms and disturbances in emotional awareness. Somatization in such cases may be the experiential manifestation of a disturbance in the cohesion of the self and/or may result from defensive operations to ward off affect. The latter may be prominent when affective arousal triggers the psychological threat of fragmentation. Somatization may diminish in such individuals when a self-object relationship is formed that bolsters and consolidates the sense of self. The integration of affect into ongoing subjective experience may also be an important aspect of psychoanalytic treatment in such patients.

  19. Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

    2016-01-01

    Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

  20. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    International Nuclear Information System (INIS)

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-01-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  1. [Hypochondriac symptoms in late-onset depression: the relationship between hypochondria and somatic state of patients].

    Science.gov (United States)

    Ivanets, N N; Avdeeva, T I; Kinkul'kina, M A

    2013-01-01

    Authors studied 276 women with late-onset depression. Concomitant chronic somatic diseases were identified in 90%. The presence of disease and its nosological definition did not impact on the development of hypochondriac symptoms in patients with late-onset depression. Patients with hypochondriac late-onset depression more often had disability pension due to somatic disease because they more often referred to internists in case of similar objective severity of somatic pathology. It was singled out three variants of the relationship between hypochondria and somatic state: hypernosognostic (a complete coincidence of hypochondria content with actual somatic pathology; anosognostic (a lack of coincidence) and disharmonic (a partial coincidence). The themes of hypochondria in late-nset depressions were correlated with a total number of somatic diseases and their severity. At the same time, there was no correlation between the content of hypochondria and the character of somatic disease.

  2. Correlation Between Clinical-Pathologic Factors and Long-Term Follow-Up in Young Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yue Zhao

    2015-08-01

    Full Text Available OBJECTIVE: Diagnosis of breast cancer in young patients (≤35 correlates with a worse prognosis compared to their older counterparts (>35. The aim of this study is to evaluate the relevance of clinical-pathologic factors and prognosis in young (≤35 breast cancer patients. METHODS: One hundred thirty-two patients of operable breast cancer who were younger than 35 are analyzed in this study. They were treated in our hospital between January 2006 and December 2012. Patients are classified into four molecular subtypes based on the immunohistochemical profiles of estrogen receptor (ER, progesterone receptor (PR, human epidermal growth factor receptor 2 (HER2, and Ki-67. Clinical and pathologic factors have been combined to define a specific classification of three risk levels to evaluate the prognosis of these young women. RESULTS: Patients whose ages are less than 30 have poorer prognosis than patients whose ages are between 31 and 35. The status of lymph nodes post-surgery seems to be the only factor related to patient age in young patients. The patients in level of ER+ or PR+ and HER2−/+ status have the worst prognosis in hormone receptor–positive breast cancer. Group 3 in risk factor grouping has the poorer prognosis than the other two groups. CONCLUSIONS: Patient age and axillary lymph nodes post-surgery are the independent and significant predictors of distant disease-free survival, local recurrence-free survival, and overall survival. The absence of PR relates to poor prognosis. The risk factor grouping provides a useful index to evaluate the risk of young breast cancer to identify subgroups of patients with a better prognosis.

  3. Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy confirmed Gleason score 3 + 4 prostate cancer.

    Science.gov (United States)

    Gondo, Tatsuo; Poon, Bing Ying; Matsumoto, Kazuhiro; Bernstein, Melanie; Sjoberg, Daniel D; Eastham, James A

    2015-01-01

    To identify preoperative factors predicting Gleason score downgrading after radical prostatectomy (RP) in patients with biopsy Gleason score 3+4 prostate cancer and to determine if prediction of downgrading can identify potential candidates for active surveillance (AS). We identified 1317 patients with biopsy Gleason score 3+4 prostate cancers who underwent RP at the Memorial Sloan-Kettering Cancer Center between 2005 and 2013. Several preoperative and biopsy characteristics were evaluated by forward selection regression, and selected predictors of downgrading were analysed by multivariable logistic regression. Decision curve analysis was used to evaluate the clinical utility of the multivariate model. Gleason score was downgraded after RP in 115 patients (9%). We developed a multivariable model using age, prostate-specific antigen density, percentage of positive cores with Gleason pattern 4 cancer out of all cores taken, and maximum percentage of cancer involvement within a positive core with Gleason pattern 4 cancer. The area under the curve for this model was 0.75 after 10-fold cross validation. However, decision curve analysis revealed that the model was not clinically helpful in identifying patients who will downgrade at RP for the purpose of reassigning them to AS. While patients with pathological Gleason score 3 + 3 with tertiary Gleason pattern ≤4 at RP in patients with biopsy Gleason score 3 + 4 prostate cancer may be potential candidates for AS, decision curve analysis showed limited utility of our model to identify such men. Future study is needed to identify new predictors to help identify potential candidates for AS among patients with biopsy confirmed Gleason score 3 + 4 prostate cancer. © 2014 The Authors. BJU International © 2014 BJU International.

  4. Hydro-dynamic CT preoperative staging of gastric cancer: correlation with pathological findings. A prospective study of 107 cases

    International Nuclear Information System (INIS)

    D'Elia, F.; Zingarelli, A.; Grani, M.; Palli, D.

    2000-01-01

    The aim of this study was to evaluate the accuracy of dynamic CT in the preoperative staging of gastric cancer. One hundred seven patients affected by gastric cancer diagnosed by endoscopic biopsy were prospectively staged by dynamic CT prior to tumor resection. After an oral intake of 400-600 ml of tap water and an intravenous infusion of a hypotonic agent, 200 ml of non-ionic contrast agent were administered by power injector using a biphasic technique. The CT findings were prospectively analyzed and correlated with the pathological findings at surgery. The accuracy of dynamic CT for tumor detection was 80 and 99 % in early and advanced gastric cancer, respectively, with overall detection rate of 96 % (103 of 107). Three early (pT1) and one advanced (pT2) cancers were undetected. Tumor stage as determined by dynamic CT agreed with pathological findings in 83 of 107 patients with an overall accuracy of 78 %. The accuracy of CT in detecting increasing degrees of depth of tumor invasion when compared with pathological TNM staging was 20 % (3 of 15) and 87 % (80 of 92) in early and advanced cancer, respectively. The sensitivity, specificity, and accuracy of CT in the preoperative staging (pT3-pT4 vs pT1-pT2) was 93, 90, and 91.6 %, respectively. The sensitivity, specificity, and accuracy of CT in assessing metastasis to regional lymph nodes was 97.2, 65.7, and 87 %, respectively. Computed tomography correctly staged liver metastases in 105 of 107 patients with an overall sensitivity of 87.5 % and specificity of 99 %. The sensitivity of peritoneal involvement was 30 % when ascites or peritoneal nodules were absent. Our findings show that dynamic CT can play a role in the preoperative definition of gastric cancer stage. The results can be used to optimize the therapeutic strategy for each individual patient prior to surgery, thus avoiding unnecessary intervention and allowing careful planning of extended surgery in eligible patients. (orig.)

  5. Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

    2010-01-01

    Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

  6. MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

    Directory of Open Access Journals (Sweden)

    Okyaz Eminaga

    Full Text Available The uncertainties inherent in clinical measures of prostate cancer (CaP aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.MUC1 IHC was performed on a multi-institutional tissue microarray (TMA resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test.The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS (HR: 1.24, CI 1.03-1.49, P = 0.02, although not with disease specific survival (DSS, P>0.5. On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS, but was weakly associated with overall survival (OS.In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

  7. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

    NARCIS (Netherlands)

    Verleye, Leen; Ottevanger, Petronella B.; Kristensen, Gunnar B.; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E. L.; Reed, Nick S.; Verheijen, René H. M.; Gaarenstroom, Katja N.; Mosgaard, Berit; Seoane, Jose M.; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant

  8. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial

    NARCIS (Netherlands)

    Verleye, L.I.A.; Ottevanger, P.B.; Kristensen, G.B.; Ehlen, T.; Johnson, N.; Burg, M.E. van der; Reed, N.S.; Verheijen, R.H.; Gaarenstroom, K.N.; Mosgaard, B.; Seoane, J.M.; Velden, J. Van der; Lotocki, R.; Graaf, W.T.A. van der; Penninckx, B.; Coens, C.; Stuart, G.; Vergote, I.

    2011-01-01

    OBJECTIVE: To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with

  9. Somatization in Parkinson's Disease

    DEFF Research Database (Denmark)

    Carrozzino, Danilo; Bech, Per; Patierno, Chiara

    2017-01-01

    The current systematic review study is aimed at critically analyzing from a clinimetric viewpoint the clinical consequence of somatization in Parkinson's Disease (PD). By focusing on the International Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we...... consequence of such psychiatric symptom should be further evaluated by replacing the clinically inadequate diagnostic label of psychogenic parkinsonism with the psychosomatic concept of persistent somatization as conceived by the Diagnostic Criteria for Psychosomatic Research (DCPR)....

  10. The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters

    Energy Technology Data Exchange (ETDEWEB)

    Al Sarakbi, W; Sasi, W [St George' s University of London, Blackshaw Road, Tooting, London, SW17 OQT (United Kingdom); Jiang, WG [University Department of Surgery, Wales College of Medicine, Cardiff University, CF14 4XN (United Kingdom); Roberts, T; Newbold, RF [Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom); Mokbel, K [St George' s University of London, Blackshaw Road, Tooting, London, SW17 OQT (United Kingdom); Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, Middlesex, UB8 3PH (United Kingdom)

    2009-08-21

    SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.

  11. The location of locoregional recurrence in pathologic T3N0, non-irradiated lower rectal cancer

    International Nuclear Information System (INIS)

    Kim, Mi Sun; Keum, Ki Chang; Rhee, Woo Joong; Kim, Hyun Ju; Kim, Min Ji; Choi, Seo Hee; Nam, Ki Chang; Koom, Woong Sub

    2013-01-01

    To investigate the patterns of locoregional recurrence of pathologic T3N0 (pT3N0) lower rectal cancer omitting postoperative radiotherapy (RT) and explore the potential of modification of a RT field. From Jan 2003 to Nov 2011, 35 patients omitting preoperative or postoperative RT for pT3N0 lower rectal cancer were included. We defined the lower rectal cancer as the tumor with the inferior margin located below the virtual line-a convergent level between rectal wall and levator ani muscle. All patients had radiologic examinations for recurrence evaluation during the follow-up duration. The median follow-up duration was 66.4 months (range, 1.4 to 126.1 months). Eight (22.9%) of the 35 patients had recurrence. Three (8.6%) was local recurrence (LR) only, 3 (8.6%) was distant metastasis (DM) only, and 2 (5.7%) was LR with DM. All LR were located at primary tumor sites. The overall survival rate, LR-free survival rate, and DM-free survival rate at 5 years was 79.8%, 83%, and 87%, respectively. All LR developed from tumors over 5 cm. However, there was no statistical significance (p = 0.065). There was no other risk factor for LR. Even though the patients included in this study had pathologically favorable pT3N0 rectal cancer, LR developed in 14.3% of patients. Most of the LR was located at primary tumor sites prior to surgery. Based on these findings, it might seem reasonable to consider postoperative RT with a smaller radiation field to the primary tumor site rather than the conventional whole pelvic irradiation.

  12. Staging primary breast cancer. Are there tumour pathological features that correlate with a false-negative axillary ultrasound?

    International Nuclear Information System (INIS)

    Johnson, S.; Brown, S.; Porter, G.; Steel, J.; Paisley, K.; Watkins, R.; Holgate, C.

    2011-01-01

    Aim: To investigate whether the histopathological characteristics of primary breast cancer tumours could predict the likelihood of false-negative axillary ultrasound. Materials and methods: Screening and symptomatic patients were identified from pathology records and imaging and pathology records reviewed. True and false-negative axillary staging ultrasound groups were compared statistically in terms of tumour size, pathological type and grade, lymphovascular invasion, and oestrogen receptor (ER) status. Results: Of 155 women with normal ultrasounds, 45 (29%) were node positive at axillary surgery. Breast tumour size was significantly different with the average size smaller in the true-negative group: 21 versus 30 mm (p < 0.02). The histological type varied significantly between the groups, with more lobular carcinomas in the false-negative group [6/110 (5%) versus 6/45 (13%), p < 0.001]. The false-negative group was also more likely to show lymphovascular invasion in the breast [6/110 (5%) versus 14/45 (31%), p < 0.001]. There was no significant difference in tumour grade or ER status. Conclusion: The present study has found significant differences in tumour characteristics between women with true-negative and false-negative axillary staging ultrasound in terms of size, primary tumour histological type and presence of lymphovascular invasion. In particular, axillary ultrasound in primary lobular carcinoma may be less accurate and a negative result is more likely to be spurious than with primary ductal carcinomas.

  13. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  14. [Using (1)H-nuclear magnetic resonance metabolomics and gene ontology to establish pathological staging model for esophageal cancer patients].

    Science.gov (United States)

    Chen, X; Wang, K; Chen, W; Jiang, H; Deng, P C; Li, Z J; Peng, J; Zhou, Z Y; Yang, H; Huang, G X; Zeng, J

    2016-07-01

    By combining the metabolomics and computational biology, to explore the relationship between metabolic phenotype and pathological stage in esophageal cancer patients, to find the mechanism of metabolic network disturbance and develop a new method for fast preoperative clinical staging. A prospective cohort study (from April 2013 to January 2016) was conducted. The preoperative patients from Sichuan Provincial People's Hospital, who were diagnosed with esophageal cancer from May 2013 to April 2014 were included, and their serum samples were collected to detect (1)H-nuclear magnetic resonance (NMR) metabolomics for the purpose of drawing the metabolic fingerprinting in different stages of patients with esophageal cancer. The data were processed with these methods-principal components analysis: partial least squares regression and support vector machine, for the exploration of the enzyme-gene network regulatory mechanism in abnormal esophageal cancer metabolic network regulation and to build the quantitative prediction model of esophageal cancer staging in the end. All data were processed on high-performance computing platforms Matalab. The comparison of data had used Wilcoxon test, variance analysis, χ(2) test and Fisher exact test. Twenty patients with different stages of esophageal cancer were included; and their serum metabolic fingerprinting could differentiate different tumor stages. There were no difference among the five teams in the age (F=1.086, P>0.05), the body mass index (F=1.035, P>0.05), the distance from the incisors to tumor (F=1.078, P>0.05). Among the patients with different TNM stages, there was a significant difference in plasma metabolome. Compared to ⅡB, ⅢA, Ⅳstage patients, increased levels of butanone, ethanol amine, homocysteine, hydroxy acids and estriol, together with decreased levels of glycoprotein, creatine, choline, isobutyricacid, alanine, leucine, valine, were observed inⅠB, ⅡA stage patients. Four metabolic markers

  15. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Gonen, M.; Kuk, D. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States); Saltz, L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY (United States); Schrag, D. [Dana Farber Cancer Institute, Boston, MA (United States); Goodman, K. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Shia, J. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Schwartz, L.H. [Columbia University Medical Center/New York Presbyterian Hospital, Department of Radiology, New York, NY (United States)

    2012-04-15

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K{sup trans}, k{sub ep}, v{sub e}, AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P {<=} 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K{sup trans} (mean 0.5 min{sup -1} vs. 0.2 min{sup -1}, P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  16. Right- and left-sided colon cancer - clinical and pathological differences of the disease entity in one organ.

    Science.gov (United States)

    Mik, Michal; Berut, Maciej; Dziki, Lukasz; Trzcinski, Radzislaw; Dziki, Adam

    2017-02-01

    Some researchers suggest that cancers located in the right vs. the left side of the colon are different and they can be regarded as distinct disease entities. The aim of this study was to analyze differences in clinical, epidemiological and pathological features of patients with right-sided (RCC) and left-sided (LCC) colon cancer. One thousand two hundred and twenty-four patients were operated on due to colorectal cancer. A group of 477 patients (254 women, mean age 65.5 ±11 for the whole group) with colon cancer was included (212 RCC vs. 265 LCC). Right colon cancer patients were older (67.8 ±11.3 vs. 63.2 ±11.2; p = 0.0087). Left colon cancer patients underwent surgery for urgent indications more often (17.0% vs. 8.5%; p = 0006). Tumor diameter was greater in the RCC group (55 ±60 mm vs. 38 ±21 mm; p = 0.0003). Total number of removed lymph nodes was higher in the RCC group (11.7 ±6 vs. 8.3 ±5; p = 0.0001). Lymph node ratio was higher in the LCC group (0.45 ±0.28 vs. 0.30 ±0.25; p = 0.0063). We found a strong positive correlation between tumor diameter and the number of removed lymph nodes in the LCC group ( r = 0.531). These differences may result from the fact that RCC patients are diagnosed at an older age. The smaller number of removed lymph nodes in LCC patients may result in incorrect staging. It is still necessary to find other biological dissimilarities of adenocarcinoma located on different sides of the colon.

  17. Clinical and Pathological Staging Validation in the Eighth Edition of the TNM Classification for Lung Cancer: Correlation between Solid Size on Thin-Section Computed Tomography and Invasive Size in Pathological Findings in the New T Classification.

    Science.gov (United States)

    Aokage, Keiju; Miyoshi, Tomohiro; Ishii, Genichiro; Kusumoto, Masahiro; Nomura, Shogo; Katsumata, Shinya; Sekihara, Keigo; Hishida, Tomoyuki; Tsuboi, Masahiro

    2017-09-01

    The aim of this study was to validate the new eighth edition of the TNM classification and to elucidate whether radiological solid size corresponds to pathological invasive size incorporated in this T factor. We analyzed the data on 1792 patients who underwent complete resection from 2003 to 2011 at the National Cancer Center Hospital East, Japan. We reevaluated preoperative thin-section computed tomography (TSCT) to determine solid size and pathological invasive size using the fourth edition of the WHO classification and reclassified them according to the new TNM classification. The discriminative power of survival curves by the seventh edition was compared with that by the eighth edition by using concordance probability estimates and Akaike's information criteria calculated using a univariable Cox regression model. Pearson's correlation coefficient was calculated to elucidate the correlation between radiological solid size using TSCT and pathological invasive size. The overall survival curves in the eighth edition were well distinct at each clinical and pathological stage. The 5-year survival rates of patients with clinical and pathological stage 0 newly defined were both 100%. The concordance probability estimate and Akaike's information criterion values of the eighth edition were higher than those of the seventh edition in discriminatory power for overall survival. Solid size on TSCT scan and pathological invasive size showed a positive linear relationship, and Pearson's correlation coefficient was calculated as 0.83, which indicated strong correlation. This TNM classification will be feasible regarding patient survival, and radiological solid size correlates significantly with pathological invasive size as a new T factor. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  18. Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1 gene reveals association with early age of diagnosis in colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Austin Y Shull

    Full Text Available The Cub and Sushi Multiple Domains 1 (CSMD1 gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A.Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%. The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15:1, a ratio significantly higher than the expected 2:1 ratio (p = 0.014. This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%. Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years than those without somatic mutations (average age, 68 years. The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%, suggesting extensive cytosine methylation predisposing to somatic mutations.Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1 alterations can correlate with earlier clinical

  19. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  20. Hypochondriasis and somatization.

