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Sample records for neoplasia polmonare con

  1. Neoplasia: The Second Decade

    PubMed Central

    Rehemtulla, Alnawaz

    2008-01-01

    This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles. PMID:19048110

  2. Cervical Neoplasia Probe Control

    Energy Science and Technology Software Center (ESTSC)

    1997-01-24

    This software, which consists of a main executive and several subroutines, performs control of the optics, image acquisition, and Digital Signal Processing (DSP) of this image, of an optical based medical instrument that performs fluoresence detection of precancerous lesions (neoplasia) of the human cervix. The hardware portion of this medical instrument is known by the same name Cervical Neoplasia Probe (CNP)

  3. Multiple Endocrine Neoplasia Syndromes.

    PubMed

    Clark, Pamela

    2015-01-01

    Multiple endocrine neoplasia (MEN) is a term used to describe a group of hereditary carcinoma syndromes. Patients carrying a characteristic autosomal dominant gene aberration exhibit various endocrine carcinomas, as well as other anatomical abnormalities. Unfortunately, familial endocrine carcinoma patients are too often unrecognized by primary care providers, resulting in delayed diagnosis and treatment, with profound consequences related to morbidity and mortality. This article will introduce the various MEN syndromes and the infusion nurse's role in the care of these individuals and their families. PMID:26536410

  4. Immunohistochemistry of Pancreatic Neoplasia

    PubMed Central

    Kaur, Sukhwinder; Shimizu, Tomohiro; Baine, Michael J.; Kumar, Sushil; Batra, Surinder K.

    2013-01-01

    Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody–antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples. PMID:23359148

  5. Tissue eosinophilia in head and neck squamous neoplasia: an update.

    PubMed

    Jain, M; Kasetty, S; Khan, S; Jain, N K

    2014-09-01

    Eosinophils are multifunctional granulocytes that play an imperative role in health and disease. They have also been found to be a crucial component of peri- and intratumoral inflammatory infiltrate. Tumor-associated tissue eosinophilia (TATE) has been observed and described in many tumors, including head and neck neoplasia. The process of eosinophil recruitment and its function in tumors has not been exactly defined yet. Correlation of tissue eosinophilia with prognosis has shown variable results ranging from favourable to unfavourable prognosis or even having no influence on patients outcome. Eosinophils are hypothesized to have tumor defensive as well as tumor promotive function. This dichotomous role of tissue eosinophilia with regard to prognosis has also been noted in head and neck neoplasia and premalignancies. So, the present review attempts to discuss TATE and its possible pros and cons in head and neck neoplasia. PMID:25265347

  6. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  7. Animal models of pituitary neoplasia.

    PubMed

    Lines, K E; Stevenson, M; Thakker, R V

    2016-02-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  8. Intrathoracic neoplasia: Epidemiology and etiology

    SciTech Connect

    Weller, R.E.

    1992-05-01

    Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.

  9. Surgery for cervical intraepithelial neoplasia

    PubMed Central

    Martin-Hirsch, Pierre PL; Paraskevaidis, Evangelos; Bryant, Andrew; Dickinson, Heather O; Keep, Sarah L

    2014-01-01

    Background Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. Objectives To assess the effectiveness and safety of alternative surgical treatments for CIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. Main results Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. Authors’ conclusions The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity. PMID:20556751

  10. Marine mammal neoplasia: a review.

    PubMed

    Newman, S J; Smith, S A

    2006-11-01

    A review of the published literature indicates that marine mammal neoplasia includes the types and distributions of tumors seen in domestic species. A routine collection of samples from marine mammal species is hampered, and, hence, the literature is principally composed of reports from early whaling expeditions, captive zoo mammals, and epizootics that affect larger numbers of animals from a specific geographic location. The latter instances are most important, because many of these long-lived, free-ranging marine mammals may act as environmental sentinels for the health of the oceans. Examination of large numbers of mortalities reveals incidental proliferative and neoplastic conditions and, less commonly, identifies specific malignant cancers that can alter population dynamics. The best example of these is the presumptive herpesvirus-associated metastatic genital carcinomas found in California sea lions. Studies of tissues from St. Lawrence estuary beluga whales have demonstrated a high incidence of neoplasia and produced evidence that environmental contamination with high levels of polychlorinated biphenols and dichlorophenyl trichloroethane might be the cause. In addition, viruses are suspected to be the cause of gastric papillomas in belugas and cutaneous papillomas in Florida manatees and harbor porpoises. While experimental laboratory procedures can further elucidate mechanisms of neoplasia, continued pathologic examination of marine mammals will also be necessary to follow trends in wild populations. PMID:17099143

  11. Rare Neoplasia of the Stomach

    PubMed Central

    Schulz, Christian; Schütte, Kerstin; Malfertheiner, Peter

    2015-01-01

    Background Gastric adenocarcinoma accounts for more than 90% of malignant lesions of the stomach. Besides this entity, numerous neoplastic lesions with malignant or benign characteristics as well as lesions with uncertain malignant potential occur. This review gives an overview on rare neoplasia of the stomach, focusing on gastric polyps, gastrointestinal stromal tumors, gastric lymphoma and neuroendocrine neoplasia. Summary A broad spectrum of rare neoplastic lesions of the stomach with significant differences in malignant potential and with specific demands of interventional therapy is known. In addition to the use of high-definition endoscopy techniques, the histopathological assessment of lesions and of the surrounding mucosa is mandatory to characterize and differentiate malignant and benign tumors. Key Message Rare neoplasia of the stomach is detected in approximately 6% of patients undergoing esophagogastroduodenoscopy. Diligent examination of the gastric mucosa remains essential to detect mucosal and submucosal lesions. Practical Implications Presenting with a broad spectrum of symptoms, ranging from unspecific abdominal discomfort to gastrointestinal bleeding or symptoms of gastric outlet obstruction, different rare neoplastic lesions of the stomach with demand of specific diagnostic and therapeutic work-up occur. Diligent endoscopic evaluation of the entire gastric mucosa, preferably by high-definition endoscopy techniques, is essential in addition to histopathological examination of lesional and surrounding tissue. PMID:26674659

  12. Multiple endocrine neoplasia (MEN) syndromes.

    PubMed

    Walls, Gerard V

    2014-04-01

    Multiple endocrine neoplasia (MEN) syndromes are characterised by the combined occurrence of two or more endocrine tumours in a patient. These autosomal dominant conditions occur in four types: MEN1 due to inactivating MEN1 mutations; MEN2A and MEN2B (MEN3) due to activating mutations of RET and MEN4 due to inactivating cyclin-dependent kinase inhibitor 1B (CDKN1B) mutations. Each MEN syndrome exhibits different combinations of pancreatic islet, anterior pituitary, parathyroid, medullary thyroid and adrenal tumours. This article provides an overview of the clinical features, treatments and molecular genetics of each endocrine tumour syndrome. PMID:24931355

  13. Emerging Entities in Renal Neoplasia.

    PubMed

    Mehra, Rohit; Smith, Steven C; Divatia, Mukul; Amin, Mahul B

    2015-12-01

    This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell-papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease-related RCC, succinate dehydrogenase-deficient RCC, and hereditary leiomyomatosis-RCC syndrome-associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors. Emphasis is placed on common gross and morphologic features, differential diagnoses, use of ancillary studies for making accurate diagnoses, molecular alterations, and predicted biologic behavior based on previous studies. PMID:26612218

  14. Gestational trophoblastic neoplasia: an update.

    PubMed

    Morgan, Jacqueline M; Lurain, John R

    2008-11-01

    Gestational trophoblastic neoplasia (GTN) includes invasive mole, choriocarcinoma, and placental site trophoblastic tumors. The overall cure rate in treating these tumors currently exceeds 90%. Thorough evaluation and staging allow selection of appropriate therapy that maximizes chances for cure while minimizing toxicity. Nonmetastatic (stage I) and low-risk metastatic (stages II and III, World Health Organization score < 7) GTN can be treated with single-agent chemotherapy, resulting in a survival rate approaching 100%. High-risk metastatic GTN (stage IV, WHO score > or = 7) requires initial multiagent chemotherapy with or without adjuvant radiation and surgery to achieve a survival rate of 80% to 90%. PMID:18928664

  15. New concepts in neoplasia as applied to diagnostic pathology

    SciTech Connect

    Fenoglio-Preiser, C.M.; Weinstein, R.S.; Kaufman, N.

    1986-01-01

    This book contains 13 selections. Some of the titles are: Cellular Aspects of Neoplasia; Oncogenes and Cancer; Chromosome and Oncogene Rearrangements in Leukemia and Lymphoma; Ionizing Radiation and Neoplasia; and Papillomaviruses and Neoplasia in Man.

  16. Colorectal Neoplasia and Inflammatory Bowel Disease.

    PubMed

    Cannon, Jamie

    2015-12-01

    Inflammatory bowel disease is associated with an increased risk of gastrointestinal neoplasia. Ulcerative colitis increases the risk of colorectal cancer, and patients with this condition should undergo routine colonoscopic surveillance to detect neoplasia. Crohn's disease increases the risk of malignancy in inflamed segments of bowel, which may include small bowel, colon, rectum, and anus. PMID:26596926

  17. Dietary fibre and colonic neoplasia.

    PubMed Central

    Freeman, H J

    1979-01-01

    Dietary plant fibre, or plantix, is thought to play a significant role in the pathogenesis of colon cancer in humans. It is a complex polymeric substance that has several distinct components resistant to hydrolysis by the digestive enzymes of humans. These components include cellulose, hemicelluloses, pectins, lignin, gums, mucilages and, in certain instances, algal polysaccharides. These polymers have different physicochemical properties, and recent evidence from experimental studies in animals treated with carcinogens suggests that some may exert protective effects in the intestine and others may enhance colon carcinogenesis. This review synthesizes information on the chemical composition, methods of analysis and physicochemical properties of dietary plant fibre and reviews available studies examining the role of fibre in colonic neoplasia in animals and humans. PMID:466603

  18. Common multigenic activation in different human neoplasias.

    PubMed Central

    Hanania, N; Shaool, D; Harel, J; Wiels, J; Tursz, T

    1983-01-01

    It was previously shown that a common multigenic component, designated as tumor-specific DNA (tsDNA), was transcriptionally active in human lymphoid neoplasias and only slightly active, if at all, in normal lymphoid cells, including the Priess cell line immortalized by Epstein-Barr virus. In the Burkitt lymphoma-derived Raji cell line, tsDNA corresponded to 2500-3000 distinct transcription units, arbitrarily defined as encoding mRNA chains of 1000 kds each. In the present study, radioactive Raji cell tsDNA was isolated by a recycling procedure which eliminates transcribed DNA sequences common to both the Raji cell and the Priess cell, and was used as a probe for homologous transcripts. The major part of this probe could be hybridized to RNAs from all the human neoplasias studied: cultured cell lines derived from leukemias, malignant lymphomas or sarcomas, leukemic cells or solid tumors (sarcomas and carcinomas) recovered from patients. In contrast, only a minor portion of Raji cell tsDNA could be hybridized to RNAs from non-malignant cells, normal human lymphoid cells or fibroblasts grown in culture, fetal and chorioplacental tissues. It is concluded that a common multigenic set is activated in a wide variety of, and perhaps in all, human neoplasias. PMID:6315395

  19. Vulvar Intraepithelial Neoplasia (VIN) and Condylomata.

    PubMed

    Nelson, Erin L; Bogliatto, Fabrizio; Stockdale, Colleen K

    2015-09-01

    Human papillomavirus (HPV) infection of the lower genital tract is common and its effects are variable. The majority of infections are transient and the related pathology is self-resolving. Condyloma accuminatum is caused predominantly by HPV 6, 11 and can be managed with medical or surgical therapy. Vulvar intraepithelial neoplasia is a treatable precursor to vulvar cancer with 2 main forms: one related to HPV and the other to chronic vulvar inflammatory conditions. It may be treated medically, surgically, or potentially via the use of therapeutic HPV vaccines. Preventive utilization of a quadrivalent HPV vaccine has the potential to decrease HPV-related lower genital disease burden substantially. PMID:26133495

  20. Neurofibromatosis type I: spinal neoplasia without symptoms.

    PubMed

    Gulati, Sheffali; Leekha, Surbhi; Gupta, Arun K; Kalra, Veena

    2004-09-01

    Neurofibromatosis1 (NF-1) or von Recklinghausen disease is the most common of the neurocutaneous syndromes. It is characterized by presence of hamartomas in multiple organs. Inheritance is autosomal dominant but spontaneous mutations are seen in half the cases. The authors are reporting a classical case of this syndrome with spinal neoplasia which was interestingly asymptomatic. Authorities seem to agree that because the risk of developing intradural disease is significant in patients with NF-1, a routine MRI of the entire spine should be obtained. PMID:15448395

  1. Quantitative proteomics investigation of pancreatic intraepithelial neoplasia

    PubMed Central

    Pan, Sheng; Chen, Ru; Reimel, Beth Ann; Crispin, David A.; Mirzaei, Hamid; Cooke, Kelly; Coleman, Joshua F.; Lane, Zhaoli; Bronner, Mary P.; Goodlett, David R.; McIntosh, Martin; Traverso, William; Aebersold, Ruedi; Brentnall, Teresa A.

    2009-01-01

    Patients with pancreatic cancer are usually diagnosed at late stages, when the disease is incurable. Pancreatic intraepithelial neoplasia (PanIN) 3, is believed to be the immediate precursor lesion of pancreatic adenocarcinoma, and would be an ideal stage to diagnose patients, when intervention and cure are possible and patients are curable. In this study, we used quantitative proteomics to identify dysregulated proteins in PanIN 3 lesions. Altogether, over 200 dysregulated proteins were identified in the PanIN 3 tissues, with a minimum of a 1.75 fold change compared to the proteins in normal pancreas. These dysregulated PanIN 3 proteins play roles in cell motility, the inflammatory response, the blood clotting cascade, the cell cycle and its regulation, and protein degradation. Further network analysis of the proteins identified c-MYC as an important regulatory protein in PanIN 3 lesions. Finally, three of the overexpressed proteins, laminin beta-1, galectin-1, and actinin-4 were validated by IHC analysis. All three of these proteins were overexpressed in the stroma or ductal epithelial cells of advanced PanIN lesions, as well as in pancreatic cancer tissue. Our findings suggest that these three proteins may be useful as biomarkers for advanced PanIN and pancreatic cancer if further validated. The dysregulated proteins identified in this study may assist in the selection of candidates for future development of biomarkers for detecting early and curable pancreatic neoplasia. PMID:19373808

  2. Cyclin D1 and human neoplasia.

    PubMed Central

    Donnellan, R; Chetty, R

    1998-01-01

    Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which is involved in both normal regulation of the cell cycle and neoplasia. In the G1 (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent kinase (cdk) partner, is responsible for transition to the S (DNA synthesis) phase by phosphorylating the product of the retinoblastoma gene (pRB), which then releases transcription factors important in the initiation of DNA replication. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transformation to a malignant phenotype. Analysis of these changes provides important diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's role in malignancy at the various sites, provides a basis on which future treatment directed against this molecule can proceed. PMID:9624412

  3. Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).

    PubMed

    Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

    2008-09-01

    Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs. PMID:18817002

  4. [Iodothyronine deiodinases expression in thyroid neoplasias].

    PubMed

    Meyer, Erika L Souza; Wagner, Márcia S; Maia, Ana Luiza

    2007-07-01

    The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism. PMID:17891232

  5. Photochemoprevention of cutaneous neoplasia through natural products.

    PubMed

    Filip, A; Clichici, S; Daicoviciu, D; Adriana, M; Postescu, I D; Perde-Schrepler, M; Olteanu, D

    2009-03-01

    Non-melanoma skin cancers such as squamous cell carcinoma and basal cell carcinoma are the most common types of human tumors, representing 30% of the new cases of malignancies diagnosed each year. Ultraviolet radiation (UV) from the sun is a major cause of non-melanoma skin cancer in humans. The prevention and mainly the photochemoprevention with natural products represent a simple but very effective strategy in the management of cutaneous neoplasia. Here we review the progress in the research of new and existing agents developed to protect the skin exposed to UV. We also discuss the current state of knowledge on their photosuppression mechanism in humans as well as in animal models, and efficiency in cancer prevention. PMID:19300410

  6. Anal Warts and Anal Intradermal Neoplasia

    PubMed Central

    Echenique, Ignacio; Phillips, Benjamin R.

    2011-01-01

    For the last five millennia we have been dealing with the annoyance of verrucas. Anogenital human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States and is increasing in incidence. As in other gastrointestinal conditions, HPV infection can lead to a stepwise transition from normal cells to dysplastic cells and then to invasive anal cancer. Knowledge of the natural history of HPV infection, risk factors, diagnostic tools, and therapeutic methods gives us the tools to adequately prevent, evaluate, treat, and counsel our patients. In this review, the authors detail the diagnosis, management, and treatment of anal condyloma and anal intraepithelial neoplasia with a focus on prevention, early detection, and treatment using current data and technology. PMID:22379403

  7. Photodynamic therapy of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  8. Optical coherence tomography in vulvar intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.

    2012-11-01

    Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (μoct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of μoct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the μoct are different between normal vulvar tissue and VIN lesions (p<0.0001). Moreover, no correlation is found between the epidermal layer thickness and μoct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.

  9. Development and progression of colorectal neoplasia

    PubMed Central

    Manne, Upender; Shanmugam, Chandrakumar; Katkoori, Venkat R.; Bumpers, Harvey L.; Grizzle, William E.

    2012-01-01

    A variety of genetic and molecular alterations underlie the development and progression of colorectal neoplasia (CRN). Most of these cancers arise sporadically due to multiple somatic mutations and genetic instability. Genetic instability includes chromosomal instability (CIN) and microsatellite instability (MSI), which is observed in most hereditary non-polyposis colon cancers (HNPCCs) and accounts for a small proportion of sporadic CRN. Although many biomarkers have been used in the diagnosis and prediction of the clinical outcomes of CRNs, no single marker has established value. New markers and genes associated with the development and progression of CRNs are being discovered at an accelerated rate. CRN is a heterogeneous disease, especially with respect to the anatomic location of the tumor, race/ethnicity differences, and genetic and dietary interactions that influence its development and progression and act as confounders. Hence, efforts related to biomarker discovery should focus on identification of individual differences based on tumor stage, tumor anatomic location, and race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapeutic approaches to target these molecules in developing personalized medicine. Such strategies have the potential of reducing the personal and socio-economic burden of CRNs. Here, we systematically review molecular and other pathologic features as they relate to the development, early detection, diagnosis, prognosis, progression, and prevention of CRNs, especially colorectal cancers (CRCs). PMID:22112479

  10. Gestational trophoblastic neoplasia in the 1990s.

    PubMed Central

    Goldstein, D. P.

    1991-01-01

    Major advances have been achieved during the past 40 years in the epidemiology, etiology, pathology, endocrinology, immunology, diagnosis, and treatment of molar pregnancy (MP) and gestational trophoblastic neoplasia (GTN). MP is now recognized as composing two distinct entities--complete and partial, with distinct histopathology, genetics, and clinical presentations. Proper management is dependent on a thorough understanding of each type. Early diagnosis and effective treatment of patients with GTN has resulted in 100 percent cure rates in non-metastatic disease and in the majority of patients with metastases. In most instances, resistant disease leading to death results from delayed diagnosis and overwhelming tumor burden. Moreover, in most instances successful treatment can be accomplished with preservation of fertility and normal pregnancy outcome anticipated. A rare variant of choriocarcinoma called placental site trophoblastic tumor (PSTT) has been described, which, although curable by surgery when localized, is usually fatal when disseminated. It is anticipated that during the decade of the nineties the scientific work in progress will lead to earlier diagnosis and improved survival in resistant cases. PMID:1667240

  11. [Clinical characteristics of multiple endocrine neoplasia].

    PubMed

    Conte-Devolx, Bernard; Niccoli, Patricia

    2010-01-01

    Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are autosomal dominant inherited multiglandular diseases with familial and individual age-related penetrance and variable expression. The most frequent endocrine features of MEN1 are parathyroid involvement (> 95%), duodeno-pancreatic endocrine tissue involvement (80%), pituitary adenoma (30%), and adrenal cortex tumors (25%), with no clear syndromic variants. Identification of the germline MEN1 mutation confirms the diagnosis, but there is no phenotype-genotype correlation. All patients with MEN2 have medullary thyroid carcinoma (MTC). The most distinctive MEN2 variants are MEN2A (MTC+pheochromocytoma+hyperparathyroidism), MEN2B (MTC+pheo), and isolated familial MTC (FMTC). The prognosis of MEN2 is linked to the progression of MTC, which depends mainly on the stage at diagnosis and the quality of initial surgical treatment. This emphasizes the need for early diagnosis and management. The specific RET codon mutation correlates with the MEN2 syndromic variant and with the age of onset and aggressiveness of MTC. Consequently, RET mutational status should guide major management decisions, such as whether and when to perform thyroidectomy. PMID:20669560

  12. Anal intraepitelial neoplasia: A narrative review.

    PubMed

    Elorza, Garazi; Saralegui, Yolanda; Enríquez-Navascués, Jose María; Placer, Carlos; Velaz, Leyre

    2016-01-01

    Anal intraepitelial neoplasia (AIN) constitutes a major health problem in certain risk groups, such as patients with immunosuppression of varied origin, males who have sexual relations with other males, and females with a previous history of vaginal or cervical abnormalities in cytology. Its relationship with the human papillomavirus (HPV) infection has been well documented; however, many of the factors involved in the progression and regression of the viral infection to dysplasia and anal carcinoma are unknown. AIN can be diagnosed through cytology of the anal canal or biopsy guided by high-resolution anoscopy. However, the need for these techniques in high-risk groups remains controversial. Treatment depends on the risk factors and given the high morbidity and high recurrence rates the utility of the different local treatments is still a subject of debate. Surgical biopsy is justified only in the case of progression suggesting lesions. The role of the vaccination in high-risk patients as primary prevention has been debated by different groups. However, there is no general consensus on its use or on the need for screening this population. PMID:26765233

  13. [Heredity in renal and prostatic neoplasia].

    PubMed

    Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

    1997-09-01

    There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of RCC, but some are associated with high risk of pheochromocytoma and low risk of RCC. The VHL gene is evolutionary conserved and encodes for a specific protein (pVHL). VHL protein downregulates transcriptional elongation and so suppresses the expression of proto-oncogenes and growth factors. Recently reintroduction of wild-type, non mutant, VHL gene into VHL deficient RCC cell line 786-O had no demonstrable effect on their in vitro growth but inhibited their ability to form tumors in nude mice. So far, VHL mutations or hypermethylations have been found in 76% of sporadic RCC. On the contrary, up to now, no 3p allele loss or VHL mutations have been detected in pRCC. Preliminary studies in familiar pRCC are pointing on genetic changes on chromosomes 1, 7, 16 and 17. As far as prostate cancer is regarded, men with a family history of prostate cancer have an age dependent, significantly increased PCa risk. For familiar clustering, of PCa the two main factors are early age at onset of the disease and the number of multiple affected family members. Hereditary prostate cancer is a subset of familiar prostate cancer with a pattern of distribution consistent with Mendelian inheritance. Hereditary prostate cancer is clinically defined as a clustering of 3 or more relatives within any nuclear family; or the occurrence of prostate cancer in each of 3 generations in either the probands paternal or maternal lineage; or a cluster of 2 relatives affected within 55 years of age or less. Therefore, hereditary prostate cancer may be seen as a multistep carcinogenesis, and clustering may be explained by Mendelian inheritance of a rare (frequency in population 0.36%) dominant, highly penetrant, allele. The estimated cumulative risk of developing PCa, is 88% for carriers as compared with 5% for non carriers. There are conflicting reports of an associated increased incidence of breast cancer in female relatives of men with familiar prostate cancer. In conclusion, there is a clear associatio PMID:9417296

  14. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  15. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  16. Pathophysiology of ocular surface squamous neoplasia

    PubMed Central

    Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S.; Burton, Matthew J.

    2014-01-01

    The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

  17. Pathophysiology of ocular surface squamous neoplasia.

    PubMed

    Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S; Burton, Matthew J

    2014-12-01

    The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC ? TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

  18. Animal models of multiple endocrine neoplasia.

    PubMed

    Wiedemann, Tobias; Pellegata, Natalia S

    2016-02-01

    Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant diseases with high penetrance characterized by proliferative lesions (usually hyperplasia or adenoma) arising in at least two endocrine tissues. Four different MEN syndromes have been so far identified: MEN type 1 (MEN1), MEN2A (also referred to as MEN2), MEN2B (or MEN3) and MEN4, which have slightly varying tumor spectra and are caused by mutations in different genes. MEN1 associates with loss-of-function mutations in the MEN1 gene encoding the tumor suppressor menin. The MEN2A and MEN2B syndromes are due to activating mutations in the proto-oncogene RET (Rearranged in Transfection) and are characterized by different phenotypic features of the affected patients. MEN4 was the most recent addition to the family of the MEN syndromes. It was discovered less than 10 years ago thanks to studies of a rat strain that spontaneously develops multiple endocrine tumors (named MENX). These studies identified an inactivating mutation in the Cdkn1b gene, encoding the putative tumor suppressor p27, as the causative mutation of the rat syndrome. Subsequently, germline mutations in the human ortholog CDKN1B were also found in a subset of patients with a MEN-like phenotype and this led to the identification of MEN4. Small animal models have been instrumental in understanding important biochemical, physiological and pathological processes of cancer onset and spread in intact living organisms. Moreover, they have provided us with insight into gene function(s) and molecular mechanisms of disease progression. We here review the currently available animal models of MEN syndromes and their impact on the elucidation of the pathophysiology of these diseases, with a special focus on the rat MENX syndrome that we have been characterizing. PMID:26184857

  19. A new insight into fecal hemoglobin concentration-dependent predictor for colorectal neoplasia.

    PubMed

    Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Wang, Po-En; Lin, Sheng-Che; Chen, Yao-Der; Liao, Chao-Sheng; Yeh, Yen-Po; Lee, Yi-Chia; Chiu, Han-Mo; Chen, Hsiu-Hsi

    2014-09-01

    We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community-based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5-84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2-67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1-84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose-response relationship than females, yielding gender-specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose-dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC-guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population-based screening for colorectal cancer. PMID:24482014

  20. Development of germ cell neoplasia in situ in chinchilla rabbits.

    PubMed

    Vigueras-Villaseñor, Rosa María; Montelongo Solís, Paola; Chávez-Saldaña, Margarita; Gutiérrez-Pérez, Oscar; Cortés Trujillo, Lucero; Rojas-Castañeda, Julio César

    2016-05-01

    The present study was designed to describe the development of germ cell neoplasia in situ in Chinchilla rabbit by administration of estradiol. The study was performed in rabbits distributed into two groups: control and 17 β-estradiol. The determination of histological alterations and POU5F1 and c-kit proteins employed as biomarkers for the diagnosis of this neoplasia was carried out. Testicular descent and complete spermatogenesis were observed in the control group. The protein biomarkers were negative. However, in the rabbits treated with estradiol, the testes remained undescended with the gonocytes undifferentiated to spermatogonia. There were histological lesions owing to germ cell neoplasia in situ and positive to POU5F1 and c-kit proteins. These findings indicate that the chinchilla rabbit is an ideal model to study this neoplasia in which the histological characteristics and biomarkers of the disease could be clearly observed. Using this model we suggested that the persisting gonocytes could be responsible for the development of germ cell neoplasia in situ. PMID:26617392

  1. Inflammatory bowel disease associated neoplasia: A surgeon’s perspective

    PubMed Central

    Althumairi, Azah A; Lazarev, Mark G; Gearhart, Susan L

    2016-01-01

    Inflammatory bowel disease (IBD) is associated with increased risk of colorectal cancer (CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and inter-observer variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients’ morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes. PMID:26811640

  2. HIF2 and endocrine neoplasia: an evolving story.

    PubMed

    Maher, Eamonn R

    2013-06-01

    In this issue of Endocrine-Related Cancer, Toledo et al. report the identification of activating mutations in the HIF2 (EPAS1) transcription factor in a subset of sporadic pheochromocytomas and paragangliomas. These findings add significantly to an evolving and complex story of the role of hypoxic gene response pathways in human endocrine neoplasia. PMID:23653463

  3. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

    MUÑOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJÓN, Francisco

    2010-01-01

    Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia. PMID:24833969

  4. Colorectal neoplasia in juvenile polyposis or juvenile polyps.

    PubMed Central

    Giardiello, F M; Hamilton, S R; Kern, S E; Offerhaus, G J; Green, P A; Celano, P; Krush, A J; Booker, S V

    1991-01-01

    Juvenile (retention) polyps are usually solitary lesions in the colorectum but may be multiple in juvenile polyposis. The association between juvenile polyps and colorectal neoplasia is controversial. We present three patients with juvenile polyposis who had colorectal adenomas or adenomatous epithelium in juvenile polyps at ages 3, 4, and 7 years. In a retrospective study of 57 additional patients with one or more juvenile polyps, 10 patients (18%) had colorectal neoplasia including three with adenocarcinoma, two with tubular adenoma, and six with adenomatous epithelium in a juvenile polyp (one had both adenomatous epithelium and an adenocarcinoma). Nine of these 10 patients had juvenile polyposis defined by the presence of at least three juvenile polyps; and eight of the nine had a family history of juvenile polyps. Colorectal neoplasia occurred at young age (mean (SEM) 37 (5) years). Our findings suggest that patients with juvenile polyps who have three or more juvenile polyps or a family history of juvenile polyps should undergo surveillance for colorectal neoplasia. Images Figure 1 PMID:1656892

  5. In vivo and in vitro hyperspectral imaging of cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

    2014-02-01

    Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

  6. Bacterial vaginosis and cervical intraepithelial neoplasia--cause or coincidence?

    PubMed

    Uthayakumar, S; Boyle, D C; Barton, S E; Nayagam, A T; Smith, J R

    1998-11-01

    Evidence regarding a causal relationship between bacterial vaginosis and cervical intraepithelial neoplasia has so far been incomplete and conflicting. To determine whether bacterial vaginosis is associated with cervical intraepithelial neoplasia a retrospective study was conducted at the Genitourinary Medicine Clinic at Southlands Hospital, Shoreham-by-Sea, UK. Three hundred patients who presented to the clinic with a first diagnosis of genital warts in the absence of other sexually transmitted diseases were recruited. Results of cervical cytology and where abnormal, histology on colposcopically directed punch biopsies were collected. Bacterial vaginosis was diagnosed by the detection of clue cells on Gram-staining of a high vaginal swab, positive amine test, vaginal pH above 4.5 and the presence of characteristic vaginal discharge. Odds ratio showed an increased prevalence of cervical intraepithelial neoplasia associated with bacterial vaginosis. The results suggest that a prospective cross sectional study should be performed to formally test the hypothesis that bacterial vaginosis predisposes to cervical intraepithelial neoplasia. PMID:15512183

  7. HISTOLOGICAL PROGRESSION OF HEPATIC NEOPLASIA IN RAINBOW TROUT ('SALMO GAIRDNERI')

    EPA Science Inventory

    The histological progression of hepatic neoplasia has not been as systematically studied in rainbow trout as it has been in rodents. Two putative preneoplastic lesions have been identified, the eosinophilic focus and the basophilic focus, but whether these correspond to similar l...

  8. Components of Metabolic Syndrome and Metachronous Colorectal Neoplasia

    PubMed Central

    Ashbeck, Erin L.; Jacobs, Elizabeth T.; Martínez, María Elena; Gerner, Eugene W.; Lance, Peter; Thompson, Patricia A.

    2009-01-01

    Background The consistent association between obesity and colorectal cancer is thought to be explained by metabolic disturbances common, but not exclusive, to the obese. Methods We assessed the relation between metachronous neoplasia and the components of metabolic syndrome (MetS) as defined by the National Cholesterol Education Program’s Adult Treatment Panel III in 2,392 participants of two previously conducted chemoprevention trials. Waist circumference, fasting plasma glucose, trigylcerides, high-density lipoprotein, and systolic and diastolic blood pressure were measured at baseline. Results MetS classification was associated with increased odds of metachronous neoplasia among women [odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.01–1.85] but not among men (OR, 0.99; 95% CI, 0.81–1.21). High waist circumference in men (OR, 1.41; 95% CI, 1.15–1.72) and women (OR, 1.41; 95% CI, 1.05–1.90) and elevated fasting glucose in women (OR, 1.46; 95% CI, 1.09–1.96), as defined by Adult Treatment Panel III cutpoints, were associated with increased odds, whereas none of the other criteria were independently associated with metachronous neoplasia. When each trait was evaluated using quartiles, elevated glucose among women and large waist circumference among men were significantly associated with metachronous lesions. Exploratory analysis of waist circumference and fasting glucose suggested an interaction, where only the combination of large waist circumference and elevated glucose conferred significant increased odds of metachronous neoplasia among both men (OR, 1.36; 95% CI, 1.04–1.78; Pinteraction = 0.08) and women (OR, 1.83; 95% CI, 1.26–2.67; Pinteraction = 0.12). Conclusions These results suggest that, of the specific components of MetS, those that capture impaired glucose uptake increased the odds of metachronous neoplasia. PMID:19318435

  9. Homozygotes for the autosomal dominant neoplasia syndrome (MEN1)

    SciTech Connect

    Brandi, M.L.; Falchetti, A.; Tonelli, F. ); Weber, G.; Svensson, A.; Larsson, C. ); Castello, R.; Furlani, L.; Scappaticci, S.; Fraccaro, M.

    1993-12-01

    Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development. 28 refs., 2 figs.

  10. [Treatment of vulvar intra-epithelial neoplasias with Imiquimod].

    PubMed

    Paternotte, J; Hebert, T; Ouldamer, L; Marret, H; Body, G

    2015-01-01

    The incidence of vulvar intra-epithelial neoplasia (VIN) is increasing in the developed countries especially in young women. There is little consensus regarding the optimal management. Surgery used to be the gold standard. Alternatives to surgery are now needed for the treatment of VIN. Many studies investigated the effectiveness of Imiquimod 5% cream in this pathology. We present a literature review of the results published on the subject. PMID:26047969

  11. [Thorium-induced neoplasia of the spleen? (author's transl)].

    PubMed

    Schumacher, K A; Bargon, G

    1978-08-01

    A patient is presented in whom multiple lienal circular foci are seen 25 years after application of a thorium-containing contrast medium for vascular visualization, over and above the well-known characteristic ThO2 deposits in the liver and spleen. The article discusses the problem whether these circular foci which meet the angiographic criteria of an angioblastic sarcoma, should be considered as a thiorium-induced neoplasia. PMID:567836

  12. Association between cysticercosis and neoplasia: a study based on autopsy findings.

    PubMed

    Cavellani, Camila Lourencini; da Silva, Aline Cristina Souza; Ribeiro, Grace Kelly Naves de Aquino; Oliveira, Lívia Ferreira; Ferraz, Mara Lúcia Fonseca; Teixeira, Vicente de Paula Antunes

    2013-01-01

    Chronic infections including the cysticercosis induce inflammatory cells to produce free radicals and synthesize carcinogenic toxins. The cells with genetic mutations proliferate in a disorganized manner, leading to the development of neoplasia. The aim of the present study was to demonstrate the relation between cysticercosis and neoplasia. Patients autopsied were divided into 4 groups: patients with neoplasia and cysticercosis (NC), patients with neoplasia only (NN), patients with cysticercosis only (CC), and patients without neoplasia or cysticercosis (WW). Of 2012 autopsy reports analyzed, 0.4 showed NC. In groups CC and NC, the most common location of the parasite was the brain. There was a predominance of three or more cysticerci in groups NC and CC. In the NC group, all had malignant neoplasms, and was predominance of benign neoplasm in NN group. The digestive system was the most frequent neoplasia. By calculating odds ratio, rate of neoplasia in patients with cysticercosis was 0.74. In conclusion, the demographic profile of patients with cysticercosis and neoplasia is similar to that of patients with cysticercosis alone. The incidence of cysticercosis and neoplasia was greater in older patients suggesting that immunosenescence may contribute to development of neoplasia promoted by cysticercosis. PMID:24288510

  13. Association between Cysticercosis and Neoplasia: A Study Based on Autopsy Findings

    PubMed Central

    Cavellani, Camila Lourencini; da Silva, Aline Cristina Souza; Ribeiro, Grace Kelly Naves de Aquino; Oliveira, Lívia Ferreira; Ferraz, Mara Lúcia Fonseca; Teixeira, Vicente de Paula Antunes

    2013-01-01

    Chronic infections including the cysticercosis induce inflammatory cells to produce free radicals and synthesize carcinogenic toxins. The cells with genetic mutations proliferate in a disorganized manner, leading to the development of neoplasia. The aim of the present study was to demonstrate the relation between cysticercosis and neoplasia. Patients autopsied were divided into 4 groups: patients with neoplasia and cysticercosis (NC), patients with neoplasia only (NN), patients with cysticercosis only (CC), and patients without neoplasia or cysticercosis (WW). Of 2012 autopsy reports analyzed, 0.4 showed NC. In groups CC and NC, the most common location of the parasite was the brain. There was a predominance of three or more cysticerci in groups NC and CC. In the NC group, all had malignant neoplasms, and was predominance of benign neoplasm in NN group. The digestive system was the most frequent neoplasia. By calculating odds ratio, rate of neoplasia in patients with cysticercosis was 0.74. In conclusion, the demographic profile of patients with cysticercosis and neoplasia is similar to that of patients with cysticercosis alone. The incidence of cysticercosis and neoplasia was greater in older patients suggesting that immunosenescence may contribute to development of neoplasia promoted by cysticercosis. PMID:24288510

  14. Unregulated smooth-muscle myosin in human intestinal neoplasia

    PubMed Central

    Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P.; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Järvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S.; Lucassen, Anneke; Tomlinson, Ian P. M.; Launonen, Virpi; Ristimäki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H. Lee; Aaltonen, Lauri A.

    2008-01-01

    A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz–Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia. PMID:18391202

  15. Activation of ras oncogenes preceding the onset of neoplasia

    SciTech Connect

    Kumar, R.; Barbacid, M. ); Sukumar, S. )

    1990-06-01

    The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.

  16. Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar hyperplasias.

    PubMed Central

    Tate, J. E.; Mutter, G. L.; Boynton, K. A.; Crum, C. P.

    1997-01-01

    Squamous neoplasms of the female genital tract, including vulvar intraepithelial neoplasia, presumably are derived from a single cell. This study addressed this hypothesis and determined the clonal status of other squamous epithelial alterations associated with vulvar carcinoma, including hyperplasia and lichen sclerosis. X chromosome inactivation patterns of 22 epithelial lesions and matched normal epithelium were determined using a polymerase chain reaction (PCR)-based assay targeting the X-linked human androgen receptor gene (HUMARA). Clonality was inferred by comparing matched lesional and control tissues as follows: 1) monoclonal, if intensity of either PCR product was skewed relative to normal reference epithelium (control), 2) polyclonal, if both lesional and control were unskewed, and 3) unknown, if both lesion and control tissues were skewed toward the same allele. Two cases were excluded because of noninformative homozygous HUMARA alleles. Of 8 vulvar intraepithelial neoplasias analyzed, 7 were scored monoclonal and 1 polyclonal. Of 12 hyperplasias, 6 were monoclonal, including one with lichen sclerosis, 2 were polyclonal, and in 4, the clonal status could not be determined. The PCR-based clonal assay supports a monoclonal derivation for vulvar intraepithelial neoplasia and, in some cases, vulvar hyperplasia, and lichen sclerosis. The finding of monoclonal hyperplasia and lichen sclerosis suggests that clonal expansion may evolve before the development of morphological atypia in these epithelia. Images Figure 1 Figure 2 PMID:9006346

  17. Malignant mast cell neoplasia with local metastasis in a horse.

    PubMed

    Reppas, G P; Canfield, P J

    1996-02-01

    A 12-year-old Arab stallion was presented with a chronically swollen right carpus resulting in profound lameness of the same leg. An incisional biopsy of subcutaneous tissue from the right carpus submitted for cytology and histopathology revealed large numbers of eosinophils interspersed by substantial numbers of variably sized and granulated mast cells. Fungal culture of a subcutaneous tissue sample taken from the right carpus was negative. Serial full blood counts revealed persistent mature eosinophilia, not accompanied by a mastocytaemia, neutrophilia without left shift and persistent hyperfibrinogenaemia. After humane destruction, dissection of the affected limb revealed a thick layer of connective tissue deposited around the right carpal joint. Within the connective tissue were embedded many small 0.25-1 cm diameter yellow gritty nodules, which consisted of dystrophic calcification and necrotic cell debris. The tendons enveloped by the connective tissue mass had limited function. The right axillary lymph node was moderately enlarged, yellow-brown and moist. Histopathological examination revealed a moderately well differentiated mast cell neoplasm with evidence of metastasis to the regional lymph node. In horses, malignant mast cell neoplasia is rare, while metastasis has only been reported in one other horse. Eosinophilia associated with equine mast cell neoplasia has not been reported previously but is recorded in mast cell neoplasia in the dog. PMID:16031886

  18. Cystic neoplasia of the pancreas: pathology and biology.

    PubMed

    Adsay, N Volkan

    2008-03-01

    In contrast with solid tumors, most of which are invasive ductal adenocarcinoma with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. Those that are mucinous, namely, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), constitute the most important category, not only because they are the most common, but more importantly because they have well-established malignant potential, representing an adenomacarcinoma sequence. While many are innocuous adenomas--in particular, those that are small and less complex, and in the case of IPMN, those that are branch-duct type are more commonly benign, some harbor or progress into in situ or invasive carcinomas. For this reason, pancreatic cysts with mucinous differentiation ought to be evaluated carefully, preferably by experts familiar with subtle evidences of malignancy in these tumors. In the past few years, the definition of IPMNs and MCNs has become more refined. The presence of ovarian-type stroma has now almost become a requirement for the diagnosis of MCN, and when defined as such, MCN is seen almost exclusively in women of perimenopausal age group as thick-walled multilocular cystic mass in the tail of the pancreas in contrast with IPMN which afflicts an elder population, both genders in almost equal numbers, and occur predominantly in the head of the organ. While mucinous lesions have well-established pre-malignant properties, most of the entities that fall into the nonmucinous true cyst category such as serous tumors, lymphoepithelial cysts, congenital cysts, and squamoid cyst of ducts have virtually no malignant potential. In contrast, the rare cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia such as the rare cystic ductal adenocarcinomas, cystic endocrine neoplasia, and most importantly, solid-pseudopapillary tumor (SPT) in which cystic change is so common that it used to be incorporated into its name ("solid-cystic," "papillary-cystic") are malignant neoplasia, albeit variable degrees of aggressiveness. SPT holds a distinctive place among pancreatic neoplasia because of its highly peculiar characteristics, undetermined cell lineage, occurrence almost exclusively in young females, association with beta-catenin pathway, and also by being a very low-grade curable malignancy. In conclusion, cystic lesions in the pancreas constitute a biologically and pathologically diverse category most (but not all) of which are either benign or treatable diseases; however, a substantial subset, especially mucinous ones, has malignant potential that requires careful analysis. PMID:17957438

  19. Ras/Erk MAPK signaling in epidermal homeostasis and neoplasia.

    PubMed

    Khavari, Thomas A; Rinn, John

    2007-12-01

    Epidermis provides the cutaneous barrier to the external environment and undergoes a continual process of proliferative self-renewal, with human epidermis undergoing complete turnover approximately 1,000 times in a lifetime. Recent work suggests that this ongoing proliferative replenishment of epidermal cells depends, in part, on continual signals for cell division and survival transmitted by the Ras/Erk MAPK pathway. Such constant cell proliferation, however, requires tight regulation to avoid the uncontrolled tissue expansion characteristic of epidermal neoplasia. Recent studies provide new insight into Ras/Erk MAPK pathway function in the control of normal skin development and homeostasis as well as how its deregulation promotes epidermal tumorigenesis. PMID:18000402

  20. Metastatic alveolar rhabdomyosarcoma in multiple endocrine neoplasia type 2A.

    PubMed

    Jones, Ashley E; Albano, Edythe A; Lovell, Mark A; Hunger, Stephen P

    2010-12-01

    Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, accounts for 3% of childhood malignancies. Multiple Endocrine Neoplasia (MEN) type 2A is an autosomal dominant syndrome associated with near universal development of medullary thyroid carcinoma. We describe a previously unreported association of MEN-2A with metastatic alveolar RMS and review the literature on associated hereditary cancer predisposition syndromes and current therapeutic options. The high penetrance of malignancy in patients with MEN warrants a heightened suspicion for the development of nonendocrine malignancies. The diagnosis of RMS should prompt consideration of screening for familial genetic syndromes in certain patients. PMID:20533522

  1. New perspectives on neoplasia and the RNA world.

    PubMed

    Hall, Peter A; Russell, Se Hilary

    2005-06-01

    Key tenets of modern biology are the central place of protein in cell regulation and the flow of genetic information from DNA to RNA to protein. However, it is becoming increasingly apparent that genomes are much more complex than hitherto thought with remarkably complex regulatory systems. The notion that the fraction of the genome involved in coding protein is all that matters is increasingly being questioned as the roles of non-coding RNA (ncRNA) in cellular systems becomes recognised. The RNA world, including microRNA (miRNA), small inhibitory RNA (siRNA) and other RNA species, are now recognised as being crucial for the regulation of chromatin structure, gene expression, mRNA processing and splicing, mRNA stability and translational control. Furthermore such ncRNA systems may be perturbed in disease states and most notably in neoplasia, including in haematological malignancies. Here the burgeoning evidence for a role of miRNA in neoplasia is reviewed and the importance of understanding the RNA world emphasised. PMID:16216032

  2. Aortic chondroid neoplasia in two Labrador Retriever dogs.

    PubMed

    Kohnken, R; Durham, J A; Premanandan, C; Scansen, B A

    2015-12-01

    In the same week, two Labrador Retriever dogs presented to The Ohio State University Veterinary Medical Center for cardiac evaluation. The presenting signs in both dogs included: weight loss, weakness, lethargy, and decreased femoral pulses. The first dog presented in cardiogenic shock and biventricular congestive heart failure, which initially responded to treatment; however, the dog was euthanized due to deteriorating clinical condition. In contrast, the second dog had a milder clinical course without signs of congestive heart failure, and remained stable over the 2-month period of clinical evaluation prior to euthanasia. Echocardiographic evaluation revealed a dilated cardiomyopathy phenotype in the first dog, while a space-occupying intraluminal mass originating at the aortic valve with preserved left ventricular systolic function was observed in the second dog. At autopsy, each dog had a large obstructive luminal mass affecting the ascending aorta and arch. Histopathology revealed that the mass in the first dog was consistent with a benign chondroma, while in the second dog the morphologic characteristics, mitotic activity, and infiltrative growth justified a diagnosis of chondrosarcoma. This report presents the contrasting clinical disease progression and findings in two dogs with aortic neoplasia, with a proposed pathogenesis of cardiac failure secondary to aortic neoplasia. PMID:26521222

  3. Analysis of digitized cervical images to detect cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Ferris, Daron G.

    2004-05-01

    Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.

  4. Barrier methods of contraception and cervical intraepithelial neoplasia.

    PubMed

    Coker, A L; Hulka, B S; McCann, M F; Walton, L A

    1992-01-01

    This North Carolina-based case-control study examined risk factors for cervical intraepithelial neoplasia (CIN). Cases were 103 women with biopsy-confirmed CIN II or III who were recruited from a referral dysplasia clinic. Controls were 258 family practice patients with normal cervical cytology. All subjects were interviewed regarding their sexual and reproductive history, Pap smear screening, active and passive cigarette exposures, and contraceptive use patterns. When compared with controls, cases were half as likely to have ever used barrier methods of contraception; the adjusted odds ratio was 0.5 (95% CI 0.2-0.9). The risk of CIN II/III decreased further with increasing years of barrier method use. Recency, latency, and age at first barrier method use were all associated with a reduced risk of CIN. Men and women should carefully consider the range of benefits of barrier method use as a means to reduce their risk of unwanted pregnancies, sexually transmitted diseases, and cervical neoplasia. PMID:1591917

  5. Ocular Surface Squamous Neoplasia (OSSN): A Retrospective Study

    PubMed Central

    Malladi, Padma; Kavitha

    2015-01-01

    Background Ocular surface squamous neoplasia (OSSN) is a term used to describe neoplastic epithelial abnormalities of conjunctiva and cornea, ranging from Squamous Dysplasia to Invasive Squamous Cell Carcinoma. In recent times, the incidence of OSSN seems to be on the rise, especially in developing countries like India. Aim To analyse demographic characteristics and compare the clinical presentation, treatment outcomes, and histopathology features of Ocular Surface Squamous Neoplasia (OSSN). Design Retrospective cross-sectional study. Materials and Methods We analysed 113 cases of OSSN who presented to the out-patient department of Sarojini Devi Eye Hospital, Regional Institute of Ophthalmology over a period of three years from February 2012 to January 2015. Results In patients, who presented with OSSN age ranged from 18 to 78 years, mean age being 45.20 years. Males were predominantly affected accounting for 65.48%. A nodule at the limbus is the commonest presentation. About 23% of the patients tested positive for HIV in whom mean age of presentation was 34 years. Among HIV positive patients 78.26% had SCC. Conclusion Increased incidence of OSSN was observed in males and people with outdoor occupations. Nodular type of lesion is the commonest variety. HIV positive individuals have an increased incidence of OSSN with invasive characteristics. Hence, ophthalmologists need to be aware of this association and a thorough workup is warranted for all patients presenting with OSSN, especially in the younger age group. Our study Also suggests that OSSN may be the first manifestation of underlying HIV infection. PMID:26675568

  6. In vivo confocal microscopy of ocular surface squamous neoplasia

    PubMed Central

    Parrozzani, R; Lazzarini, D; Dario, A; Midena, E

    2011-01-01

    Purpose To analyse in vivostructural and cellular features of ocular surface squamous neoplasia using clinical confocal microscopy. Methods Ten consecutive cases of untreated ocular surface squamous neoplasia were in vivoinvestigated using clinical confocal microscopy (ConfoScan4, Nidek Co. Ltd, Gamagori, Japan) with a × 40 surface non-contact objective lens. Confocal microscopy images were compared with cytologic samples obtained by scraping technique. Results Confocal microscopy examination revealed large areas of superficial cells debris and/or keratin debris accompanied by syncytial-like groupings, loss of the normal structure of the conjunctival epithelium andor of the corneal basal epithelium layer, papillomatous organization, large fibrovascular structures, and fine vessels perpendicular to the tumour surface. Sub-epithelial (pre-Bowman) space involvement was documented in four cases (50%). Irregular healthy tissue infiltration at the lateral edge of the lesion was documented in two cases (20%) whereas abrupt demarcation between neoplastic cells and normal epithelium was documented in eight cases (80%). In vivocyto-morphologic study using clinical confocal microscopy showed cellular anisocytosis, pleocytosis, and anisonucleosis, enlarged nuclei with high nuclear to cytoplasmic ratio, high reflective cytoplasm and indistinct cytoplasmic borders in all cases (100%). Conclusion CCM appears to be a promising and non-invasive method for in vivostructural and cellular analysis of OSSN. PMID:21311574

  7. In situ increased chemokine expression in human cervical intraepithelial neoplasia.

    PubMed

    Carrero, Yenddy; Mosquera, Jesús; Callejas, Diana; Alvarez-Mon, Melchor

    2015-04-01

    Chemokines play a role in tumor-inflammation and angiogenesis that could be involved in tumor progression. Monocyte chemoattractant protein-1 (MCP-1), Interleukin-8 (IL-8) and macrophage inflammatory proteins (MIP) have been identified in tumor tissues of patients with different neoplasms. Therefore, the aim of the current study was to investigate the expressions of MCP-1, IL-8 and MIP-1α, mononuclear leukocyte infiltration and leukocyte/chemokine expressions in cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and controls. MCP-1, IL-8 and MIP-1α expressions and leukocyte infiltration were determined by indirect immunofluorescence in cervix biopsies from CIN patients (n=65) and 7 normal controls. Increased expressions of MCP-1 and IL-8 in CIN were observed. Increment of lymphocyte infiltration and coexpression of CD3/MCP-1 and CD3/IL-8 were found in CIN. CD3/MCP-1 cell percentage was found decreased and CD3/IL-8 percentage increased according to the CIN evolution. MIP-1α remained similar to control values. The increased expression of MCP-1 and IL-8 in cervical neoplasia may lead to tumor progression. PMID:25661067

  8. Optimal management of low-risk gestational trophoblastic neoplasia.

    PubMed

    Goldstein, Donald P; Berkowitz, Ross S; Horowitz, Neil S

    2015-11-01

    Low-risk gestational trophoblastic neoplasia is a highly curable form of gestational trophoblastic neoplasia that arises largely from molar pregnancy and, on rare occasions, from other types of gestations. Risk is defined as the risk of developing drug resistance as determined by the WHO Prognostic Scoring System. All patients with non-metastatic disease and patients with risk scores <7 are considered to have low-risk disease. The sequential use of methotrexate and actinomycin D is associated with a complete remission rate of 80%. The most commonly utilized regimen for the treatment of patients resistant to single-agent chemotherapy is a multiagent regimen consisting of etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide. The measurement of human chorionic gonadotropin provides an accurate and reliable tumor marker for diagnosis, monitoring the effects of chemotherapy and follow-up to determine recurrence. Pregnancy is allowed after 12 months of normal serum tumor marker. Pregnancy outcomes are similar to those of normal population. PMID:26517533

  9. Diagnosis and therapies for gastric non-invasive neoplasia

    PubMed Central

    Kato, Motohiko

    2015-01-01

    There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia (NIN) were divided into low grade and high grade (including intra-mucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection (ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future. PMID:26640329

  10. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    MedlinePLUS

    ... Genetic disorder catalog Conditions > X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (often ... 2014 What is XMEN? X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically ...

  11. Association between calcium intake and colorectal neoplasia in Puerto Rican Hispanics.

    PubMed

    Palacios, Cristina; Lopez, Maritza; Ortiz, Ana Patricia; Correa, Marcia Cruz

    2010-12-01

    Epidemiological studies show that a high calcium intake reduces the risk of colon cancer. The objective was to study the association between calcium intake and colorectal neoplasia in a clinic-based sample of Hispanics adults from Puerto Rico. As part of this cross-sectional study, a total of 433 subjects were recruited from surgery and gastroenterology clinics at the University of Puerto Rico. Calcium intake was estimated using a food frequency questionnaire (FFQ) of calcium rich foods. Socio-demographics, health history and colonoscopy results were obtained from the primary study. Chi square and odds ratios (OR) for colorectal neoplasia (adenomas and/ or adenocarcinoma) were calculated for total calcium, dietary calcium and for calcium supplement use. In total, 312 (72%) from 433 participants completed the FFQ and had available colonoscopy results; from these, 196 (62.5%) were free of neoplasia and 117 (37.5%) had colorectal neoplasia. Colorectal neoplasia subjects were older, a lower proportion were females and less educated than those without neoplasia (p < 0.01). Total calcium intake (median 1180 mg/d) was greater in those free of neoplasia compared to colorectal neoplasia subjects (median 1036 mg/d; p<0.05). A high total calcium intake and the use of calcium supplements significantly reduced the OR (crude and age adjusted) for colorectal neoplasia; although these associations lost statistical significance after additionally adjusting for gender and educational level. In conclusion, a high calcium intake and the use of calcium supplements may be protective against colorectal neoplasia, although a greater sample may be required to observe significant associations in a multivariate model. PMID:21866684

  12. Surgical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

    Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. Authors’ conclusions The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice. PMID:21249698

  13. Microtopographic Inspection and Fractal Analysis of Skin Neoplasia

    NASA Astrophysics Data System (ADS)

    Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón

    2008-04-01

    Early detection of skin cancer is fundamental to a successful treatment. Changes in the shape, including the relief, of skin lesions are an indicator of a possible malignity. Optical microtopographic inspection of skin lesions can be used to identify diagnostic patterns of benign and malign skin' lesions. Statistical parameters like the mean roughness (Ra) may allow the discrimination between different types of lesions and degree of malignity. Fractal analysis of bi-dimensional and 3D images of skin lesions can validate or complement that assessment by calculation of its fractal dimensions (FD). On the study herein reported the microtopographic inspection of the skin lesions were performed using the optical triangulation based microtopographer developed at the Physics Department of the University of Minho, MICROTOP.03.MFC. The patients that participated in this research work were men and women older than 15 years with the clinical and histopathology diagnoses of: melanoma, basocellular carcinoma, epidermoide carcinoma, actinic keratosis, keratoacantosis and benign nevus. Latex impressions of the lesions were taken and microtopographically analyzed. Characteristic information for each type of studied lesion was obtained. For melanoma it was observed that on the average these tumors present an increased roughness of around 67 percent compared to the roughness of the healthy skin. This feature allows the distinction from other tumors as basocellular carcinoma (were the roughness increase was in the average of 49 percent) and benign lesions as the epidermoide cyst (37 percent) or the seborrhea keratosis (4 percent). Tumor size and roughness are directly proportional to the grade of malignality. The characterization of the fractal geometry of 2D (histological slides) and 3D images of skin lesions was performed by obtaining its FD evaluated by means of the Box counting method. Results obtained showed that the average fractal dimension of histological slide images (FDh) corresponding to some neoplasia is higher (1.334+/-0.072) than those for healthy skin (1.091+/-0.082). A significant difference between the fractal dimensions of neoplasia and healhty skin (>0.001) was registered. The FD of microtopography maps (FDm) can also distinguish between healthy and malignant tissue in general (2.277+/-0.070 to 2.309+/-0.040), but not discriminate the different types of skin neoplasias. The combination of the rugometric evaluation and fractal geometry characterization provides valuable information about the malignity of skin lesions and type of lesion.

  14. A retrospective study of skull base neoplasia in 42 dogs.

    PubMed

    Rissi, Daniel R

    2015-11-01

    This study describes the prevalence and distribution of 42 cases of skull base neoplasia in dogs between 2000 and 2014. The average age of affected individuals was 9.5 years, and there was no sex or breed predisposition. The most common skull base neoplasms were meningioma (25 cases) and pituitary adenoma (9 cases). Less common tumors included craniopharyngioma (2 cases), nerve sheath tumor (2 cases), and 1 case each of pituitary carcinoma, meningeal oligodendrogliomatosis, presumed nasal or sinonasal carcinoma, and multilobular tumor of bone. All neoplasms caused some degree of compression of adjacent structures. The distribution of the tumors was greatest in the sellar region (n = 18), followed by the paranasal region (n = 12), caudal cranial fossa (n = 10), central cranial fossa (n = 1), and rostral cranial fossa (n = 1). PMID:26462763

  15. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    SciTech Connect

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-06-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.

  16. Myeloid Neoplasias: What Molecular Analyses Are Telling Us

    PubMed Central

    Gutiyama, Luciana M.; Coutinho, Diego F.; Lipkin, Marina V.; Zalcberg, Ilana R.

    2012-01-01

    In the last decades, cytogenetic and molecular characterizations of hematological disorders at diagnosis and followup have been most valuable for guiding therapeutic decisions and prognosis. Genetic and epigenetic alterations detected by different procedures have been associated to different cancer types and are considered important indicators for disease classification, differential diagnosis, prognosis, response, and individualization of therapy. The search for new biomarkers has been revolutionized by high-throughput technologies. At this point, it seems that we have overcome technological barriers, but we are still far from sorting the biological puzzle. Evidence based on translational research is required for validating novel genetic and epigenetic markers for routine clinical practice. We herein discuss the importance of genetic abnormalities and their molecular pathways in acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. We also discuss how novel genomic abnormalities may interact and reassess concepts and classifications of myeloid neoplasias. PMID:23056961

  17. Uterine arteriovenous malformations following gestational trophoblastic neoplasia: a systematic review.

    PubMed

    Touhami, Omar; Gregoire, Jean; Noel, Patricia; Trinh, Xuan Bich; Plante, Marie

    2014-10-01

    Uterine arteriovenous malformation (AVM) following gestational trophoblastic neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal bleeding or life-threatening heavy bleeding, even after complete resolution of the tumor following chemotherapy. This analysis aimed to perform an extensive systematic review highlighting clinical symptoms, imaging, management and prognosis of this rare complication of GTN. We also describe an additional case of uterine AVM following GTN. We conducted a literature search using Medline, Embase and Cochrane library to analyze the clinical data of 49 published cases of uterine AVM following GTN. Median age of the women diagnosed with AVM was 29 years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were nulligravida. Complete molar pregnancy was the most common initial gestational trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in the myometrium is the most relevant finding on ultrasonography but the gold standard for the definitive diagnosis of AVMs is angiographic examination. Uterine artery embolization was the most common treatment option performed in 82% of the patients and was successful in controlling the bleeding in 85% of cases. We identified 20 pregnancies after successful embolization of uterine AVM following a GTN and 90% of them were successful. Because of the risk of life-threatening heavy bleeding, the diagnosis of uterine AVM should always be considered in patients with a history of recurrent unexplained vaginal bleeding after gestational trophoblastic neoplasia. Angiographic embolization is successful in the majority of cases and does not appear to compromise future pregnancy. PMID:25126982

  18. Intratubular germ cell neoplasia of the testis: a brief review.

    PubMed

    Al-Hussain, Turki; Bakshi, Nasir; Akhtar, Mohammed

    2015-05-01

    Germ cell tumors of the testis may be divided into 3 broad categories according to age at presentation. The tumors in the pediatric age group include teratoma and yolk sac tumor. These tumors are generally not associated with convincing intratubular neoplasia. The second group consists of tumors presenting in third and fourth decade of life and include seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma as well as mixed germ cell tumors. The precursor cell for these tumors is an abnormal gonocyte that fails to differentiate completely into spermatogonia. These abnormal cells stay dormant in the gonad during intrauterine life as well as infancy and childhood, but undergo proliferation during puberty and can be identified as intratubular germ cell neoplasia unclassified (IGCNU). These tumor cells continue to manifest protein expression pattern that resembles primitive germ cells (PLAP, c-KIT, OCT3/4). After a variable interval following puberty, IGCNU cells may acquire ability to penetrate the seminiferous tubules and present as an overt germ cell tumor. Acquisition of isochrome 12 and other genetic abnormalities are usually associated with this transition. The level of DNA methylation generally determines the phenotype of the germ cell tumor. The third type of germ cell tumors is spermatocytic seminoma, which is a rare tumor encountered later in life usually in fifth and sixth decade. The cell of origin of this tumor is probably postpubertal mature spermatogonia which acquire abnormal proliferative capability probably due to gain of chromosome 9 resulting in activation and amplification of genes such as DMRT1. The tumor cells manifest many of the proteins normally expressed by mature sperms such as VASA, SSX2, and occasionally OCT2. Although spermatocytic seminoma may also have an intratubular growth phase, it completely lacks features of IGCNU. PMID:25844678

  19. A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

    PubMed Central

    Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

    2014-01-01

    Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35?918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. PMID:24385598

  20. Histologic differentiation and mucin phenotype in white opaque substance-positive gastric neoplasias

    PubMed Central

    Ueo, Tetsuya; Yonemasu, Hirotoshi; Yao, Kenshi; Ishida, Tetsuya; Togo, Kazumi; Yanai, Yuka; Fukuda, Masahide; Motomura, Mitsuteru; Narita, Ryoich; Murakami, Kazunari

    2015-01-01

    Background and study aims: The authors previously reported that the white opaque substance (WOS) in gastric epithelial neoplasia was caused by accumulation of lipid droplets by immunohistochemical and immunoelectron microscopic studies of adipophilin, which was recently identified and validated as a marker of lipid droplets. The aim of the current study was to investigate the characteristics of the histologic differentiation and mucin phenotype in WOS-positive gastric epithelial neoplasias. Patients and methods: A total of 130 gastric epithelial neoplasias (45 adenomas and 85 early adenocarcinomas) from 120 patients were retrospectively evaluated. The presence or absence of WOS was evaluated by M-NBI. Lipids were examined by immunohistochemical staining for adipophilin. Tissue phenotypes were immunohistochemically classified as intestinal (I), gastrointestinal (GI), and gastric (G) using antibodies against CD10, MUC2, MUC5AC and MUC6.?The histologic differentiation and mucin phenotype of WOS-positive neoplasias were characterized and examined according to adipophilin expression. Results: The presence of WOS by M-NBI was correlated with histologic differences between adenoma or differentiated type adenocarcinoma and mixed type or undifferentiated type adenocarcinoma (P?=?0.0153). Adipophilin was only expressed in primary adenoma and well to moderately differentiated adenocarcinoma components but not in undifferentiated components. WOS and adipophilin expression were only observed in neoplasias with I or GI phenotypes, but not in those with the G phenotype (P?neoplasias might indicate differentiation into a mature histological subtype with GI or I mucin phenotype. PMID:26716119

  1. Multiple endocrine neoplasia type 2A: case report.

    PubMed

    P?un, D L; Poian?, C; Petri?, R; Radian, S; Miulescu, R D?nciulescu; Constantinescu, G; Orban, C

    2013-01-01

    Multiple endocrine neoplasia type 2A (MEN 2A) is a complex autosomal dominant inherited syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary parathyroid hyperplasia. In patients with only one or two clinical features, identification of a germline RET(REarranged in Transfection) mutation or the identification of the clinical features of MEN 2A in other first degree relatives is required to make the diagnosis. We present the case of a family with MEN 2A syndrome confirmed by genetic analysis which identified RET gene mutation in 634 codon in father - DV - aged 48 years and also in daughter DM -aged 20 years. The specific feature in this case is that the index case was the daughter (diagnosed and operated for pheochromocytoma at the age of 19 years), the father being diagnosed later with medullary thyroid carcinoma by mutational screening in all family members. This family supports the phenomenon of anticipation, in which severity increases and the age of onset decreases in successive generations, the syndrome being discovered earlier and with a worse prognostic in the daughter. PMID:24331334

  2. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed Central

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  3. Anal intraepithelial neoplasia--is treatment better than observation?

    PubMed

    Orchard, M; Roman, A; Parvaiz, A C

    2013-01-01

    Anal Intraepithelial Neoplasia (AIN) is an increasingly common condition for which the best treatment has not been well established. Traditional management was based on a 'watch and wait' strategy, but as the natural history of AIN and its progression to anal cancer is becoming better understood, more active treatment strategies are warranted. A best evidence topic in surgery was written according to a structured protocol to address the question whether treatment is indicated in patients with AIN. A total of 169 papers were identified using the defined search criteria. This included only one randomised controlled trial. Case series were therefore also included to help answer the question. The details of the papers were tabulated including relevant outcomes and study weaknesses. We conclude that treatment of high grade AIN, particularly in high risk groups is recommended to try to avoid progression to anal cancer. Treatment options that have shown some benefit include topical use of imiquimod cream or ablation directed by high resolution anoscopy. PMID:23643642

  4. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

    PubMed

    de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

    2015-11-01

    Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. PMID:26335596

  5. Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

    PubMed

    Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

    2016-02-01

    Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. PMID:26626780

  6. Anal cancer and intraepithelial neoplasia screening: A review

    PubMed Central

    Leeds, Ira L; Fang, Sandy H

    2016-01-01

    This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

  7. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-14

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  8. Challenges in automated detection of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Srinivasan, Yeshwanth; Yang, Shuyu; Nutter, Brian; Mitra, Sunanda; Phillips, Benny; Long, Rodney

    2007-03-01

    Cervical Intraepithelial Neoplasia (CIN) is a precursor to invasive cervical cancer, which annually accounts for about 3700 deaths in the United States and about 274,000 worldwide. Early detection of CIN is important to reduce the fatalities due to cervical cancer. While the Pap smear is the most common screening procedure for CIN, it has been proven to have a low sensitivity, requiring multiple tests to confirm an abnormality and making its implementation impractical in resource-poor regions. Colposcopy and cervicography are two diagnostic procedures available to trained physicians for non-invasive detection of CIN. However, many regions suffer from lack of skilled personnel who can precisely diagnose the bio-markers due to CIN. Automatic detection of CIN deals with the precise, objective and non-invasive identification and isolation of these bio-markers, such as the Acetowhite (AW) region, mosaicism and punctations, due to CIN. In this paper, we study and compare three different approaches, based on Mathematical Morphology (MM), Deterministic Annealing (DA) and Gaussian Mixture Models (GMM), respectively, to segment the AW region of the cervix. The techniques are compared with respect to their complexity and execution times. The paper also presents an adaptive approach to detect and remove Specular Reflections (SR). Finally, algorithms based on MM and matched filtering are presented for the precise segmentation of mosaicism and punctations from AW regions containing the respective abnormalities.

  9. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months. PMID:25118474

  10. Familial multiple endocrine neoplasia: the first 100 years.

    PubMed

    Carney, J Aidan

    2005-02-01

    In 1903, Erdheim described the case of an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands. Fifty years later, Underdahl et al reported 8 patients with a syndrome of pituitary, parathyroid, and pancreatic islet adenomas. In 1954, Wermer found that the syndrome was transmitted as a dominant trait. In 1959, Hazard et al described medullary (solid) thyroid carcinoma (MTC), a tumor that later was found to be a component of two endocrine syndromes. The first of these described by Sipple in 1961 comprised pheochromocytoma, MTC, and parathyroid adenoma. The second, described by Williams et al in 1966, was the combination of mucosal neuromas, pheochromocytoma, and MTC. In 1968, Steiner et al introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of endocrine tumors; they designated the Wermer syndrome as MEN 1 and the Sipple syndrome as MEN 2. In 1974, Sizemore et al concluded that the MEN 2 category included two groups of patients with MTC and pheochromocytoma: one with parathyroid disease and a normal appearance (MEN 2A) and the other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). Later, additional nonendocrine conditions (von Recklinghausen neurofibromatosis and von Hippel-Lindau disease) were found accompanying other more recently described familial MEN syndromes, indicating that these diseases are very complicated disorders. PMID:15644784

  11. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout.

    PubMed

    Hamilton, T E; van Belle, G; LoGerfo, J P

    1987-08-01

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship. PMID:3612986

  12. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout

    SciTech Connect

    Hamilton, T.E.; van Belle, G.; LoGerfo, J.P.

    1987-08-07

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship.

  13. Reproductive outcomes after hydatiform mole and gestational trophoblastic neoplasia.

    PubMed

    Gadducci, Angiolo; Lanfredini, Nora; Cosio, Stefania

    2015-01-01

    Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus. PMID:26288335

  14. RAP1 GTPase Overexpression is Associated with Cervical Intraepithelial Neoplasia

    PubMed Central

    Pascoal-Xavier, Marcelo Antonio; Figueiredo, Anna Carolina Cançado; Gomes, Luciana Inácia; Peruhype-Magalhães, Vanessa; Calzavara-Silva, Carlos Eduardo; Costa, Marcelo Azevedo; Reis, Ilka Afonso; Bonjardim, Claudio Antônio; Kroon, Erna Geessien

    2015-01-01

    RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a putative oncogene that is highly expressed in several malignant cell lines and types of cancers, including some types of squamous cell carcinoma. However, the participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross-sectional study of paraffin-embedded cervical biopsies to determine the association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue was performed on 183 paraffin-embedded cervical biopsies that were classified as normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN 2/3 (p<0.001) specimens was observed and was in agreement with the histopathologic diagnosis. A progressive increase in the RAP1 expression levels increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI) 1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR?=?19.86, 95% CI 6.40-70.79) nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression analysis showed that this progressive increase in RAP1 expression more strongly impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful biomarker for the diagnosis of CIN. PMID:25856570

  15. Foamy gland changes in gastric-type endocervical neoplasia.

    PubMed

    Stewart, Colin J R; Frost, Felicity; Leake, Robyn; Mohan, G Raj; Tan, Jason

    2015-12-01

    Foamy gland (FG) change is a distinctive morphological alteration most widely recognised in adenocarcinomas of the prostate and pancreas, and characterised by cells showing prominent cytoplasmic microvacuolation often with deceptively bland nuclear appearances. To our knowledge, FG alteration has not been described in endocervical neoplasia. We report four patients with gastric-type endocervical neoplasms (3 invasive and 1 in situ) in which FG change was present in 30-80% of the tumour cells. The mean age was 56.5 years (range 45-66 years) and three patients, one of whom also had post-coital bleeding, had atypical glandular cells detected on cervical cytology. Three cases showed a pure gastric phenotype and benign gastric-type changes including pyloric metaplasia, tunnel clusters and/or lobular endocervical glandular hyperplasia were also present. These cases were MUC6 positive and p16 negative on immunohistochemistry while HPV was not detected. One adenocarcinoma showed a mixed histological pattern including usual-type endocervical carcinoma and gastric-type adenocarcinoma: only the latter component expressed MUC6 and this case was p16 and HPV18 positive. This report expands the morphological spectrum exhibited by gastric-type endocervical lesions and the range of anatomical sites in which neoplasms with FG features may be encountered. PMID:26517626

  16. Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia.

    PubMed

    Long, Kevin C; Menon, Raman; Bastawrous, Amir; Billingham, Richard

    2016-03-01

    The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established. PMID:26929753

  17. A Possible New Multiple Endocrine Neoplasia Mutation in a Patient with a Prototypic Multiple Endocrine Neoplasia Presentation

    PubMed Central

    Buzzola, Rino; Kurukulasuriya, Lilamani Romayne; Touza, Mariana; Litofsky, Norman S.; Brietzke, Stephen; Sowers, James R.

    2016-01-01

    Background Multiple endocrine neoplasia (MEN) type 1 syndrome is an uncommon inherited disorder characterized by the occurrence of tumors involving two or more endocrine glands. These tumors include pheochromocytoma, adrenal cortical and neuroendocrine tumors including (bronchopulmonary, thymic, gastric), lipomas, angiofibromas, collagenomas, and meningiomas. MEN-4 is very rare and has been characterized by the occurrence of parathyroid and anterior pituitary tumors in association with tumors of the adrenals, kidneys, and reproductive organs. Summary We report the case of a 40-year-old male without significant family history of endocrine disease who was found to have primary hyperparathyroidism, a pituitary tumor causing acromegaly, thyroid cancer, renal cell carcinoma, and pancreatic cysts. We posit that this represents a new version of MEN-4. While renal tumors (angiomyolipoma) have been reported as part of the MEN-4 phenotype, to our knowledge, this is the first case reported of the association of MEN-1 and/or MEN-4 phenotype with this unique constellation of tumors, including renal cell carcinoma. Interestingly, this patient tested negative (DNA sequencing/deletion) for MEN-1 (menin), MEN-4 (CDKN1B) and VHL genes. Key Message Thus, while this case has clinical characteristics consistent with either MEN-1 or MEN-4, it may represent a unique genetic variant. PMID:26989398

  18. A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions

    PubMed Central

    2014-01-01

    Background The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. Results To characterize the transcriptional changes of early breast neoplasia, we sequenced 3′- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. Conclusions This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. PMID:24887547

  19. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    PubMed Central

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-01-01

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

  20. DNA-Cytometry of Progressive and Regressive Cervical Intraepithelial Neoplasia

    PubMed Central

    Hanselaar, Antonius G. J. M.; Poulin, Neal; Pahlplatz, Martin M. M.; Garner, David; MacAulay, Calum; Matisic, Jasenka; LeRiche, Jean; Palcic, Branko

    1998-01-01

    A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN), who had received follow?up by cytology only. Automated image cytometry of Feulgen?stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group). The second group of 26 smears with dysplastic changes had shown regression to normal (regressive group). The goal of the study was to determine if differences in cytometric features existed between the progressive and regressive groups. CIN categories I, II and III were represented in both groups, and measurements were pooled across diagnostic categories. Images of up to 700 intermediate cells were obtained from each slide, and cells were scanned exhaustively for the detection of diagnostic cells. Discriminant function analysis was performed for both intermediate and diagnostic cells. The most significant differences between the groups were found for diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells could be classified with 60% accuracy. Cytometric features which afforded the best discrimination were characteristic of the chromatin organization in diagnostic cells (nuclear texture). Slide classification was performed by thresholding the number of cells which exhibited progression associated changes (PAC) in chromatin configuration, with an accuracy of 93 and 73% for diagnostic and intermediate cells, respectively. These results indicate that regardless of the extent of nuclear atypia as reflected in the CIN category, features of chromatin organization can potentially be used to predict the malignant or progressive potential of CIN lesions. PMID:9584897

  1. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

    PubMed

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-07-01

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

  2. Multiple endocrine neoplasias: advances and challenges for the future

    PubMed Central

    Alevizaki, M.; Stratakis, C. A.