    Science.gov (United States)

    Kellner, R

    1987-11-20

    Between 60% and 80% of healthy individuals experience somatic symptoms in any one week. About 10% to 20% of a random sample of people worry intermittently about illness. A substantial proportion of patients present physicians with somatic complaints for which no organic cause can be found. Patients who are hypochondriacal do not understand the benign nature of functional somatic symptoms and interpret these as evidence of disease. Hypochondriacal concerns range from common short-lived worries to persistent and distressing fears or convictions of having a disease. Hypochondriasis can be secondary to other psychiatric disorders (eg, melancholia or panic disorder), and hypochondriacal attitudes remit when the primary disorder is successfully treated. Patients with primary hypochondriasis are also anxious or depressed, but the fear of disease, or the false belief of having a disease, persists and is the most important feature of their psychopathology. There are substantial differences among hypochondriacal patients in their personalities and psychopathologies. Psychotherapy as well as psychotropic drugs are effective in the treatment of functional somatic symptoms. There are no adequate controlled studies on the value of psychotherapy in hypochondriasis; the recommended guidelines are based on uncontrolled studies of hypochondriasis and on controlled studies of the psychotherapy in similar disorders. The prognosis of functional somatic symptoms as well as that of hypochondriasis is good in a substantial proportion of patients.

  1. Subclinical myopathy in patients with colorectal cancer: clinical-pathological characterization and search for tissue markers

    Directory of Open Access Journals (Sweden)

    Massimo Vecchiato

    2012-03-01

    Full Text Available Skeletal muscle in patients with cancer undergoes many morphological changes due to immuno-inflammatory factors of tumor origin or treatment.T he latest event of these changes is cancer cachexia. Aim of the study is to identify myopathic features in skeletal muscle biopsies from weight stable patients with colorectal cancer and without cachexia or asthenia / weakness, that could possibly provide new diagnostic and prognostic cancer biomarkers. Morphometric analyses and immunohistochemical studies were performed on intraoperative muscle biopsies from patients with colorectal cancer and from weight stable patients undergoing surgery for benign non-inflammatory conditions. A rectus abdominis biopsy was taken in all patients and controls.A correlation between histopathologic findings and clinical characteristics, circulating inflammatory biomarkers and markers of muscle necrosis,surgery data and cancer phenotype were investigated.. Forty four patients (21male/23 female and 17 controls (6 male/11 female (p=NS were studied. In cancer patients’biopsies we observed asubclinical myopathy characterized by an abnormal distribution of myonuclei, which are localized inside the myofiber rather than at the periphery, and by the presence of regenerating muscle fibers. The percentage of myofibers with internalized nuclei is significantly higher in patients (median= 9%, IQR= 3.7-18.8 than in controls (median= 2.7%, IQR= 1.7-3.2 ( p=0.0002. In patients we observed an inverse correlation between the number of centronucleated fibers and the presence of node metastasis (N+(ρ=-0.64 (p=0.002. Patients affected with colorectal cancer display early sign of a myopathy, characterized by centronucleated and regenerating myofibers. This myopathy appears to be associated with an early stage of neoplasia and it could be an adaptive response of muscle to cancer. We hope a future application of these findings as a possible early diagnostic and prognostic biomarker of

  2. Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

    Science.gov (United States)

    Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

    2017-04-01

    Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Limited accuracy of DCE-MRI in identification of pathological complete responders after chemoradiotherapy treatment for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, Marc J. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Tong, Tong [Fudan University Medical Center, Department of Radiology, Shanghai (China); Weiser, Martin [Memorial Sloan Kettering Cancer Center, Department of Surgery, Divison of Colorectal Surgery, New York, NY (United States); Zheng, Junting; Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Zakian, Kristen L. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States)

    2017-04-15

    To examine whether post-chemoradiotherapy (CRT) DCE-MRI can identify rectal cancer patients with pathologic complete response (pCR). From a rectal cancer surgery database 2007-2014, 61 consecutive patients that met the following inclusion criteria were selected for analysis: (1) stage II/III primary rectal adenocarcinoma; (2) received CRT; (3) underwent surgery (4); underwent rectal DCE-MRI on a 1.5-T MRI scanner. Two experienced radiologists, in consensus, drew regions of interest (ROI) on the sagittal DCE-MRI image in the tumour bed. These were exported from ImageJ to in-house Matlab code for modelling using the Tofts model. K{sup trans}, K{sub ep} and v{sub e} values were compared to pathological response. Of the 61 initial patients, 37 had data considered adequate for fitting to obtain perfusion parameters. Among the 13 men and 24 women, median age 53 years, there were 8 pCR (22 %). K{sup trans} could not distinguish patients with pCR. For patients with 90 % or greater response, mean K{sup trans} and K{sub ep} values were statistically significant (p = 0.032 and 0.027, respectively). Using a cutoff value of K{sup trans} = 0.25 min{sup -1}, the AUC was 0.71. K{sup trans} could be used to identify patients with 90 % or more response to chemoradiotherapy for rectal cancer with an AUC of 0.7. (orig.)

  4. Clinico-pathological investigation of resectable gastric cancer in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Takashi; Saeki, Toshiaki; Hirai, Toshihiro; Toge, Tetuya; Niimoto, Minoru; Hattori, Takao; Ootaki, Megu; Munaka, Masaki

    1989-01-01

    This is a review of 1074 patients with resectable gastric cancer who have satisfied the following criteria: primary cancer, histological confirmation, the description of exposed or non-exposed patients, and certification of atomic bomb survivor's health handbook in exposed patients. There were 250 men and 162 women in the exposed group, and 460 men and 203 women in the non-exposed group. Gastric cancer was detected in 29.6% for the exposed group and 7.4% for the non-exposed group, although the patients had not complained of any symptoms. These figures tended to increase annually, probably benefiting from health examination. The difference between the exposed and non-exposed patients tended to be smaller when preoperative stages and the percentage of macroscopic early cancer were adjusted by age and the presence of complaints. The difference in histology between the groups also tended to be smaller. In the exposed group, however, men and women tended to have well differentiated cancer and poorly differentiated cancer, respectively. Since A-bomb survivors consist of radiation exposed population and are managed under intensive medical care, adjustment of some factors is necessary in comparing A-bomb survivors with general population. (Namekawa, K)

  5. High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer.

    Science.gov (United States)

    Makhoul, Issam; Griffin, Robert J; Siegel, Eric; Lee, Jeannette; Dhakal, Ishwori; Raj, Vinay; Jamshidi-Parsian, Azemat; Klimberg, Suzanne; Hutchins, Laura F; Kadlubar, Susan

    2016-06-01

    Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. Research in antiangiogenic cancer treatment has been marked by the development of the monoclonal antibody bevacizumab, which targets VEGF in many solid tumors. As patients do not equally benefit from bevacizumab, it has become necessary to define the profile of patients who will benefit from the drug. We have conducted a prospective phase II study in 39 patients using bevacizumab in breast cancer in the neoadjuvant setting, and found improved pathologic complete response (pCR) when bevacizumab was added to chemotherapy in patients with hormone receptor negative and invasive ductal carcinoma. Blood samples were collected at baseline and serially while patients were on treatment. Circulating angiogenesis-related proteins angiopoietin (ANG)1, ANG2, basic fibroblast growth factor, IL-1a, matrix metalloproteinase 9, platelet derived growth factor - BB, platelet endothelial cell adhesion molecule -1, Tie2, VEGF, and vascular endothelial growth factor receptor 2 were measured at baseline and during treatment. This correlative study was conducted to identify specific serum angiogenic factor profiles that might be associated with pCR in the neoadjuvant setting in breast cancer patients receiving bevacizumab and chemotherapy. Elevated baseline serum Tie2 and basic fibroblast growth factor were associated with pCR in response to this combination. Changes in serum levels of these proteins were seen during treatment but were not significantly different between the pCR and non-pCR groups. Baseline-circulating Tie2 levels may help distinguish patients who will have pCR from those who will not and may form the basis for future development of antiangiogenic therapy in breast cancer. Larger studies are needed to validate these findings. ClinicalTrials.gov Identifier: NCT00203502.

  6. Preoperatively Assessable Clinical and Pathological Risk Factors for Parametrial Involvement in Surgically Treated FIGO Stage IB-IIA Cervical Cancer.

    Science.gov (United States)

    Canaz, Emel; Ozyurek, Eser Sefik; Erdem, Baki; Aldikactioglu Talmac, Merve; Yildiz Ozaydin, Ipek; Akbayir, Ozgur; Numanoglu, Ceyhun; Ulker, Volkan

    2017-10-01

    Determining the risk factors associated with parametrial involvement (PMI) is of paramount importance to decrease the multimodality treatment in early-stage cervical cancer. We investigated the preoperatively assessable clinical and pathological risk factors associated with PMI in surgically treated stage IB1-IIA2 cervical cancer. A retrospective cohort study of women underwent Querleu-Morrow type C hysterectomy for cervical cancer stage IB1-IIA2 from 2001 to 2015. All patients underwent clinical staging examination under anesthesia by the same gynecological oncologists during the study period. Evaluated variables were age, menopausal status, body mass index, smoking status, FIGO (International Federation of Obstetrics and Gynecology) stage, clinically measured maximal tumor diameter, clinical presentation (exophytic or endophytic tumor), histological type, tumor grade, lymphovascular space invasion, clinical and pathological vaginal invasion, and uterine body involvement. Endophytic clinical presentation was defined for ulcerative tumors and barrel-shaped morphology. Two-dimensional transvaginal ultrasonography was used to measure tumor dimensions. Of 127 eligible women, 37 (29.1%) had PMI. On univariate analysis, endophytic clinical presentation (P = 0.01), larger tumor size (P PMI. In multivariate analysis endophytic clinical presentation (odds ratio, 11.34; 95% confidence interval, 1.34-95.85; P = 0.02) and larger tumor size (odds ratio, 32.31; 95% confidence interval, 2.46-423.83; P = 0.008) were the independent risk factors for PMI. Threshold of 31 mm in tumor size predicted PMI with 71% sensitivity and 75% specificity. We identified 18 patients with tumor size of more than 30 mm and endophytic presentation; 14 (77.7%) of these had PMI. Endophytic clinical presentation and larger clinical tumor size (>3 cm) are independent risk factors for PMI in stage IB-IIA cervical cancer. Approximately 78% of the patients with a tumor size of more than 3 cm and endophytic

  7. Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Hee Jin Lee

    Full Text Available Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB, residual disease in breast and nodes (RDBN, tumor response ratio, Sataloff's classification, and Miller-Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan-Meier curves.Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.

  8. Comparison of Estrogen Receptor Assay Results from Pathology Reports with Results from Central Laboratory Testing: Implications for Population-Based Studies of Breast Cancer

    Science.gov (United States)

    Collins, LC; Marotti, J; Baer, HJ; Deitz, AC; Colditz, GA; Tamimi, RM

    2014-01-01

    Population-based studies of women with breast cancer commonly utilize information culled from pathology reports rather than central pathology review. The reliability of this information, particularly with regard to tumor biomarker results, is of concern. To address this, we evaluated the concordance between estrogen receptor (ER) results as determined from the original pathology reports and ER results obtained on the same specimens following testing in a single laboratory. Tissue microarrays (TMAs) were constructed from paraffin blocks of 3,167 breast cancers that developed in women enrolled in the Nurses’ Health Study. ER immunostains were performed on all TMA sections in single run. Results of ER immunostains performed on the TMA sections were compared with ER assay results abstracted from pathology reports. Among 1,851 cases of invasive breast cancer in which both ER results from pathology reports and central ER test results were available, the reported ER status and the ER status as determined from immunostains on TMAs were in agreement in 1,651 cases (87.3 %; kappa value 0.64, ppathology reports is a reasonable, albeit imperfect, alternative to central laboratory ER testing for large, population-based studies of patients with breast cancer. PMID:18230800

  9. Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal Irradiation After Current Standard Systemic Management.

    Science.gov (United States)

    Yu, Jeong Il; Park, Won; Choi, Doo Ho; Huh, Seung Jae; Nam, Seok Jin; Kim, Seok Won; Lee, Jeong Eon; Kil, Won Ho; Im, Young-Hyuck; Ahn, Jin Seok; Park, Yeon Hee; Cho, Eun Yoon

    2015-08-01

    This study was conducted to establish a prognostic model in patients with pathologic N1 (pN1) breast cancer who have not undergone elective nodal irradiation (ENI) under the current standard management and to suggest possible indications for ENI. We performed a retrospective study with patients with pN1 breast cancer who received the standard local and preferred adjuvant chemotherapy treatment without neoadjuvant chemotherapy and ENI from January 2005 to June 2011. Most of the indicated patients received endocrine and trastuzumab therapy. In 735 enrolled patients, the median follow-up period was 58.4 months (range, 7.2-111.3 months). Overall, 55 recurrences (7.4%) developed, and locoregional recurrence was present in 27 patients (3.8%). Recurrence-free survival was significantly related to lymphovascular invasion (P = .04, hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.03-2.88), histologic grade (P = .03, HR, 2.57; 95% CI, 1.05-6.26), and nonluminal A subtype (P = .02, HR, 3.04; 95% CI, 1.23-7.49) in multivariate analysis. The prognostic model was established by these 3 prognostic factors. Recurrence-free survival was less than 90% at 5 years in cases with 2 or 3 factors. The prognostic model has stratified risk groups in pN1 breast cancer without ENI. Patients with 2 or more factors should be considered for ENI. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study.

    Science.gov (United States)

    Rugge, M; de Boni, M; Pennelli, G; de Bona, M; Giacomelli, L; Fassan, M; Basso, D; Plebani, M; Graham, D Y

    2010-05-01

    Intestinal-type gastric cancer (GC) still ranks among the high-incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy-based) ranking of GC risk. To test the gastritis OLGA-staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression. Ninety-three Italian patients were followed up for more than 12 years (range: 144-204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow-up (T2). All invasive or intra-epithelial gastric neoplasia were consistently associated with high-risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P gastritis OLGA-staging conveys relevant information on the clinico-pathological outcome of gastritis and therefore for patient management. According to OLGA-staging and H. pylori-status, gastritis patients could be confidently stratified and managed according to their different cancer risks.

  11. Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care.

    Directory of Open Access Journals (Sweden)

    Mark A Valasek

    Full Text Available Low-grade appendiceal mucinous neoplasm (LAMN and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites; however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria.To determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP.The anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral.161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6% contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50% as adenocarcinoma and 23 cases (50% as LAMN; however, the reference pathologist diagnosed 29 cases (63.0% as LAMN, 13 cases (28.3% as adenocarcinoma, and 4 cases (8.7% as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23, LAMN (39.1%, 9 of 23, or simple mucocele (4.3%, 1 of 23. The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46 with an unweighted observed kappa value of 0.48 (95% CI, 0.27-0.69, consistent with moderate interobserver agreement. All of the observed discordance (28.3% for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5% had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic

  12. Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

    Science.gov (United States)

    Wei, Jian-Jun; William, Josette; Bulun, Serdar

    2014-01-01

    Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

  13. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    DEFF Research Database (Denmark)

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.

    2008-01-01

    In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells Udgivelsesdato: 2008/5...

  14. Pathological diagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer: a framework for developing an objective pathological diagnostic system using the Delphi method, from the Pathology Working Group of the Japanese Society for Cancer of the Colon and Rectum.

    Science.gov (United States)

    Kojima, Motohiro; Shimazaki, Hideyuki; Iwaya, Keiichi; Kage, Masayoshi; Akiba, Jun; Ohkura, Yasuo; Horiguchi, Shinichiro; Shomori, Kohei; Kushima, Ryoji; Ajioka, Yoichi; Nomura, Shogo; Ochiai, Atsushi

    2013-07-01

    The goal of this study is to create an objective pathological diagnostic system for blood and lymphatic vessel invasion (BLI). 1450 surgically resected colorectal cancer specimens from eight hospitals were reviewed. Our first step was to compare the current practice of pathology assessment among eight hospitals. Then, H&E stained slides with or without histochemical/immunohistochemical staining were assessed by eight pathologists and concordance of BLI diagnosis was checked. In addition, histological findings associated with BLI having good concordance were reviewed. Based on these results, framework for developing diagnostic criterion was developed, using the Delphi method. The new criterion was evaluated using 40 colorectal cancer specimens. Frequency of BLI diagnoses, number of blocks obtained and stained for assessment of BLI varied among eight hospitals. Concordance was low for BLI diagnosis and was not any better when histochemical/immunohistochemical staining was provided. All histological findings associated with BLI from H&E staining were poor in agreement. However, observation of elastica-stained internal elastic membrane covering more than half of the circumference surrounding the tumour cluster as well as the presence of D2-40-stained endothelial cells covering more than half of the circumference surrounding the tumour cluster showed high concordance. Based on this observation, we developed a framework for pathological diagnostic criterion, using the Delphi method. This criterion was found to be useful in improving concordance of BLI diagnosis. A framework for pathological diagnostic criterion was developed by reviewing concordance and using the Delphi method. The criterion developed may serve as the basis for creating a standardised procedure for pathological diagnosis.

  15. Quality of pathology reports for advanced ovarian cancer: are we missing essential information? An audit of 479 pathology reports from the EORTC-GCG 55971/NCIC-CTG OV13 neoadjuvant trial.