    2011-01-01

    Several important advances have been made over the last 2 years, since the last international workshop on multiple endocrine neoplasias (MENs) that was held in Marseilles, France (MEN2006). The series of articles that are included in this issue summarize the most important of these advances as they were presented in Delphi, Greece, during the 11th International Workshop on MENs, September 25–27, 2008 (MEN2008). This editorial summarizes some of these advances: the identification of the AIP, and the PDE11A and PDE8B genes by genome-wide association (GWA) studies as predisposing genes for pituitary and adrenal tumours, respectively, the discovery of p27 mutations in a new form of MEN similar to MEN type 1 (MEN 1) that is now known as MEN 4, the molecular investigations of Carney triad (CT), a disorder that associates paragangliomas (PGLs), gastrointestinal stromal tumour (GISTs), and pulmonary chondromas (PCH) with pheochromocytomas and adrenocortical adenomas and other lesions, and the molecular elucidation of the association of GISTs with paragangliomas (Carney–Stratakis syndrome) that is now known to be because of SDHB, SDHC, and SDHD mutations. Molecular investigations in Carney complex (another MEN also described by Dr. Carney, who during the meeting, along with Dr. Charles E. (‘Gene’) Jackson was honoured for his life-long and many contributions to the field) have also revealed the role of cyclic AMP signalling in tumorigenesis. As our knowledge of the molecular causes of MENs increases, the challenge is to translate these discoveries in better treatments for our patients. Indeed, new advances in the preventive diagnosis and molecular treatment of MEN 1 and MEN 2, respectively, continued unabated, and an update on this front was also presented at MEN2008 and is included in this issue. PMID:19522821

  3. Cyclooxygenase-1 and -2: molecular targets for cervical neoplasia.

    PubMed

    Kim, Hee Seung; Kim, Taehun; Kim, Mi-Kyung; Suh, Dong Hoon; Chung, Hyun Hoon; Song, Yong Sang

    2013-06-01

    Cyclooxygenase (COX) is a key enzyme responsible for inflammation, converting arachidonic acid to prostaglandin and thromboxane. COX has at least two isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues for maintaining physiologic homeostasis, COX-2 is induced by inflammatory stimuli including cytokines and growth factors. Many studies have shown that COX-2 contributes to cancer development and progression in various types of malignancy including cervical cancer. Human papillomavirus, a necessary cause of cervical cancer, induces COX-2 expression via E5, E6 and E7 oncoproteins, which leads to prostaglandin E2 increase and the loss of E-cadherin, promotes cell proliferation and production of vascular endothelial growth factor. It is strongly suggested that COX-2 is associated with cancer development and progression such as lymph node metastasis. Many studies have suggested that non-selective COX-2 inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors might show anti-cancer activity in COX-2 -dependent and -independent manners. Two phase II trials for patients with locally advanced cervical cancer showed that celecoxib increased toxicities associated with radiotherapy. Contrary to these discouraging results, two phase II clinical trials, using rofecoxib and celecoxib, demonstrated the promising chemopreventive effect for patients with cervical intraepithelial neoplasia 2 or 3. However, these agents cause a rare, but serious, cardiovascular complication in spite of gastrointestinal protection in comparison with NSAIDs. Recent pharmacogenomic studies have showed that the new strategy for overcoming the limitation in clinical application of COX-2 inhibitors shed light on the use of them as a chemopreventive method. PMID:25337538

  4. Cyclooxygenase-1 and -2: Molecular Targets for Cervical Neoplasia

    PubMed Central

    Kim, Hee Seung; Kim, Taehun; Kim, Mi-Kyung; Suh, Dong Hoon; Chung, Hyun Hoon; Song, Yong Sang

    2013-01-01

    Cyclooxygenase (COX) is a key enzyme responsible for inflammation, converting arachidonic acid to prostaglandin and thromboxane. COX has at least two isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues for maintaining physiologic homeostasis, COX-2 is induced by inflammatory stimuli including cytokines and growth factors. Many studies have shown that COX-2 contributes to cancer development and progression in various types of malignancy including cervical cancer. Human papillomavirus, a necessary cause of cervical cancer, induces COX-2 expression via E5, E6 and E7 oncoproteins, which leads to prostaglandin E2 increase and the loss of E-cadherin, promotes cell proliferation and production of vascular endothelial growth factor. It is strongly suggested that COX-2 is associated with cancer development and progression such as lymph node metastasis. Many studies have suggested that non-selective COX-2 inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors might show anti-cancer activity in COX-2 -dependent and -independent manners. Two phase II trials for patients with locally advanced cervical cancer showed that celecoxib increased toxicities associated with radiotherapy. Contrary to these discouraging results, two phase II clinical trials, using rofecoxib and celecoxib, demonstrated the promising chemopreventive effect for patients with cervical intraepithelial neoplasia 2 or 3. However, these agents cause a rare, but serious, cardiovascular complication in spite of gastrointestinal protection in comparison with NSAIDs. Recent pharmacogenomic studies have showed that the new strategy for overcoming the limitation in clinical application of COX-2 inhibitors shed light on the use of them as a chemopreventive method. PMID:25337538

  5. CXC chemokine receptor 7 expression in cervical intraepithelial neoplasia

    PubMed Central

    TANG, TIAN; XIA, QINGJIE; XI, MINGRONG

    2016-01-01

    Cervical intraepithelial neoplasia (CIN), also known as transformation and dysplasia of cervical intraepithelial cells, is the precancerous lesion of squamous cell carcinoma. CXC chemokine receptor 7 (CXCR7) has been indicated in tumor development and metastasis of multiple malignancies or precancerous lesion. However, the protein expression and function of CXCR7 in different stages of human CIN remains unclear. The present study examined CXCR7 protein expression in cervical tissue samples from 34 patients, including 7 patients with normal cervical tissues (negative control), 10 patients with stage I of CIN (CIN I), 8 patients with CIN II and 9 patients with CIN III. Receiver operating characteristic curves (ROC) were established to evaluate the prognostic value of CXCR7 in differentiating various stages of CIN. Immunohistochemical staining showed that protein expression of CXCR7 was higher in CIN tissues compared with the normal cervical epithelium (P<0.05). High-grade CIN tissues expressed a higher level of CXCR7 compared to low-grade samples. The ROC curve of integral optical density analysis showed that CXCR7 could discriminate CIN I–III from normal cervical epithelium with 88.9% sensitivity and 71.4% specificity, and CIN II–III from the negative control and CIN I with 92.7% sensitivity and 50.0% specificity. ROC curve of area analysis also showed that CXCR7 could discriminate CIN I–III from normal cervical epithelium with 70.4% sensitivity and 100.0% specificity, and CIN II–III from the negative control and CIN I with 50.0% sensitivity and 90.0% specificity. An increase in CXCR7 expression may represent a novel predictor of CIN. The wide expression of CXCR7 in CIN also supports the assumption that CXCR7 plays a role in precancerous lesion progression, as well as proliferation, migration and angiogenesis. PMID:26870336

  6. High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia

    NASA Astrophysics Data System (ADS)

    Shin, Dongsuk

    Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.

  7. Current treatment options for management of anal intraepithelial neoplasia

    PubMed Central

    Weis, Stephen E

    2013-01-01

    Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects. PMID:23788834

  8. CpG island methylation profile of pancreatic intraepithelial neoplasia

    PubMed Central

    Sato, Norihiro; Fukushima, Noriyoshi; Hruban, Ralph H; Goggins, Michael

    2009-01-01

    Infiltrating adenocarcinoma of the pancreas is thought to develop through well-defined precursor lesions called pancreatic intraductal neoplasia (PanIN). Despite the exponential growth in our understanding of genetic events that characterize the progression of PanINs to invasive carcinoma, little is known about the role of epigenetic alterations in these precursor lesions. To define the timing and prevalence of methylation abnormalities during early pancreatic carcinogenesis, we investigated the CpG island methylation profile in the various grades of PanINs. Using methylation-specific PCR, we analyzed DNA samples from 65 PanIN lesions for methylation status of eight genes recently identified by microarray approach as aberrantly hypermethylated in invasive pancreatic cancer. Aberrant methylation at any of the eight genes was identified in 68% of all the PanIN lesions examined, and, notably, aberrant methylation was identified in more than 70% of the earliest lesions (PanIN-1A). The average number of methylated loci was 1.1 in PanIN-1A, 0.8 in PanIN-1B, 1.1 in PanIN-2, and 2.9 in PanIN-3 lesions (P = 0.01 for PanIN -3 vs earlier PanINs). Among the genes analyzed, NPTX2 demonstrated an increase in methylation prevalence from PanIN-1 to PanIN-2 (P = 0.0008), and from PanIN-2 to PanIN-3 for SARP2 (P = 0.001), Reprimo (P = 0.01), and LHX1 (P = 0.03). These results suggest that aberrant CpG island hypermethylation begins in early stages of PanINs, and its prevalence progressively increases during neoplastic progression. PMID:18157091

  9. COMPUTED TOMOGRAPHIC FEATURES OF PHARYNGEAL NEOPLASIA IN 25 DOGS.

    PubMed

    Carozzi, Gregorio; Zotti, Alessandro; Alberti, Monica; Rossi, Federica

    2015-11-01

    Computed tomography (CT) is commonly used to investigate head tumors in dogs, however little information is available for lesions of the pharyngeal area. The purpose of this multicentric, retrospective, cross-sectional study was to describe the CT findings in a sample of dogs with pathologically confirmed pharyngeal neoplasia and determine whether any CT features allowed differentiation of tumor type. Location of lesions, size and shape, margins, relationship with surrounding structures and vessels, attenuation characteristics and enhancement pattern, regional lymph node changes, and presence of metastasis were recorded by three observers (1 DECVDI). The effect of final diagnosis on each CT feature was tested. A total of 25 dogs were included: 15 with carcinomas, five sarcomas, four melanomas, and one lymphoma. The oropharynx and laryngopharynx were more frequently involved. Among tumor groups, lesions were of similar size, irregularly shaped, had ill-defined margins, and had moderate-to-marked heterogeneous contrast enhancement. Lysis of hyoid bones was recorded in two carcinomas and infiltration of the lingual artery occurred in one case. Marked medial retropharyngeal lymphoadenomegaly was recorded in 11 of 14 carcinomas, in all sarcomas and in two of four melanomas. The single lymphoma case showed ill-defined thickening of the oropharyngeal and laryngeal wall with retropharyngeal and mandibular lymphadenomegaly. Lung metastases were found in two of five sarcomas and two of four melanomas. Findings from the current study did not support the hypothesis that CT features could be used to predict pharyngeal tumor type in dogs. However, CT was helpful for determining mass extension, lymph node involvement, and distant metastatic spread. PMID:26173553

  10. Atrial Fibrillation and Colonic Neoplasia in African Americans

    PubMed Central

    Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z.; Ashktorab, Hassan

    2015-01-01

    Background Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. Methods We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. Results The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9–2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7–1.6, P = 0.7) were not significantly associated AF compared to control group. Conclusions AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors. PMID:26317627

  11. Medical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

    Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

    2014-01-01

    Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups. Authors’ conclusions Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored. PMID:21491403

  12. Diagnosing Ocular Surface Squamous Neoplasia in East Africa

    PubMed Central

    Nguena, Marie B.; van den Tweel, Jan G.; Makupa, William; Hu, Victor H.; Weiss, Helen A.; Gichuhi, Stephen; Burton, Matthew J.

    2014-01-01

    Objective To examine the reliability of clinical examination and in vivo confocal microscopy (IVCM) in distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. Design Case-control study. Participants Sixty individuals with conjunctival lesions (OSSN and benign) and 60 age-matched controls with normal conjunctiva presenting to Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Methods Participants were examined and photographed, and IVCM was performed. Patients with conjunctival lesions were offered excisional biopsy with histopathology and a human immunodeficiency virus (HIV) test. The IVCM images were read masked to the clinical appearance and pathology results. Images were graded for several specific features and given an overall categorization (normal, benign, or malignant). A group of 8 ophthalmologists were shown photographs of conjunctival lesions and asked to independently classify as OSSN or benign. Main Outcome Measures Comparison of the histopathology diagnosis with the clinical and IVCM diagnosis. Results Fifty-two cases underwent excisional biopsy with histopathology; 34 were on the OSSN spectrum, 17 were benign, and 1 was lymphoma. The cases and controls had comparable demographic profiles. Human immunodeficiency syndrome infection was more common in OSSN compared with benign cases (58.8% vs. 5.6%; odds ratio, 24.3, 95% confidence interval [CI], 2.8–204; P = 0.003). Clinically, OSSN lesions more frequently exhibited feeder vessels and tended to have more leukoplakia and a gelatinous appearance. Overall, the ophthalmologists showed moderate agreement with the histology result (average kappa = 0.51; 95% CI, 0.36–0.64). The masked grading of IVCM images reliably distinguished normal conjunctiva. However, IVCM was unable to reliably distinguish between benign lesions and OSSN because of an overlap in their appearance (kappa = 0.44; 95% CI, 0.32–0.57). No single feature was significantly more frequent in OSSN compared with benign lesions. The sensitivity and specificity of IVCM for distinguishing OSSN from benign conjunctival lesions were 38.5% and 66.7%, respectively. Conclusions In East Africa, conjunctival pathology is relatively common and can present significant diagnostic challenges for the clinician. In this study, neither clinical examination nor IVCM was found to reliably distinguish OSSN from benign conjunctival pathology because of an overlap in the features of these groups. Therefore, IVCM cannot currently replace histopathology, and management decisions should continue to rely on careful clinical assessment supported by histopathology as indicated. PMID:24321141

  13. The gene for multiple endocrine neoplasia type 1: recent findings.

    PubMed

    Marx, S J; Agarwal, S K; Heppner, C; Kim, Y S; Kester, M B; Goldsmith, P K; Skarulis, M C; Spiegel, A M; Burns, A L; Debelenko, L V; Zhuang, Z; Lubensky, I A; Liotta, L A; Emmert-Buck, M R; Guru, S C; Manickam, P; Crabtree, J S; Collins, F S; Chandrasekharappa, S C

    1999-07-01

    Multiple endocrine neoplasia type 1 (MENI) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MENI mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MENI gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy. PMID:10423035

  14. RETROSPECTIVE EVALUATION OF CASES OF NEOPLASIA IN A CAPTIVE POPULATION OF EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

    PubMed

    Olds, June E; Burrough, Eric R; Fales-Williams, Amanda J; Lehmkuhl, Aaron; Madson, Darin; Patterson, Abby J; Yaeger, Michael J

    2015-06-01

    Reports of neoplasia in Chiroptera species are rare. (6, 10) This retrospective study describes five types of neoplasia identified within a captive population of male Egyptian fruit bats (Rousettus aegyptiacus) housed in a zoo from 2004 through November of 2014. Tumor types identified include fibrosarcoma, cutaneous lymphoma, benign focal bronchioloalveolar neoplasm, anaplastic sarcoma, and sebaceous epithelioma. To the author's knowledge, aside from a recent report of focal brochioloalveolar adenoma, (8) these tumor types have not previously been described in the Rousettus species, nor in chiropterans in general. Based upon these findings and other recent publications regarding R. aegyptiacus, neoplasia does appear to be a significant cause of morbidity and mortality in captive members of this megachiropterid species. PMID:26056887

  15. Long-term management of ovarian neoplasia in two cockatiels (Nymphicus hollandicus).

    PubMed

    Keller, Krista A; Beaufrère, Hugues; Brandão, João; McLaughlin, Leslie; Bauer, Rudy; Tully, Thomas N

    2013-03-01

    Cockatiels (Nymphicus hollandicus) are commonly diagnosed with ovarian neoplasia. However, there is very little information regarding medical management of this disease condition and subsequent patient response. Long-term medical therapy of 2 cockatiels eventually diagnosed with ovarian neoplasia is described along with responses to the treatment regimens. Each bird had initial signs consistent with reproductive disease (chronic egg laying, ascites, and lethargy) and respiratory distress. The diagnosis of ovarian adenocarcinoma was confirmed on postmortem examination of both birds. The birds were conservatively managed by periodic coelomocentesis and gonadotropin-releasing hormone (GnRH) agonist administration for 9 and 25 months, respectively. A positive response to GnRH agonist therapy was documented in 1 of the 2 birds. These 2 cases demonstrate that periodic coelomocentesis with or without GnRH agonist therapy may be a viable option for the long-term management of ovarian neoplasia and reproductive-organ-associated ascites in cockatiels. PMID:23772456

  16. Cervical and Vulvar Intraepithelial Neoplasia after Treatment with Oral Isotretinoin for Severe Acne Vulgaris.

    PubMed

    Al Hallak, M N; Zouain, N

    2009-01-01

    Oral isotretinoin is the drug of choice for severe acne vulgaris, but its use is still controversial in preventing, treating or stopping the progression of the cervical intraepithelial neoplasia [6, 7, 8]. It induces cell differentiation, inhibits cell proliferation, stimulates host immune reaction, inhibits the oncogene expression, augments cell-mediated cytotoxicity, and induces apoptosis [5]. The isotretinoin has many side effects including teratogenicity. There is no previous report of developing cervical intraepithelial neoplasia (CIN) or vulvar intraepithelial neoplasia (VIN) after introducing oral isotretinoin to a patient. We are reporting a 37-year-old female with no risk factors for cervical cancer who had developed CIN-I and VIN-I during a 6-month treatment period of oral isotretinoin for her severe acne vulgaris. Interestingly, the patient had complete spontaneous pathologic-proven remission after stopping the isotretinoin. Further case reports are warranted to support this incidence. PMID:20652114

  17. Etiology, pathogenesis and epizootiology of hematopoietic neoplasia in the soft-shell clam, Mya arenaria

    SciTech Connect

    Paquette, G.E.

    1992-01-01

    Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus particles can be re-isolated and induce neoplasia. The activities of the RT are temperature dependent, found at 6[degrees]C, but not at 25[degrees]C and 37[degrees]C. The incidence rate for neoplasia in Narragansett Bay, Rhode Island was 7.7% and for combined other locations, 3.7% (26/699). HN was present in clams throughout the year at varying levels. The highest incidence occurred in October (11.5%); the lowest incidence in April (1.2%) and June (2.5%). The outcome of the disease depends on the water temperature and degree of severity of neoplasia in the clams. Death rate was greatest when water temperature was at 15[degrees]C (100%). High severity clams had the highest death rate (100%). Chronicity of persistent neoplasia occurred more at 10[degrees]C (19%) than at 6[degrees]C (15%) or 15[degrees]C (0%). Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. Neoplasia causes metabolic alteration in clams. Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. The time to remission was longer at 6[degrees]C than 10[degrees]C. Neoplasia causes metabolic alteration in clams. This shown by a significant increase in uric acid, asparatate transminase and triglycerides and a decrease in urea in the hemolymph. The cell membrane of neoplastic hemocytes also shows differences in their binding pattern to lectin than the normal hemocytes, indicating a change in cell surface glycoprotein probably induced by the retrovirus.

  18. Total vaginectomy for refractory vaginal intraepithelial neoplasia III of the vaginal vault

    PubMed Central

    Youn, Ju Hyun; Lee, Min Ah; Ju, Woong; Kim, Seoung Cheol

    2016-01-01

    Vaginal intraepithelial neoplasia III, is a relatively rare disease. Consequently standard treatments for this disease were not established until recently. Although several convenient methods, such as laser ablation, 5-fluorouracil topical injection, and radiation therapy, have been applied for treating these lesions, surgical treatments, including vaginectomy, have not yet been attempted, as they would likely be accompanied by technical difficulties and various complications. Herein, we report a case of refractory vaginal intraepithelial neoplasia III in the vaginal vault that was successfully treated with a total vaginectomy. PMID:26866041

  19. [Gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in patient with partial hydatidiform mole].

    PubMed

    Matos, Michelle; Ferraz, Leda; Lopes, Patrícia de Fátima; Lozoya, Consuelo; Amim Junior, Joffre; Rezende-Filho, Jorge; Braga, Antonio

    2015-07-01

    We report here a case of gestational trophoblastic neoplasia after spontaneous normalization of human chorionic gonadotropin in a patient with a partial hydatidiform mole. This is the second occurrence of this event to be reported and the first one with proven immunohistochemical evidence. Besides showing the treatment for this pregnancy complication, this case report discusses the possibility of reducing the duration of post-molar follow-up, as well as strategies for early recognition of gestational trophoblastic neoplasia after spontaneous remission of molar pregnancy. PMID:26247255

  20. A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma

    PubMed Central

    Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe

    2014-01-01

    Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870

  1. Multiple head and neck neoplasia following radiation for benign disease during childhood

    SciTech Connect

    Sirota, D.K.; Eden, A.R.; Biller, H.F.

    1988-06-01

    A woman received radiation therapy to the adenoids for benign disease at the age of 10 years and subsequently developed an adenocarcinoma of the middle ear, a parathyroid adenoma, and a papillary carcinoma of the thyroid gland in adulthood. This appears to be the first such case on record. The literature of neoplasia after head and neck irradiation is briefly reviewed.

  2. Proceedings From the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting

    PubMed Central

    Faro, Edited by Sebastian

    2006-01-01

    The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.

  3. A rare presentation of multiple endocrine neoplasia (MEN) type 2A syndrome

    PubMed Central

    Weledji, Elroy Patrick

    2015-01-01

    Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease. PMID:26858832

  4. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.

  5. A rare presentation of multiple endocrine neoplasia (MEN) type 2A syndrome.

    PubMed

    Weledji, Elroy Patrick

    2016-02-01

    Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease. PMID:26858832

  6. Clonal evolution in two patients with autoimmune disease and lymphoreticular neoplasia.

    PubMed

    Adam, M; Thorburn, M J; Gibbs, W N; Brooks, S E; Hanchard, B

    1970-06-01

    Two cases are described, one with proven lymphosarcoma and doubtful autoimmune disease, and the second with the reverse situation, in which circulating abnormal mononuclear cells showed PHA responsiveness and an abnormal chromosomal constitution (clonal evolution). These findings are discussed in the light of previous cytogenetic studies of lymphoreticular neoplasia and autoimmune disease and the relationship between these two conditions. PMID:4393772

  7. Limbal pseudoepitheliomatous hyperplasia mimicking ocular surface squamous neoplasia in palpebral vernal keratoconjunctivitis.

    PubMed

    Malhotra, Chintan; Jain, Arun K; Thapa, Bikram

    2013-01-01

    Purpose. Pseudoepitheliomatous hyperplasia at the limbus can mimic an ocular surface squamous neoplasia. It is an uncommon manifestation of vernal keratoconjunctivitis and has been reported previously in limbal VKC. It, however, has not been reported as a manifestation in the palpebral form of the disease and needs to be kept in the differential diagnosis of a limbal mass lesion in vernal keratoconjunctivitis. Case Report. We report the case of a 24 year old male patient having palpebral VKC and presenting with a papillomatous limbal mass with focal areas of keratinization mimicking an ocular surface squamous neoplasia. An excision biopsy was performed, and the specimen sent for histopathologywhich revealed features of pseudoepitheliomatous hyperplasia with no evidence of dysplasia or malignant transformation. The subepithelium revealed a dense plasma-rich inflammation. Discussion. We report this relatively uncommon presentation of limbal pseudoepitheliomatous hyperplasia mimicking an ocular surface squamous neoplasia in palpebral vernal keratoconjunctivitis. Wide excision as is required for an ocular surface neoplasia may thus be avoided if this entity is recognized in vernal keratoconjunctivitis. PMID:23840996

  8. Limbal Pseudoepitheliomatous Hyperplasia Mimicking Ocular Surface Squamous Neoplasia in Palpebral Vernal Keratoconjunctivitis

    PubMed Central

    Jain, Arun K.; Thapa, Bikram

    2013-01-01

    Purpose. Pseudoepitheliomatous hyperplasia at the limbus can mimic an ocular surface squamous neoplasia. It is an uncommon manifestation of vernal keratoconjunctivitis and has been reported previously in limbal VKC. It, however, has not been reported as a manifestation in the palpebral form of the disease and needs to be kept in the differential diagnosis of a limbal mass lesion in vernal keratoconjunctivitis. Case Report. We report the case of a 24 year old male patient having palpebral VKC and presenting with a papillomatous limbal mass with focal areas of keratinization mimicking an ocular surface squamous neoplasia. An excision biopsy was performed, and the specimen sent for histopathologywhich revealed features of pseudoepitheliomatous hyperplasia with no evidence of dysplasia or malignant transformation. The subepithelium revealed a dense plasma-rich inflammation. Discussion. We report this relatively uncommon presentation of limbal pseudoepitheliomatous hyperplasia mimicking an ocular surface squamous neoplasia in palpebral vernal keratoconjunctivitis. Wide excision as is required for an ocular surface neoplasia may thus be avoided if this entity is recognized in vernal keratoconjunctivitis. PMID:23840996

  9. THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALOMETHANES (THMS) IN THE DRINKING WATER

    EPA Science Inventory

    THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALO METHANES (THMs) IN THE DRINKING WATER
    Christopher Sistrunk and Tony DeAngelo, North Carolina Central University and US Environmental Protection Agency
    The THMs are the most widely distributed and the most co...

  10. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.

  11. Folate-genetics and colorectal neoplasia: What we know and need to know next

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTH...

  12. Measuring the size of neoplasia in colonoscopy using Depth-From-Defocus.

    PubMed

    Chadebecq, Françcois; Tilmant, Christophe; Bartoli, Adrien

    2012-01-01

    Colonoscopy is the reference medical examination for the diagnosis and treatment of neoplasia in gastroenterology. During the examination, the expert explores the colon cavity with a gastroscope in order to detect neoplasias - abnormal growths of tissue - and to diagnose which ones could be malignant. The Paris classification of superficial neoplastic lesions is the gold standard set of criteria for this type of diagnosis. One of the major criteria is the size. However, this is tremendously difficult to accurately estimate from images. This is because the absolute scale of the observed tissues is not directly conveyed in the 2D endoscopic image. We propose an image-based method to estimate the size of neoplasias. The core idea is to combine Depth-From-Focus (DFF) and Depth-From-Defocus (DFD). This allows us to recover the absolute scale by automatically detecting the blur/unblur breakpoint while the expert pulls the gastroscope away from a neoplasia. Our method is passive: it uses the image data only and thus does not require hardware modification of the gastroscope. We report promising experimental results on phantom and patient datasets. PMID:23366181

  13. Neoplasias mielodisplásicas o mieloproliferativas (PDQ)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocíticas crónicas o juveniles, y la LMC atípica.

  14. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development.

    PubMed

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders; Skakkebaek, Niels E; Main, Katharina M; Rajpert-De Meyts, Ewa

    2015-09-01

    Development of human gonads is a sex-dimorphic process which evolved to produce sex-specific types of germ cells. The process of gonadal sex differentiation is directed by the action of the somatic cells and ultimately results in germ cells differentiating to become functional gametes through spermatogenesis or oogenesis. This tightly controlled process depends on the proper sequential expression of many genes and signalling pathways. Disturbances of this process can be manifested as a large spectrum of disorders, ranging from severe disorders of sex development (DSD) to - in the genetic male - mild reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which are essentially the same precursor lesion but with different morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published since 2006. We present a model for pathogenesis of GCNIS/GDB in TDS/DSD, with the risk of malignancy determined by the presence of the testis-inducing Y chromosome and the degree of masculinisation. The associations between phenotype and the risk of neoplasia are likely further modulated in each individual by the constellation of the gene polymorphisms and environmental factors. PMID:26410164

  15. Spectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review

    PubMed Central

    Lauper, Julia M.; Krause, Alison; Vaughan, Thomas L.; Monnat, Raymond J.

    2013-01-01

    Background Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid (‘premature aging’) syndrome which is associated with an elevated risk of cancer. Objectives Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population. Methods We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates. Results We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia. Conclusions WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population. PMID:23573208

  16. The Early Detection of Pancreatic Cancer: What Will it Take to Diagnose and Treat Curable Pancreatic Neoplasia?

    PubMed Central

    Lennon, Anne Marie; Wolfgang, Christopher L.; Canto, Marcia Irene; Klein, Alison P.; Herman, Joseph M.; Goggins, Michael; Fishman, Elliot K.; Kamel, Ihab; Weiss, Matthew J.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.

    2014-01-01

    Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific, approaches for screening for curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. PMID:24924775

  17. Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model

    NASA Astrophysics Data System (ADS)

    Coghlan, Lezlee; Utzinger, Urs; Drezek, Rebekah A.; Heintzelmann, Doug; Zuluaga, Andres F.; Brookner, Carrie; Richards-Kortum, Rebecca R.; Gimenez-Conti, Irma; Follen, Michele

    2000-12-01

    Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350-370 nm excitation and 400-450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.

  18. Neoplasias mieloproliferativas y síndromes mielodisplásicos—Versión para profesionales de salud

    Cancer.gov

    Información del Instituto Nacional del Cáncer para profesionales de salud sobre el tratamiento de las neoplasias mieloproliferativas, así como referencias a estudios clínicos y otros temas relacionados.

  19. Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN).

    PubMed

    Küffer, R; Lombardi, T

    2002-02-01

    Oral precancerous lesions are traditionally classified as leukoplakia, erythroplakia, erythroleukoplakia, and distinguished from precancerous conditions. Major attention is focused on leukoplakia, and no distinction made whether dysplasia is or not present. Malignant transformation is a multistep process that should be approached also from the histological, and not merely from the clinical standpoint. Intraepithelial neoplasia, a notion created for the uterine cervix and already extended to other mucosae, should be adapted to the oral mucosa and used as diagnostic term. OIN (oral intraepithelial neoplasia) is not only a change in terminology, but also a progress in the unifying concept of precursors of squamous cell carcinoma, suppressing the useless discussion between severe dysplasia and carcinoma in situ. Furthermore, grading lesions as low or high grade OIN increases diagnostic consistency. OIN is suspected on three clinical patterns reflecting histological changes: mosaic, irregular keratosis, erythroplakia (or intermediate aspects), but dysplastic mucosa may also appear normal clinically. PMID:11854058

  20. The role of surgery in the management of gestational trophoblastic neoplasia.

    PubMed

    Doll, Kemi M; Soper, John T

    2013-07-01

    Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases. PMID:23803756

  1. Condylomata of the uterine cervix and koilocytosis of cervical intraepithelial neoplasia.

    PubMed Central

    Pilotti, S; Rilke, F; De Palo, G; Della Torre, G; Alasio, L

    1981-01-01

    In 202 women with koilocytotic atypia in cervical smears, 136 had predominantly small condylomata of the uterine cervix, and 66 had cervical intraepithelial neoplasia (CIN) of varying degree either with koilocytosis of the neoplasia or associated with condylomata. Koilocytosis correlated well with the histological diagnosis of condylomata, but occasionally it obscured the cytological evidence of CIN. Human papilloma virus particles were found in the cells of condylomata in 10 cases and in those of CIN II with koilocytosis in two cases of 21 examined ultrastructurally. There was evidence that the condyloma of the uterine cervix is a well-defined morphological entity and also that cytopathie changes similar to those seen in condylomata are present in some cases of CIN. Images PMID:6265503

  2. Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans.

    PubMed Central

    Kossakowska, A. E.; Huchcroft, S. A.; Urbanski, S. J.; Edwards, D. R.

    1996-01-01

    Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumours. In this study we have analysed the expression of five MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions of human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-11 (stromelysin 3) were most consistently expressed by carcinomas. Based on detection of either MMP-9 or MMP-11 mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequently, these results were compared with results for carcinomas of colon and lung and malignant non-Hodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-11 characterised all carcinomas as well as carcinomas in situ but was not detectable in NHL. Our data therefore argue that there are remarkably similar patterns of specific functions involved in ECM remodelling that correlate with malignancy in different human tumours of different histogenesis. However, MMP-11 expression is a characteristic of tumours of epithelial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-11 may play a regulatory role in the invasion and metastasis of carcinomas. Images Figure 1 PMID:8645587

  3. 2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia.

    PubMed

    Wood, Brent L; Arroz, Maria; Barnett, David; DiGiuseppe, Joseph; Greig, Bruce; Kussick, Steven J; Oldaker, Teri; Shenkin, Mark; Stone, Elizabeth; Wallace, Paul

    2007-01-01

    Immunophenotyping by flow cytometry has become standard practice in the evaluation and monitoring of patients with hematopoietic neoplasia. However, despite its widespread use, considerable variability continues to exist in the reagents used for evaluation and the format in which results are reported. As part of the 2006 Bethesda Consensus conference, a committee was formed to attempt to define a consensus set of reagents suitable for general use in the diagnosis and monitoring of hematopoietic neoplasms. The committee included laboratory professionals from private, public, and university hospitals as well as large reference laboratories that routinely operate clinical flow cytometry laboratories with an emphasis on lymphoma and leukemia immunophenotyping. A survey of participants successfully identified the cell lineage(s) to be evaluated for each of a variety of specific medical indications and defined a set of consensus reagents suitable for the initial evaluation of each cell lineage. Elements to be included in the reporting of clinical flow cytometric results for leukemia and lymphoma evaluation were also refined and are comprehensively listed. The 2006 Bethesda Consensus conference represents the first successful attempt to define a set of consensus reagents suitable for the initial evaluation of hematopoietic neoplasia. PMID:17803189

  4. Differential expression of circulating microRNAs according to severity of colorectal neoplasia.

    PubMed

    Ho, Gloria Y F; Jung, Hwa J; Schoen, Robert E; Wang, Tao; Lin, Juan; Williams, Zev; Weissfeld, Joel L; Park, Jung Y; Loudig, Olivier; Suh, Yousin

    2015-09-01

    There is a need to develop a colorectal cancer (CRC) screening test that is noninvasive, cost effective, and sensitive enough to detect preneoplastic lesions. This case-control study examined the feasibility of using circulating extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal neoplasia of various severity and hence for early detection of colorectal neoplasia. Archived serum samples of 10 normal controls and 31 cases, including 10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were profiled for circulating miRNAs using next-generation sequencing. Multiple linear regression, adjusting for age, gender, and smoking status, compared controls and the 3 case groups for levels of 175 miRNAs that met stringent criteria for miRNA sequencing analysis. Of the 175 miRNAs, 106 miRNAs were downregulated according to severity of neoplasia and showed a relative decrease in the expression from controls to nonadvanced adenoma to advanced adenoma to CRC (Ptrend < 0.05). Pairwise group comparisons showed that 39 and 80 miRNAs were differentially expressed in the advanced adenoma and CRC groups compared with the controls, respectively. Differences in miRNA levels between the nonadvanced adenoma group and controls were modest. Our study found that expression of many miRNAs in serum was inversely correlated with the severity of colorectal neoplasia, and differential miRNA profiles were apparent in preneoplastic cases with advanced lesions, suggesting circulating miRNAs could serve as potential biomarkers for CRC screening. PMID:25770825

  5. Loss of p53 enhances the induction of colitis-associated neoplasia by dextran sulfate sodium.

    PubMed

    Chang, Wen-Chi L; Coudry, Renata A; Clapper, Margie L; Zhang, Xiaoyan; Williams, Kara-Lynn; Spittle, Cynthia S; Li, Tianyu; Cooper, Harry S

    2007-11-01

    Loss of p53 function is an early event in colitis-associated neoplasia in humans. We assessed the role of p53 in a mouse model of colitis-associated neoplasia. Colitis was induced in p53-/-, p53+/- and p53+/+ mice using three or four cycles of dextran sulfate sodium (DSS) followed by 120 days of water. Mice were examined for incidence, multiplicity and types of neoplastic lesions. Lesions were examined for mutations in beta-catenin (exon 3), K-ras (codons 12/13) and p53 (exons 5-8) by sequencing and for cellular localization of beta-catenin by immunohistochemistry. The incidence of neoplastic lesions was 57, 20 and 20% in p53-/-, p53+/- and p53+/+ mice, respectively (P = 0.013). p53-/- mice had a greater number of total lesions (P < 0.0001), cancers (P = 0.001) and dysplasias (P = 0.009) per mouse than either p53+/- or p53+/+ mice. Flat lesions were associated with the p53-/- genotype, whereas polypoid lesions were associated with the p53+/- and p53+/+ genotypes (P < 0.0001). beta-Catenin mutations were present in 75% of lesions of p53+/+ mice and absent in lesions from p53-/- mice (P = 0.055). Nuclear expression of beta-catenin was seen only in polypoid lesions (91%). No K-ras or p53 mutations were detected. These data indicate that loss of p53 enhances the induction of colitis-associated neoplasia, particularly flat lesions, and dysregulation of beta-catenin signaling plays an important role in the formation of polypoid lesions in this mouse model. As observed in humans, p53 plays a protective role in colitis-associated neoplasia in the DSS model. PMID:17557903

  6. Clinical Inquiry: Does qHPV vaccine prevent anal intraepithelial neoplasia and condylomata in men?

    PubMed

    Shum, Johnny; Kelsberg, Gary; Safranek, Sarah

    2015-09-01

    Yes. Quadrivalent human papillomavirus (qHPV) vaccine reduces rates of anal intraepithelial neoplasia (AIN) by 50% to 54%, and persistent anal infection by 59%, associated with the 4 types of HPV in the vaccine (6, 11, 16, and 18) in young men who have sex with men (MSM); it also reduces external genital lesions by 66%, and persistent HPV infection associated with the same 4 HPV types by 48 to 59% in all young men, heterosexual men, and MSM. PMID:26546954

  7. Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.

    PubMed

    Owston, Michael A; Ramsay, Edward C; Rotstein, David S

    2008-12-01

    A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids. PMID:19110704

  8. Is there any association between hormonal contraceptives and cervical neoplasia in a poor Nigerian setting?

    PubMed Central

    Ajah, Leonard Ogbonna; Chigbu, Chibuike Ogwuegbu; Ozumba, Benjamin Chukwuma; Oguanuo, Theophilus Chimezie; Ezeonu, Paul Olisaemeka

    2015-01-01

    Background The association between hormonal contraception and cervical cancer is controversial. These controversies may hamper the uptake of hormonal contraceptives. Objective To determine the association between hormonal contraceptives and cervical neoplasia. Materials and methods This was a case-control study in which Pap-smear results of 156 participants on hormonal contraceptives were compared with those of 156 participants on no form of modern contraception. Modern contraception is defined as the use of such contraceptives as condoms, pills, injectables, intrauterine devices, implants, and female or male sterilization. Those found to have abnormal cervical smear cytology results were subjected further to colposcopy. Biopsy specimens for histology were collected from the participants with obvious cervical lesions or those with suspicious lesions on colposcopy. The results were analyzed with descriptive and inferential statistics at a 95% level of confidence. Results A total of 71 (45.5%), 60 (38.5%), and 25 (16.0%) of the participants on hormonal contraceptives were using oral contraceptives, injectable contraceptives, and implants, respectively. Cervical neoplasia was significantly more common among participants who were ?35 years old (6% versus 1%, P<0.0001), rural dwellers (6% versus 3.5%, P<0.0001), unmarried (7.6% versus 3.5%, P<0.0001), unemployed (6.8% versus 3.5%, P<0.0001), less educated (6% versus 3.8%, P<0.0001), and had high parity (6.8% versus 3.6%, P<0.0001). There was no statistical significant difference in cervical neoplasia between the two groups of participants (7 [4.5%] versus 6 [3.8%], P=1.0). Conclusion There was no association between hormonal contraceptives and cervical neoplasia in this study. PMID:26251619

  9. Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

    SciTech Connect

    Borowsky, A D; Dingley, K; Ubick, E; Turteltaub, K; Cardiff, R D; DeVere-White, R

    2006-06-01

    2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.

  10. Synchronous Nesidioblastosis, Endocrine Microadenoma, and Intraductal Papillary Mucinous Neoplasia in a Man Presenting With Hyperinsulinemic Hypoglycemia.

    PubMed

    De Sousa, Sunita M C; Haghighi, Koroush S; Qiu, Min Ru; Greenfield, Jerry R; Chen, Daniel L T

    2016-01-01

    Herein, we report the first case of concomitant nesidioblastosis, pancreatic neuroendocrine tumor, and intraductal papillary mucinous neoplasia. The combination is significant as each of these pathological entities is independently very rare. The patient was a 33-year-old man who presented with symptomatic hyperinsulinemic hypoglycemia and no risk factors for pancreatic disease. Abdominal imaging showed an isolated 12 mm pancreatic lesion, whilst selective arterial calcium stimulation testing demonstrated multiple territories of insulin excess. He proceeded to subtotal pancreatectomy. Histopathology revealed an endocrine microadenoma, ? and ? cell nesidioblastosis, and multifocal intraductal papillary mucinous neoplasia. The endocrine microadenoma and nesidioblastosis stained for insulin, suggesting both likely contributed to hypoglycemia. Glucagon immunohistochemistry was also positive, though there were no clinical features of glucagon excess. Hypoglycemia resolved postoperatively. This case and other evidence from the literature suggest that hyperplasia and neoplasia may occur sequentially in the pancreas, and that endocrine and exocrine tumorigenesis may be linked in some individuals. Further study is required to identify a unifying mechanism, and to elucidate potential ramifications in the management of patients with pancreatic neoplasms. PMID:26658039

  11. Coexistent familial nonmultiple endocrine neoplasia medullary thyroid carcinoma and papillary thyroid carcinoma associated with RET polymorphism.

    PubMed

    Gul, Kamile; Ozdemir, Didem; Ugras, Serdar; Inancli, Serap S; Ersoy, Reyhan; Cakir, Bekir

    2010-07-01

    Familial nonmultiple endocrine neoplasia medullary thyroid cancer accounts for 10% to 15% of hereditary medullary thyroid carcinoma and is characterized by lack of accompanying endocrine or nonendocrine diseases. Simultaneous occurrence of medullary and papillary thyroid carcinoma in the same patient is rare and known as collision tumor. Here, the authors present familial nonmultiple endocrine neoplasia medullary thyroid cancer in 4 sisters, all having RET proto-oncogene polymorphism in exon 15 at codon 904 and 2 having additional polymorphism in exon 13 at codon 769. The index case had concomitant medullary and papillary thyroid carcinomas, which are suggested to be completely different tumors in terms of incidence, cell origin, histopathologic features and prognosis. Histopathologically, she also had Hashimoto thyroiditis in the remaining thyroid tissue and medullary thyroid carcinoma metastasis in 3 cervical lymph nodes. This case is the first in the literature to report coexistent familial nonmultiple endocrine neoplasia medullary thyroid cancer and papillary thyroid carcinoma related with a RET polymorphism (S904S in exon 15). PMID:20463576

  12. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review.

    PubMed

    Sharp, Linda; Little, Julian

    2004-03-01

    Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested. PMID:14977639

  13. Combination of Paris and Vienna Classifications may Optimize Follow-Up of Gastric Epithelial Neoplasia Patients

    PubMed Central

    Hu, Wen; Ai, Xin-Bo; Zhu, Yi-Miao; Han, Tie-Mei; Shen, Bo; Pan, Wen-Sheng

    2015-01-01

    Background The aim of this study was to evaluate the efficiency of the combination of Paris and Vienna classifications in a follow-up study of gastric epithelial neoplasia (GEN) patients. Material/Methods This study was conducted between January 2003 and September 2010, during which 170 biopsy-proven GEN patients were followed up by gastroenterologists and pathologists according to our follow-up regimen (modified Vienna classification). Results In total, 161 patients with low-grade neoplasia (LGN) and 9 patients with high-grade neoplasia (HGN) were randomly enrolled in our study. Eighteen patients with depressed appearance were observed, of which 9 patients had HGN and 9 patients had low-grade dysplasia (LGD). Three patients with type 0-IIa were observed with low-grade adenoma (LGA), and type 0–I was observed in 2 patients with LGN. Endoscopic or surgical treatments were performed to avoid potential malignancy or bleeding. Two patients with ulcer lesions, 2 patients with non-depressed type 0 appearance, and 3 patients without visible lesions were shown to have higher-grade lesions during follow-up. The misdiagnosis rate of forceps biopsy – 62.07% – was determined by comparing pre- and post-resection diagnoses of 29 patients. Conclusions The combination of the Paris and Vienna classifications for GEN may optimize the follow-up routines for patients with suspicious precancerous lesions and may significantly improve the detection of early gastric cancer (EGC) while helping gastroenterologists select the best therapy option. PMID:25841675

  14. Familial aggregation of diabetes and hypertension in a case-control study of colorectal neoplasia.

    PubMed

    Brauer, Paula M; McKeown-Eyssen, Gail E; Jazmaji, Vartouhi; Logan, Alexander G; Andrews, David F; Jenkins, David; Marcon, Norman; Saibil, Fred; Cohen, Lawrence; Stern, Hartley; Baron, David; Greenberg, Gordon; Diamandis, Eleftherios; Kakis, Gary; Singer, William; Steiner, George

    2002-10-15

    Familial aggregation of diseases potentially associated with metabolic syndrome (diabetes mellitus, hypertension, and cardiovascular diseases) was assessed in a colonoscopy-based case-control study of colorectal neoplasia in Toronto and Ottawa, Canada, in 1993-1996. Each familial disease was analyzed by logistic regression using generalized estimating equations. Case probands had incident adenomatous polyps (n = 172) or incident (n = 25) or prevalent (n = 132) colorectal cancer (CRC), while control probands (n = 282) had a negative colonoscopy and no history of CRC or polyps. Significant effect modification was evident in the data, with the strongest positive associations between familial diabetes and colorectal neoplasia among older probands with symptoms (parents: odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.2, 4.8; siblings: OR = 5.8, 95% CI: 2.6, 13.3). Familial hypertension was also associated with colorectal neoplasia among probands with symptoms (OR = 1.7, 95% CI: 1.1, 2.6). In stratified analyses, familial diabetes, hypertension, and stroke were positively associated with adenomatous polyps in subgroups of probands who were older and/or had symptoms, while only familial diabetes was possibly associated with CRC. Associations in other proband groups may have been obscured by high cumulative incidence of parental CRC. Family studies are needed to understand the contribution of specific environmental and genetic factors in accounting for the disease aggregations. PMID:12370158

  15. Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia.

    PubMed Central

    Knowles, D. M.

    1989-01-01

    The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 6 Figure 7 PMID:2495724

  16. Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia.

    PubMed

    Knowles, D M

    1989-04-01

    The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2495724

  17. p16, Ki-67, and BD ProExC immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia.

    PubMed

    Walts, Ann E; Bose, Shikha

    2009-07-01

    p16, Ki-67, and BD ProExC (TriPath Imaging, Inc., Burlington, NC) have each been shown to be helpful adjuncts in the diagnosis and grading of human papillomavirus-associated cervical intraepithelial neoplasia. However, no clear guidelines are available regarding their use in routine practice. This study was designed to evaluate the efficacy of the 3 stains alone and in combinations to determine the most useful strategy in the diagnosis of cervical intraepithelial neoplasia and provide guidance in instances with discordant staining patterns. Serial sections of 136 formalin-fixed paraffin-embedded cervical samples with consensus diagnoses of 39 benign-reactive, 46 low-grade cervical intraepithelial neoplasia (CIN I/human papillomavirus), and 51 high-grade cervical intraepithelial neoplasia (CINII/III) were immunostained using p16, Ki-67, and BD ProExC antibodies. Results of high-risk human papillomavirus testing were available in 70 cases. Immunostaining patterns were designated as negative, intermediate, and strongly positive based on the patterns observed most commonly in benign-reactive, low-grade cervical intraepithelial neoplasia, and high-grade cervical intraepithelial neoplasia lesions, respectively. A concordant staining pattern with all 3 stains correctly identified benign-reactive, low-grade cervical intraepithelial neoplasia, and high-grade cervical intraepithelial neoplasia cases. p16 was the most sensitive and specific individual stain (sensitivity, 33%; specificity, 93%; positive predictive value [PPV], 81%; negative predictive value [NPV], 58%). Performing all 3 immunostains and using concordant results of any 2 improved diagnostic accuracy (sensitivity, 35%; specificity, 98%; PPV, 93%; NPV, 67%). However, a significant proportion of low-grade cervical intraepithelial neoplasia cases showed aberrant staining patterns with 52% staining negative and 9% staining strongly positive. Low-grade cervical intraepithelial neoplasia cases with the negative staining pattern were more likely to be negative for high-risk human papillomavirus, whereas those showing the strongly positive staining pattern were high-risk human papillomavirus positive. Performing p16 and BD ProExC initially followed by Ki-67 only when p16 and BD ProExC yielded discordant results provided similar diagnostic accuracy at reduced cost because only one third of the cases required the additional stain. PMID:19269017

  18. Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett's-associated neoplasia

    NASA Astrophysics Data System (ADS)

    Thekkek, Nadhi; Lee, Michelle H.; Polydorides, Alexandros D.; Rosen, Daniel G.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2015-05-01

    Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett's-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett's-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, or esophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope (HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC=0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance.

  19. Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia.

    PubMed

    Litster, Annette L; Sorenmo, Karin U

    2006-06-01

    Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/subcutaneous head and trunk. Stage 1a was the most common tumour stage at first diagnosis (n=20), followed by stage 4 (both stage 4a and stage 4b; n=10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n=30) and those with tumours involving the spleen or lymph nodes (n=11) showed longer survival times for the cutaneous-only group (P=0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n=6) or a single tumour (n=19), cats with single tumours survived longer than those with multiple tumours (P=0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. PMID:16476559

  20. Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

    NASA Astrophysics Data System (ADS)

    Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

    2008-02-01

    Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

  1. HPV-type distribution and reproducibility of histological diagnosis in cervical neoplasia in Poland.

    PubMed

    Nowakowski, Andrzej; de Souza, Sabrina Collas; Jach, Robert; Rosillon, Dominique; Ksi??ek, Alicja; Holl, Katsiaryna

    2015-07-01

    This study was performed to assess attribution of high grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) to human papillomavirus (HPV) genotypes and secondarily to assess reproducibility of HG-CIN/ICC diagnosis obtained in Poland. Formaldehyde fixed, paraffin embedded blocks of HG-CIN/ICC from two distant institutions were sent to a central laboratory together with original histological diagnoses. Central/expert review of histopathological specimens was performed and agreement between local and central/expert diagnoses was calculated. HPV detection and genotyping in the samples was carried out with the use of SPF10-LiPA25 technology. Results were analyzed for 205 HG-CIN and 193 ICC cases with centrally confirmed diagnoses. Kappa coefficients and 95 % confidence intervals for HG-CIN and ICC diagnoses were: 0.13 (0.09;0.17) and 0.19 (0.11;0.26) respectively. Cohen's kappa coefficients for lesions with representative number of samples ranged from 0.01 for cervical intraepithelial neoplasia grade 2 to 0.75 for adenocarcinoma. HPV DNA was detected in 96.1 and 91.2 % of the confirmed HG-CIN and ICC specimens respectively. HPV positive HG-CIN was most commonly attributed to HPV types: 16 (62.8), 33 (7.8), 31 (6.6), 52 (3.7), 45 (2.6) and 58 (2.6 %). HPV positive ICC was most commonly attributed to HPV types: 16 (72.1), 18 (10.8), 33 (5.7), 45 (3.4) and 31 (1.7 %). Reproducibility of histological diagnosis of HG-CIN/ICC obtained in Poland generally increases with the severity of lesion and is lowest for cervical intraepithelial neoplasia grade 2 and highest for adenocarcinoma. Over 80 % of ICC cases are vaccine-preventable in Poland. PMID:25547828

  2. Genetic Variation in the Lipoxygenase Pathway and Risk of Colorectal Neoplasia

    PubMed Central

    Kleinstein, Sarah E.; Heath, Laura; Makar, Karen W.; Poole, Elizabeth M.; Seufert, Brenna L.; Slattery, Martha L.; Xiao, Liren; Duggan, David J.; Hsu, Li; Curtin, Karen; Koepl, Lisel; Muehling, Jill; Taverna, Darin; Caan, Bette J.; Carlson, Christopher S.; Potter, John D.; Ulrich, Cornelia M.

    2013-01-01

    Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with non-steroidal anti-inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population-based case-control studies of colon cancer (1424 cases/1780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wildtype=5, OR>5/≥5=0.42, 95% CI 0.20-0.92; p=0.01). Four SNPs in FLAP (rs17239025), ALOX 12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at p≤0.05. One SNP in FLAP (rs12429692) was associated with adenoma risk. A false discovery rate (FDR) was applied to account for false positives due to multiple testing; the ALOX15 associations were noteworthy at 25% FDR. Colorectal neoplasia risk appeared to be modified by NSAID use in individuals with variant alleles in FLAP and ALOX15. One noteworthy interaction (25% FDR) was observed for rectal cancer. Genetic variability in arachidonate lipoxygenases may affect risk of colorectal neoplasia, particularly for rectal cancer. Additionally, genetic variability in FLAP and ALOX15 may modify the protective effect of NSAID use against colorectal neoplasia. PMID:23404351

  3. Diagnostic yield of non-guided flexible bronchoscopy for peripheral pulmonary neoplasia

    PubMed Central

    Labbé, Catherine; Beaudoin, Stéphane; Martel, Simon; Delage, Antoine; Joubert, Philippe; Drapeau, Christine; Provencher, Steeve

    2015-01-01

    Background The role of conventional bronchoscopy for peripheral pulmonary neoplasia remains controversial. We aimed to assess the diagnostic yield and the added value of non-guided bronchial aspiration, bronchoalveolar lavage (BAL), and brushing for the diagnosis of pulmonary neoplasia not visible endoscopically. Methods We retrospectively assessed 207 consecutive patients with a final diagnosis of peripheral lung malignancy who underwent bronchoscopy with non-guided aspiration, brushing, and BAL as their initial evaluation. The influence of clinical and radiological factors on diagnostic yield was assessed using univariate logistic regression analyses. Results The overall sensitivity of non-guided bronchoscopy was 25.6%, whereas sensitivities for bronchial aspiration, BAL, and brushing were 14.2%, 11.6%, and 16.5%, respectively. Younger age, larger lesion, central/intermediate distance from the hilum, presence of a bronchus sign, and higher standardized uptake value (SUV) on positron emission tomography scan were predictors of a higher diagnostic yield. Conversely, forced expiratory volume in one second, fellow implication in the procedure, and tumor histology did not influence sensitivity. The overall sensitivity of bronshoscopy was >40% for tumors >4?cm, located in the central/intermediate thirds of the lung, showing a bronchus sign, with an SUV >12 or occurring in patients <50 years of age. Conversely, the sensitivity was <10% for tumors <2?cm, located peripherally or with an SUV <4. Conclusion Neoplasia characteristics may help targeting situations in which conventional bronchoscopy could be used as the initial diagnostic procedure when advanced techniques are unavailable. However, advanced diagnostic tools should probably be proposed as the initial modality for the diagnosis of peripheral malignant lesions when available. PMID:26273409

  4. Minichromosome maintenance complex component 7 has an important role in the invasion of papillary urothelial neoplasia

    PubMed Central

    GUAN, BINGXIN; WANG, XIAOYING; YANG, JINGYAN; ZHOU, CHENGJUN; MENG, YAN

    2015-01-01

    The aims of the present study were to investigate the expression of minichromosome maintenance complex component 7 (MCM7) and determine its association with tumor proliferation and invasion in pathological tumor (pT)a and pT1 papillary urothelial neoplasia. The MCM7, MCM3 and Ki67 proteins were detected in 154 cases of urothelial neoplasia using immunohistochemical analysis. The expression of MCM7 significantly increased (P<0.001) as the pathological stage and grade progressed between inverted papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), pTa tumor and pT1 tumor. However, no statistically significant difference in MCM7 staining was observed between low-grade pTa tumors and PUNLMP (P=0.2294). In contrast to MCM7, MCM3 was highly expressed in all stages of urothelial neoplasia, with no statistically significant differences observed between the tumor types (P=0.2993, 0.3885 and 0.8489 for pTa tumors, PUNLMP and inverted papiloma, respectively). Furthermore, MCM7 expression was elevated with increased tumor grade and was positively correlated with Ki67 expression (rs=0.9106, P<0.001). However, MCM3 expression was not correlated with MCM7 or Ki67 expression (rs=0.0734, P=0.3657 and rs=0.0638, P=0.4318, respectively). In conclusion, MCM7 overexpression may simultaneously promote tumor proliferation and invasion. Furthermore, it may be a reliable marker for the pathological differential diagnosis of pTa and pT1 papillary urothelial neoplasms; therefore, MCM7 expression may be used to predict tumor prognosis and behavior. PMID:26622601

  5. Adherence to therapy for Barrett’s esophagus-associated neoplasia

    PubMed Central

    Cassani, Lisa; Slaughter, James C

    2015-01-01

    Objectives Multiple endoscopic sessions may be necessary for treatment and surveillance of Barrett’s esophagus (BE)-associated neoplasia. Adherence to an endoscopic therapeutic regimen is important for longitudinal management of BE. The objective of this study was to identify the factors associated with adherence to therapy for BE-associated neoplasia. Methods We retrospectively identified patients with BE whom were referred to a tertiary center for endoscopic mucosal resection (EMR) or radiofrequency ablation (RFA) between 2009 and 2012. Demographic and clinical data were extracted from the medical record. Results We had 69 subjects meet our inclusion criteria. Referral diagnosis was low-grade dysplasia in 9 (13%) subjects, high-grade dysplasia in 33 (48%) subjects and adenocarcinoma in 26 (38%) subjects. The majority (55%) lived more than 100 miles from the treatment center. The primary third-party payer was US Medicare for 54% of the subjects and private insurance for 36% of them; 45% of the subjects were seen in the clinic by the treating endoscopist, prior to endoscopic therapy and 71% underwent EMR as the initial treatment, while 29% underwent RFA without prior EMR. We found that 72% of subjects were adherent to therapy, including: 23 (33%) completing endoscopic therapy with documented post-treatment surveillance, 18 (26%) with ongoing endoscopic therapy, and 9 (13%) whom underwent esophagectomy. Subjects seen in gastroenterology clinical consultation were significantly more likely to demonstrate adherence than those referred for open access endoscopy (Lasso OR 2.31). Conclusions Patients seen in a clinical consultation prior to endoscopic therapy for BE-associated neoplasia were more likely to demonstrate treatment adherence, compared to patients referred for open-access endoscopy. A clinic visit prior to therapy may define expectations regarding treatment course and increase the likelihood of patient adherence.

  6. Mapping of multiple intestinal neoplasia (Min) to proximal chromosome 18 of the mouse

    SciTech Connect

    Luongo, C.; Gould, K.A.; Moser, A.R. ); Su, Likuo; Kinzler, K.W.; Vogelstein, B. ); Dietrich, W.; Lander, E.S. )

    1993-01-01

    The Min (multiple intestinal neoplasia) mutation of the mouse has been mapped by analyzing the inheritance of restriction fragment length polymorphisms and simple sequence length polymorphisms in progeny from two intraspecific crosses segregating for the Min mutation. Min, a mutant allele of Apc, the mouse homo- log of the human APC (adenomatous polyposis coli) gene, maps to proximal chromosome 18. The synteny between Apc and Mcc, the mouse homolog of the human MCC (mutated in colorectal cancer) gene, is conserved between mouse and human, although the gene order in the Apc to Mcc interval is different from that in the APC to MCC interval. 29 refs., 3 figs.

  7. Early presentation of metastatic medullary carcinoma in multiple endocrine neoplasia, type IIA: implications for therapy.

    PubMed

    Gill, J R; Reyes-Múgica, M; Iyengar, S; Kidd, K K; Touloukian, R J; Smith, C; Keller, M S; Genel, M

    1996-09-01

    A girl 5 years 11 months of age, belonging to an extensive kindred with multiple endocrine neoplasia, type IIA (MEN IIA), was found to have multifocal medullary thyroid carcinoma with metastasis in one paraglandular lymph node after positive findings on a calcium-pentagastrin stimulation test. Her sister, 3 years 8 months of age, also had an elevated calcitonin level, and thyroidectomy revealed C-cell hyperplasia and a focus of medullary thyroid carcinoma. These two cases underscore the need for prophylactic thyroidectomies in MEN IIA patients as young as 5 years of age and strict yearly provocative screening beginning at age 1 year. PMID:8804341

  8. Streptococcus bovis infectious endocarditis and occult gastrointestinal neoplasia: experience with 25 consecutive patients treated surgically.

    PubMed

    Alozie, Anthony; Köller, Kerstin; Pose, Lumi; Raftis, Maximilian; Steinhoff, Gustav; Westphal, Bernd; Lamprecht, Georg; Podbielski, Andreas

    2015-01-01

    To assess the prevalence of gastrointestinal neoplasia in patients with Streptococcus bovis infectious endocarditis we performed a retrospective cohort analysis of all episodes of S. bovis infectious endocarditis treated at our institution between January 2000 through December 2014. Twenty-five patients were identified for this purpose. 12/25 patients received colonoscopy and 1/25 of the patients was assessed with CT colonography. Of the 13 who underwent colonic assessment, 11 were diagnosed with colonic neoplasms at different stages of development. In the absence of any strong contraindication, gastroenteroscopic evaluation in all patients diagnosed with S. bovis infectious endocarditis should be pursued. PMID:26473016

  9. A historical appreciation of bronchopulmonary neuroendocrine neoplasia: resolution of a carcinoid conundrum.

    PubMed

    Modlin, Irvin M; Bodei, Lisa; Kidd, Mark

    2014-08-01

    In the three-quarters of a century that have elapsed since the first description of a bronchial carcinoid, the field has progressed from serendipitous radiological or bronchoscopic diagnosis to computed tomography, magnetic resonance imaging, and somatostatin receptor imaging identification. Similarly, pathologic techniques have advanced from a naïve assessment of neoplasia to a delineation of several tumor subtypes and an understanding of the neuroendocrine basis of the disease process. A key unresolved question is the identification of the genetic and environmental activators that are responsible for the initiation of pulmonary neuroendocrine cell proliferation and neoplastic transformation. PMID:25065925

  10. Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).

    PubMed Central

    Morrison, P J; Nevin, N C

    1996-01-01

    Multiple endocrine neoplasia type 2B (MEN 2B), or the mucosal neuroma syndrome, is an autosomal dominant hamartoneoplastic syndrome. Features include multiple mucosal neuromas, phaeochromocytoma, medullary thyroid carcinoma, and Marfanoid body habitus with a characteristic dysmorphic facies. The gene responsible is the receptor tyrosine kinase (RET) proto-oncogene on chromosome 10. The mutational spectrum of MEN 2B is remarkably narrow, with over 95% of cases being caused by a single methionine to threonine substitution in the intracellular tyrosine kinase domain. Recent biochemical evidence suggests that this mutation alters the substrate specificity of intracellular signal transduction. Images PMID:8880581

  11. Influence of disseminated neoplasia, trematode infections and gametogenesis on surfacing and mortality in the cockle Cerastoderma edule.

    PubMed

    Morgan, E; O'Riordan, R M; Kelly, T C; Culloty, S C

    2012-02-17

    Cerastoderma edule is a widely distributed bivalve mollusc, commercially exploited throughout Europe and is also an important food source for birds and crustaceans. Recently, mass surfacing and mortalities of cockles have been observed and reported at sites in Ireland and elsewhere, particularly in the summer months. One such site is Flaxfort Strand, Courtmacsherry Bay, County Cork, Ireland, an important feeding area used by many seabirds during the summer months. For the past few years large numbers of surfaced cockles have been observed at the site in a moribund condition. Samples of cockles from this area were collected over the summer months and their health status assessed. Cockles that had surfaced (moribund) and those still buried in the sediment were quantified and screened: sex, gonadal maturity and size class of cockles were also determined. Disseminated neoplasia and trematodes were observed in screened cockles. The most significant finding during the study was that mortalities and surfacing of cockles was related to a greater incidence of disseminated neoplasia. No neoplasia was observed in the smallest and largest size classes. There was a significantly higher prevalence of neoplasia in moribund cockles than in buried cockles, whereas in both groups a similar concentration of trematode metacercariae was observed in the screened tissues. Also, most of the cockles that had surfaced were either in the process of spawning or were spent. Overall a much larger percentage of moribund cockles exhibited both trematode infections plus neoplasia compared with buried cockles. A combination of the presence of neoplasia and trematodes, along with stress related to spawning, may immunocompromise the cockless, causing the animals to surface and become moribund. PMID:22422131

  12. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions.

    PubMed

    Clapper, Margie Lee; Cooper, Harry Stanley; Chang, Wen-Chi Lee

    2007-09-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) - induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the presence of inflammation and assess the ability of select agents to inhibit this process. Cyclic administration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological features that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen (azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc), p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a preventable disease. PMID:17723178

  13. Implementation of a program to improve the quality of colonoscopy increases the neoplasia detection rate: a prospective study

    PubMed Central

    Viola, Luis Alberto; Cassella, Federico; Wonaga, Andrés; Arnao Dellamea, Gloria; Di Paola, Leandro; Ubeira Salim, Rodrigo; Fernández, José Luis

    2016-01-01

    Background and study aims: Endoscopists worldwide have been encouraged to report quality indicators in order to evaluate their performance. We aimed to determine whether a program to improve the quality of colonoscopy results in better rates of neoplasia detection. Patients and methods: This is a prospective study set in a private endoscopy center. From May 2009 to March 2010, we evaluated 1573 consecutive colonoscopies (group 1). After the implementation of a quality program, from February 2011 to January 2012, we prospectively evaluated 1583 colonoscopies (group 2). Our quality-enhancing intervention consisted of instructing both patients and endoscopists. We measured the cecal intubation rate and the neoplasia detection rate. Overall neoplasias, high-risk adenomas, carcinomas, right colon adenomas, and adenomas detected in screening studies were analyzed. Results: Cecal intubation was documented in 1384 cases from group 1 (88 %) and 1534 from group 2 (96.9 %) (P < 0.0001). The neoplasia detection rates in groups 1 and 2 were, respectively: neoplasias 288 (18.3 %) and 427 (27 %) (P < 0.0001), high-risk adenomas 76 (4.8 %) and 142 (9 %) (P < 0.0001), carcinomas 16 (1 %) and 21 (1.3 %) (P = 0.52), right colon adenomas 112 (7.1 %) and 154 (9.7 %) (P = 0.01), and adenomas 141 (16.5 %) and 233 (28 %) (P < 0.0001). Conclusions: Implementation of a quality program improves the neoplasia detection rate. Because of the small number of cancerous lesions found in both groups, we were unable to identify differences in the carcinoma detection rate. PMID:26793787

  14. Canine neoplasia

    PubMed Central

    Prier, J. E.; Brodey, R. S.

    1963-01-01

    The authors review current knowledge of spontaneous neoplasms in the dog. The prevalence of certain types of canine tumour has been studied, and comparisons have been made with the occurrence of similar neoplasms in man. Where there are appropriate analogies between the two species, the dog with spontaneous tumours can be used for studies that are not practicable in man. Nutritional and morphological studies have been done on cells cultured from canine tumours. Some consistency has been demonstrated in the morphology of cultures of different tumours of the same type. Nutritional studies with the transmissible venereal sarcoma of the dog have shown the cells to be subject to a growth-repressing effect by SH-containing amino-acids. Attempts to transmit tumours to other dogs or other species have generally been unsuccessful. A transplantable tumour developed in a mouse injected with non-cellular material from a canine thyroid carcinoma, but it is not certain that the tumour was induced. Cell-culture studies have shown that some tumours yield a factor that is cytopathogenic for normal cells, but none has been shown capable of inducing neoplasms in vivo. ImagesFIG. 3FIG. 4FIG. 5FIG. 1FIG. 2FIG. 6 PMID:14058226

  15. Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia.

    PubMed

    Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X

    2015-12-01

    Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique. PMID:26220210

  16. Complex APC germline mutation associated metaplasia and intraepithelial neoplasia (CAM-IEN) of the gallbladder.

    PubMed

    Böger, Christine; Haag, Jochen; Egberts, Jan-Hendrik; Röcken, Christoph

    2016-01-01

    Preneoplasic and neoplastic changes of the gallbladder of patients with a familial adenomatous polyposis (FAP) are rare, and very little is known about their incidence in patients with an attenuated FAP. We herein report on a unique case of a woman with an attenuated FAP who shows eight distinct, partially preneoplastic differentiation patterns within the gallbladder mucosa, which are: (1) regular gallbladder epithelium, (2) low grade biliary intraepithelial neoplasia, (3) papillary adenoma, (4) Paneth cell metaplasia, (5) goblet cell metaplasia, (6) pancreatic metaplasia, (7) pseudopyloric metaplasia, and (8) neuroendocrine differentiation. Moreover, this is the first case of a KRAS mutation in a gallbladder adenoma of a patient with an APC germline mutation, which is highly suggestive of an early event of malignant transformation. As a consequence of our findings, clinicians should draw special attention to the gallbladder of FAP patients, and a simultaneous protective cholecystectomy of FAP patients, which undergo colectomy and show conspicuous changes of the gallbladder mucosa, should be performed in these patients in order to eliminate the risk of a synchronous or metachronous gallbladder neoplasia. PMID:26643927

  17. Low-grade mucinous neoplasia in a cecal diverticulum: A case report

    PubMed Central

    Nakatani, Kazuyoshi; Tokuhara, Katsuji; Sakaguchi, Tatsuma; Ryota, Hironori; Yoshioka, Kazuhiko; Kon, Masanori

    2015-01-01

    Introduction Low-grade mucinous neoplasia is an uncommon benign tumor that develops in the appendix. The development of mucocele disease has never been reported in a colonic diverticulum. We present a case developing low-grade mucinous neoplasia in a cecal diverticulum. Presentation of case A tumor in the ileocecal region was found during a medical examination of a 66-year-old woman. Three months later, the tumor was still present and the patient developed abdominal pain. Laparoscopic ileocecal resection with D2 lymph node dissection was performed. Histopathological examination revealed a low-grade mucinous neoplasm in a cecal diverticulum. Discussion Colonic mucoceles reportedly originate from the appendix. There are no previous reports of mucocele disease in a colonic diverticulum worldwide. This report reviews and discusses the management of the appendiceal mucoceles. Conclusion The incidence of colonic diverticula has recently begun to increase in Japan. The possibility of a mucocele within a colonic diverticulum should be considered in patients with submucosal colonic tumors. PMID:26318130

  18. Super-efficient starch absorption. A risk factor for colonic neoplasia?

    PubMed

    Thornton, J R; Dryden, A; Kelleher, J; Losowsky, M S

    1987-10-01

    We tested the hypothesis that super-efficient starch absorption, by reducing the supply of carbohydrate to the colon, may be associated with and possibly promote colonic neoplasia. By means of breath hydrogen measurements following a potato meal and comparison with the hydrogen response to lactulose, the amount of starch escaping small bowel absorption was measured in 10 patients who had a colonic adenoma removed endoscopically and in 10 controls. The subjects' consumption of starch and fiber was assessed. Percentage unabsorbed starch was approximately half as much in the patients (5.3%) compared with the controls (10.9%, P less than 0.05). Consumption of starch and dietary fiber, and mouth-to-cecum transit times were not significantly different. Unabsorbed starch was calculated to contribute to 6.0 g/day colonic carbohydrate in the patients and 10.9 g/day in the controls (P less than 0.05). This study confirms that unabsorbed starch provides an important quantity of colonic carbohydrate and suggests that super-efficient starch absorption, by reducing this provision, may promote colonic neoplasia. PMID:2820674

  19. Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review.

    PubMed

    Hoyme, H E; Seaver, L H; Jones, K L; Procopio, F; Crooks, W; Feingold, M

    1998-10-01

    Hemihyperplasia is characterized by asymmetric growth of cranium, face, trunk, limbs, and/or digits, with or without visceral involvement. It may be an isolated finding in an otherwise normal individual, or it may occur in several syndromes. Although isolated hemihyperplasia (IHH) is of unknown cause, it may represent one end of the clinical spectrum of the Wiedemann-Beckwith syndrome (WBS). Uniparental paternal disomy of 11p15.5 or altered expression of insulin-like growth factor 2 (IGF2) from the normally silent maternal allele have been implicated as causes of some cases of WBS. IHH and other mild manifestations of WBS may represent patchy overexpression of the IGF2 gene following defective imprinting in a mosaic fashion. The natural history of IHH varies markedly. An association among many overgrowth syndromes and a predisposition to neoplasia is well recognized. Heretofore the risk for tumor development in children with IHH was unknown. We report on the results of a prospective multicenter clinical study of the incidence and nature of neoplasia in children evaluated because of IHH. One hundred sixty-eight patients were ascertained. A total of 10 tumors developed in nine patients, for an overall incidence of 5.9%. Tumors were of embryonal origin (similar to those noted in other overgrowth disorders), including Wilms tumor, hepatoblastoma, adrenal cell carcinoma, and leiomyosarcoma of the small bowel in one case. These data support a tumor surveillance protocol for children with IHH similar to that performed in other syndromes associated with overgrowth. PMID:9781907

  20. Cumulative effects of genetic markers and the detection of advanced colorectal neoplasias by population screening.

    PubMed

    Kurlapska, A; Serrano-Fernández, P; Baszuk, P; Gupta, S; Starzy?ska, T; Ma?ecka-Panas, E; Dabrowski, A; D?bniak, T; Kurzawski, G; Suchy, J; Rogoza-Mateja, W; Scott, R J; Lubi?ski, J

    2015-09-01

    Genetic markers associated with colorectal cancer may be used in population screening for the early identification of patients at elevated risk of disease. We genotyped 3059 individuals with no cancer family history for eight markers previously associated with colorectal cancer. After colonoscopy, the genetic profile of cases with advanced colorectal neoplasia (213) was compared with the rest (2846). rs2066847 and rs6983267 were significantly associated with the risk of advanced colorectal neoplasia but with limited effect on their own [odds ratio (OR) 1.59; 95% confidence interval (CI) 1.02-2.41; p?=?0.033 and OR 1.45; 95% CI 1.02-2.12; p?=?0.044, respectively]. Cumulative effects, in contrast, were associated with high risk: the combination of rs2066847, rs6983267, rs4779584, rs3802842 and rs4939827 minimized the number of markers considered, while maximizing the relative size of the carrier group and the risk associated to it, for example, for at least two cumulated risk markers, OR is 2.57 (95% CI 1.50-4.71; corrected p-value 0.0079) and for three or more, OR is 3.57 (95% CI 1.91-6.96; corrected p-value 0.00074). The identification of cumulative models of - otherwise - low-risk markers could be valuable in defining risk groups, within an otherwise low-risk population (no cancer family history). PMID:25117299

  1. Validity of colposcopy in the diagnosis of early cervical neoplasia--a review.

    PubMed

    Olaniyan, Olayinka Babafemi

    2002-12-01

    This study was conducted to quantify by meta-analysis the validity of colposcopy in the diagnosis of early cervical neoplasia in order to assess the justification of its integral role in this regard. Eight longitudinal studies were selected, which compared correlation of colposcopic impression with colposcopically directed biopsy results. The prevalence of disease in the studies ranged from 40 to 89%. Colposcopic accuracy was 89%, which agreed exactly with histology in 61% of cases. The sensitivity and specificity of colposcopy for the threshold normal versus all cervical abnormalities were 87-99% and 26-87% respectively. For the threshold normal and low grade SIL versus high grade SIL, the values were 30-90% and 67-97%. Likelihood ratios increased with disease severity. Colposcopy performed better in differentiation of high grade from low grade disease than in differentiation of low grade disease from normal cervix. Colposcopy is a valid tool for the diagnosis of early cervical neoplasia. Its integral role in the management of early cervical disease is justified. PMID:12685410

  2. Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles.

    PubMed

    Khondee, Supang; Rabinsky, Emily F; Owens, Scott R; Joshi, Bishnu P; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D

    2015-02-10

    Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, P<0.01. On immunohistochemistry, we observed a significant reduction in phospho-S6 but not ?-catenin expression and reduced tumor cell proliferation, suggesting greater inhibition of downstream mTOR signaling. We observed significantly reduced renal toxicity for peptide-labeled rapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity. PMID:25483425

  3. Novel optical detection system for in vivo identification and localization of cervical intraepithelial neoplasia.

    PubMed

    Schomacker, Kevin T; Meese, Thomas M; Jiang, Chunsheng; Abele, Charles C; Dickson, Karen; Sum, Stephen T; Flewelling, Ross F

    2006-01-01

    A noncontact optical detection system is developed for the in vivo identification and localization of high-grade cervical intraepithelial neoplasia (CIN 2,3). Diagnostic scans of the entire human cervix are performed following acetic acid application employing three integrated optical measurements: laser-induced fluorescence spectroscopy, white light diffuse reflectance spectroscopy, and video imaging. Full cervical scans comprising 499 interrogation locations at 1-mm spatial resolution are completed in 12 s. Diffuse reflectance and fluorescence spectra with signal-to-noise ratios of better than 100-to-1 are collected between 360 and 720 nm in increments of 1 nm, with an inherent spectral resolution of 8 nm. Glare reduction and optical vignetting are handled with a novel illumination scheme and subsequent spectral arbitration algorithms. The system is designed and found to be well below acceptable safe optical exposure levels. Typical reproducibility across multiple systems is approximately 5%, providing reliable and accurate detection of in vivo cervical neoplasia in normal clinical use. PMID:16822059

  4. Zeranol may increase the risk of leptin-induced neoplasia in human breast.

    PubMed

    Xu, Pingping; Ye, Weiping; Zhong, Saiyi; Jen, Robert; Li, Hong; Feng, Eric; Lin, Shu-Hong; Liu, Jie-Yu; Lin, Young C

    2011-01-01

    Breast cancer and obesity are serious health problems and their relationship has been studied for many years. Leptin is mainly secreted by adipocytes and plays a key role in breast cancer development. Leptin expression is up-regulated in obese individuals and promotes breast cancer cell growth. On the other hand, exposure to environmental estrogens has been found to be directly related to breast cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter used in the beef industry in the US. This study focused on the evaluation of Z and Z-containing sera (ZS) and its adverse health risk to human consumption of Z-containing meat produced from Z-implanted beef cattle. We hypothesized that Z increases the risk of breast neoplasia in women, particularly in obese women. A cell proliferation assay, ELISA analysis, RT-PCR and Western blot analysis were conducted. Our study demonstrated that Z and ZS collected from Z-implanted heifers stimulated the proliferation of primary cultured human normal breast epithelial cells (HNBECs) by up-regulating cyclin D1 expression. Leptin increased the sensitivity of HNBECs to Z, and Z increased the ability of HNBECs to secrete leptin. These results suggest an interaction between leptin and Z in HNBECs. Furthermore, Z may play a role in leptin-induced breast neoplasia. PMID:22870137

  5. A Multiscale Model Evaluates Screening for Neoplasia in Barrett’s Esophagus

    PubMed Central

    Curtius, Kit; Hazelton, William D.; Jeon, Jihyoun; Luebeck, E. Georg

    2015-01-01

    Barrett’s esophagus (BE) patients are routinely screened for high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC) screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC) in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1) the probability that small cancers are missed during biopsy-based screening, (2) the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3) the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence. PMID:26001209

  6. Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

    2015-12-01

    Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

  7. C-C Chemokine Receptor 1 Expression in Human Hematolymphoid Neoplasia

    PubMed Central

    Anderson, Matthew W.; Zhao, Shuchun; Ai, Weiyun Z.; Tibshirani, Robert; Levy, Ronald; Lossos, Izidore S.; Natkunam, Yasodha

    2015-01-01

    Chemokine receptor 1 (CCR1) is a G protein–coupled receptor that binds to members of the C-C chemokine family. Recently, CCL3 (MIP-1α), a high-affinity CCR1 ligand, was identified as part of a model that independently predicts survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the role of chemokine signaling in the pathogenesis of human lymphomas is unclear. In normal human hematopoietic tissues, we found CCR1 expression in intraepithelial B cells of human tonsil and granulocytic/monocytic cells in the bone marrow. Immunohistochemical analysis of 944 cases of hematolymphoid neoplasia identified CCR1 expression in a subset of B- and T-cell lymphomas, plasma cell myeloma, acute myeloid leukemia, and classical Hodgkin lymphoma. CCR1 expression correlated with the non–germinal center subtype of DLBCL but did not predict overall survival in follicular lymphoma. These data suggest that CCR1 may be useful for lymphoma classification and support a role for chemokine signaling in the pathogenesis of hematolymphoid neoplasia. PMID:20154287

  8. C-C chemokine receptor 1 expression in human hematolymphoid neoplasia.

    PubMed

    Anderson, Matthew W; Zhao, Shuchun; Ai, Weiyun Z; Tibshirani, Robert; Levy, Ronald; Lossos, Izidore S; Natkunam, Yasodha

    2010-03-01

    Chemokine receptor 1 (CCR1) is a G protein-coupled receptor that binds to members of the C-C chemokine family. Recently, CCL3 (MIP-1alpha), a high-affinity CCR1 ligand, was identified as part of a model that independently predicts survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the role of chemokine signaling in the pathogenesis of human lymphomas is unclear. In normal human hematopoietic tissues, we found CCR1 expression in intraepithelial B cells of human tonsil and granulocytic/monocytic cells in the bone marrow. Immunohistochemical analysis of 944 cases of hematolymphoid neoplasia identified CCR1 expression in a subset of B- and T-cell lymphomas, plasma cell myeloma, acute myeloid leukemia, and classical Hodgkin lymphoma. CCR1 expression correlated with the non-germinal center subtype of DLBCL but did not predict overall survival in follicular lymphoma. These data suggest that CCR1 may be useful for lymphoma classification and support a role for chemokine signaling in the pathogenesis of hematolymphoid neoplasia. PMID:20154287

  9. Neoplasia Driven by Mutant c-KIT Is Mediated by Intracellular, Not Plasma Membrane, Receptor Signaling?

    PubMed Central

    Xiang, Zhifu; Kreisel, Frederike; Cain, Jennifer; Colson, AnnaLynn; Tomasson, Michael H.