    Science.gov (United States)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E L; Reed, Nick S; Verheijen, René H M; Gaarenstroom, Katja N; Mosgaard, Berit; Seoane, Jose M; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant chemotherapy and interval debulking surgery. Four hundred and seventy nine pathology reports from 40 institutions in 11 different countries were checked for the following quality indicators: macroscopic description of all specimens, measuring and weighing of major specimens, description of tumour origin and differentiation. All specimens were macroscopically described in 92.3% of the reports. All major samples were measured and weighed in 59.9% of the reports. A description of the origin of the tumour was missing in 20.5% of reports of the primary debulking group and in 23.4% of the interval debulking group. Assessment of tumour differentiation was missing in 10% of the reports after primary debulking and in 20.8% of the reports after interval debulking. Completeness of reports is positively correlated with accrual volume and adversely with hospital volume or type of hospital (academic versus non-academic). Quality of reports differs significantly by country. This audit of ovarian cancer pathology reports reveals that in a substantial number of reports basic pathologic data are missing, with possible adverse consequences for the quality of cancer care. Specialisation by pathologists and the use of standardised synoptic reports can lead to improved quality of reporting. Further research is needed to better define pre- and post-operative diagnostic criteria for ovarian cancer treated with neoadjuvant chemotherapy. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. A clinical and pathological study of acute rectal injury by the radiation therapy of uterine cervix cancer

    International Nuclear Information System (INIS)

    Honke, Yoshifumi; Katsuta, Shizutomo; Katayama, Hiroshi; Haruma, Ken; Fujiwara, Atsushi; Suenaga, Kenji.

    1983-01-01

    The clinical features, magnifying colonoscopic findings and pathological findings of acute radiation proctitis were investigated in 40 cases of uterine cervix cancer and the following results were obtained. 1)As a clinical simptom, diarrhea was observed in about half of all cases. 2)The value of serum total protein and number of leukocyte decreased until the dose of 30 Gy (3000 rads) and no remarkable change of them were observed afterwards. Hemoglobin value did not change throughout the whole clinical course. 3)Magnifying colonoscopic findings showed remarkable change with increase of the dose and especially irregularity of pit was observed in all cases. 4)In pathological findings, edema, degenerative change of epitherial cells and decreased number of goblet cells were observed from the beginning. In cases that received more than 50 Gy (5000 rads), fibrosis developed and the epithelium showed strong regeneration. Also Paneth cells were observed in 5 out of 40 cases. 5)Remarkable change was not observed before or after the radiation by barium enema. (author)

  17. Accelerated radiochemotherapy in pancreatic cancer is not necessarily related to a pathologic pancreatic function decline in the early period

    International Nuclear Information System (INIS)

    Horst, Eckehard; Seidel, Matthias; Micke, Oliver; Ruebe, Christian; Glashoerster, Marco; Schaefer, Ulrich; Willich, Normann A.

    2002-01-01

    Purpose: To evaluate the functional effects of ionizing radiation in patients with unresectable pancreatic cancer in the early period after accelerated radiochemotherapy (ART). Methods and Materials: To analyze the exocrine component, the amino acid consumption test and fecal elastase 1 were performed in 13 patients immediately before and 4-8 weeks after ART. Pancreatic duct morphology was evaluated before therapy. Weight loss and clinical steatorrhea were recorded. Endocrine parameters were examined according to standardized criteria. Results: The relative change of the amino acid consumption test results and the median elastase concentration was 41.2% and 56.4%, respectively. Five patients still had normal test results after ART and 5 patients developed pathologic values. The median relative weight loss of the total body weight was 7.7% ± 4.5%. No steatorrhea occurred. Of the 5 patients with normal values, 3 had a mean organ dose of 41 Gy. The endocrine function measurements remained unchanged. Conclusion: Although a nominal reduction of exocrine function parameters occurred in most patients, ART was not necessarily related to a pathologic level in the early period. Diabetes was not established. The functional impairment that was existent in the patient population presumably contributed to the weight loss. Pancreatic enzyme preparations may also play a role in maintaining an anabolic state during and after radiochemotherapy

  18. The chemistry, physiology and pathology of pH in cancer.

    Science.gov (United States)

    Swietach, Pawel; Vaughan-Jones, Richard D; Harris, Adrian L; Hulikova, Alzbeta

    2014-03-19

    Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid-base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H(+)-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H(+)-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H(+)/H(+)-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H(+)/H(+)-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors.

  19. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

    Science.gov (United States)

    Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

    2018-06-01

    To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

  20. A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

    Science.gov (United States)

    Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W

    2017-02-01

    There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Podoplanin expression in cancer-associated fibroblasts predicts unfavourable prognosis in patients with pathological stage IA lung adenocarcinoma.

    Science.gov (United States)

    Kubouchi, Yasuaki; Yurugi, Yohei; Wakahara, Makoto; Sakabe, Tomohiko; Haruki, Tomohiro; Nosaka, Kanae; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Shiomi, Tatsushi; Nakamura, Hiroshige; Umekita, Yoshihisa

    2018-02-01

    Podoplanin expression in cancer-associated fibroblasts (CAFs) has been proposed as an unfavourable indicator in squamous cell carcinoma of the lung, but little is known about its clinical significance in early-stage lung adenocarcinoma. We evaluated the prognostic impact of podoplanin expression in patients with pathological stage (p-stage) IA lung adenocarcinoma as categorised by the 8th edition of the tumour-node-metastasis classification for lung cancer. Immunohistochemical analyses using anti-podoplanin antibody were performed on resected specimens from 158 patients with p-stage IA lung adenocarcinoma. When more than 10% of cancer cells or CAFs showed immunoreactivity with podoplanin, the specimens were classified as podoplanin-positive. Podoplanin-positive status in cancer cells (n = 8) was not correlated with clinicopathological factors or with patient prognosis. Podoplanin-positive status in CAFs (n = 41) was correlated significantly with poorer tumour differentiation (P < 0.001), the presence of lymphatic invasion (P < 0.001) and high-grade (solid and/or micropapillary) components constituting ≥1% of the entire tumour (P < 0.001). The log-rank test showed that podoplanin-positive status in CAFs was associated significantly with shorter disease-free survival (DFS) (P < 0.001) and disease-specific survival (P = 0.015). In Cox's multivariate analysis, podoplanin-positive status in CAFs had the most significant effect on shorter DFS [hazard ratio (HR) = 4.411, P = 0.004], followed by the presence of high-grade components (HR = 3.581, P = 0.013). Podoplanin expression in CAFs could be an independent predictor of increased risk of recurrence in patients with p-stage IA lung adenocarcinoma. © 2017 John Wiley & Sons Ltd.

  2. Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer.

    Directory of Open Access Journals (Sweden)

    Sheng Chen

    Full Text Available BACKGROUND: To evaluate the relationship between body mass index (BMI and response to neoadjuvant chemotherapy (NCT for breast cancer among Chinese women. PATIENTS AND METHODS: A total of 307 eligible patients were assigned to receive four cycles of paclitaxel and carboplatin before standard surgery for breast cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were categorized as obese, overweight, normal weight, or underweight based on BMI according to World Health Organization (WHO criteria. Pathological complete response (pCR was defined as no invasive cancer in the breast or axillary tissue. A logistic regression and the Chi-squared test were used for detecting the predictors of pCR and determining the relationship between BMI category and pCR rate in the subgroup analysis with respect to other variables. RESULTS: Categorical BMI, estrogen receptor (ER, and progesterone receptor (PR status were independent predictors of pCR according to the multivariate analysis. Patients with BMI≥25 were less likely to achieve a pCR to NCT compared with patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis. In the subgroup analysis, the predictive value of BMI for pCR to NCT was significantly shown in post-menopausal patients (p = 0.004 and hormonal receptor status-negative patients (p = 0.038. The incidence of treatment-induced toxicity was similar among the different BMI categories. CONCLUSION: Higher BMI was associated with worse pCR to NCT. Further approaches to investigating the mechanism of this influence of BMI on treatment response and a more appropriate schedule for calculating NCT dose for high-BMI-patients should be considered.

  3. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Drisis, Stylianos; Stathopoulos, Konstantinos; Chao, Shih-Li; Lemort, Marc [Institute Jules Bordet, Radiology Department, Brussels (Belgium); Metens, Thierry [Erasme University Hospital, Radiology Department, Brussels (Belgium); Ignatiadis, Michael [Institute Jules Bordet, Oncology Department, Brussels (Belgium)

    2016-05-15

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  4. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Quality assurance in pathology in colorectal cancer screening and diagnosis.

    Science.gov (United States)

    Quirke, P; Risio, M; Lambert, R; von Karsa, L; Vieth, M

    2012-09-01

    Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on quality assurance in pathology in colorectal cancer screening and diagnosis includes 23 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

    Science.gov (United States)

    Hilly, Ohad; Raz, Raanan; Vaisbuch, Yona; Strenov, Yulia; Segal, Karl; Koren, Rumelia; Shvero, Jacob

    2012-11-01

    Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx. Copyright © 2011 Wiley Periodicals, Inc.

  6. Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients.

    Science.gov (United States)

    Urru, Silvana Anna Maria; Gallus, Silvano; Bosetti, Cristina; Moi, Tiziana; Medda, Ricardo; Sollai, Elisabetta; Murgia, Alma; Sanges, Francesca; Pira, Giovanna; Manca, Alessandra; Palmas, Dolores; Floris, Matteo; Asunis, Anna Maria; Atzori, Francesco; Carru, Ciriaco; D'Incalci, Maurizio; Ghiani, Massimo; Marras, Vincenzo; Onnis, Daniela; Santona, Maria Cristina; Sarobba, Giuseppina; Valle, Enrichetta; Canu, Luisa; Cossu, Sergio; Bulfone, Alessandro; Rocca, Paolo Cossu; De Miglio, Maria Rosaria; Orrù, Sandra

    2018-01-08

    To provide further information on the clinical and pathological prognostic factors in triple-negative breast cancer (TNBC), for which limited and inconsistent data are available. Pathological characteristics and clinical records of 841 TNBCs diagnosed between 1994 and 2015 in four major oncologic centers from Sardinia, Italy, were reviewed. Multivariate hazard ratios (HRs) for mortality and recurrence according to various clinicopathological factors were estimated using Cox proportional hazards models. After a mean follow-up of 4.3 years, 275 (33.3%) TNBC patients had a progression of the disease and 170 (20.2%) died. After allowance for study center, age at diagnosis, and various clinicopathological factors, all components of the TNM staging system were identified as significant independent prognostic factors for TNBC mortality. The HRs were 3.13, 9.65, and 29.0, for stage II, III and IV, respectively, vs stage I. Necrosis and Ki-67 > 16% were also associated with increased mortality (HR: 1.61 and 1.99, respectively). Patients with tumor histotypes other than ductal invasive/lobular carcinomas had a more favorable prognosis (HR: 0.40 vs ductal invasive carcinoma). No significant associations with mortality were found for histologic grade, tumor infiltrating lymphocytes, and lymphovascular invasion. Among lymph node positive TNBCs, lymph node ratio appeared to be a stronger predictor of mortality than pathological lymph nodes stage (HR: 0.80 for pN3 vs pN1, and 3.05 for >0.65 vs <0.21 lymph node ratio), respectively. Consistent results were observed for cancer recurrence, except for Ki-67 and necrosis that were not found to be significant predictors for recurrence. This uniquely large study of TNBC patients provides further evidence that, besides tumor stage at diagnosis, lymph node ratio among lymph node positive tumors is an additional relevant predictor of survival and tumor recurrence, while Ki-67 seems to be predictive of mortality, but not of recurrence.

  7. Multi-parametric MRI of rectal cancer – Do quantitative functional MR measurements correlate with radiologic and pathologic tumor stages?

    International Nuclear Information System (INIS)

    Attenberger, U.I.; Pilz, L.R.; Morelli, J.N.; Hausmann, D.; Doyon, F.; Hofheinz, R.; Kienle, P.; Post, S.; Michaely, H.J.; Schoenberg, S.O.; Dinter, D.J.

    2014-01-01

    Purpose: The purpose of this study is two-fold. First, to evaluate, whether functional rectal MRI techniques can be analyzed in a reproducible manner by different readers and second, to assess whether different clinical and pathologic T and N stages can be differentiated by functional MRI measurements. Materials and methods: 54 patients (38 men, 16 female; mean age 63.2 ± 12.2 years) with pathologically proven rectal cancer were included in this retrospective IRB-approved study. All patients were referred for a multi-parametric MRI protocol on a 3 Tesla MR-system, consisting of a high-resolution, axial T2 TSE sequence, DWI and perfusion imaging (plasma flow –s PF Tumor ) prior to any treatment. Two experienced radiologists evaluated the MRI measurements, blinded to clinical data and outcome. Inter-reader correlation and the association of functional MRI parameters with c- and p-staging were analyzed. Results: The inter-reader correlation for lymph node (ρ 0.76–0.94; p < 0.0002) and primary tumor (ρ 0.78–0.92; p < 0.0001) apparent diffusion coefficient and plasma flow (PF) values was good to very good. PF Tumor values decreased with cT stage with significant differences identified between cT2 and cT3 tumors (229 versus 107.6 ml/100 ml/min; p = 0.05). ADC Tumor values did not differ significantly. No substantial discrepancies in lymph node ADC Ln values or short axis diameter were found among cN1-3 stages, whereas PF Ln values were distinct between cN1 versus cN2 stages (p = 0.03). In the patients without neoadjuvant RCT no statistically significant differences in the assessed functional parameters on the basis of pathologic stage were found. Conclusion: This study illustrates that ADC as well as MR perfusion values can be analyzed with good interobserver agreement in patients with rectal cancer. Moreover, MR perfusion parameters may allow accurate differentiation of tumor stages. Both findings suggest that functional MRI parameters may help to discriminate

  8. PREDICTORS FORMATION OF SOCIAL MALADJUSTMENT IN PATIENTS WITH PARANOID SCHIZOPHRENIA WITH CONCOMITANT SOMATIC-NEUROLOGICAL DISORDERS

    Directory of Open Access Journals (Sweden)

    Valeriy Semionovici PIDKORYTOV

    2017-05-01

    Full Text Available The investigation of the level of stress in patients with paranoid schizophrenia with concomitant somatic-neurological disorders and quality of life as predictors of the formation of their social exclusion. The influence of somatic-neurological pathology for paranoid schizophrenia at different levels of stress.

  9. Early Diagnosis of Breast Cancer using Molecular, Biochemical and Pathological Markers

    OpenAIRE

    Salah E.D. El-Assal; Adel A. El-Tarras; Samir M. Abd-alla

    2011-01-01

    Problem statement: Laboratory diagnosis of breast cancer in most of the hospitals has traditionally been performed using cell culture and the direct hormone receptor assay, which are money and time consuming. Approach: This study was performed in order to direct the attention toward increasing the efficiency of early diagnosis in clinical laboratories at the western region of KSA and Egypt using recent PCR-dependent protocols i.e., Randomly Amplified Polymorphic DNA (RAPDs) and Reverse Transc...

  10. Pathological review of lung cancer among A-bomb survivors at Hiroshima Atomic-bomb Hospital

    International Nuclear Information System (INIS)

    Nambu, Shigeru; Akamizu, Hiroshi; Kuramoto, Kiyoshi; Hamada, Tadao.

    1989-01-01

    Autopsy findings were reviewed in 161 A-bomb survivors with lung cancer during the period 1956-1987. The overall ratio of male to female was 2.1. In the group of A-bomb survivors exposed at ≤2,000 m from the hypocenter, the ratio of male to female in the incidence of lung cancer was 1.3. According to age groups, it was the highest in people in their seventies. Histology revealed that the incidence was 41.6% for adenocarcinoma, 29.2% for squamous cell carcinoma, 19.9% for small cell carcinoma, 6.8% for large cell carcinoma, and 2.5% for adenosquamous cell carcinoma. The incidence of small cell carcinoma was relatively high in the ≤2,000 m group. For females in the ≤2,000 m group, the incidence of adenocarcinoma was relatively low, and the incidences of squamous cell carcinoma and small cell carcinoma tended to be high. The incidence of histologic type of lung cancer varied with time: squamous cell carcinoma and small cell carcinoma were the most predominant during the period 1957-1967; since 1968, it has been gradually replacing by adenocarcinoma. In the ≤2,000 m group, however, small cell carcinoma has still been more predominant even since 1984. For 8 A-bomb survivors exposed at the age of 20 years or less, 7 had adenocarcinoma, showing a significantly higher incidence than those exposed at older ages. (Namekawa, K)

  11. Correlative study of SPECT bone scan, serum tPSA and fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis

    International Nuclear Information System (INIS)

    Xu Haiqing; Duan Jun

    2011-01-01

    Objective: To study the rules and characteristics of SPECT bone scan, serum TPSA, fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis. Methods: Nuclear medicine SPECT bone scan as the gold standard, retrospective analysis of the in vitro radioimmunoassay in 107 patients with prostate cancer serum PSA (prostate specific antigen) levels, serum fPSA/tPSA ratio and whole body bone imaging studies and pathological classification. Results: 107 patients with prostate cancer : 49 patients had bone metastases, accounting for 45.8% (49/107), in which groups of different pathological comparison between the incidence of bone metastasis significantly, the lower the degree of differentiation, the more the incidence of bone metastases high; with elevated levels of tPSA, the incidence of bone metastasis increased significantly; serum tPSA 4 - 40 ng/ml, the use of fPSA/tPSA ratio may improve the diagnostic specificity of prostate cancer. Conclusion: Patients with bone metastases of prostate cancer incidence and degree of differentiation of prostate cancer, serum PSA levels and fPSA/tPSA ratio of a certain relationship. The lower degree of differentiation,the higher the incidence of bone metastasis. (authors)

  12. Pathologic mitoses and pathology of mitosis in tumorigenesis

    Directory of Open Access Journals (Sweden)

    RG Steinbeck

    2009-12-01

    Full Text Available The gist of my hypothesis (.. is a certain abnormal chromatin constitution. Each process, which brings about this chromatin constitution, would result in the origin of a malignant tumour. Certainly, I consider irregularities with mitosis as the normal mode of the origin of an incorrectly assembled nucleus. This statement by Boveri (1914 has considered earlier observations of asymmetric divisions in human cancers (Hansemann, 1890. The hypothesis is based on the understanding of mitosis as an equational bipartition of the hereditary substance (Flemming, 1879; Roux, 1883. Latest since it was known that genes are located on chromosomes (Sturtevant, 1913, their balanced transport in anaphase appeared as a condition of correct somatic proliferation. True mitoses guarantee the constancy of terminally differentiated tissues. Politzer (1934 has performed X-ray experiments to investigate abnormal karyokinesis with regard to anomalous chromatin condensation, chromosome breakage, spindle malformation, and failure in cytokinesis. On the basis of light microscopy, further significant progress in understanding the pathology of mitosis was not possible. Tumour cases with reduced chromosome numbers seduced to the idea that mitotic activity is rather under cytoplasmic than under nuclear control (Koller, 1947.