    2007-01-01

    Activating mutations in c-KIT are associated with gastrointestinal stromal tumors, mastocytosis, and acute myeloid leukemia. In attempting to establish a murine model of human KITD816V (hKITD816V)-mediated leukemia, we uncovered an unexpected relationship between cellular transformation and intracellular trafficking. We found that transport of hKITD816V protein was blocked at the endoplasmic reticulum in a species-specific fashion. We exploited these species-specific trafficking differences and a set of localization domain-tagged KIT mutants to explore the relationship between subcellular localization of mutant KIT and cellular transformation. The protein products of fully transforming KIT mutants localized to the Golgi apparatus and to a lesser extent the plasma membrane. Domain-tagged KITD816V targeted to the Golgi apparatus remained constitutively active and transforming. Chemical inhibition of intracellular transport demonstrated that Golgi localization is sufficient, but plasma membrane localization is dispensable, for downstream signaling mediated by KIT mutation. When expressed in murine bone marrow, endoplasmic reticulum-localized hKITD816V failed to induce disease in mice, while expression of either Golgi-localized HyKITD816V or cytosol-localized, ectodomain-deleted KITD816V uniformly caused fatal myeloproliferative diseases. Taken together, these data demonstrate that intracellular, non-plasma membrane receptor signaling is sufficient to drive neoplasia caused by mutant c-KIT and provide the first animal model of myelomonocytic neoplasia initiated by human KITD816V. PMID:17060458

  10. Examination for intratubular germ cell neoplasia at operation for undescended testis in boys.

    PubMed

    Cortes, D; Thorup, J; Frisch, M; Møller, H; Jacobsen, G K; Beck, B L

    1994-03-01

    A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including 1 nonseminoma of the contralateral testis, which had been treated before surgery for an undescended testis, 1 nonseminoma found at followup, 1 seminoma and 2 intratubular germ cell neoplasms. Of the later 3 patients 1 had a 45,X/46,XY karyotype and 2 had abnormal external genitalia. Previous testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia. The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood. PMID:7905932

  11. Diverse histologic appearances in pulmonary mucinous cystic neoplasia: A case report

    PubMed Central

    Wynveen, Christine; Behmaram, Behnaz; Haasler, George; Rao, Nagarjun

    2008-01-01

    Introduction Primary pulmonary mucinous cystic neoplasia comprises a group of tumors, from benign cystadenoma to mucinous cystadenocarcinoma. Case presentation We report a case of primary pulmonary mucinous cystadenocarcinoma in a 75-year-old woman who was found to have a right hilar mass on a routine chest X-ray. A lobectomy was performed and the resection specimen revealed a multicystic mucinous tumor. Microscopically, the tumor was composed of confluent mucin-filled cystic spaces lined by columnar mucin-secreting cells which ranged from cytologically bland to moderately atypical with 'bronchioloalveolar pattern' invasion into the adjacent parenchyma. Immunohistochemically, tumor cells were positive diffusely for Cytokeratin 7, and focally for Cytokeratin 20 and Thyroid Transcription Factor-1. Conclusion This case highlights the continuous spectrum of pulmonary mucinous cystic neoplasia from benign mucinous cystadenoma to malignant mucinous cystadenocarcinoma, and the probable existence of a 'borderline' mucinous cystic tumor. Although molecular data are lacking to substantiate progression from benign to malignant in these neoplasms, the importance of recognizing the morphologic continuum lies in alerting pathologists to thoroughly examine specimens to rule out invasive foci in tumors with 'borderline' morphology. PMID:18823534

  12. Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix

    PubMed Central

    Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Lee, Ah Won; Hur, Soo Young; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.036 and P = 0.018, respectively). Importantly, PIK3CA was altered in all MIC/CSCCs by either mutation or amplification, but not in CINs. The CINs harbored significantly lower numbers of copy number alterations (CNAs) than the MIC/CSCCs as well (P = 0.036). Pathway analysis predicted that the MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR signaling pathway and cell migration that were depleted in the CINs. The mutation-based estimation of evolutionary ages identified that CIN genomes were younger than MIC/CSCC genomes. The data indicate that CIN genomes harbor unfixed mutations in addition to human papilloma virus infection but require additional driver hits such as PIK3CA, TP53, STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain the long latency from CIN to CSCC progression and provide useful information for molecular diagnosis of CIN and CSCC. PMID:25738363

  13. Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

    PubMed

    Woodhouse, Sarah J; Rose, Michelle; Desjardins, Danielle R; Agnew, Dalen W

    2015-03-01

    A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species. PMID:25867665

  14. Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation

    NASA Astrophysics Data System (ADS)

    Burns, Fredric; (Eric) Tang, Moon-Shong; Wu, Feng

    One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are summarized as follows: 1) DSBs predict carcinoma yields in regard to dose and LET in conformity to Equation A, 2) fibroma yields for 40Ar and 20Ne ions conform to Equation B, i.e. yield proportionality to D and L and 3) the positive slope of the fibroma yield to electron radiation is a third order discrepancy suggesting a more complicated response that has yet to be incorporated into the model. The results provide encouragement that once calibrated for humans, a short-term test of DSB yield might be capable of predicting cancer risks for a variety of space radiation exposure scenarios.

  15. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.

    PubMed

    Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram

    2013-10-01

    The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. PMID:24025519

  16. Neoplasias mielodisplásicas o mieloproliferativas (PDQ)—Versión para profesionales de salud

    Cancer.gov

    Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocítica crónica o juvenil y la LMC atípica.

  17. Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus.

    PubMed

    Boerwinkel, D F; Holz, J A; Hawkins, D M; Curvers, W L; Aalders, M C; Weusten, B L; Visser, M; Meijer, S L; Bergman, J J

    2015-01-01

    Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system. PMID:24602242

  18. Two case reports of pilot percutaneous cryosurgery in familial multiple endocrine neoplasia type 1.

    PubMed

    Li, Jialiang; Zhang, Changming; Chen, Jibing; Yao, Fei; Zeng, Jianying; Huang, Liwen; Yang, Xiuli; Liu, Weiqun; Chen, Feng; Xu, Keqiang; Yang, Daming; Niu, Lizhi; Zuo, Jiansheng; Xu, Kecheng; Liu, DePei

    2013-03-01

    We report 2 cases of familial multiple endocrine neoplasia type 1 syndrome (MEN 1) in related Malaysian Chinese individuals: the son had simultaneous primary lesions in the pancreatic tail, parathyroid, adrenal gland, and hypophysis, with metastatic tumors in the left lung, mediastinum and spine; his mother had simultaneous primary lesions in the pancreatic head, parathyroid, and hypophysis, with metastatic tumors in the liver, spine, ilium, chest wall, and rib. Genetic testing of the 2 patients showed the same mutation in exon 9 of MEN1 (c.1288G>T, Glu430, encoding a stop codon). The tumors with the poorest prognosis and clinical sequelae were in the pancreas of both patients, and these were treated by percutaneous cryoablation. The number of hypoglycemic episodes in the son improved for more than 120 days, and the abdominal space occupying lesion resolved in his mother. PMID:23407484

  19. Fine-scaling mapping of the gene responsible for multiple endocrine neoplasia type I (MEN1)

    SciTech Connect

    Fujimori, Minoru; Nakamura, Yusuke ); Wells, S.A. )

    1992-02-01

    The authors have constructed a high-resolution genetic linkage map in the vicinity of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). The mutation causing this disease, inherited as an autosomal dominant, predisposes carriers to development of neoplastic tumors in the parathyroid, the endocrine pancreas, and the anterior lobe of the pituitary. The 12 markers on the genetic linkage map reported here span nearly 20 cM, and linkage analysis of MEN1 pedigrees has placed the MEN1 locus within the 8-cM region between D11S480 and D11S546. The markers on this map will be useful for prenatal or presymptomatic diagnosis of individuals in families that segregate a mutant allele of the MEN1 gene.

  20. VIPoma with multiple endocrine neoplasia type 1 identified as an atypical gene mutation.

    PubMed

    Fujiya, Atsushi; Kato, Makoto; Shibata, Taiga; Sobajima, Hiroshi

    2015-01-01

    A 47-year-old man presented with persistent diarrhoea and hypokalaemia. CT revealed 4 pancreatic tumours that appeared to be VIPomas, because the patient had an elevated plasma vasoactive intestinal polypeptide level. MRI showed a low-intensity area in the pituitary suggestive of a pituitary tumour, and a parathyroid tumour was detected by ultrasonography and 99Tc-MIBI scintigraphy. Given these results, the patient was diagnosed with multiple endocrine neoplasia type 1 (MEN1) and scheduled for surgery. MEN1 is an autosomal dominant disorder associated with MEN1 mutations. Genetic testing indicated that the patient had a MEN1 gene mutation; his 2 sons had the same mutations. Most MEN1 tumours are benign, but some pancreatic and thymic tumours could become malignant. Without treatment, such tumours would result in earlier mortality. Despite its rarity, we should perform genetic testing for family members of patients with MEN1 to identify mutation carriers and improve the patients' prognosis. PMID:26564120

  1. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia.

    PubMed

    McAllister, Florencia; Bailey, Jennifer M; Alsina, Janivette; Nirschl, Christopher J; Sharma, Rajni; Fan, Hongni; Rattigan, Yanique; Roeser, Jeffrey C; Lankapalli, Rachana H; Zhang, Hao; Jaffee, Elizabeth M; Drake, Charles G; Housseau, Franck; Maitra, Anirban; Kolls, Jay K; Sears, Cynthia L; Pardoll, Drew M; Leach, Steven D

    2014-05-12

    Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that Kras(G12D) induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation. PMID:24823639

  2. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia

    PubMed Central

    McAllister, Florencia; Bailey, Jennifer M.; Alsina, Janivette; Nirschl, Christopher J.; Sharma, Rajni; Fan, Hongni; Rattigan, Yanique; Roeser, Jeffrey C.; Lankapalli, Rachana H.; Zhang, Hao; Jaffee, Elizabeth M.; Drake, Charles G.; Housseau, Franck; Maitra, Anirban; Kolls, Jay K.; Sears, Cynthia L.; Pardoll, Drew M.; Leach, Steven D.

    2014-01-01

    Summary Many human cancers are dramatically accelerated by chronic inflammation. However the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells, and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation. PMID:24823639

  3. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  4. Parent-of-origin effects in multiple endocrine neoplasia Type 2B

    SciTech Connect

    Carlson, K.M.; Bracamontes, J.; Wells, S.A. Jr.; Goodfellow, P.J.; Jackson, C.E.; Clark, R.; Lacroix, A.

    1994-12-01

    Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. The authors have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggest a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development.

  5. Cervical intraepithelial neoplasia (CIN): management by a general (non-oncological) gynaecological unit.

    PubMed

    Goon, M S; Tay, B L

    1994-12-01

    The purpose of this study is to assess how well Cervical Intraephithelial Neoplasia (CIN) was managed by a general gynaecological unit. Treatment consisted of laser ablation, conization (laser, knife, loop diathermy) and hysterectomy. Recurrence occurred in 8 (18.2%) out of 44 conizations and 2 (25.0%) out of 8 ablative procedures. While the cure rate after the first treatment was 81.1%, after subsequent treatment it became 96.2%. This study showed that it was possible for a general gynaecological unit to cure patients of their disease. The Pap smear tests were not very accurate--the sensitivity and specificity were 75.5% and 50.0% respectively while the positive predictive value and negative predictive value were 94.9% and 14.3% respectively. Similarly, colposcopically directed punch biopsy was also found to be misleading. PMID:7761881

  6. Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

    PubMed Central

    Xu, Xue; Feng, Lin; Liu, Yu; Zhou, Wei-Xun; Ma, Ying-Cai; Fei, Gui-Jun; An, Ning; Li, Yuan; Wu, Xi; Yao, Fang; Cheng, Shu-Jun; Lu, Xing-Hua

    2014-01-01

    AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor ?B (NF-?B) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-?B cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, ?2 = 6.28) and EGC (P = 0.008, ?2 = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application. PMID:25548486

  7. Diagnosis and Treatment of Gastrinomas in Multiple Endocrine Neoplasia Type 1 (MEN-1)

    PubMed Central

    Plöckinger, Ursula

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease. It is associated with a broad range of endocrine tumours, most frequently arising in the parathyroid glands, the pituitary and the pancreas. Most neuroendocrine tumours will be diagnosed in the pancreas as non-functioning neuroendocrine tumours or insulinomas. Forty-two percent of the patients will develop a gastrin-secreting neuroendocrine tumour, a gastrinoma. Gastrinomas in MEN-1 tend to be small, multiple and preferentially located in the duodenum. This paper will focus on the specific characteristics of gastrinomas in the setting of MEN-1 compared to sporadic gastrinomas. The developments in understanding the tumorigenesis of these tumours and the consequences for diagnosis and therapy will be discussed. PMID:24213225

  8. No clinical predictors of intraepithelial neoplasia in HIV-positive patients with external condilomata acuminata

    PubMed Central

    Giacaman, Paula; Martínez, María José; Chnaiderman, Jonas; Ampuero, Sandra; Santander, Ester; Ramis, Claudia; Sazunic, Ivo; Garmendia, María Luisa; Gómez, Orietta

    2011-01-01

    To identify clinical parameters in association with human papilloma virus (HPV) genotypes and histopathology diagnosis in HIV-positive patients with external condylomata acuminata (ECA), 400 Chilean HIV-positive patients were included in the study. Forty-seven patients presented ECA. Clinical parameters and socio demographic data were recorded. Histopathology study and HPV linear array genotyping assay were performed. Intraepithelial neoplasia (IEN) grade 2 or 3 was found in 8.5% of patients, associated to HPV-16. Patients were mainly single, MSM, with history of sexually transmitted disease (STD), multiple sexual partners, receiving antiretroviral therapy and with recurrent lesions. All ECA were mainly perianal, grey or pink colored, exophytic with less than two years evolution. No clinical parameter could predict the development of high grade IEN in HIV patients with ECA. It seems necessary to perform biopsy and genotype all HIV positive patients with ECA. PMID:21799573

  9. [Combined endoscopic diagnostics with catheter confocal endomicroscopy for gastric neoplasia detection].

    PubMed

    Shuleshova, A G; Zav'ialov, M O; Ul'ianov, D N; Kanare?tseva, T D

    2014-01-01

    The analysis of combined endoscopic diagnostics with catheter confocal laser endomicroscopy (CCLE) for detection of gastric neoplasia in 103 patients is presented in the article. It was described the main principles of catheter confocal laser endomicroscopy by using of Cellvizio-system ("Mauna Kea Technologies", France). All patients underwent esophagogastroduodenoscopy before catheter confocal laser endomicroscopy. Such modes as HRE-endoscopy, NBI-endoscopy and Zoom-endoscopy were used. It was revealed different neoplastic changes of stomach mucous coat and early cancer forms of stomach in 185 cases. It was noted expediency and high informational content of CCLE which leads to detect the foci of intestinal metaplasia by colonic type, foci of dysplasia and early cancer of stomach mucous coat. The role of conventional morphological study for verification of changes detected with CCLE was shown. PMID:25327669

  10. Frequent Somatic Mutation in Adult Intestinal Stem Cells Drives Neoplasia and Genetic Mosaicism during Aging.

    PubMed

    Siudeja, Katarzyna; Nassari, Sonya; Gervais, Louis; Skorski, Patricia; Lameiras, Sonia; Stolfa, Donato; Zande, Maria; Bernard, Virginie; Rio Frio, Thomas; Bardin, Allison J

    2015-12-01

    Adult stem cells may acquire mutations that modify cellular behavior, leading to functional declines in homeostasis or providing a competitive advantage resulting in premalignancy. However, the frequency, phenotypic impact, and mechanisms underlying spontaneous mutagenesis during aging are unclear. Here, we report two mechanisms of genome instability in adult Drosophila intestinal stem cells (ISCs) that cause phenotypic alterations in the aging intestine. First, we found frequent loss of heterozygosity arising from mitotic homologous recombination in ISCs that results in genetic mosaicism. Second, somatic deletion of DNA sequences and large structural rearrangements, resembling those described in cancers and congenital diseases, frequently result in gene inactivation. Such modifications induced somatic inactivation of the X-linked tumor suppressor Notch in ISCs, leading to spontaneous neoplasias in wild-type males. Together, our findings reveal frequent genomic modification in adult stem cells and show that somatic genetic mosaicism has important functional consequences on aging tissues. PMID:26607382

  11. Mortality by neoplasia and cellular telephone base stations in the Belo Horizonte municipality, Minas Gerais state, Brazil.

    PubMed

    Dode, Adilza C; Leão, Mônica M D; Tejo, Francisco de A F; Gomes, Antônio C R; Dode, Daiana C; Dode, Michael C; Moreira, Cristina W; Condessa, Vânia A; Albinatti, Cláudia; Caiaffa, Waleska T

    2011-09-01

    Pollution caused by the electromagnetic fields (EMFs) of radio frequencies (RF) generated by the telecommunication system is one of the greatest environmental problems of the twentieth century. The purpose of this research was to verify the existence of a spatial correlation between base station (BS) clusters and cases of deaths by neoplasia in the Belo Horizonte municipality, Minas Gerais state, Brazil, from 1996 to 2006 and to measure the human exposure levels to EMF where there is a major concentration of cellular telephone transmitter antennas. A descriptive spatial analysis of the BSs and the cases of death by neoplasia identified in the municipality was performed through an ecological-epidemiological approach, using georeferencing. The database employed in the survey was composed of three data banks: 1. death by neoplasia documented by the Health Municipal Department; 2. BSs documented in ANATEL ("Agência Nacional de Telecomunicações": 'Telecommunications National Agency'); and 3. census and demographic city population data obtained from official archives provided by IBGE ("Instituto Brasileiro de Geografia e Estatística": 'Brazilian Institute of Geography and Statistics'). The results show that approximately 856 BSs were installed through December 2006. Most (39.60%) of the BSs were located in the "Centro-Sul" ('Central-Southern') region of the municipality. Between 1996 and 2006, 7191 deaths by neoplasia occurred and within an area of 500 m from the BS, the mortality rate was 34.76 per 10,000 inhabitants. Outside of this area, a decrease in the number of deaths by neoplasia occurred. The greatest accumulated incidence was 5.83 per 1000 in the Central-Southern region and the lowest incidence was 2.05 per 1000 in the Barreiro region. During the environmental monitoring, the largest accumulated electric field measured was 12.4 V/m and the smallest was 0.4 V/m. The largest density power was 40.78 ?W/cm(2), and the smallest was 0.04 ?W/cm(2). PMID:21741680

  12. Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

    PubMed

    de Castro-Sobrinho, Juçara Maria; Rabelo-Santos, Silvia Helena; Fugueiredo-Alves, Rosane Ribeiro; Derchain, Sophie; Sarian, Luis Otávio Z; Pitta, Denise R; Campos, Elisabete A; Zeferino, Luiz Carlos

    2016-02-01

    Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ?20% of clue cells. Present inflammatory response was defined as ?30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia. Diagn. Cytopathol. 2016;44:80-86. © 2015 Wiley Periodicals, Inc. PMID:26644228

  13. Localized amyloidosis of the vulva with and without vulvar intraepithelial neoplasia: report of a series.

    PubMed

    Quddus, M Ruhul; Sung, C James; Simon, Rochelle A; Lawrence, W Dwayne

    2014-10-01

    Localized primary cutaneous amyloidosis is uncommon in Europe and North America and is infrequently reported in the English literature. The constituents of such deposits have not been previously examined; this series characterizes amyloid deposits in localized vulvar amyloidosis and their association with vulvar intraepithelial neoplasia. All biopsies and excisions of vulva over 18 months were reviewed. Cases with suspected amyloidosis were retrieved after institutional review board approval. Twenty cases mimicking amyloidosis were selected as controls. All study and control cases were stained with Congo red. Four Congo red-positive study cases were studied by liquid chromatography-tandem mass spectrometry. Of 27 Congo red-positive study cases, 25 were then examined by immunohistochemical stains with antibodies to cytokeratin 5 (CK5) and cytokeratin 14 (CK14). Of 149 cases reviewed, 26 localized and 1 systemic vulvar amyloidosis were identified. Liquid chromatography-tandem mass spectrometry analysis of the deposits revealed unique peptide profile consistent with CK5 and CK14. Immunohistochemical staining with antibodies to CK5 and CK14 also detected these components in the deposits. The vulvar deposit of systemic amyloidosis consisted of amyloid light chain (?)-type amyloid deposit. All control cases were negative for Congo red. Keratin-associated amyloid materials (CK5 and CK14) were found to be unique in localized vulvar amyloidosis. Leakage of keratins from the basal layer of the epithelium into the superficial dermis may have been the possible source of the deposits. It appears to be associated with both high-grade and low-grade vulvar intraepithelial neoplasias and, rarely, lichen sclerosus, seborrheic keratosis, and benign vulvar skin. PMID:25149547

  14. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia

    PubMed Central

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J.H.; Wardenaar, René; Volders, Haukeline H.; Klip, Harry G.; Hollema, Harry; Jansen, Ritsert C.; Schuuring, Ed; Wisman, G. Bea A.; van der Zee, Ate G.J.

    2012-01-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection. PMID:23018867

  15. NON-MAMMALIAN FAT-1 GENE PREVENTS NEOPLASIA WHEN INTRODUCED TO A MOUSE HEPATOCARCINOGENESIS MODEL

    PubMed Central

    Griffitts, J.; Saunders, D.; Tesiram, Y.A.; Reid, G.E.; Salih, A.; Liu, S.; Lydic, T.A.; Busik, J.V.; Kang, J.X.; Towner, R.A.

    2010-01-01

    We investigated the effect of a non-mammalian omega-3 desaturase in a mouse hepatocarcinogenesis model. Mice containing double mutations (DM) in c-myc and TGF-? (transforming growth factor-?), leading to liver neoplasia, were crossed with mice containing omega-3 desaturase. MRI analysis of triple mutant (TM) mice showed the absence of neoplasia at all time points for 92% of mice in the study. Pathological changes of TM (TGF?/c-myc/fat-1) mouse liver tissue was similar to control mouse liver tissue. Magnetic resonance spectroscopy (MRS) measurements of unsaturated fatty acids found a significant difference (p<0.005) between DM and TM transgenic (Tg) mice at 34 and 40 weeks of age. HPLC analysis of mouse liver tissue revealed markedly decreased levels of omega-6 fatty acids in TM mice when compared to DM (TGF?/c-myc) and control (CD1) mice. Mass spectrometry (MS) analysis indicated significantly decreased 16:0/20:4 and 18:1/20:4 and elevated 16:0/22:6 fatty acyl groups in both GPCho and GPEtn, and elevated 16:0/20:5, 18:0/18:2, 18:0/18:1 and 18:0/22:6 in GPCho, within TM mice compared to DM mice. Total fatty acid analysis indicated a significant decrease in 18:1n9 in TM mice compared to DM mice. Western blot analysis of liver tissue showed a significant (p<0.05) decrease in NF-?B (nuclear factor- ?B) levels at 40 weeks of age in TM mice compared to DM mice. Microarray analysis of TM versus DM mice livers at 40 weeks revealed alterations in genes involved in cell cycle regulation, cell-to-cell signaling, p53 signaling, and arachidonic acid (20:4) metabolism. Endogenous omega-3 fatty acids were found to prevent HCC development in mice. PMID:20620224

  16. The Applicability of a Human Immunohistochemical Panel to Mouse Models of Hepatocellular Neoplasia.

    PubMed

    Salleng, Kenneth J; Revetta, Frank L; Deane, Natasha G; Washington, M Kay

    2015-10-01

    Various immunohistochemical panels are used as aids to distinguish between primary hepatocellular malignancies and metastatic tumors and between benign lesions and carcinomas. We compared the immunohistochemical spectrum of hepatocellular lesions in mice with that of human hepatocellular carcinoma (HCC). Specifically, we compared the staining parameters of 128 murine foci of cellular alteration (FCA) and tumors (adenoma and HCC) from archival tissue blocks of 3 transgenic mouse models (LFABP-cyclin D1, Alb1-TGF?1, and LFABP-cyclin D1 × Alb1-TGF?1) with those of archival human HCC (n = 5). Antibodies were chosen according to their published performance and characterization in human hepatocellular tumor diagnosis and included: arginase 1 (Arg1), ?-catenin, glutamine synthetase (GS), glypican 3, hepatocyte paraffin 1 (HepPar1), and cytokeratin 19 (CK19). GS was the single best immunostain for identifying hepatocellular tumors in mice, with 100% positive staining. Data showed a trend toward loss of normal function (staining) with Arg1, with a higher percentage of positive staining in FCA than in adenomas and HCC. All FCA lacked murine ?-catenin nuclear translocation, which was present in 2 of the 7 adenomas and 22 of the 96 HCC tested. HepPar1 staining was lower than anticipated, except in trabecular HCC (16 of 22 samples were positive). Glyp3 stained very lightly, and only scattered CK19-positive cells were noted (4 of 44 cases of mouse trabecular HCC). Thus, GS appears to be the most useful marker for identifying neoplasia in the transgenic mouse models we tested and should be included in immunohistochemistry assessing hepatocellular neoplasia development. PMID:26473343

  17. Endoscopic features suggesting gastric cancer in biopsy-proven gastric adenoma with high-grade neoplasia

    PubMed Central

    Kim, Jung Ho; Kim, Yoon Jae; An, Jungsuk; Lee, Jong Joon; Cho, Jae Hee; Kim, Kyoung Oh; Chung, Jun-Won; Kwon, Kwang An; Park, Dong Kyun; Kim, Ju Hyun

    2014-01-01

    AIM: To elucidate the endoscopic features that predict the cancer following endoscopic submucosal dissection (ESD) in patients with high-grade neoplasia (HGN). METHODS: We retrospectively analyzed the medical records of patients who underwent ESD of gastric neoplasms from January 2007 to September 2010. ESD was performed in 555 cases involving 550 patients. A total of 112 lesions from 110 consecutive patients were initially diagnosed as HGN without cancer by forceps biopsy, and later underwent ESD. We classified lesions into two groups according to histologic discrepancies between the biopsy and ESD diagnosis. Gastric adenoma in the final diagnosis by ESD specimens were defined as adenoma group. Lesions with coexisting cancer after ESD were defined as cancer group. RESULTS: The mean age was 65.3 years, and 81 patients were male. There was no significant difference in the age or gender distribution between the adenoma (n = 52) and cancer (n = 60) groups. Thirty-six of these lesions (32.1%) showed histologic concordance between the forceps biopsy and ESD specimens, 16 (14.3%) showed a downgraded histology (low-grade neoplasia), and 60 (53.6%) showed an upgraded histology (cancer). A red color change of the mucosal surface on endoscopy was found in 27/52 (51.9%) of cases in the adenoma group and in 46/60 (76.7%) of cases in the cancer group (P = 0.006). Ulceration of the mucosal surface on endoscopy was found in 5 (9.6%) of 52 lesions in the adenoma group and in 17 (28.3%) of 60 lesions in the cancer group (P = 0.013). In the multivariate analysis, a reddish surface color change and mucosal ulceration were significant predictive factors correlated with cancer after ESD of the HGN by forceps biopsy. CONCLUSION: HGN with a red color change or mucosal ulceration correlated with the presence of gastric cancer. These finding may help to guide the diagnosis and treatment. PMID:25232257

  18. A retrospective study into the effects of operator experience on the accuracy of ultrasound in the diagnosis of gastric neoplasia in dogs.

    PubMed

    Easton, S

    2001-01-01

    The accuracy of three diagnostic techniques in two separate time periods was examined. In the first time period, 18 dogs were referred to the University of Bristol with signs suggestive of gastric neoplasia. Of these 18 dogs, 7 had a positive diagnosis of gastric neoplasia from histopathology samples (38% prevalence). The sensitivity of ultrasound was found to be 42.9% with a specificity of 63.6%. A year later the study was repeated with 40 cases referred for investigation. Of these 40 dogs, 16 had a positive histopathologic diagnosis of gastric neoplasia (40% prevalence). At this time the sensitivity of ultrasound had increased to 81.3 % and the specificity had increased to 70.8 %. The increase in sensitivity was attributed to an increase in operator experience in the performance of the ultrasound examination. This improvement in sensitivity and experience resulted in a greater accuracy at detecting the presence of gastric neoplasia. PMID:11245237

  19. Polypoid/papillary cystitis: a series of 41 cases misdiagnosed as papillary urothelial neoplasia.

    PubMed

    Lane, Zhaoli; Epstein, Jonathan I

    2008-05-01

    Polypoid cystitis and its more chronic phase papillary cystitis, which results as a reaction to injury to the bladder mucosa, is a benign lesion mimicking various papillary urothelial neoplasms. Analogous lesions occur throughout the urothelial tract and are referred to as polypoid urethritis, polypoid ureteritis, and polypoid pyelititis when present in the urethra, ureter, and renal pelvis, respectively. For simplicity, these lesions in different sites and papillary cystitis will typically be referred to as polypoid cystitis in this manuscript. A search of the consultation files from our institution from January 2000 to July 2007 was performed. Of 155 cases diagnosed as polypoid cystitis, we identified 41 cases that were diagnosed as papillary urothelial neoplasms by contributing pathologists and only sent to us, typically at the request of the urologist after the case had be signed out. For cases where information was available, clinical symptoms included bladder obstruction (n=7), gross hematuria (n=6), colovesicular fistula (n=4), follow-up status posttreatment of bladder and ureter carcinoma (n=4), bladder/urethral stones (n=2), benign prostate hyperplasia (n=2), follow-up after radiation for prostate cancer (n=2), long-standing urinary stents (n=2), and voiding dysfunction (n=1). Original diagnoses included noninvasive low grade papillary urothelial carcinoma (n=23), noninvasive high grade papillary urothelial carcinoma (n=6), papillary urothelial neoplasm of low malignant potential (n=5), papilloma (n=3), urothelial neoplasia (n=2), carcinoma in situ (n=1), and squamous carcinoma (n=1). The mean age at diagnosis was 63 years (range, 19 to 93 y; median 63 y). Male to female ratio was 3.1 to 1. Clinical symptoms varied with the most common manifestations, including gross hematuria, bladder/urethral stones, history of prostate cancer treated with radiation, follow-up after bladder/ureter carcinoma treatment, long-term urinary stents, and colovesicular fistulas. At cystoscopy, lesions were variably described as polypoid, trabeculations, bullous polyps, and diffuse erythema and edema. The locations of polypoid cystitis were bladder (n=34), ureteral orifice (n=2), urethra (n=2), renal pelvis (n=2), and undesignated (n=1). Architecturally, 31 cases had isolated papillary fronds with in 1 case branching papillary structures. The base of the papillary stalks were characterized as both broad and narrow (n=24), only broad (n=9), and only narrow (n=3). The overlying urothelium of polypoid cystitis was diffusely and focally thickened in 8 cases and 5 cases, respectively. Umbrella cells were identified in 32 cases. Acute and chronic inflammation was present in 28 cases, moderate in 15, and mild in 13 cases. Eleven cases showed chronic inflammation, mild in 10, and moderate in 1 case. Reactive urothelial atypia was noted in 26 cases with mitotic figures present in 22 cases, frequent in 3 and rare in 19 cases. Stroma edema was seen in 32 cases with fibrosis within the polypoid stalks seen in 16 cases. The key to correctly diagnosing polypoid/papillary cystitis is to recognize at low magnification the reactive nature of the process with an inflamed background that is edematous or densely fibrous with predominantly simple, non-branching, broad-based fronds of relatively normal thickness urothelium, and not focus at higher power on the exceptional frond that may more closely resemble a urothelial neoplasm either architecturally or cytologically. In cases where the diagnosis of papillary neoplasia is not straightforward and there is a question of polypoid cystitis, pathologists should seek clinical history that might suggest a reactive process. Because the urologist can more often better recognize the inflammatory nature of the lesion than the pathologist, the pathologist should hesitate diagnosing urothelial neoplasia when the cystoscopic impression is that of an inflammatory lesion. PMID:18379418

  20. Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2

    PubMed Central

    Romei, C.; Pardi, E.; Cetani, F.; Elisei, R.

    2012-01-01

    Multiple endocrine neoplasia (MEN) are clinical inherited syndromes affecting different endocrine glands. Three different patterns of MEN syndromes can occur (MEN 1, MEN 2A, and MEN 2B). MEN syndromes are very rare, affect all ages and both sexes are equally affected. MEN 1 is characterized by the neoplastic transformation of the parathyroid glands, pancreatic islets, anterior pituitary, and gastrointestinal tract. Heterozygous MEN 1 germline mutations have been detected in about 70–80% of patients with MEN 1. The mutations are scattered throughout the entire genomic sequence of the gene. MEN 1 patients are characterized by variable clinical features, thus suggesting the lack of a genotype-phenotype correlation. Therapeutical approaches are different according to the different endocrinopathies. The prognosis is generally good if adequate treatment is provided. In MEN 2 syndromes, the medullary thyroid cancer (MTC) is almost invariably present and can be associated with pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroid glands with hyperparathyroidism (PHPT). The different combination of the endocrine neoplasia gives origin to 3 syndromes: MEN 2A, MEN 2B, and FMTC. The clinical course of MTC varies considerably in the three syndromes. It is very aggressive in MEN 2B, almost indolent in the majority of patients with FMTC and with variable degrees of aggressiveness in patients with MEN 2A. Activating germline point mutations of the RET protooncogene are present in 98% of MEN 2 families. A strong genotype-phenotype correlation has been observed and a specific RET mutation may be responsible for a more or less aggressive clinical course. The treatment of choice for primary MTC is total thyroidectomy with central neck lymph nodes dissection. Nevertheless, 30% of MTC patients, especially in MEN 2B and 2A, are not cured by surgery. Recently, developed molecular therapeutics that target the RET pathway have shown very promising activity in clinical trials of patients with advanced MTC. MEN 2 prognosis is strictly dependent on the MTC aggressiveness and thus on the success of the initial treatment. PMID:23209466

  1. Lobular neoplasia detected in MRI-guided core biopsy carries a high risk for upgrade: a study of 63 cases from four different institutions.

    PubMed

    Khoury, Thaer; Kumar, Prasanna R; Li, Zaibo; Karabakhtsian, Rouzan G; Sanati, Souzan; Chen, Xiwei; Wang, Dan; Liu, Song; Reig, Beatriu

    2016-01-01

    There are certain criteria to recommend surgical excision for lobular neoplasia diagnosed in mammographically detected core biopsy. The aims of this study are to explore the rate of upgrade of lobular neoplasia detected in magnetic resonance imaging (MRI)-guided biopsy and to investigate the clinicopathological and radiological features that could predict upgrade. We reviewed 1655 MRI-guided core biopsies yielding 63 (4%) cases of lobular neoplasia. Key clinical features were recorded. MRI findings including mass vs non-mass enhancement and the reason for biopsy were also recorded. An upgrade was defined as the presence of invasive carcinoma or ductal carcinoma in situ in subsequent surgical excision. The overall rate of lobular neoplasia in MRI-guided core biopsy ranged from 2 to 7%, with an average of 4%. A total of 15 (24%) cases had an upgrade, including 5 cases of invasive carcinoma and 10 cases of ductal carcinoma in situ. Pure lobular neoplasia was identified in 34 cases, 11 (32%) of which had upgrade. In this group, an ipsilateral concurrent or past history of breast cancer was found to be associated with a higher risk of upgrade (6/11, 55%) than contralateral breast cancer (1 of 12, 8%; P=0.03). To our knowledge, this is the largest series of lobular neoplasia diagnosed in MRI-guided core biopsy. The incidence of lobular neoplasia is relatively low. Lobular neoplasia detected in MRI-guided biopsy carries a high risk for upgrade warranting surgical excision. However, more cases from different types of institutions are needed to verify our results. PMID:26564004

  2. A novel blueprint for 'top down' differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia.

    PubMed

    Herfs, Michael; Vargas, Sara O; Yamamoto, Yusuke; Howitt, Brooke E; Nucci, Marisa R; Hornick, Jason L; McKeon, Frank D; Xian, Wa; Crum, Christopher P

    2013-02-01

    The cervical squamocolumnar (SC) junction is the site of a recently discovered 'embryonic' cell population that was proposed as the cell of origin for cervical cancer and its precursors. How this population participates in cervical remodelling and neoplasia is unclear. In the present study, we analysed the SC junction immunophenotype during pre- and post-natal human and mouse development and in the adult, processes of metaplastic evolution of the SC junction, microglandular change, and early cervical neoplasia. Early in life, embryonic cervical epithelial cells were seen throughout the cervix and subsequently diminished in number to become concentrated at the SC junction in the adult. In all settings, there was a repetitive scenario in which cuboidal embryonic/SC junction cells gave rise to subjacent metaplastic basal/reserve cells with a switch from the SC junction positive to negative immunophenotype. This downward or basal (rather than upward or apical) evolution from progenitor cell to metaplastic progeny was termed reverse or 'top down' differentiation. A similar pattern was noted in high-grade squamous intraepithelial lesions (HSILs), suggesting that HPV infection of the cuboidal SC junction cells initiated outgrowth of basally-oriented neoplastic progeny. The progressive loss of the embryonic/SC junction markers occurred with 'top down' differentiation during development, remodelling, and early neoplasia. Interestingly, most low-grade SILs were SC junction-negative, implying infection of metaplastic progeny rather than the original SC junction cells. This proposed model of 'top down' differentiation resolves the mystery of how SC junction cells both remodel the cervix and participate in neoplasia and provides for a second population of metaplastic progeny (including basal and reserve cells), the infection of which is paradoxically less likely to produce a biologically aggressive precursor. It also provides new targets in animal models to determine why the SC junction is uniquely susceptible to carcinogenic HPV infection. PMID:23007879

  3. Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett’s esophagus

    PubMed Central

    Trindade, Arvind J.; George, Benley J.; Berkowitz, Joshua; Sejpal, Divyesh V.; McKinley, Matthew J.

    2016-01-01

    Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett’s esophagus. We report a series of 6 patients with long-segment Barrett’s esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett’s esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies. PMID:27004250

  4. Management of lichen sclerosus and intraepithelial neoplasia of the vulva in the UK.

    PubMed Central

    Tidy, J A; Soutter, W P; Luesley, D M; MacLean, A B; Buckley, C H; Ridley, C M

    1996-01-01

    Women with vulval intraepithelial neoplasia (VIN), lichen sclerosus (LS) and Paget's disease are referred either to gynaecologists or to dermatologists. We have ascertained the caseloads, referral patterns and treatment modalities used in the two specialties. A postal questionnaire was sent to 540 consultant gynaecologists and 225 consultant and senior registrar members of the British Association of Dermatologists. 350 gynaecologists and 161 dermatologists returned completed questionnaires. The workload of LS and Paget's disease was evenly distributed, with 54% of dermatologists and 58% of gynaecologists seeing more than six cases of LS per annum and less than 1% seeing more than five cases of Paget's disease. 92% of responding gynaecologists saw at least one case of VIN per year whereas 43% of dermatologists saw no cases. Patients with VIN and Paget's were referred to gynaecologists for treatment by 66% of dermatologists. Both groups are equally prepared to treat LS. Indications for treatment of VIN and LS were suspicion of invasion and symptoms. Local excision of VIN is the treatment of choice by both gynaecologists and dermatologists. LS is predominantly treated with topical steroids but gynaecologists also use topical oestrogen and testosterone. The great majority of responders favoured establishing a national register to study the outcome of vulval lesions. PMID:9014882

  5. RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+/? mice

    PubMed Central

    Nikitin, Alexander Yu.; Juárez-Pérez, María I.; Li, Song; Huang, Leaf; Lee, Wen-Hwa

    1999-01-01

    Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/? mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/? mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/? mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors. PMID:10097138

  6. Intraoperative neurocytology of primary central nervous system neoplasia: A simplified and practical diagnostic approach

    PubMed Central

    Sharma, Suash; Deb, Prabal

    2011-01-01

    Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management. PMID:22090687

  7. Disseminated neoplasia causes changes in ploidy and apoptosis frequency in cockles Cerastoderma edule.

    PubMed

    Díaz, S; Villalba, A; Insua, A; Soudant, P; Fernández-Tajes, J; Méndez, J; Carballal, M J

    2013-07-01

    A proliferative disease, usually referred as disseminated neoplasia (DN), shows high prevalence in some cockle Cerastoderma edule beds of Galicia (NW Spain). Chromosome counts, examination of chromosome morphology, DNA quantification by flow cytometry and estimation of apoptosis frequency by TUNEL assay and flow cytometry were performed in cockles with different DN severity. Metaphases obtained from gills of DN-affected cockles displayed a chromosome number ranging from 41 to 145, while normal number is 38; changes in chromosome morphology were also evident, with numerous microchromosomes occurring. Haemolymph flow cytometry analysis revealed difference in DNA content between healthy and DN-affected cockles. Aneuploid peaks ranged from 1.3n to 8.9n. Apoptosis frequency was determined on histological sections (TUNEL assay) and haemolymph samples (flow cytometry). Both techniques revealed neoplastic cells in apoptosis. The higher DN severity, the lower the percentage of apoptotic cells. According to flow cytometry results, the negative association between DN severity and apoptosis frequency only affected the neoplastic cells, whereas DN did not significantly affect the percentage of apoptotic hyalinocytes or apoptotic granulocytes. PMID:23583807

  8. Cytomorphology and PCNA expression pattern in bivalves Mytilus galloprovincialis and Cerastoderma edule with haemic neoplasia.