  13. Pathological characterisation of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

    NARCIS (Netherlands)

    Vermeulen, Marijn A; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H; Tryfonidis, Konstantinos; van Diest, Paul J; Dijkstra, Nizet H; Schröder, Carolien P; van Asperen, Christi J; Linderholm, Barbro; Benstead, Kim; Foekens, Renee; Martens, John W M; Bartlett, John M S; van Deurzen, Carolien H M

    AIM: Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC.

  14. Pathological characterisation of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

    NARCIS (Netherlands)

    Vermeulen, Marijn A.; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H.; Tryfonidis, Konstantinos; van Diest, Paul J.; Dijkstra, Nizet H.; Schroder, Carolien P.; van Asperen, Christi J.; Linderholm, Barbro; Benstead, Kim; Foekens, Renee; Martens, John W. M.; Bartlett, John M. S.; van Deurzen, Carolien H. M.

    Aim: Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC.

  15. Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Ottavio de Cobelli

    Full Text Available The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI and Prostate Imaging Reporting and Data System (PIRADS score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.A total of 223 patients who fulfilled the criteria for "Prostate Cancer Research International: Active Surveillance", were included. Mp-1.5 Tesla MRI examination staging with endorectal coil was performed at least 6-8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE, unfavorable prognosis (occurrence of both upgrading and ECE, large tumor volume (≥ 0.5 ml, and seminal vesicle invasion (SVI. Receiver Operating Characteristic (ROC curves and Decision Curve Analyses (DCA were performed for models with and without inclusion of PIRADS score.Multivariate analysis demonstrated the association of PIRADS score with upgrading (P < 0.0001, ECE (P < 0.0001, unfavorable prognosis (P < 0.0001, and large tumor volume (P = 0.002. ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.

  16. 18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi

    2012-01-01

    The background of this study was to assess the usefulness of positron emission tomography combined with computed tomography using 18 F-fluorodeoxyglucose (FDG positron emission tomography (PET)/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. Tumors with pCR had significantly higher baseline SUV (9.3±3.7 SD) compared to those with non-pCR (7.2±3.8 SD) (p=0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR. (author)

  17. Radio-induced breast cancers exhibiting aggressive anatomo-pathological characteristics: retrospective study of the long-term follow-up committee of the French Society of Child Cancers; Cancers du sein radio-induits presentant des caracteristiques anatomopathologiques agressives: etude retrospective du comite de suivi a long terme de la Societe francaise des cancers de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Demoor, C.; Mahe, M.A.; Supiot, S. [ICO Rene-Gauducheau, Nantes (France); Vathaire, F. de [Inserm UMRS 1018, institut de cancerologie Gustave-Roussy, Villejuif (France); Oberlin, O. [Institut de cancerologie Gustave-Roussy, Villejuif (France); Noel, G. [Centre Paul-Strauss, Strasbourg (France); Brillaud, V. [Institut Bergonie, Bordeaux (France); Bernier, V. [Centre Alexis-Vautrin, Nancy (France); Laprie, A. [Institut Claudius-Regaud, Toulouse (France); Claude, L. [Centre Leon-Berard, Lyon (France)

    2011-10-15

    The authors report an analysis of clinical-pathological characteristics of radio-induced breast cancers registered in six French centres. 82 breast cancers concerning 75 women have been analyzed in terms of patient age, cancer type, interval between both cancers. It appears that radio-induced cancers exhibited significantly more aggressive characteristics. The screening of young women at risk is therefore recommended for an early diagnosis and treatment. Short communication

  18. Phase 3 study of adjuvant radiotherapy versus wait and see in pT3 prostate cancer: impact of pathology review on analysis.

    Science.gov (United States)

    Bottke, Dirk; Golz, Reinhard; Störkel, Stephan; Hinke, Axel; Siegmann, Alessandra; Hertle, Lothar; Miller, Kurt; Hinkelbein, Wolfgang; Wiegel, Thomas

    2013-08-01

    In a randomised trial, radical prostatectomy (RP) followed by adjuvant radiotherapy (aRT) was compared with RP alone in patients with pT3 pN0 prostate cancer with or without positive margin at local pathology (German Cancer Society trial numbers ARO 96-02/AUO AP 09/95). A pathology review was performed on 85% of RP specimens of patients to investigate the influence of pathology review on the analysis. Patients post-RP (n=385) were randomised before achieving an undetectable prostate-specific antigen (PSA) level to either wait and see (n=192) or 60Gy aRT (n=193). Of 307 patients with undetectable PSA after RP, 262 had pathology review. These results were included prospectively into the analysis. Agreement between local and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic reliability for the different parameters was analysed by Cox regression model. Event-free rates were determined by Kaplan-Meier analysis with a median follow-up of 40 mo for the wait-and-see arm and 38.5 mo for the aRT arm. There was fair concordance between pathology review and local pathologists for seminal vesicle invasion (pT3c: 91%; κ=0.76), surgical margin status (84%; κ=0.65), and for extraprostatic extension (pT3a/b: 75%; κ=0.74). Agreement was much less for Gleason score (47%; κ=0.42), whereby the review pathology resulted in a shift to Gleason score 7. In contrast to the analysis of progression-free survival with local pathology, the multivariate analysis including review pathology revealed PSMs and Gleason score >6 as significant prognostic factors. Phase 3 studies of postoperative treatment of prostate cancer should be accomplished in the future with a pathology review. In daily practice, a second opinion by a pathologist experienced in urogenital pathology would be desirable, in particular, for high-risk patients after RP. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  19. Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells

    NARCIS (Netherlands)

    Cawood, R.; Chen, H.H.; Carroll, F.; Bazan-Peregrino, M.; Rooijen, van N.; Seymour, L.W.

    2009-01-01

    Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective

  20. Pancreatic cancer: Lack of association between apparent diffusion coefficient values and adverse pathological features

    International Nuclear Information System (INIS)

    Rosenkrantz, A.B.; Matza, B.W.; Sabach, A.; Hajdu, C.H.; Hindman, N.

    2013-01-01

    Aim: To identify retrospectively potential associations between apparent diffusion coefficient (ADC) values of pancreatic adenocarcinoma and tumour grade as well as other pathological features, using histopathological assessment from the Whipple procedure as the reference standard. Materials and methods: Thirty patients with pancreatic adenocarcinoma underwent magnetic resonance imaging (MRI) including diffusion-weighted imaging with b-values of 0 and 500 s/mm 2 before the Whipple procedure. Two radiologists independently recorded the ADC values of the tumour and benign pancreas for all cases. ADC values were compared with histopathological findings following the Whipple procedure. Results: The intra-class correlation coefficient was 0.689 for benign pancreas and 0.695 for tumours, indicating good inter-reader agreement for ADC values. The mean ADC value was significantly lower in tumours than in benign pancreas for both readers (reader 1: 1.74 ± 0.34 × 10 −3 mm 2 /s versus 2.08 ± 0.48 × 10 −3 mm 2 /s, respectively, p = 0.006; reader 2: 1.69 ± 0.41 × 10 −3 mm 2 /s versus 2.11 ± 0.54 × 10 −3 mm 2 /s, respectively, p −3 mm 2 /s versus 1.78 ± 0.33 × 10 −3 mm 2 /s, respectively, p = 0.491; reader 2: 1.62 ± 0.33 × 10 −3 mm 2 /s versus 1.75 ± 0.49 × 10 −3 mm 2 /s, respectively, p = 0.405). The area under the curve (AUC) for differentiation of poorly and well/moderately differentiated tumours was 0.611 and 0.596 for readers 1 and 2, respectively, and was not significantly better than an AUC of 0.500 for either reader (p ≥ 0.306). In addition, ADC was not significantly different for either reader between tumours with stage T3 versus stage T1/T2, between tumours with and without metastatic peri-pancreatic lymph nodes, or between tumours located in the pancreatic head versus other pancreatic regions (p ≥ 0.413). Conclusion: No associations between ADC values of pancreatic adenocarcinoma and tumour grade or other adverse pathological features

  1. Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

    International Nuclear Information System (INIS)

    Deocaris, Custer C.

    2000-04-01

    The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

  2. Mutational myriad of tumor suppressor p53 in Filipino breast cancer: results and perspectives in molecular pathology and epidemiology

    Energy Technology Data Exchange (ETDEWEB)

    Deocaris, Custer C

    2000-04-01

    The p53 tumor suppressor is by far the most widely mutated gene in human cancers. p53 encodes a 53-kDa phosphoprotein, transcription-activator whose targets include genes and gene products that orchestrate genomic stability, cellular response to DNA damage, cell cycle progression apoptosis and aging (senescence). Analysis of the p53 gene profile has previously resulted in identifying several cancer-causative factors in the human setting, as well as, in creating a unique molecular profile of a tumor useful in the design of tailored-therapies for individual cancer patients. Our results in screening for p53 abnormalities in 140 Filipino patients with primary breast lesions confined from 1997-1998 in 5 major hospitals in Manila reveal that p53 plays an important role in the development and progression of breast cancer in at least 48% of all cases. Two methods of p53 analysis are employed, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-temporal temperature gradient electrophoresis (PCR-TTGE). Inter-comparisons of method exhibit 63.3% concordance in 21 fresh breast carcinoma samples, with ELISA demonstrating 14% false-positives and 10% false-negatives. Only mutations in exon 7 (p=0.063) in the tumor samples how significant correlation with abnormal cellular elevation of p53. PCR-TTGE screening in a large series of 140 patients show that most genetic lesions are localized in exons 5 (41% of the total cases) and 6 (27% of the total cases). No mutations are, however, detected in the transactivation (exons 2-4) and oligomerization (exons 10-11) domains. Invasive carcinomas (stages II and III) are characterized with more frequent and diverse genetic alterations compared with benign tumors, most significantly at exon 5B (p=0.066) and at independently multiple sites (p=0.066). Earlier-onset cases (age of diagnosis < 50 yrs), known to be more clinico-pathologically aggressive, are diagnosed harboring more frequent p53 mutations centered at exon 7 (p=0

  3. Immune-to-brain communication in functional somatic symptoms

    NARCIS (Netherlands)

    Lacourt, T.E.|info:eu-repo/dai/nl/313935068

    2013-01-01

    When a person presents with somatic symptoms that cannot (fully) be explained by a known organic pathology, these symptoms will be labeled ‘medically unexplained’ or ‘functional’. Often, more than one symptom is present and certain constellations of symptoms give way to a diagnosis of a specific

  4. Which FDG/PET parameters of the primary tumors in colon or sigmoid cancer provide the best correlation with the pathological findings?

    International Nuclear Information System (INIS)

    Chen, Shang-Wen; Chen, William Tzu-Liang; Wu, Yi-Chen; Yen, Kuo-Yang; Hsieh, Te-Chun; Lin, Tze-Yi; Kao, Chia-Hung

    2013-01-01

    Background To compare 18 F-fluoro-2-deoxdeoxyglucose (FDG) positron emission tomography (PET) related parameters of primary colon or sigmoid cancer (CSC) with pathological findings. Methods Seventy-seven CSC patients who have undergone preoperative PET computed tomograms (PET/CT) are included in this study. Maximum PET-based tumor length (TL) and tumor width (TW) are determined using several auto-segmentation methods, and various thresholds of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measured. The PET-based TL and TW are compared with maximum pathological length and width on the pathological specimen. Results Using a 30% threshold level for maximum uptake of TL (TL30%) and TW (TW30%) yield results that provide an optimal match with maximum pathological length (R = 0.81, p < 0.001) and width (R = 0.70, p < 0.001). TW30% was an independent factor for predicting pathological T3 or T4 stages (OR = 1.26, 95% CI = 1.07–1.47, p = 0.01). The receiver-operating characteristic curves show MTV at a fixed threshold of 40% maximum uptake (MTV40%), and TW30% achieved better correlation with the advanced pathological T stage. No associations with positive N stage were observed. Conclusion Pretreatment PET/CT is a useful tool for predicting the final pathological findings for CSC patients requiring surgical procedures

  5. Low HER2/neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Formenti, Silvia C.; Spicer, Darcy; Skinner, Kristin; Cohen, Deidre; Groshen, Susan; Bettini, Anna; Naritoku, Wesley; Press, Michael; Salonga, Dennis; Tsao-Wei, Denice; Danenberg, Kathy; Danenberg, Peter

    2002-01-01

    Purpose: The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response. Methods and Materials: Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m 2 twice a week for a total of 8 weeks, and radiation delivered Weeks 2-6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of ≤10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, β-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR). Results: A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p=0.009 and p=0.006, respectively). Conversely, p53 protein

  6. Management of somatic pain induced by head-and-neck cancer treatment: definition and assessment. Guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (SFORL).

    Science.gov (United States)

    Binczak, M; Navez, M; Perrichon, C; Blanchard, D; Bollet, M; Calmels, P; Couturaud, C; Dreyer, C; Espitalier, F; Testelin, S; Albert, S; Morinière, S

    2014-09-01

    The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société Française d'Oto-rhino-Laryngologie et de Chirurgie de la Face et du Cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. A Review on Adducin from Functional to Pathological Mechanisms: Future Direction in Cancer

    Directory of Open Access Journals (Sweden)

    Karrie Mei-Yee Kiang

    2018-01-01

    Full Text Available Adducin (ADD is a family of membrane skeleton proteins including ADD1, ADD2, and ADD3 that are encoded by distinct genes on different chromosomes. Adducin is primarily responsible for the assembly of spectrin-actin network that provides physical support to the plasma membrane and mediates signal transduction in various cellular physiological processes upon regulation by protein kinase C-dependent and calcium/calmodulin-dependent pathways. Abnormal phosphorylation, genetic variations, and alternative splicing of adducin may contribute to alterations in cellular functions involved in pathogenic processes. These alterations are associated with a wide range of diseases including cancer. This paper begins with a discussion on how adducin partakes in the structural formation of membrane skeleton, its regulation, and related functional characteristics, followed by a review on the pathogenesis of hypertension, biliary atresia, and cancer with respect to increased disease susceptibility mediated by adducin polymorphism and/or dysregulation. Given the functional diversity of adducin in different cellular compartments, we aim to provide a knowledge base whereby its pathophysiological roles can be better understood. More importantly, we aim to provide novel insights that may be of significance in turning the adducin model to clinical application.

  8. Risk factors, pathological and phenotypic features of male breast cancer in Greece.

    Science.gov (United States)

    Tsoukalas, Nikolaos; Moirogiorgou, Evangelia; Tolia, Maria; Pistamaltzian, Nikolaos; Bournakis, Evangelos; Papadimitriou, Konstantinos; Demiri, Stamatina; Panopoulos, Christos; Koumakis, Georgios; Efremidis, Anna

    2014-03-01

    Breast cancer (BC) in males is a rare disease and comprises 0.5-1% of all BC cases. Due to its rarity, there are limited data regarding risk factors, biology and relevant treatment. A prospective observational study of demographic, clinical and histological characteristics of serially-admitted men with breast cancer was carried out from 1999 to 2009. Data were recorded and analyzed from a database including 1,315 cases of BC. Registered data concerned age, initial presentation, family and lifestyle history (risk factors), histological features, phenotypic subtypes and TNM staging. Twenty two men with BC were identified, with a median age of 63 years. The most common initial presentation was a palpable lump in 12 patients, nipple contraction in three and ulceration in three. According to their medical history, nine men were overweight, 10 suffered from hypertension and 12 were smokers. The most prevalent phenotype was luminal-A followed by triple-negative type. BC in none of the cases was HER 2-amplified. The majority of cases were grade II or III and stage II or III. In the present small study, we confirm that BC in males is rare. It is a disease of middle-age and presents at advanced stages. Most of patients had 1-3 risk factors for BC. Expression of hormonal receptors occurs in the majority of BC tumors in males and with rarity in HER 2 amplification.

  9. The problem of mental disorders and psychological effects of antitumour treatment in children with cancer pathology

    Directory of Open Access Journals (Sweden)

    Оксана Владимировна Пионтковская

    2015-07-01

    Full Text Available Aim – analysis of the problem of psychological and psychiatrical aspects of impact of cancer disease on child and its parents for detection of the main directions of medical and psychological help to this contingent.Results. In the younger age group the most stress factors that provoke the development of psychogenic fears, anxiety states and the derivative mood disorders are the “hospital routine” – limitation of activity (playing, motor, subjectively heavy procedures and manipulations, pain. In the group of elder children and teenagers the main stress stimulus is connected with a fear of social consequences of disease and the fact of mortally dangerous disease is interpreted in mind as a threat to the successful social functioning as something that spread its negative impact on the future life. Reactively caused mood disorders prevail in this age group over the other psychogenic formations. Behavior reactions in these cases are the secondary ones relating to the mood disorders – to the acceptance or rejection the situation of disease (as an anxious hypochondriacal fixation or as an emotional denial and ignoring the possible grave effects of cancer process.Conclusion. The diversity of problems in child psycho-oncology causes the multilevelness and versatility of medical, psychological and psychosocial help and psycho rehabilitation of children and their parents

  10. Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.

    Science.gov (United States)

    Rodilla, Verónica; Villanueva, Alberto; Obrador-Hevia, Antonia; Robert-Moreno, Alex; Fernández-Majada, Vanessa; Grilli, Andrea; López-Bigas, Nuria; Bellora, Nicolás; Albà, M Mar; Torres, Ferran; Duñach, Mireia; Sanjuan, Xavier; Gonzalez, Sara; Gridley, Thomas; Capella, Gabriel; Bigas, Anna; Espinosa, Lluís

    2009-04-14

    Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.

  11. Prediction of pathologic staging with magnetic resonance imaging after preoperative chemoradiotherapy in rectal cancer: pooled analysis of KROG 10-01 and 11-02.

    Science.gov (United States)

    Lee, Jong Hoon; Jang, Hong Seok; Kim, Jun-Gi; Lee, Myung Ah; Kim, Dae Yong; Kim, Tae Hyun; Oh, Jae Hwan; Park, Sung Chan; Kim, Sun Young; Baek, Ji Yeon; Park, Hee Chul; Kim, Hee Cheol; Nam, Taek-Keun; Chie, Eui Kyu; Jung, Ji-Han; Oh, Seong Taek

    2014-10-01

    The reported overall accuracy of MRI in predicting the pathologic stage of nonirradiated rectal cancer is high. However, the role of MRI in restaging rectal tumors after neoadjuvant CRT is contentious. Thus, we evaluate the accuracy of restaging magnetic resonance imaging (MRI) for rectal cancer patients who receive preoperative chemoradiotherapy (CRT). We analyzed 150 patients with locally advanced rectal cancer (T3-4N0-2) who had received preoperative CRT. Pre-CRT MRI was performed for local tumor and nodal staging. All patients underwent restaging MRI followed by total mesorectal excision after the end of radiotherapy. The primary endpoint of the present study was to estimate the accuracy of post-CRT MRI as compared with pathologic staging. Pathologic T classification matched the post-CRT MRI findings in 97 (64.7%) of 150 patients. 36 (24.0%) of 150 patients were overstaged in T classification, and the concordance degree was moderate (k=0.33, prectal cancer patients who received preoperative CRT. The diagnostic accuracy of restaging MRI is relatively high in rectal cancer patients who achieved clinical downstaging after CRT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    Directory of Open Access Journals (Sweden)

    I.P.C. Buzatto

    Full Text Available The purpose of this study was to retrospectively review the pathologic complete response (pCR rate from patients (n=86 with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012. Stage II patients achieved a higher response rate compared to stage III (P=0.03. The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively. Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03 and death (HR=0.21; P=0.02. In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

  13. Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

    2014-12-09

    Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

  14. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Science.gov (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  15. Effect of seasonal affective disorder and pathological tanning motives on efficacy of an appearance-focused intervention to prevent skin cancer.

    Science.gov (United States)

    Hillhouse, Joel; Turrisi, Rob; Stapleton, Jerod; Robinson, June

    2010-05-01

    To evaluate the robustness of an appearance-focused intervention to prevent skin cancer in individuals reporting seasonal affective disorder (SAD) symptoms and pathological tanning motives. Randomized, controlled clinical trial. College campus. Four hundred thirty adult female indoor tanners (200 in the intervention group and 230 control participants). A booklet discussing the history of tanning, current tanning norms, UV radiation's effects on skin, recommendations for indoor tanning use focusing on abstinence and harm reduction recommendations, and information on healthier, appearance-enhancing alternatives to tanning. Self-reported attitudes, intentions, and tanning behaviors; pathological tanning motives assessed by a questionnaire developed for this study; and SAD symptoms assessed by the Seasonal Pattern Assessment Questionnaire. Two of the 4 pathological tanning scales, opiatelike reactions to tanning and dissatisfaction with natural skin tone, were significant moderators demonstrating stronger treatment effects for individuals scoring higher on these scales. Treatment effects were equivalently positive (ie, no significant moderator effects) for all levels of SAD symptoms and all levels of the other 2 pathological tanning motive scales (ie, perceiving tanning as a problem and tolerance to the effects of tanning). The appearance-focused skin cancer prevention intervention is robust enough to reduce indoor tanning among tanners who exhibit SAD symptoms or pathological tanning motives. Tailored interventions may address individuals' motivations for tanning and their relation to maladaptive behavior, such as dissatisfaction with appearance or the need for relaxation because of anxiety.

  16. Breast conserving surgery following primary irradiation in 3-7 cm breast cancer: pathologic response and outcome

    International Nuclear Information System (INIS)

    Saint-Gaudens, Anne Bareille; Vilcoq, Jacques R.; Campana, Francois; Gautier, Chantal; Asselain, Bernard; Rocherfordiere, Anne de la; Clough, Krishna B.; Fourquet, Alain

    1997-01-01

    Purpose: To retrospectively evaluate histologic response and outcome of patients treated by primary irradiation followed by conservative surgery. Materials and Methods: Between 1981 and 1993, 1742 patients (pts.) with large 3-7 cm invasive breast cancer were treated by primary breast and nodes irradiation in our institution. Of these, 311 pts. (18%) further underwent a wide excision of the residual tumor. Median age was 55 years (yrs.) (29 - 79 yrs.). Median breast tumor size was 40 mm (35 - 70mm). 149 pts. (48%) were premenopausal. 142 pts (46%) had clinically palpable axillary nodes. Diagnosis of invasive breast cancer was performed in all patients by drill biopsy. Following diagnosis, all 311 patients were treated by external irradiation to the breast and regional nodes. Median dose to the breast was 55 Gy (50 - 64 Gy) over 5.5 weeks. Following this irradiation, all patients underwent a wide surgical excision with (140 pts; 45%) or without (171 pts; 55%) axillary node dissection. In addition, 70 pts (22.5%) received adjuvant chemotherapy and 70 pts. received hormone therapy after local treatment. All patients were then regularly followed. Results: Median residual breast tumor size after completion of irradiation was 20 mm (0 - 50mm). On pathologic examination, 34 (11%) tumors had no residual malignant cells (complete response), 137 tumors (44%) had residual fibrosis with clusters of viable cells (partial response), and 138 tumors (45%) had residual viable malignant cells (no response). Median follow up was 106 months (10 - 188 months). Actuarial 9-year overall survival rate was 69 % ± 6%. The 9-year metastasis-free interval was 58 % ± 6%. The 9-year breast recurrence rate was 22 % ± 5 %. The 9-year breast preservation rate was 84% ± 5%. Pathologic response was not predictive of outcome, either distant or local. Conclusion: This retrospective study showed that in patients with tumors too large to be treated by upfront breast-conserving surgery, primary breast

  17. MRI evaluation of residual breast cancer after neoadjuvant chemotherapy: influence of patient, tumor and chemotherapy characteristics on the correlation with pathological response.

    Science.gov (United States)

    Diguisto, Caroline; Ouldamer, Lobna; Arbion, Flavie; Vildé, Anne; Body, Gilles

    2015-01-01

    The aim of this study was to evaluate the correlation between the residual tumor measured on magnetic resonance imaging and pathological results and to assess whether this correlation varies according to patient, tumor or chemotherapy characteristics. The study population included women treated for breast cancer with indication of neoadjuvant chemotherapy in our tertiary breast cancer Unit between January 2008 and December 2011. Factors related to patients, tumor and chemotherapy were studied. Pearson's correlation coefficient between the size of the tumor on MRI and pathological response was calculated for the entire population. It was also calculated according to patient, tumor and chemotherapy characteristics. During the study period, 107 consecutive women were included. The size of residual tumor on the MRI significantly correlated with the size on pathological result with a Pearson correlation coefficient of 0.52 (pcorrelation was stronger for women aged 50 years and older (r=0.64, pcorrelation was stronger for those with triple-negative tumors (r=0.69, p=0.002) but weaker for those with tumors with a ductal carcinoma in situ component (r =0.18, p=0.42). The size of breast cancer obtained by MRI is significantly correlated to the pathological size of the tumor. This correlation was stronger among women aged 50 years and more, among post-menopausal women, and among women who had triple-negative tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Impact of FDG-PET/CT on Radiotherapy Volume Delineation in Non-Small-Cell Lung Cancer and Correlation of Imaging Stage With Pathologic Findings

    International Nuclear Information System (INIS)

    Faria, Sergio L.; Menard, Sonia; Devic, Slobodan; Sirois, Christian; Souhami, Luis; Lisbona, Robert; Freeman, Carolyn R.

    2008-01-01

    Purpose: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. Methods and Materials: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. Results: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. Conclusion: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible

  19. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    Science.gov (United States)

    Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

    2014-01-01

    To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  20. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

    Science.gov (United States)

    Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

    2018-05-03

    BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

  1. Prevalence of oral cancer patients at the Pathology Anatomy Department RSUD Tasikmalaya year 2002-2007

    Directory of Open Access Journals (Sweden)

    Murnisari Dardjan

    2007-07-01

    Full Text Available Malignancy was included which happened in the oral cavity. Oral cavity cancer is statistically fever than other parts of a body but can to be dead. The incidence of malignancy was increased in the last 50 years throughout the world. The purpose of this research is to get distribution data about oral malignancy cases frequency at Rumah Sakit Umum Daerah/RSUD Tasikmalaya. Rumah Sakit Umum Daerah Tasikmalaya is a Referal Hospital from East Priangan region, West Java Indonesia. This is retrospective descriptive research. Samples were taken from Histopathologic form data patient at RSUD Tasikmalaya from January 2002-December 2007. The result of this study indicated that 15 cases oral malignancy cases from all samples 2943 histopathology specimen in the period. The most malignancy cases of carcinoma were squamous cell carcinoma (98%. Tongue became the most area in this cases which was 46.66%. Oral malignancy were common in men 54%. The group of ages 60-70% became the majority namely 40%. The conclusion of the research indicated that carcinoma cell squamous were became the greatest part of oral malignancy types.

  2. Breast pathology after cryotherapy. Histological regression of breast cancer after cryotherapy.

    Science.gov (United States)

    Gajda, Mieczyslaw R; Mireskandari, Masoud; Baltzer, Pascal A; Pfleiderer, Stefan O; Camara, Oumar; Runnebaum, Ingo B; Kaiser, Werner A; Petersen, Iver

    2014-03-01

    A breast saving treatment is contemporary the preferred method of treatment with comparable results in comparing with mastectomy. In this study were evaluated the effects of cryotherapy by histological verification of changes in post treatment resection specimens. Fifty-three patients in age of 38-81 year with histologically confirmed breast cancer in needle biopsies were managed by cryotherapy between 1999 and 2007. The patients were operated between day 1 and 35 after cryotherapy. The histologic examination of operation materials showed in all cases at least partial tumor destruction. In general in 54.7% of all handled cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1 and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor-free cases after cryotherapy were those with cT1 stage. The experience of operator and the correct selection of appropriate patients (primarily taking the tumor size into account) play the most important role for achieving the best results.

  3. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

  4. Apoptosis and mitosis as prognostic factors in pathologically staged N1 nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Komaki, Ritsuko; Fujii, Takashi; Perkins, Penny; Ro, Jae Y.; Allen, Pamela K.; Mason, Kathryn A.; Mountain, Clifton F.; Milas, Luka

    1996-01-01

    Purpose: This study aimed to establish whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy. Methods and Materials: Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis. Results: In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis

  5. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

    Directory of Open Access Journals (Sweden)

    Xu Chaoyang

    2009-07-01

    Full Text Available Abstract Background Preoperative chemotherapy (PCT has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide, VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide and EFC (epirubicin+5-fluorouracil+cyclophosphamide were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p p Conclusion ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

  6. Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

    Science.gov (United States)

    Jin, Byung-Soo; Kang, Seok-Hyun; Kim, Duk-Yoon; Oh, Hoon-Gyu; Kim, Chun-Il; Moon, Gi-Hak; Kwon, Tae-Gyun; Park, Jae-Shin

    2015-09-01

    To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

  7. Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

    International Nuclear Information System (INIS)

    Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S.

    2011-01-01

    Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.

  8. Pulmonary tuberculosis mimicking lung cancer on radiological findings: Evaluation of chest CT findings in pathologically proven 76 patients

    International Nuclear Information System (INIS)

    Lee, Daun; Shin, Sang Soo; Kim, Yun Hyeon; Kim, Hyoung Ook; Seon, Hyun Ju; Kang, Heoung Keun

    2012-01-01

    To evaluate chest CT features of pulmonary tuberculosis mimicking lung malignancy. We retrospectively reviewed chest CT findings for 76 consecutive patients (21-84 years, average: 63 years; M : F = 30 : 46) who underwent an invasive diagnostic procedure under the suspicion of lung cancer and were pathologically diagnosed as pulmonary tuberculosis by bronchoscopic biopsy (n = 49), transthoracic needle biopsy (n = 17), and surgical resection (n = 10). We categorized the chest CT patterns of those lesions as follows: bronchial narrowing or obstruction without a central mass like lesion (pattern 1), central mass-like lesion with distal atelectasis or obstructive pneumonia (pattern 2), peripheral nodule or mass including mass-like consolidation (pattern 3), and cavitary lesion (pattern 4). CT findings were reviewed with respect to the patterns and the locations of the lesions, parenchymal abnormalities adjacent to the lesions, the size, the border and pattern of enhancement for the peripheral nodule or mass and the thickness of the cavitary wall in the cavitary lesion. We also evaluated the abnormalities regarding the lymph node and pleura. Pattern 1 was the most common finding (n = 34), followed by pattern 3 (n = 23), pattern 2 (n = 11) and finally, pattern 4 (n = 8). The most frequently involving site in pattern 1 and 2 was the right middle lobe (n = 14/45). However, in pattern 3 and 4, the superior segment of right lower lobe (n = 5/31) was most frequently involved. Ill-defined small nodules and/or larger confluent nodules were found in the adjacent lung and at the other segment of the lung in 31 patients (40.8%). Enlarged lymph nodes were most commonly detected in the right paratracheal area (n = 9/18). Pleural effusion was demonstrated in 10 patients. On the CT, pulmonary tuberculosis mimicking lung cancer most commonly presented with bronchial narrowing or obstruction without a central mass-like lesion, which resulted in distal atelectasis and obstructive

  9. Pulmonary tuberculosis mimicking lung cancer on radiological findings: Evaluation of chest CT findings in pathologically proven 76 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Daun; Shin, Sang Soo; Kim, Yun Hyeon [Chonnam National Univ. Hospital, Gwangju, (Korea, Republic of); Kim, Hyoung Ook; Seon, Hyun Ju; Kang, Heoung Keun [Chonnam National Univ. Hwasun Hospital, Hwasun (Korea, Republic of)

    2012-09-15

    To evaluate chest CT features of pulmonary tuberculosis mimicking lung malignancy. We retrospectively reviewed chest CT findings for 76 consecutive patients (21-84 years, average: 63 years; M : F = 30 : 46) who underwent an invasive diagnostic procedure under the suspicion of lung cancer and were pathologically diagnosed as pulmonary tuberculosis by bronchoscopic biopsy (n = 49), transthoracic needle biopsy (n = 17), and surgical resection (n = 10). We categorized the chest CT patterns of those lesions as follows: bronchial narrowing or obstruction without a central mass like lesion (pattern 1), central mass-like lesion with distal atelectasis or obstructive pneumonia (pattern 2), peripheral nodule or mass including mass-like consolidation (pattern 3), and cavitary lesion (pattern 4). CT findings were reviewed with respect to the patterns and the locations of the lesions, parenchymal abnormalities adjacent to the lesions, the size, the border and pattern of enhancement for the peripheral nodule or mass and the thickness of the cavitary wall in the cavitary lesion. We also evaluated the abnormalities regarding the lymph node and pleura. Pattern 1 was the most common finding (n = 34), followed by pattern 3 (n = 23), pattern 2 (n = 11) and finally, pattern 4 (n = 8). The most frequently involving site in pattern 1 and 2 was the right middle lobe (n = 14/45). However, in pattern 3 and 4, the superior segment of right lower lobe (n = 5/31) was most frequently involved. Ill-defined small nodules and/or larger confluent nodules were found in the adjacent lung and at the other segment of the lung in 31 patients (40.8%). Enlarged lymph nodes were most commonly detected in the right paratracheal area (n = 9/18). Pleural effusion was demonstrated in 10 patients. On the CT, pulmonary tuberculosis mimicking lung cancer most commonly presented with bronchial narrowing or obstruction without a central mass-like lesion, which resulted in distal atelectasis and obstructive

  10. Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images.

    Science.gov (United States)

    Levenson, Richard M; Krupinski, Elizabeth A; Navarro, Victor M; Wasserman, Edward A

    2015-01-01

    Pathologists and radiologists spend years acquiring and refining their medically essential visual skills, so it is of considerable interest to understand how this process actually unfolds and what image features and properties are critical for accurate diagnostic performance. Key insights into human behavioral tasks can often be obtained by using appropriate animal models. We report here that pigeons (Columba livia)-which share many visual system properties with humans-can serve as promising surrogate observers of medical images, a capability not previously documented. The birds proved to have a remarkable ability to distinguish benign from malignant human breast histopathology after training with differential food reinforcement; even more importantly, the pigeons were able to generalize what they had learned when confronted with novel image sets. The birds' histological accuracy, like that of humans, was modestly affected by the presence or absence of color as well as by degrees of image compression, but these impacts could be ameliorated with further training. Turning to radiology, the birds proved to be similarly capable of detecting cancer-relevant microcalcifications on mammogram images. However, when given a different (and for humans quite difficult) task-namely, classification of suspicious mammographic densities (masses)-the pigeons proved to be capable only of image memorization and were unable to successfully generalize when shown novel examples. The birds' successes and difficulties suggest that pigeons are well-suited to help us better understand human medical image perception, and may also prove useful in performance assessment and development of medical imaging hardware, image processing, and image analysis tools.