    PubMed

    Carella, Francesca; Figueras, Antonio; Novoa, Beatriz; De Vico, Gionata

    2013-07-01

    Haemic neoplasia (HN) is a pathologic condition reported in several bivalve species in different geographic areas. In this study we describe the cytomorphological features and the proliferative behaviour, assessed by the proliferating cell nuclear antigen (PCNA), of HN in common cockle Cerastoderma edule and Mediterranean mussel Mytilus galloprovicialis. In mussels the presence of at least 5 types of atypical haemocytes was detected, including A- and B-type cells, previously described in M. edulis and Mytilus sp., with predominance of A-type cells in early phases of the disease and B-type cells in more advanced stages. PCNA immunostaining was positive for 97 to 100% of the neoplastic cells, with both cytoplasmic (A cells) and nuclear patterns (B cells). Conversely, in C. edule there was no distinctive morphological cell sub-population, and staining atypical haemocytes with PCNA (range 93 to 100%) showed nuclear expression in early phases of disease and cytoplasmic expression in more advanced stages. The above findings suggest distinct histo-pathogenetic pathways for HN in mussels and common cockles. PMID:23836773

  9. Genetic mapping and predictive testing for multiple endocrine neoplasia type 1 (MEN1)

    SciTech Connect

    Pandit, S.D.; Read, C.; Liu, L.

    1994-09-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with an estimated prevalance of 20-200 per million persons. It is characterized by the combined occurence of tumors involving two or more endocrine glands, namely the parathyroid glands, the endocrine pancreas and the anterior pituitary. This disorder affects virtually all age groups with an average range of 20-60 years. Linkage analysis mapped the MEN1 locus to 11q13 near the human muscle glycogen phosphorylase (PYGM) locus. Additional genetic mapping and deletion analysis studies have refined the region containing the MEN1 locus to a 3 cM interval flanked by markers PYGM and D11S146/D11S97, a physical distance of approximately 1.5 Mb. We have identified 8 large families segregating MEN1 (71 affected from a population of 389 individuals). A high resolution reference map for the 11q13 region has been constructed using four new microsatellite markers, the CEPH reference (40 family) pedigree resource, and the CRI-MAP program package. Subsequent analyses using the LINKAGE program package and 8 MEN 1 families placed the MEN1 locus within the context of the microsatellite map. This map was used to develop a linkage-based predictive test. These markers have also been used to further refine the interval containing the MEN1 locus from the study of chromosome deletions (loss of heterozygosity, LOH studies) in paired sets of tumor and germline DNA from 87 MEN 1 affected individuals.

  10. Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving story

    PubMed Central

    Marini, Francesca; Giusti, Francesca; Brandi, Maria Luisa

    2015-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the oncosuppressor gene MEN1, in 1997, genetic testing has revealed an important approach for the early and differential diagnosis of the disease. The finding of a MEN1 mutation in a patient has important clinical implications for relatives since it allows very early disease diagnosis and identification of carriers, even before biochemical and/or clinical manifestation, permitting their inclusion in a specific program of surveillance and subsequent praecox therapy. Currently, genetic testing for MEN1 consists principally of the sequencing of coding regions and intron-exon junctions of the MEN1 gene. However, the recent acquisition of novel high throughput technologies will allow the design of innovative, accurate, complete and rapid genetic diagnosis. These new tools are able to increase the strength of the analysis and almost completely eliminate the possibility of false negative results. This review aims to give an overview on genetic testing of MEN1 syndrome, reporting the positive aspects of performing the analysis and the future perspectives for improving the performance of the test, as well as its application in clinical practice. PMID:25992327

  11. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity.

    PubMed

    Mitra, A; MacIntyre, D A; Lee, Y S; Smith, A; Marchesi, J R; Lehne, B; Bhatia, R; Lyons, D; Paraskevaidis, E; Li, J V; Holmes, E; Nicholson, J K; Bennett, P R; Kyrgiou, M

    2015-01-01

    Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n?=?52), high-grade (HSIL; n?=?92), invasive cervical cancer (ICC; n?=?5) and healthy controls (n?=?20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal?=?2/20,10%; LSIL?=?11/52,21%; HSIL?=?25/92,27%; ICC?=?2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P?

  12. Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer

    SciTech Connect

    Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.

    1985-03-15

    The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.

  13. Metabolic Profiling, a Non-invasive Approach for the Detection of Experimental Colorectal Neoplasia

    PubMed Central

    Montrose, David C.; Zhou, Xi Kathy; Kopelovich, Levy; Yantiss, Rhonda K.; Karoly, Edward D.; Subbaramaiah, Kotha; Dannenberg, Andrew J.

    2012-01-01

    Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Although non-invasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential non-invasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. UPLC/MS/MS and GC/MS were used to quantify metabolites in each of these matrices. Here we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans. PMID:22961778

  14. Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

    NASA Astrophysics Data System (ADS)

    Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

    1989-06-01

    Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

  15. Fiber optic FTIR instrument for in vivo detection of colonic neoplasia

    NASA Astrophysics Data System (ADS)

    Van Nortwick, Matthew; Hargrove, John; Wolters, Rolf; Crawford, James M.; Arroyo, May; Mackanos, Mark; Contag, Christopher H.; Wang, Thomas D.

    2009-02-01

    We demonstrate the proof of concept for use of a fiber optic FTIR instrument to perform in vivo detection of colonic neoplasia as an adjunct to medical endoscopy. FTIR is sensitive to the molecular composition of tissue, and can be used as a guide for biopsy by identifying pre-malignant tissue (dysplasia). First, we demonstrate the use of a silver halide optical fiber to collect mid-infrared absorption spectra in the 950 to 1800 cm-1 regime with high signal-to-noise from biopsy specimens of colonic mucosa tissue ex vivo. We observed subtle differences in wavenumber and magnitude of the absorbance peaks over this regime. We then show that optimal sub-ranges can be defined within this spectral regime and that spectral pre-processing can be performed to classify the tissue as normal, hyperplasia, or dysplasia with high levels of performance. We used a partial least squares discriminant analysis and a leave-one-subject-out crossvalidation strategy to classify the spectra. The results were compared with histology, and the optimal thresholds resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively for this technique. We demonstrate that mid-infrared absorption spectra can be collected remotely with an optical fiber and used to identify colonic dysplasia with high accuracy. We are now developing an endoscope compatible optical fiber to use this technique clinically for the early detection of cancer.

  16. Pure Laparoscopic Left Hemihepatectomy for Hepatic Peribiliary Cysts with Biliary Intraepithelial Neoplasia

    PubMed Central

    Umemura, Akira; Suto, Takayuki; Sasaki, Akira; Nitta, Hiroyuki; Nakamura, Seika; Endo, Fumitaka; Harada, Kazuho; Ishida, Kazuyuki

    2016-01-01

    Introduction. Hepatic peribiliary cysts (HPCs) usually originate due to the cystic dilatation of the intrahepatic extramural peribiliary glands. We describe our rare experience of pure laparoscopic left hemihepatectomy (PLLH) in a patient with HPCs accompanied by a component of biliary intraepithelial neoplasia (BilIN). Case Presentation. A 65-year-old man was referred for further investigation of mild hepatic dysfunction. Contrast-enhanced computed tomography showed dilatation of the left-sided intrahepatic bile duct, and biliary cytology showed class III cells. The patient was highly suspected of having left side-dominated cholangiocarcinoma and underwent PLLH. Microscopic findings revealed multiple cystic dilatations of the extramural peribiliary glands; hence, this lesion was diagnosed as HPCs. The resected intrahepatic bile duct showed that the normal ductal lumen comprised low columnar epithelia; however, front formation on the BilIN was observed in some parts of the intrahepatic bile duct, indicating that the BilIN coexisted with HPCs. Conclusion. We chose surgical therapy for this patient owing to the presence of some features of biliary malignancy. We employed noble PLLH as a minimally invasive procedure for this patient.

  17. Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site

    PubMed Central

    Kwon, Hyung Jun; Kim, Sang Geol; Chun, Jae Min; Hwang, Yoon Jin

    2014-01-01

    Extrahepatic bile duct (EHBD) cancer may occur metachronously, and these cancers are resectable with a favorable prognosis. We aimed to identify the pattern of metachronous EHBD cancer. We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer. A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor (pT1N0M0). A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer (pT2N1M0). Imaging studies of both patients taken at 14 and 24 mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy (PD). Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas (pT3N0M0). Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery. Through a review of the literature on these cases, we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia. The proximal remnant bile duct was most commonly involved. Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor. Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors. PMID:24659897

  18. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia.

    PubMed

    De La O, Jean-Paul; Emerson, Lyska L; Goodman, Jessica L; Froebe, Scott C; Illum, Benjamin E; Curtis, Andrew B; Murtaugh, L Charles

    2008-12-01

    Efforts to model pancreatic cancer in mice have focused on mimicking genetic changes found in the human disease, particularly the activating KRAS mutations that occur in pancreatic tumors and their putative precursors, pancreatic intraepithelial neoplasia (PanIN). Although activated mouse Kras mutations induce PanIN lesions similar to those of human, only a small minority of cells that express mutant Kras go on to form PanINs. The basis for this selective response is unknown, and it is similarly unknown what cell types in the mature pancreas actually contribute to PanINs. One clue comes from the fact that PanINs, unlike most cells in the adult pancreas, exhibit active Notch signaling. We hypothesize that Notch, which inhibits differentiation in the embryonic pancreas, contributes to PanIN formation by abrogating the normal differentiation program of tumor-initiating cells. Through conditional expression in the mouse pancreas, we find dramatic synergy between activated Notch and Kras in inducing PanIN formation. Furthermore, we find that Kras activation in mature acinar cells induces PanIN lesions identical to those seen upon ubiquitous Kras activation, and that Notch promotes both initiation and dysplastic progression of these acinar-derived PanINs, albeit short of invasive adenocarcinoma. At the cellular level, Notch/Kras coactivation promotes rapid reprogramming of acinar cells to a duct-like phenotype, providing an explanation for how a characteristically ductal tumor can arise from nonductal acinar cells. PMID:19028876

  19. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia

    PubMed Central

    De La O, Jean-Paul; Emerson, Lyska L.; Goodman, Jessica L.; Froebe, Scott C.; Illum, Benjamin E.; Curtis, Andrew B.; Murtaugh, L. Charles

    2008-01-01

    Efforts to model pancreatic cancer in mice have focused on mimicking genetic changes found in the human disease, particularly the activating KRAS mutations that occur in pancreatic tumors and their putative precursors, pancreatic intraepithelial neoplasia (PanIN). Although activated mouse Kras mutations induce PanIN lesions similar to those of human, only a small minority of cells that express mutant Kras go on to form PanINs. The basis for this selective response is unknown, and it is similarly unknown what cell types in the mature pancreas actually contribute to PanINs. One clue comes from the fact that PanINs, unlike most cells in the adult pancreas, exhibit active Notch signaling. We hypothesize that Notch, which inhibits differentiation in the embryonic pancreas, contributes to PanIN formation by abrogating the normal differentiation program of tumor-initiating cells. Through conditional expression in the mouse pancreas, we find dramatic synergy between activated Notch and Kras in inducing PanIN formation. Furthermore, we find that Kras activation in mature acinar cells induces PanIN lesions identical to those seen upon ubiquitous Kras activation, and that Notch promotes both initiation and dysplastic progression of these acinar-derived PanINs, albeit short of invasive adenocarcinoma. At the cellular level, Notch/Kras coactivation promotes rapid reprogramming of acinar cells to a duct-like phenotype, providing an explanation for how a characteristically ductal tumor can arise from nonductal acinar cells. PMID:19028876

  20. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia.

    PubMed

    Koo, Bon-Kyoung; van Es, Johan H; van den Born, Maaike; Clevers, Hans

    2015-06-16

    Rnf43 (RING finger protein 43) and Znrf3 (zinc/RING finger protein 3) (RZ) are two closely related transmembrane E3 ligases, encoded by Wnt target genes, that remove surface Wnt (wingless-int) receptors. The two genes are mutated in various human cancers. Such tumors are predicted to be hypersensitive to, yet still depend on, secreted Wnts. We previously showed that mutation of RZ in the intestine yields rapidly growing adenomas containing LGR5(+) (leucine-rich repeat-containing G-protein coupled receptor 5) stem cells and Wnt3-producing Paneth cells. We now show that removal of Paneth cells by Math1 mutation inhibits RZ(-/-) tumor formation. Similarly, deletion of Wnt3 inhibits tumorigenesis. Treatment of mice carrying RZ(-/-) intestinal neoplasia with a small molecule Wnt secretion inhibitor (porcupine inhibitor C59) strongly inhibited growth, whereas adjacent normal crypts remained intact. These results establish that paracrine Wnt secretion is an essential driver of RZ(-/-) tumor growth and imply that a therapeutic window exists for the use of porcupine inhibitors for RZ-mutant cancers. PMID:26023187

  1. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers.

    PubMed

    Mezache, Louisa; Paniccia, Bernard; Nyinawabera, Angelique; Nuovo, Gerard J

    2015-12-01

    Programmed death ligand 1 (PD L1) expression can reduce the immune response in both infectious diseases and cancers. We thus examined PD L1 expression in cervical intraepithelial neoplasias (CINs) and cancers since they each reflect infection by human papillomavirus (HPV). PD L1 protein was not evident by immunohistochemistry in histologically normal cervical epithelia (0/55) even when adjacent to CIN or cancer. PD L1 expression was much increased in CINs (20/21=95%) and cervical squamous cell cancer (56/70=80%) and localized to the dysplastic/neoplastic squamous cells and mononuclear cells, respectively. There was also a significant increase (each P<0.001) in PD L1 detection in mononuclear cells when comparing cervical squamous cell cancers to endometrial (22/115=19%) and ovarian adenocarcinomas (5/40=13%). Co-expression analyses showed that the primary inflammatory cell that contained PD L1 was the CD8+ lymphocyte that strongly concentrated around the dysplastic CIN cells and nests of invasive squamous cancer cells. These data show that PD L1 is a solid biomarker of productive HPV infection of the cervix and that it is significantly upregulated in both the carcinoma and surrounding inflammatory cells in cervical cancer when compared with other gynecologic malignancies. This suggests that anti-PD L1 therapy may have a role in the treatment of cervical cancer. PMID:26403783

  2. Putting the brakes on mammary tumorigenesis: loss of STAT1 predisposes to intraepithelial neoplasias.

    PubMed

    Schneckenleithner, Christine; Bago-Horvath, Zsuzsanna; Dolznig, Helmut; Neugebauer, Nina; Kollmann, Karoline; Kolbe, Thomas; Decker, Thomas; Kerjaschki, Dontscho; Wagner, Kay-Uwe; Müller, Mathias; Stoiber, Dagmar; Sexl, Veronika

    2011-12-01

    Multiparous Stat1-/- mice spontaneously develop mammary tumors with increased incidence: at an average age of 12 months, 55% of the animals suffer from mammary cancer, although the histopathology is heterogeneous. We consistently observed mosaic expression or down-regulation of STAT1 protein in wild-type mammary cancer evolving in the control group. Transplantation experiments show that tumorigenesis in Stat1-/- mice is partially influenced by impaired CTL mediated tumor surveillance. Additionally, STAT1 exerts an intrinsic tumor suppressing role by controlling and blocking proliferation of the mammary epithelium. Loss of STAT1 in epithelial cells enhances cell growth in both transformed and primary cells. The increased proliferative capacity leads to the loss of structured acini formation in 3D-cultures. Analogous effects were observed when Irf1-/- epithelial cells were used. Accordingly, the rate of mammary intraepithelial neoplasias (MINs) is increased in Stat1-/- animals: MINs represent the first step towards mammary tumors. The experiments characterize STAT1/IRF1 as a key growth inhibitory and tumor suppressive signaling pathway that prevents mammary cancer formation by maintaining growth control. Furthermore, they define the loss of STAT1 as a predisposing event via enhanced MIN formation. PMID:22185785

  3. Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias

    PubMed Central

    Schneckenleithner, Christine; Bago-Horvath, Zsuzsanna; Dolznig, Helmut; Neugebauer, Nina; Kollmann, Karoline; Kolbe, Thomas; Decker, Thomas; Kerjaschki, Dontscho; Wagner, Kay-Uwe; Müller, Mathias; Stoiber, Dagmar; Sexl, Veronika

    2011-01-01

    Multiparous Stat1?/? mice spontaneously develop mammary tumors with increased incidence: at an average age of 12 months, 55% of the animals suffer from mammary cancer, although the histopathology is heterogeneous. We consistently observed mosaic expression or down-regulation of STAT1 protein in wild-type mammary cancer evolving in the control group. Transplantation experiments show that tumorigenesis in Stat1?/? mice is partially influenced by impaired CTL mediated tumor surveillance. Additionally, STAT1 exerts an intrinsic tumor suppressing role by controlling and blocking proliferation of the mammary epithelium. Loss of STAT1 in epithelial cells enhances cell growth in both transformed and primary cells. The increased proliferative capacity leads to the loss of structured acini formation in 3D-cultures. Analogous effects were observed when Irf1?/? epithelial cells were used. Accordingly, the rate of mammary intraepithelial neoplasias (MINs) is increased in Stat1?/? animals: MINs represent the first step towards mammary tumors. The experiments characterize STAT1/IRF1 as a key growth inhibitory and tumor suppressive signaling pathway that prevents mammary cancer formation by maintaining growth control. Furthermore, they define the loss of STAT1 as a predisposing event via enhanced MIN formation. PMID:22185785

  4. Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

    USGS Publications Warehouse

    House, M.L.; Kim, C.H.; Reno, P.W.

    1998-01-01

    Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

  5. Neoplasia and granulomas surrounding microchip transponders in Damaraland mole rats (Cryptomys damarensis).

    PubMed

    Sura, R; French, R A; Goldman, B D; Schwartz, D R

    2011-07-01

    Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder. PMID:20724516

  6. Association between vitamin C Intake and the risk of cervical neoplasia: A meta-analysis.

    PubMed

    Cao, Dan; Shen, Kaiying; Li, Zhunan; Xu, Ying; Wu, Dan

    2016-01-01

    To assess the association between vitamin C intake and cervical neoplasia (CN) risk. Databases including PubMed, Embase, and Springer link were retrieved up to June 10, 2014 with predefined strategy. The combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for overall and subgroup analyses. The publication bias was assessed using Begg's test and Egger's test. Sensitivity analysis was also conducted. Twelve studies consisting of 1 prospective cohort study and 11 case-control studies were included. In overall analysis, vitamin C intake was significantly associated with the reduced risk of CN (OR = 0.58; 95% CI: 0.44 to 0.75; P < 0.001). Subgroup analysis stratified by vitamin C dose indicated all dose categories achieved a reduced CN risk. Furthermore, increased vitamin C intake by 50 mg/day was related to the reduced risk of CN (OR = 0.92; 95% CI: 0.89 to 0.94; P < 0.05). No publication bias was detected by Begg's test (P = 0.169) and no apparent fluctuation was observed in summary OR by sensitivity analysis. Vitamin C intake was inversely associated with the risk of CN and this association was dose-dependent. However, more randomized controlled trials are required for further validation. PMID:26731169

  7. Serum peptidome profiling analysis for the identification of potential biomarkers in cervical intraepithelial neoplasia patients.

    PubMed

    Liu, Yun; Wei, Fangqiao; Wang, Feng; Li, Changdong; Meng, Ge; Duan, Hua; Ma, Qingwei; Zhang, Weiyuan

    2015-09-25

    Cervical intraepithelial neoplasia (CIN) is a precancerous disease of cervical squamous cell carcinoma. We Used Mass Spectrometry based peptidome profile study to predict the transformation of CIN1, which is the primary stage of this lesion. . Serum samples of 34 Cervical squamous cell carcinoma patients, 31 healthy controls, and 29 CIN1 samples were analyzed. Peptides were purified by WCX magnetic beads (Bioyong), and analyzed by MALDI TOF (Bruker). Raw data were analyzed by BioExplorer software (Bioyong). The results showed 14 mass peaks with significant differences. The diagnosis model is established by analyzing peptide profiles of 15 SCC patients and 20 healthy women serum, with a sensitivity of 100% and specificity of 100.00%. In validation set, the SCC diagnosis model also had good performance with a sensitivity of 80%, a specificity of 100%. In addition, this model could predict 29 CIN1 patients with accuracy of 55.17%. These results would provide a new method to predict the trend of CIN1 and take effective measures for high risk group timely. PMID:26282206

  8. Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia

    PubMed Central

    Makino, Tomoki; Jain, Manu; Montrose, David C.; Aggarwal, Amit; Sterling, Joshua; Bosworth, Brian P.; Milsom, Jeffrey W.; Robinson, Brian D.; Shevchuk, Maria M.; Kawaguchi, Kathy; Zhang, Ning; Brown, Christopher M.; Rivera, David R.; Williams, Wendy O.; Xu, Chris; Dannenberg, Andrew J.; Mukherjee, Sushmita

    2012-01-01

    Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histological evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histological detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images demonstrated a striking similarity to the results of H&E staining, as demonstrated by the 100% concordance achieved by the study pathologists’ diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. PMID:22961775

  9. Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

    2014-03-01

    It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

  10. Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia

    PubMed Central

    Abbenhardt, Clare; Poole, Elizabeth M; Kulmacz, Richard J; Xiao, Liren; Curtin, Karen; Galbraith, Rachel L; Duggan, David; Hsu, Li; Makar, Karen W; Caan, Bette J; Koepl, Lisel; Owen, Robert W; Scherer, Dominique; Carlson, Christopher S; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

    2013-01-01

    Pancreatic phospholipase A2, product of PLA2G1B, catalyzes the release of fatty acids from dietary phospholipids.Diet is the ultimate source of arachidonic acid in cellular phospholipids, precursor of eicosanoid signaling molecules, linked to inflammation, cell proliferation and colorectal carcinogenesis. We evaluated the association of PLA2G1B tagging single-nucleotide polymorphisms with colorectal neoplasia risk. A linkage-disequilibrium-based tagSNP algorithm (r2=0.90, MAF?4%) identified three tagSNPs. The SNPs were genotyped on the Illumina platform in three population-based, case-control studies: colon cancer (1424 cases/1780 controls); rectal cancer (583/775); colorectal adenomas (485/578). Evaluating gene-wide associations, principal-component and haplotype analysis were conducted, individual SNPs were evaluated by logistic regression. Two PLA2G1B variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702 G>A Ser98Ser, p-trend=0.03; rs9657930, 1593 C>T, p-trend=0.01); principal component analysis showed that genetic variation in the gene overall was statistically significantly associated with rectal cancer (p=0.02). NSAID users with the rs2070873 variant had a reduced rectal cancer risk (P-inter=0.02). Specific associations were observed with tumor subtypes (TP53/KRAS). The results suggest that genetic polymorphisms in PLA2G1B affect susceptibility to rectal cancer. PMID:24046806

  11. Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies.

    PubMed

    Ghazi, Ali Asghar; Bagheri, Mahmoud; Tabibi, Ali; Sarvghadi, Farzaneh; Abdi, Hengameh; Hedayati, Mehdi; Pourafkari, Marina; Tirgari, Farrokh; Yu, Run

    2014-05-01

    Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region. PMID:24784869

  12. Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering

    PubMed Central

    Mourant, Judith R.; Bocklage, Thérese J.; Powers, Tamara M.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

    2009-01-01

    Objective To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. Materials and Methods A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. Results Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. Conclusions The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating ”see and treat” protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

  13. Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).

    PubMed

    LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

    2012-03-01

    Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids. PMID:22448509

  14. Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1).

    PubMed

    Turner, Jeremy J O; Christie, Paul T; Pearce, Simon H S; Turnpenny, Peter D; Thakker, Rajesh V

    2010-01-01

    Phenocopies may confound the clinical diagnoses of hereditary disorders. We report phenocopies in Multiple Endocrine Neoplasia type 1 (MEN1), an autosomal dominant disorder, characterised by the combined occurrence of parathyroid, pituitary and pancreatic tumours. We studied 261 affected individuals from 74 families referred with a clinical diagnosis of MEN1 and sought inconsistencies between the mutational and clinical data. We identified four patients from unrelated families with phenocopies. Patients 1 and 2 from families with MEN1, developed prolactinomas as the sole endocrinopathy but they did not harbour the germline MEN1 mutation present in their affected relatives. Patient 3, had acromegaly and recurrent hypercalcaemia following parathyroidectomy, whilst patient 4 had parathyroid tumours and a microprolactinoma. Patients 3 and 4 and their relatives did not have MEN1 mutations, but instead had familial hypocalciuric hypercalcaemia (FHH) due to a calcium-sensing receptor mutation (p.Arg680Cys), and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome due to a hyperparathyroidism type 2 deletional-frameshift mutation (c.1239delA), respectively. Phenocopies may mimic MEN1 either by occurrence of a single sporadic endocrine tumour in a patient with familial MEN1, or occurrence of two endocrine abnormalities associated with different aetiologies. Phenocopies arose in >5% of MEN1 families, and awareness of them is important in the clinical management of MEN1 and other hereditary disorders. PMID:19953642

  15. [A Patient with Multiple Endocrine Neoplasia Type1(MEN1)Presenting with Hypoglycemic Attacks].

    PubMed

    Bando, Kazuhiko; Ebisutani, Daizo

    2015-05-01

    Here, we report the case of a woman with multiple endocrine neoplasia type 1(MEN1) who experienced hypoglycemic attacks. At the age of 59, she underwent parathyroid tumor resection for hyperparathyroidism. At the age of 65, she presented with dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a left cerebellopontine (CP) angle tumor and a pituitary tumor. The CP angle tumor (acoustic neurionoma) was removed;the pituitary adenoma (prolactinoma) was managed by using bromocriptine. At the age of 77, she lost consciousness and was transferred to a local hospital. Her blood sugar level was 24 mg/dL. Due to the frequent recurrence of hypoglycemic attacks, she was readmitted to our hospital. MRI revealed the almost complete removal of the acoustic tumor and that her pituitary gland was atrophied. Despite her baseline pituitary hormone levels being normal, we suspected panhypopituitarism and administered cortisol (15 mg/day). As her hypoglycemia failed to improve, we performed a 75-g oral glucose tolerance test, and its result was not indicative of diabetes mellitus. Her pretest immunoreactive insulin (IRI) level was 6.8?U/mL;?IRI/?BS was 0.62, indicative of insulin hypersecretion. Contrast-enhanced abdominal computed tomography revealed multiple pancreatic tumors (insulinomas), and she underwent resection of the uncal tumor and pancreas body and tail. Her postoperative IRI level was normalized and she experienced no further hypoglycemic attacks. Based on her hyperparathyroidism, pancreatic tumor, and pituitary adenoma, we diagnosed her with MEN1. PMID:25926542

  16. Electron beam radiotherapy for the management of recurrent extensive ocular surface squamous neoplasia with orbital extension

    PubMed Central

    Murthy, Ramesh; Gupta, Himika; Krishnatry, Rahul; Laskar, Siddhartha

    2015-01-01

    Recurrent extensive ocular surface squamous neoplasia (OSSN) with orbital invasion can be successfully managed with external radiotherapy using electrons resulting in eye and vision salvage. We report a case of right eye recurrent OSSN in an immunocompetent adult Indian male, with extensive orbital involvement. The patient had two previous surgical excisions with recurrent disease. At this stage, conventionally exenteration is considered the treatment modality. However, he was treated with 5040 cGy radiotherapy (15eV electrons) resulting in complete disease regression. At the end of 3 years follow-up, the patient was disease free, maintained a vision of 20/25, with mild dry eye, well-managed with topical lubricants. Extensive OSSN with orbital invasion does not always need exenteration. External beam electron radiotherapy provides a noninvasive cure with organ and vision salvage and should be considered in extensive OSSN not amenable to simple excision biopsies. Long-term studies to evaluate the effect of radiation on such eyes are suggested. PMID:26576526

  17. Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A

    SciTech Connect

    Narod, S.A.; Morgan, K. ); Lavoue, M.F.; Lenoir, G.M.; Sobol, H. ); Calmettes, C. ); Goodfellow, P.J. )

    1992-09-01

    The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families with multiple cases of medullary carcinoma of the thyroid (MTC), including 24 families with origins in France, have been typed with nine polymorphic markers spanning the centromere of chromosome 10. No recombination was observed between the MEN2A locus and either of the four loci D10Z1 (lod score 12.79), D10S102 (lod score 6.38), D10S94 (lod score 7.76), and D10S34 (lod score 5.94). There was no evidence for genetic linkage heterogeneity in the panel of 34 families. Haplotypes were constructed for a total of 11 polymorphisms in the MEN2A region, for mutation bearing chromosomes in 24 French families and for 100 spouse controls. One haplotype was present in four MEN2A families but was not observed in any control (P<0.1). Two additional families share a core segment of this haplotype near the MEN2A gene. It is likely that these six families have a common affected ancestor. Because the incidence of pheochromocytoma among carriers varies from 0% to 74% within these six families, it is probable that additional factors modify the expression of the MEN2A gene. 39 refs., 5 figs., 4 tabs.

  18. Synergistic promoter effect of diethylstilbesterol & phenobarbitone in diethylnitrosamine induced hepatic neoplasia in rats.

    PubMed

    Arora, V K; Bhatia, A; Sood, S K

    1989-02-01

    An experimental model was designed to study the role of both diethylstilbesterol (DES) and phenobarbitone (PB) singly or in combination, in diethylnitrosamine (DEN) induced hepatic neoplasia. Experimental and control rats were injected DEN (200 mg/kg) or saline, ip. Acute morphological changes were studied at days 1, 2 and 3; and at weekly intervals for 3 wk. Four weeks after DEN pretreatment the experimental and control rats were randomized into various groups and fed DES (T1), PB (T2) or a combination of both DES and PB (T3). Five rats from each experimental group were sacrificed at 10, 20 and 30 wk. Group T3 showed gross nodules with a mean nodule score of 20.5 mm at 20 wk. Nodule score in T1, T2 and T3 at 30 wk were 7, 9 and 34.5 mm respectively. The sequential morphological lesions encountered were clear cell and acidophilic foci; acidophilic, basophilic and mixed nodules. Haemorrhage within the nodules was frequent when DES was administered either alone or in combination with PB. Oval cell proliferation and cholangiocellular lesions were produced in all experimental groups. Foci and nodules generally showed loss of glucose-6 phosphatase, adenosine triphosphatase and invariable presence of gamma-glutamyl transpeptidase and glycogen. A combination of DES and PB as promoter yielded earliest and highest nodule score. This suggests that DES and PB acted synergestically as promoters or that PB caused enzyme induction thereby enhanced the promotive effect of DES. PMID:2722221

  19. Risks for Cervical Intraepithelial Neoplasia-3 Among Adolescent And Young Women With Abnormal Cytology

    PubMed Central

    Moscicki, Anna-Barbara; Ma, Yifei; Wibbelsman, Charles; Powers, Adaleen; Darragh, Teresa M.; Nozzari, Sepideh; Shaber, Ruth; Shiboski, Stephen

    2009-01-01

    Objective To estimate the risks of cervical intraepithelial neoplasia-3 among women aged 13 to 24 years of age who were referred for abnormal cytology while receiving care in a large health maintenance organization. Methods At the time of referral, women had a colposcopic examination and biopsy if needed. Histology was sent to a centralized laboratory. Women were interviewed for risk behaviors. Data analysis included multinomial logistic regression analysis to compare 3 groups: CIN-3 to CIN-1 or less CIN-3 to CIN-2, and CIN-2 to CIN-1 or benign. Results CIN-3 was found in 6.6% (95% CI = 4.6 - 8.6%) of the 622 women referred and no cancers were detected. Risk for CIN 3 compared to CIN 1 or less included HPV 16 or 18 (odds ratio [OR] 30.93 [95% confidence interval (CI); 6.95, 137.65]), high-risk, non-16/18 HPV (OR 6.3 [95% CI; 1.3, 29.4]), and time on oral contraceptives (OR 1.36 per year of use [95% CI ; 1.08, 1.71]). Conclusion Our data support conservative care for adolescents and young women with abnormal cytology since CIN-3 was rare, and cervical cancer was never found. HPV-16 or 18 were strongly associated with for CIN-3, and testing for these types may be warranted for triage of abnormal cytology in this age group. PMID:19037044

  20. The risk of residual neoplasia in women with microinvasive squamous cervical carcinoma and positive cone margins.

    PubMed

    Phongnarisorn, C; Srisomboon, J; Khunamornpong, S; Siriaungkul, S; Suprasert, P; Charoenkwan, K; Cheewakriangkrai, C; Siriaree, S; Pantasri, T

    2006-01-01

    The objective was to evaluate the prevalence and factors affecting residual disease in women with cervical microinvasive carcinoma (MIC) with positive cone margins for high-grade lesions and invasive carcinoma. We reviewed histopathology slides of 129 women with MIC who had high-grade lesions or invasive carcinoma at cone margins. These patients underwent hysterectomy following cone biopsy between January 1994 and June 2004. Of the 129 patients, 77 (59.7%) had residual disease in the hysterectomy specimens, in which 57 (44.2%) had residual high-grade lesions. Twenty patients (15.5%) had residual invasive carcinoma: 18 were microinvasive and 2 were invasive. Factors significantly affecting the risk of residual disease included positive postconization endocervical curettage (P= 0.001), positive cone margins for invasive carcinoma (P= 0.003), and depth of stromal invasion >1 mm (P= 0.014). Cox proportional hazards analysis revealed positive cone margins for invasive carcinoma as significant predictor of residual invasive disease (hazard ratio, 3.22; 95% CI 1.21-8.60, P= 0.019) In summary, patients with MIC and positive cone margins for high-grade lesions or invasive carcinoma are at high risk of residual neoplasia. Repeat cone biopsy should be performed to determine exactly the severity of lesion before planning treatment. PMID:16681742

  1. Natural history of body weight gain, survival, and neoplasia in the F344 rat.

    PubMed

    Solleveld, H A; Haseman, J K; McConnell, E E

    1984-04-01

    This study involved the fact that knowledge of the natural incidence of neoplastic lesions is essential for interpretation of experiments designed to reveal the effects of potential carcinogens. Although the F344 rat is widely used in chronic (2-yr) testing programs, the natural history of neoplasia after 24 months is not known; thus this study, with 529 male and 529 female inbred F344 rats, was designed to deal with this aspect. This report also included information on growth and longevity. In addition, the tumor rates found in this study were compared with 2-year historic control tumor rates; results revealed the following. 1) Maximum mean body weights were 468 and 330 g for males and females, respectively. Peak weight in males was reached at 77 weeks of age and in females, at 107 weeks of age. 2) There was no clear sex difference in longevity; a median life-span (50% survival age) or 28 months was recorded in both sexes. 3) Variety of neoplastic lesions in animals that were allowed to live out their life-span was not greater than that in animals that were killed between 110 and 116 weeks of age; thus older age was not characterized by unique neoplasms. 4) The incidence of certain neoplasms increased markedly after 110-116 weeks. The data indicated that life-span studies in F344 rats had no advantages over 2-year studies. However, availability of life-span data is essential for interpretation of the 2-year studies. PMID:6584668

  2. Identification of interstitial deletions in human neoplasia by FISH-technique

    SciTech Connect

    Gogineni, S.K.; Sanchez, M.A.; Elizalde, S.A. |

    1994-09-01

    Undoubtedly, the discovery of the minute chromosome in chronic myelogenous leukemia (CML), termed the Philadelphia chromosome, has revolutionized cancer cytogenetics. Rowely`s seminal findings of a balanced translocation between chromosomes 9 and 22 opened new avenues where a simple deletion was clearly refuted. Even today, thousands of cases are being identified as simple terminal deletions by routine banding techniques in various human neoplasias. If these deletions are terminal, then how is the instability of the chromosome retained? Apparently, the precise characterization of telomeric ends has gone undetected in the past by conventional methods. It is evident that telomeres of chromosomes consist of short tandemly repeated DNA sequences (TTAGGG){sub n} which are conserved on both ends. The recent availability of chromosome-specific telomeric probes has become a cytogenetic icon for many perplexing questions. For example, we were referred a patient with acute myelogenous leukemia evolving from agnogenic myloid metaplasia. Routine cytogenetic techniques revealed a terminal deletion of one of the chromosomes 7 [del(7)(q21)]. When we hybridized the metaphases with chromosome 7q-specific telomeric probe [Oncor, Gaithersburg, MD], signal was detected at the distal q arms of the deleted chromosomes, apparently suggesting an interstial deletion. The cytogenetic diagnosis was changed to 46,SY,del(7)(q21.lq36.2). All deletions must be identified by FISH.

  3. Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms.

    PubMed Central

    Larsson, C; Shepherd, J; Nakamura, Y; Blomberg, C; Weber, G; Werelius, B; Hayward, N; Teh, B; Tokino, T; Seizinger, B

    1992-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited predisposition to neoplastic lesions of the parathyroids, pancreas, and the pituitary. We have previously located the predisposing genetic defect to the long arm of chromosome 11 by genetic linkage. In this study, 124 members of six MEN1 families, including 59 affected individuals, were genotyped for restriction fragment length polymorphisms with different DNA probes, and the genetic linkage between these marker systems and MEN1 was determined. 13 marker systems (17 DNA probes) were found to be linked to MEN1. These markers are located within a region on chromosome 11 spanning 14% meiotic recombinations, with the MEN1 locus in the middle. Four of the marker systems are on the centromeric side of MEN1, and four on the telomeric side, based on meiotic crossovers. The remaining five DNA probes are closely linked to MEN1, with no crossovers in our set of families. The 13 marker systems can be used for an accurate and reliable premorbid test for MEN1. In most clinical situations it is possible to identify a haplotype of this part of chromosome 11 with the mutant MEN1 allele in the middle. The calculated predictive accuracy is greater than 99.5% if three such marker systems are informative. Therefore, genetic linkage testing can be used for informed genetic counseling in MEN1 families, and to avoid unnecessary biochemical screening programs. PMID:1348254

  4. Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2015-06-01

    The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

  5. Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

    PubMed Central

    Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

    2013-01-01

    Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

  6. Amyloid associated with neoplasia in two captive tricolour sharkminnows Balantiocheilus melanopterus Bleeker.

    PubMed

    Russell, S; Tubbs, L; McLelland, D J; LePage, V; Young, K M; Huber, P; Lumsden, J S

    2015-06-01

    Amyloid associated with pancreatic adenocarcinoma was discovered in two captive adult tricolour sharkminnows Balantiocheilus melanopterus Bleeker found dead in a freshwater display. Enlarged abdomens expanded by bloody ascitic fluid and grossly visible masses of abnormal tissue were present surrounding sections of the stomach and intestine. Histologically, the masses were composed of areas of well-organized exocrine pancreatic acini interspersed with cords of poorly differentiated, spindle-shaped cells that compressed and effaced normal parenchyma. These cells possessed small numbers of cytoplasmic zymogen granules; the exocrine nature of these cells was confirmed using transmission electron microscopy (TEM). Fibrovascular connective tissue of the hepatopancreas and mesenteries was expanded by lightly eosinophilic, hyaline, homogeneous acellular material. Similar material greatly expanded the tunica media of large blood vessels in the hepatopancreas. After staining with Congo red or thioflavin T, this material exhibited red-green dichroism under polarized light or bright green fluorescence under ultraviolet light (255 nm), respectively. The non-branching fibrils, of indeterminate length, had an approximate diameter of 10-20 nm using TEM. Although exocrine pancreatic neoplasia is relatively common in fish, the presence of amyloid is not. To our current knowledge, the latter has not yet been described in association with a neoplastic lesion in fish. PMID:25117633

  7. Does Postevacuation ? -Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?

    PubMed

    Mousavi, Azam Sadat; Karimi, Samieh; Modarres Gilani, Mitra; Akhavan, Setareh; Rezayof, Elahe

    2014-01-01

    ? -human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate ? -HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum levels of HCG were measured in all patients before treatment and after evacuation. HCG level was measured weekly until it reached a level lower than 5?mIU/mL. Results. The only predictors of persistent GTN are HCG levels one and two weeks after evacuation. The cut-off point for the preevacuation HCG level was 6000?mIU/mL (area under the curve, AUC, 0.58; sensitivity, 38.53%; specificity, 77.4%), whereas cut-off points for HCG levels one and two weeks after evacuation were 6288?mIU/mL (AUC, 0.63; sensitivity, 50.46%; specificity, 77.0%) and 801?mIU/mL (AUC, 0.80; sensitivity, 79.82%; specificity, 71.64%), respectively. Conclusion. The rate of decrease of HCG level at two weeks after surgical evacuation is the most reliable and strongest predictive factor for the progression of molar pregnancies to persistent GTN. PMID:25006482

  8. CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia

    PubMed Central

    Pedersen, Susanne K; Mitchell, Susan M; Graham, Lloyd D; McEvoy, Aidan; Thomas, Melissa L; Baker, Rohan T; Ross, Jason P; Xu, Zheng-Zhou; Ho, Thu; LaPointe, Lawrence C; Young, Graeme P; Molloy, Peter L

    2014-01-01

    The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC100526820, is located on chromosome 6, hg19 chr6:163?834?097–163?834?982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC. The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC. PMID:24799664

  9. In vivo diagnosis of cervical intraepithelial neoplasia using 337-nm-excited laser-induced fluorescence.

    PubMed Central

    Ramanujam, N; Mitchell, M F; Mahadevan, A; Warren, S; Thomsen, S; Silva, E; Richards-Kortum, R

    1994-01-01

    Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy. PMID:7937860

  10. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1993--December 31, 1993

    SciTech Connect

    Clifton, K.H.

    1993-07-30

    The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report.

  11. Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret

    PubMed Central

    Schillebeeckx, Maximiliaan; Pihlajoki, Marjut; Gretzinger, Elisabeth; Yang, Wei; Thol, Franziska; Hiller, Theresa; Löbs, Ann-Kathrin; Röhrig, Theresa; Schrade, Anja; Cochran, Rebecca; Jay, Patrick Y.; Heikinheimo, Markku; Mitra, Robi D.; Wilson, David B.

    2014-01-01

    Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Transcriptome analysis and DNA methylation mapping were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated using a combination of laser capture microdissection, quantitative RT-PCR, in situ hybridization, and immunohistochemistry. Microarray expression profiling of whole adrenal mRNA from ovariectomized vs. intact mice demonstrated selective upregulation of gonadal-like genes including Spinlw1 and Insl3 in GDX-induced adrenocortical tumors of the mouse. A complementary candidate gene approach identified Foxl2 as another gonadal-like marker expressed in GDX-induced neoplasms of the mouse and ferret. That both “male-specific” (Spinlw1) and “female-specific” (Foxl2) markers were identified is noteworthy and implies that the neoplasms exhibit mixed characteristics of male and female gonadal somatic cells. Genome-wide methylation analysis showed that two genes with hypomethylated promoters, Igfbp6 and Foxs1, are upregulated in GDX-induced adrenocortical neoplasms. These new genetic and epigenetic markers may prove useful for studies of steroidogenic cell development and for diagnostic testing. PMID:25289806

  12. Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review)

    PubMed Central

    IMAI, ATSUSHI; MATSUNAMI, KAZUTOSHI; TAKAGI, HIROSHI; ICHIGO, SATOSHI

    2014-01-01

    Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection. PMID:24959210

  13. [International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia 2012].

    PubMed

    Hes, Ond?ej

    2014-01-01

    Kidney tumours form a broad spectrum of distinguished histopathological and molecular genetic entities. The last WHO classification is dated to 2004. Current classification has been published in October 2013 by ISUP (International Society of Urological Pathology). There were 5 new epithelials tumours: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo-)papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. Another 3 subtypes of RCC were added as "provisional" entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Modifications were performed in already existing entities: multicystic clear cell RCC (formerly multilocular cystic RCC) is newly included as a subcategory of clear cell RCC with low malignant potential. Oncocytic papillary RCC (PRCC) has not been recognized as a distinctive subcategory of PRCC yet. Hybrid oncocytic-chromophobe tumour was placed within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, current approach to our understanding of angiomyolipoma, including the epithelioid variant and angiomyolipoma with epithelial cysts was clarified. Cystic nephroma and mixed epithelial and stromal tumour were considered as a spectrum of one entity. Synovial sarcoma was placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. PMID:25418900

  14. Disseminated neoplasia in cockles Cerastoderma edule: ultrastructural characterisation and effects on haemolymph cell parameters.

    PubMed

    Díaz, Seila; Renault, Tristan; Villalba, Antonio; Carballal, María Jesús

    2011-09-01

    Disseminated neoplasia (DN) has been detected in cockles from various beds in Galicia (NW Spain). A study was performed to characterise cockle neoplastic cell ultrastructure and to evaluate the effect of this disease at different severity stages on various haemolymph cell parameters. Examination of cockle neoplastic cells with transmission electron microscopy (TEM) showed round shapes and a lack of pseudopods, a high nucleus:cytoplasm diameter ratio, Golgi complexes, abundant mitochondria, ribosomes, and numerous endoplasmic reticulum tubes and electron-lucent vesicles. Various haemolymph cell parameters (cell mortality, non-specific esterase and lysosome biovolume, reactive oxygen intermediates [ROI] production, phagocytosis ability, intracellular Ca2+ and actin levels) were compared between DN severity categories by flow cytometry; haemocyte mortality, non-specific esterase activities and lysosome biovolume were found to be higher with increasing DN severity. The phagocytic ability of neoplastic cells was sharply reduced with regard to haemocytes. The cytoplasmic-free Ca2+ level was higher and actin content lower in haemolymph cells of diseased cockles compared to unaffected ones. A significant increase in ROI production was detected in later stages of disease progression. PMID:22013755

  15. Reduced keratin expression in colorectal neoplasia and associated fields is reversible by diet and resection

    PubMed Central

    Evans, Caroline A; Rosser, Ria; Waby, Jennifer S; Noirel, Josselin; Lai, Daphne; Wright, Phillip C; Williams, Elizabeth A; Riley, Stuart A; Bury, Jonathan P; Corfe, Bernard M

    2015-01-01

    Background Patients with adenomatous colonic polyps are at increased risk of developing further polyps suggesting field-wide alterations in cancer predisposition. The current study aimed to identify molecular alterations in the normal mucosa in the proximity of adenomatous polyps and to assess the modulating effect of butyrate, a chemopreventive compound produced by fermentation of dietary residues. Methods A cross-sectional study was undertaken in patients with adenomatous polyps: biopsy samples were taken from the adenoma, and from macroscopically normal mucosa on the contralateral wall to the adenoma and from the mid-sigmoid colon. In normal subjects biopsies were taken from the mid-sigmoid colon. Biopsies were frozen for proteomic analysis or formalin-fixed for immunohistochemistry. Proteomic analysis was undertaken using iTRAQ workflows followed by bioinformatics analyses. A second dietary fibre intervention study arm used the same endpoints and sampling strategy at the beginning and end of a high-fibre intervention. Results Key findings were that keratins 8, 18 and 19 were reduced in expression level with progressive proximity to the lesion. Lesional tissue exhibited multiple K8 immunoreactive bands and overall reduced levels of keratin. Biopsies from normal subjects with low faecal butyrate also showed depressed keratin expression. Resection of the lesion and elevation of dietary fibre intake both appeared to restore keratin expression level. Conclusion Changes in keratin expression associate with progression towards neoplasia, but remain modifiable risk factors. Dietary strategies may improve secondary chemoprevention. Trial registration number ISRCTN90852168. PMID:26462274

  16. Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B

    SciTech Connect

    Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

    1988-06-01

    The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

  17. The normal structure and function of CD44 and its role in neoplasia.

    PubMed

    Sneath, R J; Mangham, D C

    1998-08-01

    CD44 is a transmembrane glycoprotein, the variant isoforms of which are coded for by alternative splicing, with the most prolific isoform being CD44 standard. CD44 is found in a wide variety of tissues including the central nervous system, lung, epidermis, liver, and pancreas, whereas variant isoforms of CD44 (CD44v) appear to have a much more restricted distribution. Variants of CD44 are expressed in tissues during development, including embryonic epithelia. Known functions of CD44 are cellular adhesion (aggregation and migration), hyaluronate degradation, lymphocyte activation, lymph node homing, myelopoiesis and lymphopoiesis, angiogenesis, and release of cytokines. The functions of CD44 are principally dependant on cellular adhesion in one setting or another. The role of CD44 in neoplasia is less well defined, although metastatic potential can be conferred on non-metastasising cell lines by transfection with a variant of CD44 and high levels of CD44 are associated with several types of malignant tumours. The physiological functions of CD44 indicate that the molecule could be involved in the metastatic spread of tumours. Many studies have investigated the pattern of CD44 distribution in tumours and some observations suggest that certain cells do not use CD44 in tumorigenesis or in the production of metastases. However, the data are extremely conflicting, and further studies are needed to establish the prognostic value of CD44 and its variant isoforms. The precise function of CD44 in the metastatic process and the degree of involvement in human malignancies has yet to be established fully. PMID:9893744

  18. Conization Using an Electrosurgical Knife for Cervical Intraepithelial Neoplasia and Microinvasive Carcinoma

    PubMed Central

    Yang, Wentao; Xu, Xiaoli; Wu, Xiaohua; Wang, Huaying; Li, Ziting; Yang, Huijuan

    2015-01-01

    Objective The aim of the present study was to evaluate the incidences of margin involvement, disease relapse, and complications in patients who had undergone conization using an electrosurgical knife (EKC) for cervical intraepithelial neoplasia (CIN) or microinvasive carcinomas (micro-CAs). Materials and Methods A retrospective case series analysis was performed with a total of 1359 patients who underwent EKC in Fudan University Shanghai Cancer Center between June 2004 and July 2010. Results The median age of the patients was 39 years old (range: 19-72). Conization revealed the presence of CIN in 1113 (81.9%) patients, micro-CA in 72 (5.3%) patients and invasive carcinomas in 44 (3.2%) patients. The remaining 130 (9.6%) patients were free of diseases in the cone specimens. Positive surgical margins, or endocervical curettages (ECCs) were found in 90 (7.6%) patients with CINs or micro-CAs. Three factors were associated with positive margins and ECCs and included age (>50 years; odds ratio (OR), 3.0, P<0.01), postmenopausal status (OR, 3.1, P<0.01) and microinvasive disease (OR, 2.7, P<0.01). One thousand and eighty-nine (92.0%) patients were followed-up regularly for a median follow-up duration of 46 months (range: 24-106 months). Disease relapse was documented in 50 (4.6%) patients. Eighty-two (6.0%) cases experienced surgical complications that needed to be addressed, including early or late hemorrhages, infections, cervical stenosis, etc. Conclusions Our patients demonstrated that EKC was an alternative technique for diagnosis and treatment of CIN or micro-CAs with relatively low rate of recurrence and acceptable rate of complications. A randomized clinical trial is warranted to compare EKC, CKC and LEEP in the management of CIN or micro-CA. PMID:26153692

  19. Immune response to JC virus T antigen in patients with and without colorectal neoplasia.

    PubMed

    Butcher, Lindsay D; Garcia, Melissa; Arnold, Mildred; Ueno, Hideki; Goel, Ajay; Boland, C Richard

    2014-07-01

    JC virus (JCV) is a polyomavirus that infects approximately 75% of the population and encodes a T antigen (T-Ag) gene, which is oncogenic and inactivates the p53 and pRb/p107/p130 protein families. Previous work in our lab has identified the presence of T-Ag in colorectal neoplasms. While JCV remains in a latent state for the majority of those infected, we hypothesized that a disturbance in immunological control may permit JCV to reactivate, which may be involved in the development of colorectal neoplasia. Our aim was to determine the cell mediated immune response to JCV T-Ag, and determine if it is altered in patients with colorectal adenomatous polyps (AP) or cancers (CRC). Peripheral blood mononuclear cells (PBMCs) isolated from the blood of patients undergoing colonoscopy or colorectal surgery were stimulated by a peptide library covering the entire T-Ag protein of JCV. Cytokine production and T cell proliferation were evaluated following T-Ag stimulation using Luminex and flow cytometry assays. JCV T-Ag peptides stimulated secretion of IL-2, which induced T cell expansion in all three groups. However, stronger IL-10 and IL-13 production was seen in patients without colorectal neoplasms. IP-10 was produced at very high levels in all groups, but not significantly differently between groups. Most patients exhibited CD4(+) and CD8(+) T cells in response to stimulation by the T-Ag clusters. The combination of IL-2 and IP-10 secretion indicates the presence of T-Ag-specific Th1 cells in all patients, which is higher in patients without carcinoma. PMID:25007286

  20. Human Papillomavirus Genotype-Specific Prevalence Across the Continuum of Cervical Neoplasia and Cancer

    PubMed Central

    Joste, Nancy E.; Ronnett, Brigitte M.; Hunt, William C.; Pearse, Amanda; Langsfeld, Erika; Leete, Thomas; Jaramillo, MaryAnn; Stoler, Mark H.; Castle, Philip E.; Wheeler, Cosette M.

    2014-01-01

    Background The New Mexico HPV Pap Registry was established to measure the impact of cervical cancer prevention strategies in the United States. Prior to widespread HPV vaccine implementation, we established the baseline prevalence for a broad spectrum of HPV genotypes across the continuum of cervical intraepithelial neoplasia (CIN) and cancer. Methods A population-based sample of 6,272 tissue specimens were tested for 37 HPV genotypes. The number of specimens tested within each diagnostic category was: 541 negative, 1,411 CIN grade 1 (CIN1), 2,226 CIN grade 2 (CIN2), and 2,094 CIN grade 3 (CIN3) or greater. Age-specific HPV prevalence was estimated within categories for HPV genotypes targeted by HPV vaccines. Results The combined prevalence of HPV genotypes included in the quadrivalent and nonavalent vaccines increased from 15.3% and 29.3% in CIN1 to 58.4% and 83.7% in CIN3, respectively. The prevalence of HPV types included in both vaccines tended to decrease with increasing age for CIN1, CIN2, CIN3, and squamous cell carcinoma, most notably for CIN3 and SCC. The six most common HPV types in descending order of prevalence were HPV-16, −31, −52, −58, −33, and −39 for CIN3 and HPV-16, −18, −31, −45, −52, and −33 for invasive cancers. Conclusions Health economic modeling of HPV vaccine impact should consider age-specific differences in HPV prevalence. Impact Population-based HPV prevalence in CIN is not well described but is requisite for longitudinal assessment of vaccine impact and to understand the effectiveness and performance of various cervical screening strategies in vaccinated and unvaccinated women. PMID:25363635

  1. A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III

    PubMed Central

    CANALES, NORMA ANGÉLICA GALICIA; MARINA, VICENTE MADRID; CASTRO, JORGE SALMERÓN; JIMÉNEZ, ALFREDO ANTÚNEZ; MENDOZA-HERNÁNDEZ, GUILLERMO; McCARRON, ELIZABETH LANGLEY; ROMAN, MARGARITA BAHENA; CASTRO-ROMERO, JULIETA IVONE

    2014-01-01

    The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as ?-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions. PMID:25009667

  2. Human papillomavirus (HPV) infections and their associations with squamous cell neoplasia.

    PubMed

    Syrjänen, K J

    1987-01-01

    Current data implicating an etiological role of Human papillomavirus (HPV) infections in precancer lesions (intraepithelial neoplasia) and squamous cell carcinoma of both the genital tract and other sites (oral cavity, larynx, skin, esophagus, nasal cavity, bronchus) can be summarized as follows: a) HPV involvement in benign, precancer, and malignant genital squamous cell lesions has been demonstrated by morphological, immunohistochemical and DNA hybridization techniques; b) HPV infections in the genital tract are sexually transmitted (STD) and associated with the same risk factors as development of cervical carcinoma; c) natural history of cervical HPV lesions is equivalent to that of CIN, i.e. they are potentially progressive to carcinoma in situ; d) latent HPV infections exist in the genital tract of both sexes; e) animal models exist, where papillomaviruses induce malignant transformation; f) HPV 11 induces transformation of human squamous epithelium in vivo (nude mouse renal subcapsule assay); g) malignant transformation of HPV lesions seems to depend on virus type and the physical state of its DNA, i.e. whether or not integrated in the host cell DNA; h) malignant transformation most probably requires synergistic actions between HPV and chemical or physical carcinogens or other infectious agents; i) genetic disposition (at least in animals) significantly contributes to malignant transformation; j) immunological defence mechanisms of the host probably are capable of modifying the course of HPV infection (efficacy in man remains to be elucidated). Many details of the molecular mechanisms still remain to be clarified, however. No applicable model systems exist to elucidate these issues, or the mechanisms leading to the progression to invasive cancer. Improved tissue culture systems for in vitro differentiation of keratinocytes should help in elucidating the biology of papillomaviruses and their interaction with cell division and differentiation. PMID:2829787

  3. Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer.

    PubMed

    Liu, P; Xin, F; Ma, C F

    2015-01-01

    Previous studies have reported that miR-196a is upregulated in cervical cancer tissues and cell lines. However, whether serum miR-196a is increased in patients with cervical cancer or cervical intraepithelial neoplasia (CIN), and its potential clinical value remained unknown. In total, 105 cervical cancer patients, 86 CIN patients, and 50 healthy volunteers were recruited. Quantitative reverse transcription-polymerase chain reaction was performed to compare the serum levels miR-196a in all participants. The associations between serum miR-196a and CIN grade/clinicopathological parameters of cervical cancer were also examined. A survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted to explore the independent risk factors for cervical cancer. Our results revealed that serum miR-196a levels were higher in patients with cervical cancer (P < 0.01) and CIN (P < 0.05) compared to those in healthy controls. Serum miR-196a was associated with CIN grade and various cervical cancer parameters including tumor size (P = 0.031), lymph node metastasis (P = 0.018), FIGO stage (P = 0.004), and grade (P = 0.011). Cervical cancer patients with higher serum miR-196a levels had a poorer overall survival rate (P = 0.004). Multivariate analysis revealed that high serum miR-196a was an independent predictor for poor survival of cervical cancer (HR = 3.510; 95%CI = 1.961-6.874; P = 0.025). In conclusion, our findings suggest that serum miR-196a overexpression is associated with CIN grade and cervical cancer progression. Therefore, serum miR-196a may be a reliable biomarker for early detection and prognosis of cervical cancer. PMID:26782446

  4. Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia

    PubMed Central

    Sopracordevole, Francesco; Mancioli, Francesca; Clemente, Nicolò; De Piero, Giovanni; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

    2015-01-01

    Abstract The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2–VaIN 3) and the cytological abnormalities on the referral pap smear. All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed. A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P?=?0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P?=?0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P?

  5. Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists.

    PubMed

    Usubutun, Alp; Mutter, George L; Saglam, Arzu; Dolgun, Anil; Ozkan, Eylem Akar; Ince, Tan; Akyol, Aytekin; Bulbul, H Dilek; Calay, Zerrin; Eren, Funda; Gumurdulu, Derya; Haberal, A Nihan; Ilvan, Sennur; Karaveli, Seyda; Koyuncuoglu, Meral; Muezzinoglu, Bahar; Muftuoglu, Kamil H; Ozdemir, Necmettin; Ozen, Ozlem; Baykara, Sema; Pestereli, Elif; Ulukus, Emine Cagnur; Zekioglu, Osman

    2012-06-01

    Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted ? values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders. PMID:22301705

  6. Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2 Managed by Watchful Waiting

    PubMed Central

    Ho, Gloria Y.F.; Einstein, Mark H.; Romney, Seymour L.; Kadish, Anna S.; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R.; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D.

    2013-01-01

    Objective This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed every 3 months without treatment. HPV genotyping, plasma levels of ascorbic acid, and red blood cell folate were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p< 0.001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared to HPV negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74 to 2.09) were at increased risk for persistent CIN; women with HPV 16/18 had the highest risk (RRs range = 1.91 to 2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50 – 2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusion Spontaneous regression of CIN 1 and CIN 2 occurs frequently within 12 months. HPV infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion. PMID:21811178

  7. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1990--December 31, 1992

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  8. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1991--December 31, 1991

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  9. A Risk Prediction Index for Advanced Colorectal Neoplasia at Screening Colonoscopy

    PubMed Central

    Schroy, Paul C.; Wong, John B.; O’Brien, Michael J.; Chen, Clara A.; Griffith, John L.

    2016-01-01

    Background Eliciting patient preferences within the context of shared decision-making has been advocated for colorectal cancer screening. Risk stratification for advanced colorectal neoplasia (ACN) might facilitate more effective shared decision-making when selecting an appropriate screening option. Our objective was to develop and validate a clinical index for estimating the probability ACN at screening colonoscopy. Methods We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average risk patients 50–79 years of age undergoing screening colonoscopy at two urban safety net hospitals. Predictors of ACN were identified using multiple logistic regression. Model performance was internally validated using bootstrapping methods. Results The final index consisted of 5 independent predictors of risk (age, smoking, alcohol intake, height and a combined sex/race/ethnicity variable). Smoking was the strongest predictor (net reclassification improvement [NRI], 8.4%) and height the weakest (NRI, 1.5%). Using a simplified weighted scoring system based on 0.5 increments of the adjusted odds ratio, the risk of ACN ranged from 3.2% (95% CI, 2.6 to 3.9) for the low-risk group (score ? 2) to 8.6% (95% CI, 7.4–9.7) for the intermediate/high-risk group (score 3–11). The model had moderate to good overall discrimination (C-statistic, 0.69; 95% CI, 0.66–0.72) and good calibration (P=0.73 to 0.93). Conclusions A simple 5-item risk index based on readily available clinical data accurately stratifies average-risk patients into low- and intermediate/high-risk categories for ACN at screening colonoscopy. Uptake into clinical practice could facilitate more effective shared decision-making for CRC screening, particularly in situations where patient and provider test preferences differ. PMID:26010311

  10. Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients

    PubMed Central

    Hwang, In Kyeom; Kim, Haeryoung; Lee, Yoon Suk; Kim, Jaihwan; Cho, Jai Young; Yoon, Yoo-Seok; Han, Ho-Seong; Hwang, Jin-Hyeok

    2015-01-01

    The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN. PMID:26183380

  11. Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis

    PubMed Central

    Uleberg, Kai-Erik; Øvestad, Irene Tveiterås; Munk, Ane Cecilie; van Diermen, Bianca; Gudlaugsson, Einar; Janssen, Emiel A. M.; Hjelle, Anne; Baak, Jan P. A.

    2014-01-01

    Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (?CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81?mg/mL (range: 0.55–1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3. PMID:25018881

  12. AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia

    PubMed Central

    Gibbon, Karen; Byrne, Carolyn R.; Arbeit, Jeffrey M.; Harwood, Catherine A.; O'Shaughnessy, Ryan F. L.

    2012-01-01

    Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy. PMID:22685591

  13. Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia.

    PubMed

    van den Einden, Loes C G; de Hullu, Joanne A; Massuger, Leon F A G; Grefte, Johanna M M; Bult, Peter; Wiersma, Anne; van Engen-van Grunsven, Adriana C H; Sturm, Bart; Bosch, Steven L; Hollema, Harry; Bulten, Johan

    2013-06-01

    No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN. A total number of 34 hematoxylin and eosin-stained slides were included in this study and were analyzed by six pathologists each with a different level of education. Slides were reviewed before and after studying a guideline with histological characteristics of DVIN. Kappa statistics were used to compare the interobserver variability. Pathologists with a substantial agreement were asked to rank items by usefulness in the recognition of DVIN. The interobserver agreement during the first session varied between 0.08 and 0.54, which slightly increased during the second session toward an agreement between -0.01 and 0.75. Pathologists specialized in gynecopathology reached a substantial agreement (kappa 0.75). The top five of criteria indicated to be the most useful in the diagnosis of DVIN included: atypical mitosis in the basal layer, basal cellular atypia, dyskeratosis, prominent nucleoli and elongation and anastomosis of rete ridges. In conclusion, the histopathological diagnosis of DVIN is difficult, which is expressed by low interobserver agreement. Only in experienced pathologists with training in gynecopathology, kappa values reached a substantial agreement after providing strict guidelines. Therefore, it should be considered that specimens with an unclear diagnosis and/or clinical suspicion for DVIN should be revised by a pathologist specialized in gynecopathology. When adhering to suggested criteria the diagnosis of DVIN can be made easier. PMID:23370772

  14. An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo.

    PubMed

    Xu, Wenqin; Stadler, Cynthia K; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M; Pye, Geoffrey W; Eiden, Maribeth V

    2013-07-01

    Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population. PMID:23798387

  15. Heat shock protein 27 and p16 immunohistochemistry in cervical intraepithelial neoplasia and squamous cell carcinoma.

    PubMed

    Tozawa-Ono, Akiko; Yoshida, Ayako; Yokomachi, Noriyuki; Handa, Rumiko; Koizumi, Hirotaka; Kiguchi, Kazushige; Ishizuka, Bunpei; Suzuki, Nao

    2012-03-01

    Heat shock protein 27 (hsp27) is expressed by squamous cell carcinoma of the uterine cervix. Results from an earlier study by our group indicted that hsp27 may be a diagnostic marker for cervical intraepithelial neoplasia (CIN) and carcinoma. p16 expression is known to be elevated in intraepithelial uterine cervical cancer and grades 2 and 3 lesions (CIN2, CIN3), but has also been reported to be negative in 5-20% of cervical cancer and CIN lesions. The aim of our study was to confirm immunohistochemically the expression of hsp27 and p16 in cervical lesions. Formalin-fixed, paraffin-embedded cervical tissue specimens obtained between 2002 and 2010 were investigated for hsp27 and p16 expression. Positive staining was detected for hsp27 in 63% of normal cervical tissues, 47% of CIN1 lesions, 75% of CIN2 lesions, 92% of CIN3 lesions, and 100% of squamous cell carcinomas (SCC); the corresponding rates for p16 positivity were 29, 47, 67, 92, and 75%, respectively. Positive staining for both hsp27 and p16 was observed in 6% of normal cervical tissues and in 19% of CIN1, 18% of CIN2, 85% of CIN3, and 75% of SCC specimens. Hsp27 or p16 positivity had a sensitivity of 95.6 or 84.7% and a specificity of 37.2 or 70.5%, respectively, for the identification of CIN3 or SCC lesions; when both hsp27 and p16 were assessed, both the sensitivity and specificity were improved. In conclusion, both hsp27 and p16 immunohistochemistry is a useful tool for the diagnosis of CIN3 lesions or cervical SCC. PMID:22302674

  16. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia.

    PubMed

    Bosch, F Xavier; Burchell, Ann N; Schiffman, Mark; Giuliano, Anna R; de Sanjose, Silvia; Bruni, Laia; Tortolero-Luna, Guillermo; Kjaer, Susanne Kruger; Muñoz, Nubia

    2008-08-19

    Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia. PMID:18847553

  17. Accuracy of Colposcopically Guided Diagnostic Methods for the Detection of Cervical Intraepithelial Neoplasia

    PubMed Central

    Müller, K.; Soergel, P.; Hillemanns, P.; Jentschke, M.

    2016-01-01

    Introduction: Many factors can affect the accuracy of colposcopically guided biopsy, endocervical curettage (ECC) and differential cytology, all of which are standard, minimally invasive procedures used to detect cervical intraepithelial neoplasia. Method: All conizations carried out between 2007 and 2013 in the gynecological department of Hannover Medical School were retrospectively reviewed. The agreement between colposcopic diagnosis and histology was evaluated retrospectively. The analysis included 593 complete datasets out of a total of 717 cases treated. Results: The overall agreement was 85.5 %; the accuracy was significantly higher (p = 0.029) when three biopsy specimens were taken rather than just one. The agreement between diagnosis and histological findings from conization was highest for women < 30 years (90.7 %) and lowest for women > 50 years (72.1 %; p = 0.008). The agreement between preoperative differential cytology and histology results after conization was 86.7 % and improved as patient age increased (p = 0.035). The agreement between ECC findings and the results of conization was only 49.1 % irrespective of patient age, transformation zone or the patientʼs menopausal status. Conclusion: The accuracy of colposcopically guided biopsy appears to increase when three biopsy specimens are taken and is particularly high for younger patients. Differential cytology was also found to be highly accurate and is particularly useful for patients aged more than 50 years. The accuracy of ECC was significantly lower; however ECC can provide important additional information in selected cases. PMID:26941452

  18. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

    PubMed Central

    Mitra, A.; MacIntyre, D. A.; Lee, Y. S.; Smith, A.; Marchesi, J. R.; Lehne, B.; Bhatia, R.; Lyons, D.; Paraskevaidis, E.; Li, J. V.; Holmes, E.; Nicholson, J. K.; Bennett, P. R.; Kyrgiou, M.

    2015-01-01

    Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression. PMID:26574055

  19. High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene

    PubMed Central

    Liu, Jehnan; Ramakrishnan, Sadeesh K.; Khuder, Saja S.; Kaw, Meenakshi K.; Muturi, Harrison T.; Lester, Sumona Ghosh; Lee, Sang Jun; Fedorova, Larisa V.; Kim, Andrea J.; Mohamed, Iman E.; Gatto-Weis, Cara; Eisenmann, Kathryn M.; Conran, Philip B.; Najjar, Sonia M.

    2015-01-01

    Objective Association between prostate cancer and obesity remains controversial. Allelic deletions of PTEN, a tumor suppressor gene, are common in prostate cancer in men. Monoallelic Pten deletion in mice causes low prostatic intraepithelial neoplasia (mPIN). This study tested the effect of a hypercaloric diet on prostate cancer in Pten+/? mice. Methods 1-month old mice were fed a high-calorie diet deriving 45% calories from fat for 3 and 6 months before prostate was analyzed histologically and biochemically for mPIN progression. Because Pten+/? mice are protected against diet-induced insulin resistance, we tested the role of insulin on cell growth in RWPE-1 normal human prostatic epithelial cells with siRNA knockdown of PTEN. Results In addition to activating PI3 kinase/Akt and Ras/MAPkinase pathways, high-calorie diet causes neoplastic progression, angiogenesis, inflammation and epithelial–mesenchymal transition. It also elevates the expression of fatty acid synthase (FAS), a lipogenic gene commonly elevated in progressive cancer. SiRNA-mediated downregulation of PTEN demonstrates increased cell growth and motility, and soft agar clonicity in addition to elevation in FAS in response to insulin in RWPE-1 normal human prostatic cells. Downregulating FAS in addition to PTEN, blunted the proliferative effect of insulin (and IL-6) in RWPE-1 cells. Conclusion High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis. PMID:25737954

  20. Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes.

    PubMed Central

    Lairmore, T C; Ball, D W; Baylin, S B; Wells, S A

    1993-01-01

    OBJECTIVE: The authors sought to determine the optimal surgical management of pheochromocytomas that develop in patients with multiple endocrine neoplasia (MEN) type 2 syndromes. SUMMARY BACKGROUND DATA: The performance of empirical bilateral adrenalectomy in patients with MEN 2A or MEN 2B, whether or not they have bilateral pheochromocytomas, is controversial. METHODS: The results of unilateral or bilateral adrenalectomy were studied in 58 patients (49 with MEN 2A and 9 with MEN 2B). Recurrence of disease was evaluated by measuring 24-hour urinary excretion rates of catecholamines and metabolites and by computed tomography (CT) scanning. RESULTS: The mean postoperative follow-up was 9.40 years. There was no operative mortality and malignant or extra-adrenal pheochromocytomas were not present. Twenty-three patients with a unilateral pheochromocytoma and a macroscopically normal contralateral gland underwent unilateral adrenalectomy. A pheochromocytoma developed in the remaining gland a mean of 11.87 years after the primary adrenalectomy in 12 (52%) patients. Conversely, 11 (48%) patients did not develop pheochromocytoma during a mean interval of 5.18 years. In the interval after unilateral adrenalectomy, no patient experienced hypertensive crises or other complications related to an undiagnosed pheochromocytoma. Ten (23%) of 43 patients having both adrenal glands removed (either at a single operation or sequentially) experienced at least one episode of acute adrenal insufficiency or Addisonian crisis, including one patient who died during a bout of influenza. CONCLUSIONS: Based on these data, the treatment of choice for patients with MEN 2A or MEN 2B and a unilateral pheochromocytoma is resection of only the involved gland. Substantial morbidity and significant mortality are associated with the Addisonian state after bilateral adrenalectomy. PMID:8099474

  1. The PapilloCheck Assay for Detection of High-Grade Cervical Intraepithelial Neoplasia.

    PubMed

    Crosbie, Emma J; Bailey, Andrew; Sargent, Alex; Gilham, Clare; Peto, Julian; Kitchener, Henry C

    2015-11-01

    Human papillomavirus (HPV) testing is used in primary cervical screening, as an adjunct to cervical cytology for the management of low grade abnormal cytology, and in a test of cure. PapilloCheck (Greiner Bio-One) is a PCR-based DNA microarray system that can individually identify 24 HPV types, including the 13 high-risk (HR) types identified by Hybrid Capture 2 (HC2). Here, we compare PapilloCheck with HC2 for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a total of 8,610 cervical cytology samples from the ARTISTIC population-based cervical screening study. We performed a retrospective analysis of 3,518 cytology samples from round 1 ARTISTIC enriched for underlying CIN2+ (n = 723) and a prospective analysis of 5,092 samples from round 3 ARTISTIC. Discrepant results were tested using the Roche reverse line blot (RLB) or Linear Array (LA) assay. The relative sensitivity and specificity of HR PapilloCheck compared with that of HC2 for the detection of CIN2+ in women aged over 30 years were 0.94 (95% confidence interval [CI], 0.91, 0.97) and 1.05 (95% CI, 1.04, 1.05), respectively. HC2 missed 44/672 (7%) CIN2+ lesions, while HR PapilloCheck missed 74/672 (11%) CIN2+ lesions. Thirty-six percent of HC2-positive normal cytology samples were HR HPV negative by both PapilloCheck and RLB/LA, indicating that the use of HR PapilloCheck rather than HC2 in population-based primary screening would reduce the number of additional tests required (e.g., reflex cytology) in women where underlying CIN2+ is extremely unlikely. HR PapilloCheck could be a suitable HPV detection assay for use in the cervical screening setting. PMID:26338859

  2. An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo

    PubMed Central

    Xu, Wenqin; Stadler, Cynthia K.; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M.; Pye, Geoffrey W.; Eiden, Maribeth V.

    2013-01-01

    Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype “KoRV-A,” whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype “KoRV-B.” KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population. PMID:23798387

  3. Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

    PubMed Central

    Molatore, Sara; Liyanarachchi, Sandya; Irmler, Martin; Perren, Aurel; Mannelli, Massimo; Ercolino, Tonino; Beuschlein, Felix; Jarzab, Barbara; Wloch, Jan; Ziaja, Jacek; Zoubaa, Saida; Neff, Frauke; Beckers, Johannes; Höfler, Heinz; Atkinson, Michael J.; Pellegata, Natalia S.

    2010-01-01

    Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use. PMID:20937862

  4. Address of early stage primary colonic neoplasia by N.O.T.E.S.

    PubMed

    Cahill, R A; Lindsey, I; Cunningham, C

    2009-06-01

    Natural Orifice Translumenal Endoscopic Surgery (N.O.T.E.S.) has the capacity to impact greatly on the practice of colorectal surgery. As much as potentially providing an alternative means of operative approach, its consideration and evolution is already also providing a wealth of instrument innovation that seems likely to greatly enhance the endoscopists' armamentarium for advanced endoluminal intervention. Furthermore, its aspirational concept is greatly advancing the progress of single site incision laparoscopic approaches and is speeding appreciation of translumenal assistance and operation. However, if N.O.T.E.S. is to occupy a distinct role in the surgical management of colorectal disease, it needs a niche indication of its own that constitutes a therapeutic advance with considerable clinical benefit for suitable patients. Conversely, sound development of a specific stream-lined operative strategy for N.O.T.E.S-type operations may exert a reciprocal swash upon conventional specialist practice. Thus spurred by N.O.T.E.S, localized resection may become standard therapy for early stage colonic neoplasia regardless of operative access although considerable clinical study is as yet required. Therefore, as much as ensuring feasibility and accuracy in the replication of conventional surgical maneuvers, the dawn of N.O.T.E.S. should be recognized as an opportunity for the inquisition of prevailing surgical principles and prejudices in order that colorectal operations are further honed towards perfection (above all it should be realized that avoidance of abdominal scarring is not the last barrier before surgical nirvana). This may represent the main legacy of transluminal investigation whether or not pure N.O.T.E.S. operating ever becomes a clinical reality in its own right. PMID:19179068

  5. Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications

    PubMed Central

    Mosquera, Juan-Miguel; Perner, Sven; Genega, Elizabeth M; Sanda, Martin; Hofer, Matthias D.; Mertz, Kirsten D.; Paris, Pamela L.; Simko, Jeff; Bismar, Tarek A.; Ayala, Gustavo; Shah, Rajal B.; Loda, Massimo; Rubin, Mark A.

    2013-01-01

    Purpose More than 1,300,000 prostate needle biopsies are performed annually in the U.S. with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer (PCA) on subsequent needle biopsies in PSA screened populations. In contemporary series, PCA is detected in about 20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histological subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in PCA has also been demonstrated to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion PCA is associated with a more aggressive clinical course. Experimental Design In this study we assessed a series of HGPIN lesions and paired PCA for the presence of TMPRSS2-ERG gene fusion. Results Fusion positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances the matching cancer shared the same fusion pattern. 60% of TMPRSS2-ERG fusion PCA had fusion negative HGPIN. Conclusions Given the more aggressive nature of TMPRSS2-ERG PCA, the findings of this study raise the possibility that gene fusion positive HGPIN lesions are harbingers of more aggressive disease. To date, pathological, molecular and clinical parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding TMPRSS2-ERG fusion PCA in subsequent biopsies. PMID:18519767

  6. Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study.