  11. Radiation dose and long term risk of cardiac pathology following radiotherapy and anthracyclin for a childhood cancer

    International Nuclear Information System (INIS)

    Guldner, Laurence; Haddy, Nadia; Pein, Francois; Diallo, Ibrahima; Shamsaldin, Akthar; Dahan, Michel; Lebidois, Jerome; Merlet, Pascal; Villain, Elisabeth; Sidi, Daniel; Sakiroglu, Olivia; Hartmann, Olivier; Leftakopoulos, Dimitri; Vathaire, Florent de

    2006-01-01

    Purpose: To determine the cardiac status in children 15 years (yrs) or more after a solid tumour treatment. Patients and Methods: Of the 447 patients, 229 were fully studied and 218 were not. The following cardiac evaluation was proposed to all the 447 consecutive patients: (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-h holter ECG; (3) 131 I-mIBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO 2 max measurement. The radiation dose delivered to 7 points in the heart was estimated for all patients who had received radiotherapy. Results: Cardiac disorder was diagnosed in 89 evaluated patients (39%) including 24 heart failures and 65 other asymptomatic cardiac diseases. When adjusting on potential confounders, cardiac disorder and cardiac failure risks were respectively linear (ERR at 1 Gy: 26%) and linear-quadratic (ERR at 1 Gy: 19%) functions of the average radiation dose received to the heart. No interaction between cumulative dose of adriamycin and average radiation dose was evidenced for cardiac disorders, but the ERR/Gy of cardiac failure was higher for patients receiving less than 350 mg/m 2 of Adriamycin. Conclusion: Long term heart pathologies are probably one of the major iatrogenic risks encored by patients who survived a childhood cancer. This study strongly emphasizes the need to limit the heart irradiation during radiotherapy, particularly, for patients who also received or were susceptible to later received adriamycin

  12. Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2007-01-01

    In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

  13. Computational Pathology

    Science.gov (United States)

    Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

    2016-01-01

    Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

  14. Cytokines in Male Fertility and Reproductive Pathologies: Immunoregulation and Beyond

    Directory of Open Access Journals (Sweden)

    Kate L. Loveland

    2017-11-01

    Full Text Available Germline development in vivo is dependent on the environment formed by somatic cells and the differentiation cues they provide; hence, the impact of local factors is highly relevant to the production of sperm. Knowledge of how somatic and germline cells interact is central to achieving biomedical goals relating to restoring, preserving or restricting fertility in humans. This review discusses the growing understanding of how cytokines contribute to testicular function and maintenance of male reproductive health, and to the pathologies associated with their abnormal activity in this organ. Here we consider both cytokines that signal through JAKs and are regulated by SOCS, and those utilizing other pathways, such as the MAP kinases and SMADs. The importance of cytokines in the establishment and maintenance of the testis as an immune-privilege site are described. Current research relating to the involvement of immune cells in testis development and disease is highlighted. This includes new data relating to testicular cancer which reinforce the understanding that tumorigenic cells shape their microenvironment through cytokine actions. Clinical implications in pathologies relating to local inflammation and to immunotherapies are discussed.

  15. Radiological and pathological findings of interval cancers in a multi-centre, randomized, controlled trial of mammographic screening in women from age 40-41 years

    International Nuclear Information System (INIS)

    Evans, A.J.; Kutt, E.; Record, C.; Waller, M.; Bobrow, L.; Moss, S.

    2007-01-01

    Aim: The aim of this study was to analyse the radiographic findings of the screening mammograms of women with interval cancer who participated in a multi-centre, randomized, controlled trial of mammographic screening in women from age 40-48 years. Materials and methods: The screening and diagnostic mammograms of 208 women with interval cancers were reviewed. Abnormalities were classified as malignant, subtle and non-specific. Results: Eighty-seven (42%) of women had true, 66 (32%) occult and 55 (26%) false-negative interval cancers. The features most frequently missed or misinterpreted were granular microcalcification (38%), asymmetric density (27%) and distortion (22%). Thirty-seven percent of abnormal previous screens were classified as malignant, 39% subtle change and 21% as non-specific. Granular calcifications were significantly more common on the diagnostic mammograms of false-negative interval cancers than those of true interval cancers (28 versus 14%, p = 0.04). Occult interval cancers were more likely to be <10 mm and <15 mm in invasive pathological size than other interval cancers (p = 0.03 and 0.005, respectively). True interval cancers were more likely to be histologically grade 3 than other interval cancers (p = 0.04). Women who developed true and false-negative interval cancers had similar background patterns, but women with occult cancers had a higher proportion of dense patterns (p < 0.05). Conclusion: Interval cancers in a young screening population have a high proportion of occult lesions that are small and occur in dense background patterns. The proportion of interval cancers that are false negative is similar that seen in older populations and granular microcalcification is the commonest missed mammographic feature

  16. Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma

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    Xiang Chen

    2014-04-01

    Full Text Available Pediatric osteosarcoma is characterized by multiple somatic chromosomal lesions, including structural variations (SVs and copy number alterations (CNAs. To define the landscape of somatic mutations in pediatric osteosarcoma, we performed whole-genome sequencing of DNA from 20 osteosarcoma tumor samples and matched normal tissue in a discovery cohort, as well as 14 samples in a validation cohort. Single-nucleotide variations (SNVs exhibited a pattern of localized hypermutation called kataegis in 50% of the tumors. We identified p53 pathway lesions in all tumors in the discovery cohort, nine of which were translocations in the first intron of the TP53 gene. Beyond TP53, the RB1, ATRX, and DLG2 genes showed recurrent somatic alterations in 29%–53% of the tumors. These data highlight the power of whole-genome sequencing for identifying recurrent somatic alterations in cancer genomes that may be missed using other methods.

  17. Integrated PET/CT in non-small cell lung cancer staging—Clinical and pathological agreement

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    A.P. Vaz

    2012-05-01

    Full Text Available Introduction: Integrated PET/CT has become a fundamental tool in the preoperative assessment of non-small cell lung cancer (NSCLC providing useful anatomical and metabolic information to characterize tumoral lesions and to detect unsuspected metastatic disease. Aim: To compare the agreement between clinical and pathological staging before and after the use of PET/CT. Material and methods: Retrospective study of patients with NSCLC who underwent potentially curative surgery throughout 10.5 years. Cohen's kappa coefficient was used to evaluate staging agreement. Results: One hundred and fifty patients were evaluated, 78% males, with a mean age of 65 (±9.6 years. Thirteen percent were submitted to neoadjuvant chemotherapy. PET/CT was performed in 41%. Global agreement between clinical and pathological staging was 51% (kappa = 0.3639. There was a statistically significant difference between the staging results in patients who underwent PET/CT, when compared to the subgroup who did not (p = 0.003. For those with PET/CT false negatives occurred in less 39%, false positives in more 12% and clinical and pathological staging coincided in more 27%. The overall results reflected an improvement in the agreement between clinical and pathological staging in the PET/CT subgroup (67%, kappa = 0.5737 vs 40%, kappa = 0.2292. PET/CT accuracy was enhanced when patients re-staged after neoadjuvant therapy were excluded and a substantial staging agreement was obtained for those who had the exam only for staging purposes (73%, kappa = 0.6323. Conclusion: Inclusion of PET/CT in NSCLC preoperative assessment improved the accuracy of the clinical staging, with a good level of agreement with pathological staging. Resumo: Introdução: A PET/TC integrada tornou-se num instrumento fundamental na avaliação pré-operatória do cancro do pulmão de não pequenas células (CPNPC, fornecendo informação anatómica e

  18. Correlation between Tumor-Infiltrating Lymphocytes and Pathological Response in Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy in H. Adam Malik General Hospital

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    Kamal Basri Siregar

    2017-08-01

    Full Text Available Background: Tumor-infiltrating lymphocytes (TILs are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value, particularly in triple-negative and human epidermal growth factor receptor-2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy, and there is a strong correlation with pathologically complete response. In this study, we analyzed whether changes in TILs take place after neoadjuvant therapy and if they correlate with pathological response to treatment. Patients and Methods: We retrospectively analyzed the specimen slides from the Department of Anatomic Pathology of H. Adam Malik General Hospital during 2011–2015. We identified 51 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. Each case was also defined as high- or low-TIL breast cancer adopting previously validated cutoffs. Results: The mean age of the 51 patients was 49.22 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 49 (96% patients, and there were 2 (4% patients with lobular carcinoma. The histopathological grading for high TILs was grade 1 in 5 patients, grade 2 in 15 patients, and grade 3 in 3 patients. High TILs that had a pathologically complete response were found in 47.8% of patients, and low TILs were found in 28.8%. There was no significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.157. Conclusions: This research has not been able to demonstrate a significant correlation between TILs and

  19. Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    Science.gov (United States)

    Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

    2016-11-01

    We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

  20. Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

    International Nuclear Information System (INIS)

    Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita; Kuroiwa, Kentaro; Drobnjak, Marija; Eastham, James; Scardino, Peter T.; Zelefsky, Michael J.

    2007-01-01

    Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm 3 and/or resulting in extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm 3 ) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci (≤0.06 cm 3 ) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment

  1. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1989-01-01

    Late effects are by definition effects that occur at least one year, and in most cases decades, after the time of exposure. The late effects considered in this chapter are limited to latent cancer incidence and mortality, and benign thyroid disease. A model is provided for estimating risks of late effects resulting from the radiation exposure likely to be received in the event of a nuclear power plant accident. It is assumed that exposure to high-LET radiation would be negligible in such an accident, and thus only risks from low-LET exposure are evaluated. Separate estimates are provided for risks of leukemia, bone cancer, lung cancer, gastrointestinal cancers, thyroid cancer, skin cancer, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. Because the time of death is also important in assessing the impact of an accident, and because the quality of life after the occurrence of cancer will often be reduced, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated

  2. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    DEFF Research Database (Denmark)

    Lottrup, G; Nielsen, J E; Maroun, L L

    2014-01-01

    , and in the majority of LCs, it was mutually exclusive of DLK1. LIMITATIONS, REASONS FOR CAUTION: The number of samples was relatively small and no true normal adult controls were available. True stereology was not used for LC counting, instead LCs were counted in three fields of 0.5 µm(2) surface for each sample...... in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of interest....

  3. Comparison of imaging-based gross tumor volume and pathological volume determined by whole-mount serial sections in primary cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2013-07-01

    Full Text Available Ying Zhang,1,* Jing Hu,1,* Jianping Li,1 Ning Wang,1 Weiwei Li,1 Yongchun Zhou,1 Junyue Liu,1 Lichun Wei,1 Mei Shi,1 Shengjun Wang,2 Jing Wang,2 Xia Li,3 Wanling Ma4 1Department of Radiation Oncology, 2Department of Nuclear Medicine, 3Department of Pathology, 4Department of Radiology, Xijing Hospital, Xi'an, People's Republic of China*These authors contributed equally to this workObjective: To investigate the accuracy of imaging-based gross tumor volume (GTV compared with pathological volume in cervical cancer.Methods: Ten patients with International Federation of Gynecology and Obstetrics stage I–II cervical cancer were eligible for investigation and underwent surgery in this study. Magnetic resonance imaging (MRI and fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET/computed tomography (CT scans were taken the day before surgery. The GTVs under MRI and 18F-FDG PET/CT (GTV-MRI, GTV-PET, GTV-CT were calculated automatically by Eclipse treatment-planning systems. Specimens of excised uterine cervix and cervical cancer were consecutively sliced and divided into whole-mount serial sections. The tumor border of hematoxylin and eosin-stained sections was outlined under a microscope by an experienced pathologist. GTV through pathological image (GTV-path was calculated with Adobe Photoshop.Results: The GTVs (average ± standard deviation delineated and calculated under CT, MRI, PET, and histopathological sections were 19.41 ± 11.96 cm3, 12.66 ± 10.53 cm3, 11.07 ± 9.44 cm3, and 10.79 ± 8.71 cm3, respectively. The volume of GTV-CT or GTV-MR was bigger than GTV-path, and the difference was statistically significant (P 0.05. Spearman correlation analysis showed that GTV-CT, GTV-MRI, and GTV-PET were significantly correlated with GTV-path (P < 0.01. There was no significant difference in the lesion coverage factor among the three modalities.Conclusion: The present study showed that GTV defined under 40% of maximum standardized

  4. Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing

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    Lei Wei

    2016-10-01

    Full Text Available Abstract Background The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering. Methods We hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions. Results Contamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients. Conclusion The results demonstrated that the

  5. Impact of body mass index on clinico-pathological parameters and outcome in patients with metastatic prostate cancer

    International Nuclear Information System (INIS)

    Mohammed, A.A.; EL-Tanni, H.; Ghanem, H.M.; El Saify, A.M.; Al-Zahrani, A.S.; EL-Khatib, H.M.; Mohammed, A.A.; Farooq, M.U.; EL-Shentenawy, A.

    2015-01-01

    This study evaluates the correlation between body mass index (BMI) and clinico pathological parameters of metastatic prostate cancer (MPC) and its impact on survival. Method During the study period, 71 MPC patients were eligible. Patients with BMI < 25.0 kg/m2 were categorized as level I and patients with BMI ⩾ 25.0 kg/m2 were categorized as level II. Demographic features and survival rates were evaluated by the Kaplan–Meier method and Cox proportional models. Results 31 patients belonged to level I while the rest belonged to level II with insignificant higher median follow-up duration in level II; ρ=0.5. In terms of age, metastasis, serum level of albumin, prostatic specific antigen, alkaline phosphatase (AKP) and Gleason score, there was no significant difference between the two levels. The cumulative survival probability in the 12th, 24th and 36th month in level I vs; level II was; 86.7%, 68.7%, 64.1% vs; 74.4%, 67.7%, 55.1%, respectively with 7 patients dead in level I compared to 14 patients dead in level II denoting a higher PC-specific death rate in the level II group. In univariate and multivariate analysis, poor prognosis was associated with increasing AKP (HR = 1.0005, 95% CI, p = 0.03; HR=1.001, 95% CI, ρ=0.03) respectively, while better prognosis was associated with no visceral metastasis (HR = 0.09, 95% CI, ρ=0.000; HR = 0.04, 95% CI, ρ=0.000) and increasing albumin levels (HR = 0.17, 95% CI, ρ=0.000; HR = 0.15, 95% CI, ρ=0.000) respectively. In multivariate analysis only, patients belonging to level I were associated with better prognosis (HR = 0.17, 95% CI, ρ=0.02). Conclusion BMI is dependent on prognostic factors in patients with MPC

  6. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the confer...

  7. Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

    Science.gov (United States)

    Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

    2015-01-01

    Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

  8. Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

    Science.gov (United States)

    Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

    2015-02-01

    Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Late somatic effects

    International Nuclear Information System (INIS)

    Gilbert, E.

    1985-01-01

    A model is provided for estimating risks of late effects resulting from low-LET radiation exposure likely to be received in the event of a nuclear power plant accident. Separate estimates are provided for risks of leukemia, cancers of the bones, lungs, gastrointestinal tract, thyroid, skin, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. In addition, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated. The model used in the earlier Reactor Safety Study has been modified to reflect additional epidemiological data and these changes are described in detail. 37 references, 1 figure, 13 tables

  10. Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

    Science.gov (United States)

    Kawai, Kazushige; Ishihara, Soichiro; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

    2017-04-01

    Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. This was a retrospective comparative study. This study was conducted at a single referral hospital. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. Although endoscopic assessment after chemoradiotherapy correlated with pathological response

  11. Pathology-based validation of FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schinagl, Dominic A.X. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Radboud University Nijmegen Medical Centre, Department of Radiation Oncology (874), P.O. Box 9101, Nijmegen (Netherlands); Span, Paul N.; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Hoogen, Frank J.A. van den [Radboud University Nijmegen Medical Centre, Department of Otorhinolaryngology, Head and Neck Surgery, Nijmegen (Netherlands); Merkx, Matthias A.W. [Radboud University Nijmegen Medical Centre, Department of Oral and Maxillofacial Surgery, Nijmegen (Netherlands); Slootweg, Piet J. [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2013-12-15

    FDG PET is increasingly incorporated into radiation treatment planning of head and neck cancer. However, there are only limited data on the accuracy of radiotherapy target volume delineation by FDG PET. The purpose of this study was to validate FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer against the pathological method as the standard. Twelve patients with head and neck cancer and 28 metastatic lymph nodes eligible for therapeutic neck dissection underwent preoperative FDG PET/CT. The metastatic lymph nodes were delineated on CT (Node{sub CT}) and ten PET segmentation tools were used to assess FDG PET-based nodal volumes: interpreting FDG PET visually (PET{sub VIS}), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PET{sub SUV}), two segmentation tools with a fixed threshold of 40 % and 50 %, and two adaptive threshold based methods. The latter four tools were applied with the primary tumour as reference and also with the lymph node itself as reference. Nodal volumes were compared with the true volume as determined by pathological examination. Both Node{sub CT} and PET{sub VIS} showed good correlations with the pathological volume. PET segmentation tools using the metastatic node as reference all performed well but not better than PET{sub VIS}. The tools using the primary tumour as reference correlated poorly with pathology. PET{sub SUV} was unsatisfactory in 35 % of the patients due to merging of the contours of adjacent nodes. FDG PET accurately estimates metastatic lymph node volume, but beyond the detection of lymph node metastases (staging), it has no added value over CT alone for the delineation of routine radiotherapy target volumes. If FDG PET is used in radiotherapy planning, treatment adaptation or response assessment, we recommend an automated segmentation method for purposes of reproducibility and interinstitutional comparison. (orig.)

  12. Osteoporosis and Somatization of Anxiety

    Directory of Open Access Journals (Sweden)

    Maria Papanikou

    2013-12-01

    Full Text Available Chronic stress can now be physiologically traced as a significant player in the creation of osteoporotic bones. The present pilot study involved 100 women (N = 42 have been diagnosed with osteopenia, N = 21 have been diagnosed with osteoporosis, N = 37 had a non-osteoporotic condition who participated in the Hellenic Society of Osteoporosis Association Support. Correlations between somatic symptoms of anxiety and osteoporosis, and among medications and somatization in women were explored. Assessments were based on a self-report demographic questionnaire and on the Short Anxiety Screening Test (SAST administered for detection of anxiety disorder and somatization. Statistical analysis detected non-significant differences regarding the correlation between anxiety symptomatology or somatization due to osteoporosis and osteopenia diagnosis. The same pattern is observed among women’s age group, the occupational and marital status. Hypothesis that the osteoporosis and osteopenia group would manifest significant relationships with the age group and medicines was confirmed, as well as between somatization and medicines that women with osteoporosis and osteopenia undertake. The results suggest that women are not prone to manifest anxiety or somatization in relation to the osteoporosis condition. However, the majority of women with osteoporosis and osteopenia consume more than two medicines other than those for osteoporosis. This quantity and combination they undertake appear to contribute and deteriorate their anxiety/somatization symptomatology. Further research based on a larger sample would give more definite results.

  13. Comparison between FDG Uptake and Pathologic or Immunohistochemical Parametersin Pre-operative PET/CT Scan of Patient with Primary Colorectal Cancer

    International Nuclear Information System (INIS)

    Na, Sae Jung; Chung, Yong An; Maeng, Lee So; Kim, Ki Jun; Sohn, Kyung Myung; Kim, Sung Hoon; Sohn, Hyung Sun; Chung, Soo Kyo

    2009-01-01

    To evaluate the relationship between F-18 FDG uptake of tumor in PET/CT scan and pathological or immunohistochemial parameters of colorectal cancer. 147 colorectal cancer patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The pathologic results such as site, size, depth of invasion (T stage), growth pattern, differentiation of primary tumor, lymph node metastasis and Dukes-Astler and Coller stage and immunohistochemical markers such as expression of EGFR, MLH1, MSH2 and Ki-67 index were reviewed. 146 out of 147 PET/CT scans with colorectal cancer showed perceptible focal FDG uptake. SUVmax showed mild positive linear correlation with size of primary tumor (r=0.277, p=0.001) and Ki-67 index (r=0.226, p=0.019). No significant difference in F-18 FDG uptake was found according to site, depth of invasion (T stage), growth pattern, differentiation of primary tumor, presence of lymph node metastasis, Dukes-Astler and Coller stage and expression of EGFR. The degree of F-18 FDG uptake in colorectal cancer was associated with the size and the degree of Ki-67 index of primary tumor. It could be thought that FDG uptake of primary tumor has a correlation with macroscopic and microscopic tumor growth

  14. Body image and self-esteem in somatizing patients.

    Science.gov (United States)

    Sertoz, Ozen O; Doganavsargil, Ozge; Elbi, Hayriye

    2009-08-01

    The aim of the present study was to determine dissatisfaction with body appearance and bodily functions and to assess self-esteem in somatizing patients. Body image and self-esteem were investigated in 128 women; 34 of those had diagnosed somatoform disorders, 50 were breast cancer patients with total mastectomy surgery alone, and 44 were healthy subjects. Body image and self-esteem were assessed using the Body Cathexis Scale and Rosenberg Self-Esteem Scale. The two clinical groups did not differ from one another (z = -1.832, P = 0.067), but differed from healthy controls in terms of body image (somatizing patients vs healthy controls, z = -3.628, P self-esteem (z = -0.936, P = 0.349) when depressive symptoms were controlled. No statistically significant difference was observed between total mastectomy patients and healthy controls in terms of self-esteem (z = -1.727, P = 0.084). The lower levels of self-esteem in somatizing patients were largely mediated by depressive symptoms. Depressed and non-depressed somatizing patients differed significantly from healthy controls with respect to their self-esteem and body image. Somatizing patients who were dissatisfied with their bodily functions and appearance had lower levels of self-esteem and high comorbidity of depression. In clinical practice it is suggested that clinicians should take into account psychiatric comorbidity, self-esteem, and body image in somatizing patients when planning treatment approaches.

  15. Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer.

    Science.gov (United States)

    Plönes, Till; Engel-Riedel, Walburga; Stoelben, Erich; Limmroth, Christina; Schildgen, Oliver; Schildgen, Verena

    2016-01-15

    Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

  16. [A case of transverse colon cancer with multiple liver metastases and hepatic pedicle lymph node involvement showing pathological complete response by XELOX plus bevacizumab].

    Science.gov (United States)

    Mukai, Toshiki; Akiyoshi, Takashi; Koga, Rintaro; Arita, Junichi; Saiura, Akio; Ikeda, Atsushi; Nagasue, Yasutomo; Oikawa, Yoshinori; Yamakawa, Keiko; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi; Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Yamamoto, Chiriko; Yamaguchi, Toshiharu

    2012-12-01

    A 70-year-old woman was referred to our hospital because of abdominal pain. Abdominal computed tomography(CT)and colonoscopy revealed transverse colon cancer with multiple liver metastases, with involvement of the hepatic pedicle and superior mesenteric artery lymph nodes. The patient received eight courses of XELOX plus bevacizumab, and CT showed a decrease in the size of the liver metastases and hepatic pedicle lymphadenopathy. Right hemicolectomy, partial hepatectomy, and hepatic pedicle lymph node resection were performed. Histopathological examination of the resected tissue revealed no residual cancer cells, suggesting a pathological complete response. The patient remains well 7 months after operation, without any signs of recurrence. Surgical resection should be considered for patients with initially unresectable colon cancer with liver metastases and hepatic pedicle lymph nodes involvement if systemic chemotherapy is effective.

  17. Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics—Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer

    Directory of Open Access Journals (Sweden)

    Till Plönes

    2016-01-01

    Full Text Available Companion diagnostics (CDx have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

  18. Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

    Science.gov (United States)

    Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

    2016-07-01

    To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

  19. Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

    Science.gov (United States)

    Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

    2016-05-01

    Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Standardized uptake value and apparent diffusion coefficient of endometrial cancer evaluated with integrated whole-body PET/MR: Correlation with pathological prognostic factors.

    Science.gov (United States)

    Shih, I-Lun; Yen, Ruoh-Fang; Chen, Chi-An; Chen, Bang-Bin; Wei, Shwu-Yuan; Chang, Wen-Chun; Sheu, Bor-Ching; Cheng, Wen-Fang; Tseng, Yao-Hui; Chen, Xin-Jia; Chen, Chi-Hau; Wei, Lin-Hung; Chiang, Ying-Cheng; Torng, Pao-Ling; Yen, Men-Luh; Shih, Tiffany Ting-Fang

    2015-12-01

    To evaluate the correlation between maximum standardized uptake value (SUVmax ) and minimum apparent diffusion coefficient (ADCmin ) of endometrial cancer derived from an integrated positron emission tomography / magnetic resonance (PET/MR) system and to determine their correlation with pathological prognostic factors. This prospective study was approved by the Institutional Review Board of the hospital, and informed consent was obtained. Between April and December 2014, 47 consecutive patients with endometrial cancer were enrolled and underwent simultaneous PET/MR examinations before surgery. Thirty-six patients with measurable tumors on PET/MR were included for image analysis. Pearson's correlation coefficient was used to evaluate the correlation between SUVmax and ADCmin of the tumors. The Mann-Whitney U-test was utilized to evaluate relationships between these two imaging biomarkers and pathological prognostic factors. The mean SUVmax and ADCmin were 14.7 ± 7.1 and 0.48 ± 0.13 × 10(-3) mm(2) /s, respectively. A significant inverse correlation was found between SUVmax and ADCmin (r = -0.53; P = 0.001). SUVmax was significantly higher in tumors with advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P correlated and are associated with pathological prognostic factors. © 2015 Wiley Periodicals, Inc.

  1. Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease

    International Nuclear Information System (INIS)

    Liao, Christopher CL; Ward, Nicholas; Marsh, Simon; Arulampalam, Tan; Norton, John D

    2010-01-01

    Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the 'GenePattern' suite of computational tools (Broad Institute, MIT, USA). Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR) test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, 'leave-one-out' cross-validation method. 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P ≤ 0.01, false discovery rate ≤ 0.05). Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100% sensitivity and specificity (95% confidence interval: 67.9-99.2%). Supervised prediction using 'leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = < 0.001; receiver-operator characteristics - ROC - error, 0.171); disease recurrence was correctly predicted in 5/6 cases and disease-free survival (median follow-up time, 25 months) was correctly predicted in 22

  2. Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease

    Directory of Open Access Journals (Sweden)

    Liao Christopher CL

    2010-08-01

    Full Text Available Abstract Background Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS. Methods Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the 'GenePattern' suite of computational tools (Broad Institute, MIT, USA. Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, 'leave-one-out' cross-validation method. Results 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P ≤ 0.01, false discovery rate ≤ 0.05. Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100% sensitivity and specificity (95% confidence interval: 67.9-99.2%. Supervised prediction using 'leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = P = P = 0.001; ROC error, 0.212. Conclusions Protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value in studies aimed at improved molecular

  3. Speech-language pathology care and short- and long-term outcomes of oropharyngeal cancer treatment in the elderly.

    Science.gov (United States)

    Webster, Kimberly T; Tippett, Donna; Simpson, Marissa; Abrams, Rina; Pietsch, Kristine; Herbert, Robert J; Eisele, David W; Gourin, Christine G

    2018-06-01

    To examine associations between speech-language pathology (SLP) care and pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients treated for oropharyngeal squamous cell cancer (SCCA). Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. SLP care was documented in 25% of patients. High-volume hospital care (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6-47.1]) were the only significant predictors of SLP care during the initial treatment period. SLP care was significantly more likely during the first year (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2-4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2-4.8]) were significantly associated with long-term SLP care. After controlling for patient, tumor, and treatment-related variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (93%), stricture (35%), weight loss (8%), and airway obstruction (34%). Survival analysis, controlling for all other variables, demonstrated improved survival for patients under SLP care (hazard ratio = 0.73 [0.57-0.95]). SLP care is underutilized in elderly oropharyngeal SCCA patients and largely utilized after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care in this population during the initial treatment period and beyond. 2c. Laryngoscope, 128:1403-1411, 2018. © 2017 The American Laryngological, Rhinological and Otological Society

  4. Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

    Science.gov (United States)

    Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

    2017-08-01

    We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers

  5. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    Science.gov (United States)

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent

  6. Somatically acquired structural genetic differences

    DEFF Research Database (Denmark)

    Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare

    2016-01-01

    Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34....

  7. Somatic embryogenesis of Carica Papaya

    International Nuclear Information System (INIS)

    Alvina Lindsay Mijen; Rusli Ibrahim

    2006-01-01

    This paper describes the somatic embryogenesis of Carica papaya. Culture medium used was1/2 strength MS basal medium supplemented with 6% sucrose, 0.27 % agar, glutamine and various concentrations of 2,4-Dichlorophenoxyacetic acid (2,4-D). After 8 weeks in culture, the best concentration of 2,4-D to induce somatic embryo is at 45.2 μM. (Author)

  8. Multiple somatic symptoms in primary care

    DEFF Research Database (Denmark)

    Goldberg, D. P.; Reed, G. M.; Robles, R.

    2016-01-01

    Objective A World Health Organization (WHO) field study conducted in five countries assessed proposals for Bodily Stress Syndrome (BSS) and Health Anxiety (HA) for the Primary Health Care Version of ICD-11. BSS requires multiple somatic symptoms not caused by known physical pathology and associated...... with distress or dysfunction. HA involves persistent, intrusive fears of having an illness or intense preoccupation with and misinterpretation of bodily sensations. This study examined how the proposed descriptions for BSS and HA corresponded to what was observed by working primary care physicians (PCPs......) in participating countries, and the relationship of BSS and HA to depressive and anxiety disorders and to disability. Method PCPs referred patients judged to have BSS or HA, who were then interviewed using a standardized psychiatric interview and a standardized measure of disability. Results Of 587 patients...

  9. Monitoring Milk Somatic Cell Counts

    Directory of Open Access Journals (Sweden)

    Gheorghe Şteţca

    2014-11-01

    Full Text Available The presence of somatic cells in milk is a widely disputed issue in milk production sector. The somatic cell counts in raw milk are a marker for the specific cow diseases such as mastitis or swollen udder. The high level of somatic cells causes physical and chemical changes to milk composition and nutritional value, and as well to milk products. Also, the mastitic milk is not proper for human consumption due to its contribution to spreading of certain diseases and food poisoning. According to these effects, EU Regulations established the maximum threshold of admitted somatic cells in raw milk to 400000 cells / mL starting with 2014. The purpose of this study was carried out in order to examine the raw milk samples provided from small farms, industrial type farms and milk processing units. There are several ways to count somatic cells in milk but the reference accepted method is the microscopic method described by the SR EN ISO 13366-1/2008. Generally samples registered values in accordance with the admissible limit. By periodical monitoring of the somatic cell count, certain technological process issues are being avoided and consumer’s health ensured.

  10. Stem Cell Pathology.

    Science.gov (United States)

    Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

    2018-01-24

    Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

  11. Prognostic Significance of Clinical/Pathological Stage IA Non-Small-Cell Lung Cancer Showing Partially Solid or Solid Tumours on Radiological Exam

    Science.gov (United States)

    Matsuura, Yosuke; Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Ishikawa, Yuichi; Okumura, Sakae

    2015-01-01

    Purpose: Although curative resection is expected to be effective in patients with clinical (c-) stage IA/pathological (p-) stage IA non-small-cell lung cancers, recurrence is often observed. Hence, the aim of this study was to identify predictors of recurrence. Methods: Between 2005 and 2009, 138 patients with c-stage IA/p-stage IA non-small-cell lung cancers underwent resection. Recurrence and recurrence-free survival (RFS) were compared with clinical, radiographic and pathological findings. Results: The 5-year cancer-specific survival rate was 97% and the RFS rate was 89% at a median follow-up time of 91 months. Recurrence was observed in 10 patients (7.2%). Significant differences were observed in RFS according to tumour dimensions on the mediastinal window image (>1.5 cm), serum carcinoembryonic antigen levels (>5.0 ng/mL), maximum standardised uptake values (SUVmax >2.5) and angiolymphatic invasion. Patients were grouped according to the number of risk factors for poor RFS. Patients with 0–1 of the identified risk factors had an RFS of 97%, where those with 2–4 factors had an RFS of 68% (p <0.001). Conclusion: Prognosis of patients exhibiting more than two of these risk factors is considerably poor. Thus, close observation and individualised adjuvant therapy may be beneficial to these patients. PMID:25740451

  12. Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement.

    Science.gov (United States)

    Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Sottocornola, Lara; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Paganelli, Corrado; Majorana, Alessandra; Gastaldi, Giorgio; Bossi, Paolo; Berruti, Alfredo; Pavanato, Giovanni; Nicolai, Piero; Maroldi, Roberto; Barasch, Andrei; Russi, Elvio G; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M

    2016-01-01

    Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis, hypo-salivation and xerostomia, trismus, radiation caries etc.), are often debilitating. These effects tend to be underestimated and insufficiently addressed in the medical community. A multidisciplinary group of head and neck cancer specialists met in Milan with the aim of reaching a consensus on clinical definitions and management of these toxicities. The Delphi Appropriateness method was used for developing the consensus, and external experts evaluated the conclusions. This paper contains 10 clusters of statements about the clinical definitions and management of head and neck cancer treatment sequels (dental pathologies and osteo-radionecroses) that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecroses (10 clusters of statements), whereas this second part deals with trismus and xerostomia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy. A preliminary study

    International Nuclear Information System (INIS)

    Sumura, Masahiro; Shigeno, Kazushi; Hyuga, Taiju; Yoneda, Tatsuaki; Shiina, Hiroaki; Igawa, Mikio

    2007-01-01

    The objective of this study was to determine whether real-time elastography can be used to detect prostate cancer as a relatively non-invasive modality based on the tissue strain value. Seventeen patients underwent real-time elastography in conjunction with digital rectal examination (DRE), conventional gray-scale transrectal ultrasonography (TRUS), color Doppler ultrasonography (CDUS), and magnetic resonance imaging (MRI) prior to radical prostatectomy. The elastogram was compared to findings of conventional modalities and pathological findings of prostatectomy specimens. To obtain the elastogram, compression of the prostate was performed along with a visual indicator on a video screen. Twenty of 27 pathologically confirmed tumors were detected with real-time elastography. The cancer detection rate with real-time elastography was superior to the rates of other modalities and nearly equal to both on the anterior side (75.0%) and the posterior side (73.7%) of the prostate. A higher tumor detection rate for real-time elastography was observed for tumors with a higher Gleason score and larger tumor volume. In our preliminary study, real-time elastography in conjunction with gray-scale TRUS is a non-invasive modality to detect prostate cancer. (author)

  14. Germline contamination and leakage in whole genome somatic single nucleotide variant detection.

    Science.gov (United States)

    Sendorek, Dorota H; Caloian, Cristian; Ellrott, Kyle; Bare, J Christopher; Yamaguchi, Takafumi N; Ewing, Adam D; Houlahan, Kathleen E; Norman, Thea C; Margolin, Adam A; Stuart, Joshua M; Boutros, Paul C

    2018-01-31

    The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge. The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases. The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.

  15. Clinical and pathologic differences between BRCA1-, BRCA2-, and non-BRCA-associated breast cancers in a multiracial developing country.

    Science.gov (United States)

    Yip, Cheng-Har; Taib, N A; Choo, W Y; Rampal, S; Thong, M K; Teo, S H

    2009-10-01

    Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population. We conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self-reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed. A total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)-negative and progesterone receptor (PR)-negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non-BRCA subjects. We found a strong association between triple-negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non-BRCA carriers; but the difference was not statistically significant. These results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2-associated and non-BRCA-associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non-BRCA-associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.

  16. Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy-proven Gleason score 3+4 prostate cancer

    Science.gov (United States)

    Gondo, Tatsuo; Poon, Bing Ying; Matsumoto, Kazuhiro; Bernstein, Melanie; Sjoberg, Daniel D.; Eastham, James A.

    2014-01-01

    Objective To identify preoperative factors predicting Gleason score downgrading after radical prostatectomy in patients with biopsy Gleason score 3+4 prostate cancer. To determine if prediction of downgrading can identify potential candidates for active surveillance. Patients and Methods We identified 1317 patients with biopsy Gleason score 3+4 prostate cancer who underwent radical prostatectomy at Memorial Sloan-Kettering Cancer Center between 2005 and 2013. Several preoperative and biopsy characteristics were evaluated by forward selection regression, and selected predictors of downgrading were analyzed by multivariable logistic regression. Decision curve analysis was performed to evaluate the clinical utility of the multivariate model. Results Gleason score was downgraded after radical prostatectomy in 115 patients (9%). We developed a multivariable model using age, prostate specific antigen density, percent of positive cores with Gleason 4 cancer out of all cores taken, and maximum percent of cancer involvement within a positive core with Gleason 4 cancer. The area under the curve for this model was 0.75 after ten-fold cross validation. However, decision curve analysis revealed that the model was not clinically helpful in identifying patients who will downgrade at radical prostatectomy for the purpose of reassigning them to active surveillance. Conclusion While patients with pathology Gleason score 3+3 with tertiary Gleason pattern 4 or lower at radical prostatectomy in patients with biopsy Gleason score 3+4 prostate cancer may be potential candidates for active surveillance, decision curve analysis showed limited utility of our model to identify such men. Future study is needed to identify new predictors to help identify potential candidates for active surveillance among patients with biopsy-proven Gleason score 3+4 prostate cancer. PMID:24725760

  17. Germline PMS2 and somatic POLE exonuclease mutations cause hypermutability of the leading DNA strand in biallelic mismatch repair deficiency syndrome brain tumours.

    Science.gov (United States)

    Andrianova, Maria A; Chetan, Ghati Kasturirangan; Sibin, Madathan Kandi; Mckee, Thomas; Merkler, Doron; Narasinga, Rao Kvl; Ribaux, Pascale; Blouin, Jean-Louis; Makrythanasis, Periklis; Seplyarskiy, Vladimir B; Antonarakis, Stylianos E; Nikolaev, Sergey I

    2017-11-01

    Biallelic mismatch repair deficiency (bMMRD) in tumours is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1, and results in a characteristic mutational profile. In this article, we describe the genetic basis of ultramutated high-grade brain tumours in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high-grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant, p.R802*, in the PMS2 gene. Additionally, by genome sequencing of these tumours, we found extremely high somatic mutation rates (237/Mb and 123/Mb), as well as somatic mutations in the proofreading domain of POLE polymerase (p.P436H and p.L424V), which replicates the leading DNA strand. Most interestingly, we found, in both cancers, that the vast majority of mutations were consistent with the signature of POLE exo - , i.e. an abundance of C>A and C>T mutations, particularly in special contexts, on the leading strand. We showed that the fraction of mutations under positive selection among mutations in tumour suppressor genes is more than two-fold lower in ultramutated tumours than in other glioblastomas. Genetic analyses enabled the diagnosis of the two consanguineous childhood brain tumours as being due to a combination of PMS2 germline and POLE somatic variants, and confirmed them as bMMRD/POLE exo - disorders. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

    Science.gov (United States)

    Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

    2009-05-01

    Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

  19. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

    Science.gov (United States)

    Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

    2016-11-01

    To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

  20. T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

    Science.gov (United States)

    Kim, Sungwon; Han, Kyunghwa; Seo, Nieun; Kim, Hye Jin; Kim, Myeong-Jin; Koom, Woong Sub; Ahn, Joong Bae; Lim, Joon Seok

    2018-06-01

    To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm 3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

  1. Pathological and Biochemical Outcomes among African-American and Caucasian Men with Low Risk Prostate Cancer in the SEARCH Database: Implications for Active Surveillance Candidacy.

    Science.gov (United States)

    Leapman, Michael S; Freedland, Stephen J; Aronson, William J; Kane, Christopher J; Terris, Martha K; Walker, Kelly; Amling, Christopher L; Carroll, Peter R; Cooperberg, Matthew R

    2016-11-01

    Racial disparities in the incidence and risk profile of prostate cancer at diagnosis among African-American men are well reported. However, it remains unclear whether African-American race is independently associated with adverse outcomes in men with clinical low risk disease. We retrospectively analyzed the records of 895 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database in whom clinical low risk prostate cancer was treated with radical prostatectomy. Associations of African-American and Caucasian race with pathological biochemical recurrence outcomes were examined using chi-square, logistic regression, log rank and Cox proportional hazards analyses. We identified 355 African-American and 540 Caucasian men with low risk tumors in the SEARCH cohort who were followed a median of 6.3 years. Following adjustment for relevant covariates African-American race was not significantly associated with pathological upgrading (OR 1.33, p = 0.12), major upgrading (OR 0.58, p = 0.10), up-staging (OR 1.09, p = 0.73) or positive surgical margins (OR 1.04, p = 0.81). Five-year recurrence-free survival rates were 73.4% in African-American men and 78.4% in Caucasian men (log rank p = 0.18). In a Cox proportional hazards analysis model African-American race was not significantly associated with biochemical recurrence (HR 1.11, p = 0.52). In a cohort of patients at clinical low risk who were treated with prostatectomy in an equal access health system with a high representation of African-American men we observed no significant differences in the rates of pathological upgrading, up-staging or biochemical recurrence. These data support continued use of active surveillance in African-American men. Upgrading and up-staging remain concerning possibilities for all men regardless of race. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Pathological differences in radical prostatectomy specimens between low- and intermediate-risk prostate cancer patients. Indications for permanent seed implantation monotherapy

    International Nuclear Information System (INIS)

    Sakamoto, Naotaka; Monji, Keisuke; Yuuki, Kohei; Yoshikawa, Masahiro; Iguchi, Atsushi

    2010-01-01

    To clarify the indications for permanent seed implantation monotherapy in patients with intermediate-risk prostate cancer, pathological differences in radical prostatectomy specimens between low- and intermediate-risk prostate cancer were assessed. Fifty-three cases in the low-risk group and 96 cases in the intermediate-risk group had their radical prostatectomy specimens pathologically evaluated between April 2000 and January 2009. Patients with radical prostatectomy specimens of pT2 and Gleason score ≤3+4 were defined as the favorable group, while those with ≥pT3a and/or Gleason score ≥4+3 were defined as the unfavorable group. The favorable group was made up of 67.9%, 81.2%, 73.9%, 73.3%, 23.5% and 24.0% low-risk group cases, ≤T2a, GS 3+3 and 10< prostatic specific antigen (PSA)≤20 ng/ml cases, ≤T2a, GS 3+4 and PSA ≤10 ng/ml cases, ≤T2a, GS 3+4 and 10< PSA≤20 ng/ml cases, ≤T2a, GS 4+3 and PSA ≤20 ng/ml cases and T2b, GS ≤4+3 and PSA ≤20 ng/ml cases, respectively. The rate of unfavorable group in cases with ≤T2a, GS 4+3 and PSA ≤20 ng/ml, and cases with T2b, GS ≤4+3 and PSA ≤20 ng/ml was statistically higher than that in the low-risk group. Accordingly, cancer volume in cases with T2b, GS ≤4+3 and PSA ≤ 20 ng/ml was statistically larger than that in the low-risk group. Cancer volume in intermediate-risk groups other than ≤T2a, GS 3+4 and PSA ≤10 ng/ml tended to be larger than that in the low-risk group. As for radical prostatectomy specimens, the pathological findings of cases with ≤T2a, GS 3+4 and PSA ≤10 ng/ml were similar to those of cases in the low-risk group. The outcome for permanent seed implantation monotherapy with a conventional dose in cases with ≤T2a, GS 3+4 and PSA ≤10 ng/ml may be similar to that of cases in the low-risk group from a pathological aspect. (author)

  3. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N. A. T.; Smit, V. T. H. B. M.; Kessels, L.; van Bochove, A.; van Laarhoven, H. W.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van Leeuwen-Stok, A. E.; van der Hoeven, J. J. M.; van de Velde, C. J. H.; Nortier, J. W. R.; Kroep, J. R.

    2016-01-01

    Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the

  4. PET CT Thresholds for Radiotherapy Target Definition in Non-Small-Cell Lung Cancer: How Close are we to the Pathologic Findings?

    International Nuclear Information System (INIS)

    Wu Kailiang; Ung, Yee C.; Hornby, Jennifer

    2010-01-01

    Purpose: Optimal target delineation threshold values for positron emission tomography (PET) and computed tomography (CT) radiotherapy planning is controversial. In this present study, different PET CT threshold values were used for target delineation and then compared pathologically. Methods and Materials: A total of 31 non-small-cell lung cancer patients underwent PET CT before surgery. The maximal diameter (MD) of the pathologic primary tumor was obtained. The CT-based gross tumor volumes (GTV CT ) were delineated for CT window-level thresholds at 1,600 and -300 Hounsfield units (HU) (GTV CT1 ); 1,600 and -400 (GTV CT2 ); 1,600 and -450 HU (GTV CT3 ); 1,600 and -600 HU (GTV CT4 ); 1,200 and -700 HU (GTV CT5 ); 900 and -450 HU (GTV CT6 ); and 700 and -450 HU (GTV CT7 ). The PET-based GTVs (GTV PET ) were autocontoured at 20% (GTV 20 ), 30% (GTV 30 ), 40% (GTV 40 ), 45% (GTV 45 ), 50% (GTV 50 ), and 55% (GTV 55 ) of the maximal intensity level. The MD of each image-based GTV in three-dimensional orientation was determined. The MD of the GTV PET and GTV CT were compared with the pathologically determined MD. Results: The median MD of the GTV CT changed from 2.89 (GTV CT2 ) to 4.46 (GTV CT7 ) as the CT thresholds were varied. The correlation coefficient of the GTV CT compared with the pathologically determined MD ranged from 0.76 to 0.87. The correlation coefficient of the GTV CT1 was the best (r = 0.87). The median MD of GTV PET changed from 5.72cm to 2.67cm as the PET thresholds increased. The correlation coefficient of the GTV PET compared with the pathologic finding ranged from 0.51 to 0.77. The correlation coefficient of GTV 50 was the best (r = 0.77). Conclusion: Compared with the MD of GTV PET , the MD of GTV CT had better correlation with the pathologic MD. The GTV CT1 and GTV 50 had the best correlation with the pathologic results.

  5. SOMATIC EMBRYOGENESIS AND MORPHOANATOMY OF Ocotea porosa SOMATIC EMBRYOS

    Directory of Open Access Journals (Sweden)

    Luciana Luiza Pelegrini

    2013-01-01

    Full Text Available Ocotea porosa seeds have strong tegument dormancy, recalcitrant behavior, low and irregular germination and that makes its natural propagation difficult. The aim of this study was to establish a protocol of regeneration of Ocotea porosa from somatic embryogenesis. Immature embryonic axes were inoculated on WPM culture medium supplemented with 2.4-D (200 μM combined or not with hydrolyzed casein or glutamine (0.5 or 1 g l-1, during 90 days. The repetitive embryogenesis was induced on medium with 2.4-D (22.62 μM combined with 2-iP (2.46 μM followed by transfer to culture medium with hydrolyzed casein or glutamine (1 g l-1 during 90 days. The maturation of somatic embryos was tested in culture medium containing NAA (0.5 μM and 2-iP (5; 10 and 20 μM. The highest percentage of somatic embryos induction (8.3% was observed in WPM culture medium containing 200 μM 2.4-D and 1 g L-1 hydrolyzed casein and the development of somatic embryos occurred indirectly. Repetitive somatic embryogenesis was promoted in WPM medium containing hydrolyzed casein or glutamine. However, the culture medium containing hydrolyzed casein promoted the maintenance of embryogenic capacity for more than two years. During the maturity phase, there was a low progression of globular embryos to cordiform and torpedo stages. The different ontogenetic stages of somatic embryos of Ocotea porosa were characterized by histological studies.

  6. SOMATIC EMBRYOGENESIS AND MORPHOANATOMY OF Ocotea porosa SOMATIC EMBRYOS

    Directory of Open Access Journals (Sweden)

    Luciana Luiza Pelegrini

    2013-12-01

    Full Text Available http://dx.doi.org/10.5902/1980509812343Ocotea porosa seeds have strong tegument dormancy, recalcitrant behavior, low and irregular germinationand that makes its natural propagation difficult. The aim of this study was to establish a protocol ofregeneration of Ocotea porosa from somatic embryogenesis. Immature embryonic axes were inoculatedon WPM culture medium supplemented with 2.4-D (200 μM combined or not with hydrolyzed casein orglutamine (0.5 or 1 g l-1, during 90 days. The repetitive embryogenesis was induced on medium with 2.4-D(22.62 μM combined with 2-iP (2.46 μM followed by transfer to culture medium with hydrolyzed caseinor glutamine (1 g l-1 during 90 days. The maturation of somatic embryos was tested in culture mediumcontaining NAA (0.5 μM and 2-iP (5; 10 and 20 μM. The highest percentage of somatic embryos induction(8.3% was observed in WPM culture medium containing 200 μM 2.4-D and 1 g L-1 hydrolyzed casein andthe development of somatic embryos occurred indirectly. Repetitive somatic embryogenesis was promotedin WPM medium containing hydrolyzed casein or glutamine. However, the culture medium containinghydrolyzed casein promoted the maintenance of embryogenic capacity for more than two years. Duringthe maturity phase, there was a low progression of globular embryos to cordiform and torpedo stages.The different ontogenetic stages of somatic embryos of Ocotea porosa were characterized by histologicalstudies.

  7. Predictive value of PET-CT for pathological response in stages II and III breast cancer patients following neoadjuvant chemotherapy with docetaxel.

    Science.gov (United States)

    García García-Esquinas, Marta A; Arrazola García, Juan; García-Sáenz, José A; Furió-Bacete, V; Fuentes Ferrer, Manuel E; Ortega Candil, Aída; Cabrera Martín, María N; Carreras Delgado, José L

    2014-01-01

    To prospectively study the value of PET-CT with fluorine-18 fluorodeoxyglucose (FDG) to predict neoadjuvant chemotherapy (NAC) response of locoregional disease of stages II and III breast cancer patients. A written informed consent and approval were obtained from the Ethics Committee. PET-CT accuracy in the prediction of pathologic complete response (pCR) after NAC was studied in primary tumors and lymph node metastasis in 43 women (mean age: 50 years: range: 27-71 years) with histologically proven breast cancer between December 2009 and January 2011. PET-CT was performed at baseline and after NAC. SUV(max) percentage changes (ΔSUV(max)) were compared with pathology findings at surgery. Receiver-operator characteristic (ROC) analysis was used to discriminate between locoregional pCR and non-pCR. In patients not achieving pCR, it was investigated if ΔSUV(max) could accurately identify the residual cancer burden (RCB) classes: RCB-I (minimal residual disease (MRD)), RCB-II (moderate RD), and RCB-III (extensive RD). pCR was obtained in 11 patients (25.6%). Residual disease was found in 32 patients (74.4%): 16 (37.2%) RCB-I, 15 (35.6%) RCB-II and 2 (4.7%) RCB-III. Sensitivity, specificity, and accuracy to predict pCR were 90.9%, 90.6%, and 90.7%, respectively. Specificity was 94.1% in the identification of a subset of patients who had either pCR or MRD. Accuracy of ΔSUV(max) in the locoregional disease of stages II and III breast cancer patients after NAC is high for the identification of pCR cases. Its specificity is potentially sufficient to identify a subgroup of patients who could be managed with conservative surgery. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  8. Length and somatic mosaicism of CAG and GGN rpeats in the androgen receptor gene and the risk of prostate cancer in men with benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Tayeb, Mohammed T.; Sharp, Linda; Haites, N. E.; Murray, G.I.; McLeod, H.L.

    2004-01-01

    The most common malignancy in men worldwide is cancer of the prostate and determinants of prostate cancer (PRCa)risk remain lrgely unidentified. Many candidate genes may be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. we analysed the polymorphic CAG and GGN repeats sequence in exon 1of the AR gene to determine if the number of repeats might be an indicator of PRCa risk in patients with BPH. The study evaluated 28 patients who presented with PRCa at lest 6 years after the diagnosis of BPH and 56 material patients with BPH who did not progress to PRCa over a comparable period. The study showed no evidence for association between the size of AR CAG and CGN repeats and the risk of the development of PRCa in patients with BPH. However BPH patients with AR CAG instability had a 12-fold increased risk devlopment of PRCa. While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease. (author)

  9. Colorectal cancer and the 7th revision of the TNM staging system: review of changes and suggestions for uniform pathologic reporting.

    Science.gov (United States)

    Obrocea, F L; Sajin, Maria; Marinescu, Elena Cristina; Stoica, D

    2011-01-01

    Colorectal cancer (CRC) is a neoplastic disease with a continuously growing incidence in Romania and throughout the world. Although the surgery remains the first line treatment for most of the cases, newly discovered targeted molecular therapies - effective for some patients, but with various side effects and significant financial burden for the national health systems - requires not only stratification of patients in prognostic groups but also evaluation of some non-anatomic factors with major impact on the prognosis and therapeutic strategy. The AJCC/UICC TNM staging system, in his 7th revision, effective for cases diagnosed on or after January 1, 2010, responds to these needs. On the other hand, the role of the pathologist is increasing in terms of workload and amount of information to be included in the pathology report in order to deliver a personalized diagnosis. There are concerns worldwide regarding relevance, validity and completeness of pathologic reporting of CRC in the absence of a uniform reporting format. Therefore, suggestions for a standardized pathology report of CRC are made, based on TNM 7 and recent, up-to-date conclusive published data.

  10. Powerful qPCR assays for the early detection of latent invaders: interdisciplinary approaches in clinical cancer research and plant pathology.

    Science.gov (United States)

    Luchi, Nicola; Capretti, Paolo; Pazzagli, Mario; Pinzani, Pamela

    2016-06-01

    Latent invaders represent the first step of disease before symptoms occur in the host. Based on recent findings, tumors are considered to be ecosystems in which cancer cells act as invasive species that interact with the native host cell species. Analogously, in plants latent fungal pathogens coevolve within symptomless host tissues. For these reasons, similar detection approaches can be used for an early diagnosis of the invasion process in both plants and humans to prevent or reduce the spread of the disease. Molecular tools based on the evaluation of nucleic acids have been developed for the specific, rapid, and early detection of human diseases. During the last decades, these techniques to assess and quantify the proliferation of latent invaders in host cells have been transferred from the medical field to different areas of scientific research, such as plant pathology. An improvement in molecular biology protocols (especially referring to qPCR assays) specifically designed and optimized for detection in host plants is therefore advisable. This work is a cross-disciplinary review discussing the use of a methodological approach that is employed within both medical and plant sciences. It provides an overview of the principal qPCR tools for the detection of latent invaders, focusing on comparisons between clinical cancer research and plant pathology, and recent advances in the early detection of latent invaders to improve prevention and control strategies.

  11. Significant differe nces in demographic, clinical, and pathological features in relation to smoking and alcohol consumption among 1,633 head and neck cancer patients

    Directory of Open Access Journals (Sweden)

    Raquel Ajub Moyses

    2013-06-01

    Full Text Available OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project - Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation.

  12. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  13. Value of serum VEGFC content detection for evaluating the clinical pathological characteristics and malignant degree of esophageal cancer

    Directory of Open Access Journals (Sweden)

    Xiao-Ling Wang

    2017-02-01

    Full Text Available Objective: To analyze serum VEGF-C content in patients with esophageal cancer and its correlation with tumor stage, lymph node metastasis and cancer cell viability. Methods: A total of 112 patients with esophageal cancer treated in our hospital were selected as observation group, healthy subjects receiving physical examination in our hospital during the same time were selected as control group, serum VEGF-C content was compared between two groups of patients, and the correlation between VEGF-C level and tumor stage, lymph node metastasis as well as cancer cell viability was analyzed. Results: Serum VEGF-C level of observation group was higher than that of normal control group; serum tumor markers SCC, CEA, CA199, CA125 and CA50 levels were higher than those of normal control group; serum VEGF-C level of patients with esophageal cancer was positively correlated with tumor stage, lymph node metastasis and cancer cell viability. Conclusion: Serum VEGF-C content in patients with esophageal cancer is well correlated with tumor stage, lymph node metastasis and cancer cell viability, and regular detection of VEGF-C level can be the effective means to evaluate the therapeutic effect and predict treatment outcome.

  14. Skin cancer patients profile at faculty of medicine