    PubMed

    Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

    2014-12-01

    We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97-1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03-1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01-1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15-1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15-1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings. PMID:25146172

  7. LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

    PubMed Central

    Lertkhachonsuk, Ruangsak; Paiwattananupant, Krissada; Tantbirojn, Patou; Rattanatanyong, Prakasit; Mutirangura, Apiwat

    2015-01-01

    Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN). Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN. Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p = 0.003) and the uCuC of LINE-1 increased in the malignant trophoblast group (p ? 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowest p value for distinguishing between the two groups (p < 0.001). The combination of the pretreatment ?-hCG level (?100,000?mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively. Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN. PMID:26448937

  8. A comparative evaluation of Raman and fluorescence spectroscopy for optical diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.

    2011-08-01

    We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.

  9. Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirus testing.

    PubMed

    Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

    2000-12-01

    Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57-132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93-88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72-82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. PMID:11076654

  10. Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia

    PubMed Central

    Shadeo, Ashleen; Chari, Raj; Lonergan, Kim M; Pusic, Andrea; Miller, Dianne; Ehlen, Tom; Van Niekerk, Dirk; Matisic, Jasenka; Richards-Kortum, Rebecca; Follen, Michele; Guillaud, Martial; Lam, Wan L; MacAulay, Calum

    2008-01-01

    Background The highest rates of cervical cancer are found in developing countries. Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN). CIN lesions described as mild dysplasia (CIN I) are likely to spontaneously regress while CIN III lesions (severe dysplasia) are likely to progress if untreated. Thoughtful consideration of gene expression changes paralleling the progressive pre invasive neoplastic development will yield insight into the key casual events involved in cervical cancer development. Results In this study, we have identified gene expression changes across 16 cervical cases (CIN I, CIN II, CIN III and normal cervical epithelium) using the unbiased long serial analysis of gene expression (L-SAGE) method. The 16 L-SAGE libraries were sequenced to the level of 2,481,387 tags, creating the largest SAGE data collection for cervical tissue worldwide. We have identified 222 genes differentially expressed between normal cervical tissue and CIN III. Many of these genes influence biological functions characteristic of cancer, such as cell death, cell growth/proliferation and cellular movement. Evaluation of these genes through network interactions identified multiple candidates that influence regulation of cellular transcription through chromatin remodelling (SMARCC1, NCOR1, MRFAP1 and MORF4L2). Further, these expression events are focused at the critical junction in disease development of moderate dysplasia (CIN II) indicating a role for chromatin remodelling as part of cervical cancer development. Conclusion We have created a valuable publically available resource for the study of gene expression in precancerous cervical lesions. Our results indicate deregulation of the chromatin remodelling complex components and its influencing factors occur in the development of CIN lesions. The increase in SWI/SNF stabilizing molecule SMARCC1 and other novel genes has not been previously illustrated as events in the early stages of dysplasia development and thus not only provides novel candidate markers for screening but a biological function for targeting treatment. PMID:18248679

  11. Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting

    PubMed Central

    Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

    2000-01-01

    Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076654

  12. Relationship between HPV typing and the status of G2 cell cycle regulators in cervical neoplasia.

    PubMed

    Hashiguchi, Yasunori; Tsuda, Hiroshi; Nishimura, Sadako; Inoue, Takeshi; Kawamura, Naoki; Yamamoto, Kumio

    2004-09-01

    We examined human papillomavirus (HPV) typing and the status of ATM, chk2, CDC25C, cdc2 and cyclinB1 in cervical intraepithelial neoplasia (CIN) and invasive cancer (IC). A total of 93 samples [normal: 10; CIN: 34 (CINI:9, CINII:12, CINIII:13); IC: 49 (stage I:10, stage II:21, stage III:15, stage IV:3)] were included in this study. HPV status was evaluated by the PCR non-radioactive HPV detection system. We analyzed ATM, chk2, CDC25C, cdc2 and cyclinB1 protein expression by immunohistochemistry. HPV DNA was detected in 73.5% of 34 CINs and 89.8% of 49 ICs. Detection of HPV subtypes 16 and 18 was more frequent in ICs (46.9%) than in CINs (23.5%) (p=0.0387). Abnormal expression of ATM, chk2, CDC25C, cdc2 and cyclinB1 were 2.9%, 32.4%, 2.9% 20.6% and 0% in CINs and 8.2%, 30.6%, 10.2%, 46.9% and 12.2% in ICs. The alteration of cdc2 was higher in ICs than in CINs (p=0.0198). Altered expression of cdc2 was higher in HPV16 and 18 cases (69.6%) than in other cases (26.9%) (p=0.0042). However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant. Cdc2 is implicated in cervical carcinogenesis and may be related to p53 inactivation by HPV. PMID:15289842

  13. Inverted (hobnail) high-grade prostatic intraepithelial neoplasia and invasive inverted pattern

    PubMed Central

    ÖZNUR, MELTEM; KOCA, SEVIM BAYKAL; YILDIZ, PELIN; BAHADIR, BURAK; BEHZATO?LU, KEMAL

    2015-01-01

    High-grade prostatic intraepithelial neoplasia (HGPIN) is considered to be an important precursor for prostatic adenocarcinoma. The present study aimed to investigate the histological features of the uncommon inverted (hobnail) pattern of HGPIN in transrectal ultrasonographic (TRUS) prostatic needle biopsies from 13 cases. These 13 diagnosed cases of inverted HGPIN were identified out of a total of 2,034 TRUS biopsies (0.63%), obtained from patients suspected to have prostate cancer. The hobnail pattern is comprised of secretory cell nuclei, which are histologically localized at the luminal surface of the prostate gland, rather than the periphery, and exhibit reverse polarity. Histological examinations were performed and the results demonstrated that 5 of the 13 cases exhibited pure inverted histology, while HGPIN was observed to be histologically associated with other patterns in the remaining 8 patients. In addition, an association with adenocarcinoma was identified in 7 of the 13 cases. All 7 carcinomas accompanied by inverted HGPIN were conventional acinar adenocarcinoma cases; of note, for these 7 cases, the Gleason score was 7 for each. One acinar adenocarcinoma case accompanying inverted HGPIN demonstrated hobnail characteristics in large areas of the invasive component. It was observed that nuclei were proliferated in the invasive cribriform glands, which was comparable to that of inverted HGPIN, and were located on the cytoplasmic luminal surface; a similar morphology was also observed in individual glands. In conclusion, the results of the present study suggested that the hobnail HGPIN pattern may be of diagnostic importance due to its high association with adenocarcinoma and the high Gleason scores in the accompanying carcinomas. PMID:26622858

  14. Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

    USGS Publications Warehouse

    Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

    2009-01-01

    Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

  15. Peroxisome proliferator-activated receptor-? is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia

    PubMed Central

    DOU, XIAOTAN; XIAO, JUNHUA; JIN, ZILIANG; ZHENG, PING

    2015-01-01

    The aim of the present study was to evaluate the expression of peroxisome proliferator-activated receptor (PPAR)-? in inflammatory bowel disease (IBD), and to also identify the association between PPAR-? and the clinical features of patients with IBD. An azoxymethane (AOM)/dextran sodium sulfate (DSS) animal model of colitis-associated neoplasia was established to investigate the protective effect of 5-aminosalicylic acid (5-ASA) and to explore the changes in the expression of PPAR-? during this process. A total of 66 specimens of colorectal tissue obtained from biopsy performed on IBD patients and 30 healthy control individuals were immunohistochemically stained for PPAR-?. An AOM/DSS animal model of colitis-associated neoplasia was then established. Reverse transcription quantitative polymerase chain reaction was conducted and it was found that, compared with the control group and patients with Crohn's disease (CD), the expression of PPAR-? in the intestinal tissue of patients with ulcerative colitis (UC) was significantly decreased (P=0.027 and 0.046, respectively). The expression of PPAR-? was found to be negatively associated with the disease activity of UC and was not associated with the severity of disease, site of lesions or CD characteristics. Administration of 5-ASA decreased the colitis and tumor burden of colons. The expression level of PPAR-? in the intestinal tissue was also increased in the AOM/DSS/5-ASA group compared with AOM/DSS group (P<0.001). PPAR-? is an important factor in the pathogenesis of UC and colitis-associated cancer. The present study found that 5-ASA significantly alleviates the colitis and tumor burden in a mouse model of AOM/DSS-induced colitis-associated neoplasia, and promotes the expression of PPAR-? in the intestinal tract. PMID:26622660

  16. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

    PubMed Central

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-01-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  17. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    PubMed

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  18. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis

    PubMed Central

    Mitra, Anita; Arbyn, Marc; Stasinou, Sofia Melina; Martin-Hirsch, Pierre; Bennett, Phillip; Paraskevaidis, Evangelos

    2014-01-01

    Objective To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes. Design Systematic review and meta-analysis of cohort studies. Data sources Medline and Embase. Eligibility criteria Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint. Analysis Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I2 statistics. Results 15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (P<0.0001). Pregnancy rates did not differ between women with an intention to conceive (two studies; 88% v 95%, 0.93, 0.80 to 1.08) and the number requiring more than 12 months to conceive (three studies, 15% v 9%, 1.45, 0.89 to 2.37). Although the rates for total miscarriages (10 studies; 4.6% v 2.8%, 1.04, 0.90 to 1.21) and miscarriage in the first trimester (four studies; 9.8% v 8.4%, 1.16, 0.80 to 1.69) was similar for treated and untreated women, cervical treatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16?558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women. Conclusion There is no evidence suggesting that treatment for cervical intraepithelial neoplasia adversely affects fertility, although treatment was associated with a significantly increased risk of miscarriages in the second trimester. Research should explore mechanisms that may explain this increase in risk and stratify the impact that treatment may have on fertility and early pregnancy outcomes by the size of excision and treatment method used. PMID:25352501

  19. Use of Vandetanib in Metastatic Medullary Carcinoma of Thyroid in a Pediatric Patient With Multiple Endocrine Neoplasia 2B.

    PubMed

    Narayanan, Vidya K; Ronghe, Milind; MacGregor, Fiona B; Bradshaw, Nicola; Davidson, Rosemarie; Welbury, Richard; Reed, Nicholas; Shaikh, Mohamad G

    2016-03-01

    We describe a child with advanced, metastatic, inoperable medullary carcinoma of thyroid associated with multiple endocrine neoplasia 2B and rearranged during transfection mutation with a positive response to vandetanib treatment. He responded well with a fall in calcitonin levels and a reduction in size of the thyroid malignancy, lymph nodes, and pulmonary metastases. He has been on vandetanib for 4 years with good clinical and biochemical response. Vandetanib has a role in the treatment of patients including children with inoperable locally advanced and metastatic medullary carcinoma of thyroid. More information is needed on its use in children and long-term outcome. PMID:26479990

  20. Feature-based analysis of mouse prostatic intraepithelial neoplasia in histological tissue sections

    PubMed Central

    Ruusuvuori, Pekka; Valkonen, Mira; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2016-01-01

    This paper describes work presented at the Nordic Symposium on Digital Pathology 2015, in Linköping, Sweden. Prostatic intraepithelial neoplasia (PIN) represents premalignant tissue involving epithelial growth confined in the lumen of prostatic acini. In the attempts to understand oncogenesis in the human prostate, early neoplastic changes can be modeled in the mouse with genetic manipulation of certain tumor suppressor genes or oncogenes. As with many early pathological changes, the PIN lesions in the mouse prostate are macroscopically small, but microscopically spanning areas often larger than single high magnification focus fields in microscopy. This poses a challenge to utilize full potential of the data acquired in histological specimens. We use whole prostates fixed in molecular fixative PAXgene™, embedded in paraffin, sectioned through and stained with H&E. To visualize and analyze the microscopic information spanning whole mouse PIN (mPIN) lesions, we utilize automated whole slide scanning and stacked sections through the tissue. The region of interests is masked, and the masked areas are processed using a cascade of automated image analysis steps. The images are normalized in color space, after which exclusion of secretion areas and feature extraction is performed. Machine learning is utilized to build a model of early PIN lesions for determining the probability for histological changes based on the calculated features. We performed a feature-based analysis to mPIN lesions. First, a quantitative representation of over 100 features was built, including several features representing pathological changes in PIN, especially describing the spatial growth pattern of lesions in the prostate tissue. Furthermore, we built a classification model, which is able to align PIN lesions corresponding to grading by visual inspection to more advanced and mild lesions. The classifier allowed both determining the probability of early histological changes for uncategorized tissue samples and interpretation of the model parameters. Here, we develop quantitative image analysis pipeline to describe morphological changes in histological images. Even subtle changes in mPIN lesion characteristics can be described with feature analysis and machine learning. Constructing and using multidimensional feature data to represent histological changes enables richer analysis and interpretation of early pathological lesions. PMID:26955503

  1. HPV Genotype Distribution in Cervical Intraepithelial Neoplasia among HIV-Infected Women in Pune, India

    PubMed Central

    Mane, Arati; Nirmalkar, Amit; Risbud, Arun R.; Vermund, Sten H.; Mehendale, Sanjay M.; Sahasrabuddhe, Vikrant V.

    2012-01-01

    Background The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer. Methods HIV-infected women (N?=?278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint. Results CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and ‘carcinogenic’ HPV genotypes were present in 35.3% (98/278) HIV-infected women. ‘Possibly carcinogenic’ and ‘non/unknown carcinogenic’ HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (?2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple ‘carcinogenic’ HPV genotypes were present in just over a quarter (27.8%) of women with ‘carcinogenic’ HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with ‘carcinogenic’ HPV type detection were reporting ?2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy. Conclusion HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies. PMID:22723879

  2. Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia.

    PubMed

    Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Mo, Lein-Ray; Lin, Jaw-Town; Wang, Hsiu-Po; Lee, Ching-Tai

    2015-12-01

    Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities.We retrospectively enrolled the patients with flat-type "large" (length ?3?cm extending ?1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events.Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8?min; P?

  3. Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2

    PubMed Central

    Kluijfhout, Wouter P.; van Beek, Dirk-Jan; Verrijn Stuart, Annemarie A.; Lodewijk, Lutske; Valk, Gerlof D.; van der Zee, David C.; Vriens, Menno R.; Borel Rinkes, Inne H.M.

    2015-01-01

    Abstract The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young. A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years. For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P?

  4. Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Schwarz, Richard Alan

    Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue specimens from 15 oral cancer patients. Improved contrast between neoplastic and healthy tissue was observed using 2-NBDG and EGF-Alexa 647.

  5. COMBINATION OF COMPUTED TOMOGRAPHIC IMAGING CHARACTERISTICS OF MEDIAL RETROPHARYNGEAL LYMPH NODES AND NASAL PASSAGES AIDS DISCRIMINATION BETWEEN RHINITIS AND NEOPLASIA IN CATS.

    PubMed

    Nemanic, Sarah; Hollars, Katelyn; Nelson, Nathan C; Bobe, Gerd

    2015-11-01

    Feline nasal diseases are a diagnostic challenge. The objective of this retrospective, cross-sectional study was to determine whether computed tomography (CT) imaging characteristics of the medial retropharyngeal lymph nodes (MRPLN), alone or in combination with CT imaging characteristics of the nasal passages, could aid in differentiation between rhinitis and nasal neoplasia. Cats were recruited from record archives at two veterinary facilities during the period of 2008-2012. Selection criteria were presentation for chronic nasal discharge, contrast-enhanced CT of the head that included the MRPLN, and rhinoscopic nasal biopsy resulting in diagnosis of rhinitis or neoplasia. For each CT scan, two board-certified veterinary radiologists recorded MRPLN size, attenuation, heterogeneity, contrast-medium enhancement, margination, shape, presence of a lymph node hilus, perinodal fat, turbinate lysis, paranasal bone lysis, and nasal mass. Both readers were unaware of patient information at the time of CT interpretation. Thirty-four cats with rhinitis and 22 cats with neoplasia were included. Computed tomographic characteristics significantly associated with neoplasia included abnormal MRPLN hilus (OR 5.1), paranasal bone lysis (OR 5.6), turbinate lysis (5.6), mass (OR 26.1), MRPLN height asymmetry (OR 4.5), and decreased MRPLN precontrast heterogeneity (OR 7.0). The combined features predictive of neoplasia were a nasal mass with abnormal hilus (OR 47.7); lysis of turbinates/paranasal bones with abnormal MRPLN hilus (OR 16.2). Findings supported the hypothesis that combining CT features of the nasal passages and MRPLN aided in differentiating rhinitis from neoplasia in cats. PMID:26194153

  6. Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

    PubMed Central

    Di Sante, Gabriele; Pestell, Timothy G.; Casimiro, Mathew C.; Bisetto, Sara; Powell, Michael J.; Lisanti, Michael P.; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M.; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W.; Pestell, Richard G.

    2016-01-01

    Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD+-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1−/− cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD+-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

  7. Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-Induced Fish Model of Liver Injury

    PubMed Central

    Van Wettere, Arnaud J.; Law, J. Mac; Hinton, David E.; Kullman, Seth W.

    2014-01-01

    Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks post-exposure. Within six weeks hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of tgfb1,tgfb receptor 2, smad3a, smad3b, ctnnb1, myc, mmp2, mmp14a, mmp14b, timp2a, timp2b, timp3, col1a1a, and col1a1b, and a less pronounced increase in mmp13 and col4a1expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-β1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis, and demonstrated that the TGF-β pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis. PMID:23197195

  8. Loss of Sirt1 promotes prostatic intraepithelial neoplasia, reduces mitophagy, and delays PARK2 translocation to mitochondria.

    PubMed

    Di Sante, Gabriele; Pestell, Timothy G; Casimiro, Mathew C; Bisetto, Sara; Powell, Michael J; Lisanti, Michael P; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W; Pestell, Richard G

    2015-01-01

    Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD(+)-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1(-/-) cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD(+)-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

  9. Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients

    PubMed Central

    Starita, Noemy; Annunziata, Clorinda; Waddell, Keith M.; Buonaguro, Luigi; Buonaguro, Franco M.; Tornesello, Maria Lina

    2015-01-01

    The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/105 cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n = 11) and B2 (n = 6). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions. PMID:26509162

  10. Neoplasia and Neoplasm Associated Lesions in Laboratory Colonies of Zebrafish Emphasizing Key Influences of Diet and Aquaculture System Design

    PubMed Central

    Spitsbergen, Jan M.; Buhler, Donald R.; Peterson, Tracy S.

    2014-01-01

    During the past decade the zebrafish has emerged as a leading model for mechanistic cancer research due to its sophisticated genetic and genomic resources, its tractability for tissue targeting of transgene expression, its efficiency for forward genetic approaches to cancer model development, and its cost-effectiveness for enhancer and suppressor screens once a cancer model is established. However, in contrast to other laboratory animal species widely used as cancer models, much basic cancer biology information is lacking in zebrafish. As yet data are not published regarding dietary influences on neoplasm incidences in zebrafish. Little information is available regarding spontaneous tumor incidences or histologic types in wild-type (wt) lines of zebrafish. So far a comprehensive database documenting the full spectrum of neoplasia in various organ systems and tissues in not available for zebrafish as it is for other intensely studied laboratory animal species. This manuscript confirms that as in other species diet and husbandry can profoundly influence tumor incidences and histologic spectra in zebrafish. We show that in many laboratory colonies wt lines of zebrafish exhibit elevated neoplasm incidences and neoplasm associated lesions such as heptocyte megalocytosis. We present experimental evidence showing that certain diet and water management regimens can result in high incidences of neoplasia and neoplasm associated lesions. We document the wide array of benign and malignant neoplasms affecting nearly every organ, tissue and cell type in zebrafish, in some cases as a spontaneous aging change, and in other cases due to carcinogen treatment or genetic manipulation. PMID:23382343

  11. Pathologic findings of follow-up surgical excision for lobular neoplasia on breast core biopsy performed for calcification.

    PubMed

    Zhao, Chengquan; Desouki, Mohamed Mokhtar; Florea, Anca; Mohammed, Khaled; Li, Xin; Dabbs, David

    2012-07-01

    This study aimed to ascertain pathologic findings of surgical follow-up excision (FUE) on patients who had radiologic finding of calcifications and lobular neoplasia (LN) on core biopsy. Breast core biopsy specimens from 2006-2011 with a diagnosis of pure classic-type LN (lobular carcinoma in situ [LCIS] and atypical lobular hyperplasia [ALH]) with no history of invasive carcinoma (IC) or ductal carcinoma in situ (DCIS) were studied. Two hundred thirty-seven patients with the diagnosis of calcium on radiologic studies had FUE and were included in the study. Cases were divided into group 1 (pure ALH, n = 163) and group 2 (pure LCIS, n = 74). The interval between the core biopsy and FUE ranged from 0.2 to 7 months (mean, 1.5 ± 1.1 months). The risk of upstaging on FUE (DCIS or IC) is as follows: LCIS, 8.1% (6/74) and ALH, 3.1% (5/163). The data indicate that there is a low risk of upstaging to DCIS/IC from a core biopsy diagnosis of lobular neoplasia. PMID:22706860

  12. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

    PubMed

    Zheng, Han-Han; Jiang, Xue-Liang

    2016-04-01

    Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal neoplasia than patients with IBD, but not PSC. Stratification by IBD type show that the presence of PSC is associated with an increased risk for the development of colorectal neoplasia in patients with UC; however, there is a nonsignificant association in CD patients. When the risk of colorectal cancer alone is analysed, the conclusion does not change. PMID:26938805

  13. Screening for colorectal cancer and advanced colorectal neoplasia in kidney transplant recipients: cross sectional prevalence and diagnostic accuracy study of faecal immunochemical testing for haemoglobin and colonoscopy

    PubMed Central

    2012-01-01

    Objective To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of advanced colorectal neoplasia and evaluating the diagnostic accuracy of faecal haemoglobin testing compared with colonoscopy in a population of kidney transplant recipients at otherwise average risk. Design Cross sectional prevalence and diagnostic accuracy study with index test of faecal haemoglobin and reference standard of colonoscopy. Setting Outpatient clinics in metropolitan and regional hospitals in South Australia. Participants 229 kidney transplant recipients aged 50 years and over, who were at least 6 months (mean 9.0 (SD 8.4) years) post-transplant and otherwise at average risk of colorectal cancer, completed the study between June 2008 and October 2011. Interventions Faecal immunochemical testing (Enterix Insure) for human haemoglobin, followed by colonoscopy with histological evaluation of retrieved samples. Main outcome measures Prevalence of advanced colorectal neoplasia, defined as an adenoma at least 10 mm in diameter, villous features, high grade dysplasia, or colorectal cancer; sensitivity, specificity, and predictive values of faecal haemoglobin testing for advanced neoplasia compared with colonoscopy. Results Advanced colorectal neoplasia was found in 29 (13%, 95% confidence interval 9% to 18%) participants, including 2% (n=4) with high grade dysplasia and 2% (n=5) with colorectal cancer. Faecal testing for haemoglobin was positive in 12% (n=28); sensitivity, specificity, and positive and negative predictive values for advanced neoplasia were 31.0% (15.3% to 50.8%), 90.5% (85.6% to 94.2%), 32.1% (15.9% to 52.4%), and 90.1% (85.1% to 93.8%). Colonoscopy was well tolerated, with no significant adverse outcomes. To identify one case of advanced neoplasia, 8 (6 to 12) colonoscopies were needed. Conclusions Kidney transplant recipients aged over 50 years have a high prevalence of advanced colorectal neoplasia. Faecal haemoglobin screening for colorectal neoplasia has similar performance characteristics in transplant recipients to those reported in general population studies, with poor sensitivity but reasonable specificity. Surveillance colonoscopy might be a more appropriate approach in this population. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000154303. PMID:22833618

  14. The Con Test

    ERIC Educational Resources Information Center

    Fletcher, Michael

    2009-01-01

    In this article, the author describes the format of the Con Test, an Australian television game show which followed the same general rules and game play as the UK show PokerFace. At the end of each round a contestant needs to decide whether or not he or she should fold. A contestant needs to know how likely it is that he or she is in last place.…

  15. Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

    PubMed Central

    Wang, Shu-Fang; Yang, Yun-Sheng; Wei, Li-Xin; Lu, Zhong-Sheng; Guo, Ming-Zhou; Huang, Jin; Peng, Li-Hua; Sun, Gang; Ling-Hu, En-Qiang; Meng, Jiang-Yun

    2012-01-01

    AIM: To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS: Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and treatment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stomachs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with white-light imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the “microvascular pattern and surface pattern” classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar’s test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar’s test (P < 0.05). CONCLUSION: Higher diagnostic accuracy, sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN. PMID:23002348

  16. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population. Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions. The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present. PMID:23645327

  17. Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia

    PubMed Central

    2009-01-01

    Background A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in MLL-related leukemia. Recently, we have established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described in the literature. Methods Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: CBFB-MYH11 (n = 13), PML-RARA (n = 12); RUNX1-RUNX1T1 (n = 12), normal karyotype (n = 11), and MLL gene fusions other than MLL-SEPT2 (n = 10). We also studied all three MLL-SEPT2 myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient. Results When compared with normal controls, we found a 12.8-fold reduction of wild-type SEPT2 and MLL-SEPT2 combined expression in cases with the MLL-SEPT2 gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type MLL and MLL-SEPT2 combined expression (p = 0.028). The down-regulation of SEPT2 in MLL-SEPT2 myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other MLL gene fusions). In addition, MLL expression was also down-regulated in the group of MLL fusions other than MLL-SEPT2, when compared with the normal control group (p = 0.023) Conclusion We found a significant down-regulation of both SEPT2 and MLL in MLL-SEPT2 myeloid neoplasias. In addition, we also found that MLL is under-expressed in AML patients with MLL fusions other than MLL-SEPT2. PMID:19445675

  18. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    EPA Science Inventory

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats

    Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-
    Mendel rat when administered either by corn oil gavage or in drin...

  19. THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINATED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING WATER TO MALE F344/N RATS

    EPA Science Inventory

    THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS.

    Abstract:

    The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...

  20. Neoplasias de células plasmáticas (incluso mieloma múltiple)—Versión para profesionales de salud

    Cancer.gov

    Información del Instituto Nacional del Cáncer para profesionales de salud sobre el tratamiento del mieloma múltiple y otras neoplasias de células plasmáticas, así como referencias a estudios clínicos, investigación, estadísticas y otros temas.

  1. Neoplasias de células plasmáticas (incluso mieloma múltiple)—Versión para pacientes

    Cancer.gov

    Información del Instituto Nacional del Cáncer sobre el tratamiento del mieloma múltiple y otras neoplasias de células plasmáticas, así como referencias a estudios clínicos, investigación, estadísticas y otros temas relacionados.

  2. A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process.

    PubMed

    Carr, Norman J; Cecil, Thomas D; Mohamed, Faheez; Sobin, Leslie H; Sugarbaker, Paul H; González-Moreno, Santiago; Taflampas, Panos; Chapman, Sara; Moran, Brendan J

    2016-01-01

    Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results. PMID:26492181

  3. Case of multiple endocrine neoplasia 2B with probable ectopic adrenocorticotropic hormone-secreting liver metastasis from medullary thyroid carcinoma.

    PubMed

    Kurozumi, Akira; Okada, Yosuke; Arao, Tadashi; Nakamoto, Yuji; Togashi, Kaori; Tanaka, Yoshiya

    2013-09-01

    A 31 year old woman was diagnosed with multiple endocrine neoplasia (MEN) 2B at 10 years old. Dark pigmentation gradually developed on her skin and her serum adrenocorticotropic hormone (ACTH) was high, suggesting concurrent ectopic ACTH syndrome (EAS). Corticotropin-releasing hormone (CRH) loading test ruled out Cushing's disease and supported the diagnosis of EAS. Multiple low attenuation mass in the liver was observed in a computed tomography (CT) scan, and was suspected as ectopic ACTH-secreting metastatic tumor from medullary thyroid carcinoma (MTC). ACTH production by MTC is relatively rare, particularly in patients with MEN; patients with ectopic ACTH-secreting liver metastatic tumor from MTC in MEN 2B have never been reported previously. PMID:24077587

  4. Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias

    PubMed Central

    Scala, Stefania; Portella, Giuseppe; Fedele, Monica; Chiappetta, Gennaro; Fusco, Alfredo

    2000-01-01

    High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A control adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor size. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event. PMID:10759549

  5. Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

    SciTech Connect

    Peppa, Melpomeni; Brountzos, Elias; Economopoulos, Nicolaos; Boutati, Eleni; Pikounis, Vasilios; Patapis, Paul; Economopoulos, Theofanis; Raptis, Sotirios A.; Hadjidakis, Dimitrios

    2009-07-15

    Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

  6. In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia

    NASA Astrophysics Data System (ADS)

    Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

    2013-03-01

    Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

  7. Molecular Biomarkers of Pancreatic Intraepithelial Neoplasia and Their Implications in Early Diagnosis and Therapeutic Intervention of Pancreatic Cancer

    PubMed Central

    Guo, Junli; Xie, Keping; Zheng, Shaojiang

    2016-01-01

    Lack of early detection and effective interventions is a major reason for the poor prognosis and dismal survival rates for pancreatic cancer. Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor of invasive pancreatic ductal adenocarcinoma (PDAC). Each stage in the progression from PanIN to PDAC is well characterized by multiple significant genetic alterations affecting signaling pathways. Understanding the biological behavior and molecular alterations in the progression from PanIN to PDAC is crucial to the identification of noninvasive biomarkers for early detection and diagnosis and the development of preventive and therapeutic strategies for control of pancreatic cancer progression. This review focuses on molecular biomarkers of PanIN and their important roles in early detection and treatment of pancreatic cancer. PMID:26929736

  8. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  9. A pilot study of the endomicroscopic assessment of tumor extension in Barrett’s esophagus–associated neoplasia before endoscopic resection

    PubMed Central

    Dolak, Werner; Mesteri, Ildiko; Asari, Reza; Preusser, Matthias; Tribl, Barbara; Wrba, Friedrich; Schoppmann, Sebastian F.; Hejna, Michael; Trauner, Michael; Häfner, Michael; Püspök, Andreas

    2015-01-01

    Background and study aims: Barrett’s esophagus (BE)?–?associated neoplasia can be treated endoscopically, but accurate assessment before intervention is challenging. This study aimed to investigate the role of confocal laser endomicroscopy (CLE) as an adjunct in the endoscopic treatment of BE-associated neoplasia by assessing lateral tumor and subsquamous tumor (SST) extension. Patients and methods: In the context of a prospective, single-arm pilot clinical trial, patients referred for endoscopic resection of BE-associated neoplasia (high grade dysplasia and esophageal adenocarcinoma) underwent high definition, white light endoscopy with narrow-band imaging (NBI). Then, CLE mapping of suspected neoplastic lesions was performed by another endoscopist, partially blinded to the previous findings, before the patients underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), depending on lesion size and anticipated histology. Results: In 7 of 38 patients (18?%), CLE revealed additional neoplastic tissue compared with prior white light endoscopy and NBI: 2 concomitant lesions, 2 cases of lateral tumor extension within the Barrett’s epithelium, and 3 cases of previously undetected SST extension. Overall, en bloc resection (tumor-free lateral margin) was achieved in 28 of 34 neoplastic lesions (82?%), and complete resection (tumor-free lateral and basal margins) in 21 of 34 neoplastic lesions (62?%). Conclusions: CLE-assisted endoscopic resection of BE-associated neoplasia was safe and effective in this study, as proved by a high additional diagnostic yield of CLE (including visualization of occult SST extension) and a favorable rate of en bloc resection. The clinical value of CLE for assisting endoscopic therapy of BE-associated neoplasia deserves further evaluation in randomized controlled trials. PMID:26134766

  10. Inactivating Mutation in the Prostaglandin Transporter Gene, SLCO2A1, Associated With Familial Digital Clubbing, Colon Neoplasia, and NSAID Resistance

    PubMed Central

    Guda, Kishore; Fink, Stephen P.; Milne, Ginger L.; Molyneaux, Neil; Ravi, Lakshmeswari; Lewis, Susan M.; Dannenberg, Andrew J.; Montgomery, Courtney G.; Zhang, Shulin; Willis, Joseph; Wiesner, Georgia L.; Markowitz, Sanford D.

    2014-01-01

    HPGD and SLCO2A1 genes encode components of the prostaglandin catabolic pathway, HPGD encoding the degradative enzyme 15-PGDH, and SLCO2A1 encoding the prostaglandin transporter PGT that brings substrate to 15-PGDH. HPGD null mice show increased PGE2, marked susceptibility to developing colon tumors, and resistance to colon tumor prevention by NSAIDs. But in humans, HPGD and SLCO2A1 mutations have only been associated with familial digital clubbing. We here characterize a family with digital clubbing and early onset colon neoplasia. Whole exome sequencing identified a heterozygous nonsense mutation (G104X) in the SLCO2A1 gene segregating in three males with digital clubbing. Two of these males further demonstrated notably early onset colon neoplasia, one with an early onset colon cancer and another with an early onset sessile serrated colon adenoma. Two females also carried the mutation, and both these women developed sessile serrated colon adenomas without any digital clubbing. Males with clubbing also showed marked elevations in the levels of urinary prostaglandin E2 metabolite, PGE-M; whereas, female mutation carriers were in the normal range. Furthermore, in the male proband urinary PGE-M remained markedly elevated during NSAID treatment with either celecoxib or sulindac. Thus, in this human kindred, a null SLCO2A1 allele mimics the phenotype of the related HPGD null mouse, with increased prostaglandin levels that cannot be normalized by NSAID therapy, plus with increased colon neoplasia. The development of early onset colon neoplasia in male and female human SLCO2A1 mutation carriers suggests that disordered prostaglandin catabolism can mediate inherited susceptibility to colon neoplasia in man. PMID:24838973

  11. Genetic variants on chromosome 8q24 and colorectal neoplasia risk: a case-control study in China and a meta-analysis of the published literature.

    PubMed

    Li, Mian; Zhou, Yanhong; Chen, Peizhan; Yang, Huan; Yuan, Xiaoyan; Tajima, Kazuo; Cao, Jia; Wang, Hui

    2011-01-01

    Previous studies have found that common genetic variants on chromosome 8q24 are associated with the risk of developing colorectal neoplasia. We conducted a hospital-based case-control study, including 435 cases and 788 unrelated controls to investigate the associations between common variants on 8q24 and the risk of colorectal cancer in a Chinese population. We also evaluated the association of rs6983267 with colorectal neoplasia in the published literature via a meta-analysis study. We found that rs6983267 was significantly associated with the risk of colorectal cancer in the Chinese population, with an adjusted odds-ratio (OR) for the GT heterozygotes and GG homozygotes of 1.30 (95% CI=?0.98-1.71, P?=?0.069) and 1.66 (95% CI?=?1.18-2.34, P?=?0.004), respectively, compared to the TT homozygotes, with a P-trend value of 0.003. No association was found for the other three loci (rs16901979, rs1447295 and rs7837688). In the meta-analysis of the published genetic association studies, the rs6983267 variant was found to be associated with an increased risk of colorectal neoplasia. The heterozygous GT carriers showed a 20% increased risk of colorectal neoplasia (OR=?1.20, 95% CI=?1.16-1.25; random effects model) with a summary OR for homozygous GG carriers of 1.39 (95% CI=?1.32-1.48; random effects model) compared to the TT genotype carriers. We found no significant differences between the association of rs6983267 and colorectal cancer and colorectal adenomas. In summary, our study confirms that the variant rs6983267 is a risk factor for colorectal neoplasia in various populations, including the Chinese population. PMID:21455501

  12. The expanding family of SMARCB1(INI1)-deficient neoplasia: implications of phenotypic, biological, and molecular heterogeneity.

    PubMed

    Agaimy, Abbas

    2014-11-01

    Since the description of atypical teratoid/rhabdoid tumors of the central nervous system and renal/extrarenal malignant rhabdoid tumors in children, the clinicopathologic spectrum of neoplasms having in common a highly variable rhabdoid cell component (0% to 100%) and consistent loss of nuclear SMARCB1 (INI1) expression has been steadily expanding to include cribriform neuroepithelial tumor of the ventricle, renal medullary carcinoma and a subset of collecting duct carcinoma, epithelioid sarcoma, subsets of miscellaneous benign and malignant soft tissue tumors, and rare rhabdoid carcinoma variants of gastroenteropancreatic, sinonasal, and genitourinary tract origin. Although a majority of SMARCB1-deficient neoplasms arise de novo, the origin of SMARCB1-deficient neoplasia in the background of a phenotypically or genetically definable differentiated SMARCB1-intact "parent neoplasm" has been convincingly demonstrated, highlighting the rare occurrence of rhabdoid tumors as "double-hit neoplasia." As a group, SMARCB1-deficient neoplasms occur over a wide age range (0 to 80 y), may be devoid of rhabdoid cells or display uniform rhabdoid morphology, and follow a clinical course that varies from benign to highly aggressive causing death within a few months irrespective of aggressive multimodality therapy. Generally applicable criteria that would permit easy recognition of these uncommon neoplasms do not exist. Diagnosis is based on site-specific and entity-specific sets of clinicopathologic, immunophenotypic, and/or molecular criteria. SMARCB1 immunohistochemistry has emerged as a valuable tool in confirming or screening for SMARCB1-deficient neoplasms. This review summarizes the different phenotypic and topographic subgroups of SMARCB1-deficient neoplasms including sporadic and familial, benign and malignant, and rhabdoid and nonrhabdoid variants, highlighting their phenotypic heterogeneity and molecular complexity. PMID:25299309

  13. Biomarkers and transcription levels of cancer-related genes in cockles Cerastoderma edule from Galicia (NW Spain) with disseminated neoplasia.

    PubMed

    Ruiz, Pamela; Díaz, Seila; Orbea, Amaia; Carballal, Maria J; Villalba, Antonio; Cajaraville, Miren P

    2013-07-15

    Disseminated neoplasia (DN) is a pathological condition reported for several species of marine bivalves throughout the world, but its aetiology has not yet been satisfactorily explained. It has been suggested that chemical contamination could be a factor contributing to neoplasia. The aim of the present study was to compare cell and tissue biomarkers and the transcription level of cancer-related genes in cockles (Cerastoderma edule) affected by DN with those of healthy cockles in relation to chemical contaminant burdens. For this, cockles were collected from a natural bed in Cambados (Ria de Arousa, Galicia) in May 2009. The prevalence of DN was 12.36% and 3 degrees of DN severity were distinguished. No significant differences in metal accumulation, non-specific inflammatory responses and parasites were observed between healthy and DN-affected cockles. Lysosomal membrane stability was significantly reduced in cockles affected by DN, which indicates a poorer health condition. Very low frequencies of micronuclei were recorded and no significant differences were detected between DN severity groups. Haemolymph analyses showed a higher frequency of mitotic figures and binucleated cells in cockles affected by moderate and heavy DN than in healthy ones. Neoplastic animals showed significantly higher transcription levels of p53 and ras than healthy cockles and mutational alterations in ras gene sequence were detected. Low concentrations of metals, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and phthalate esters were measured in cockles from Cambados. In conclusion, cockles affected by DN suffer a general stress situation and have altered patterns of cancer-related gene transcription. Further studies are in progress to elucidate mechanisms of carcinogenesis in this species. PMID:23665240

  14. Reduction in cervical intraepithelial neoplasia in young women in British Columbia after introduction of the HPV vaccine: An ecological analysis.

    PubMed

    Ogilvie, Gina S; Naus, Monika; Money, Deborah M; Dobson, Simon R; Miller, Dianne; Krajden, Mel; van Niekerk, Dirk J; Coldman, Andrew J

    2015-10-15

    We report on the rates of cervical intraepithelial neoplasia (CIN) in young women aged 15-22 years of age in British Columbia before and after the introduction of an HPV vaccine program. Rates of cervical intraepithelial neoplasia (CIN) 2+ for each age stratum (15-22) in the calendar years 2004-2012 for the province of British Columbia were obtained from the BC Cancer Agency's population-based cervical cancer program. Incidence rate ratios (IRR) of CIN2+ were described and compared before and after HPV vaccine program introduction in cohorts born in vaccine eligible years, and in non-vaccine eligible years using piece-wise Poisson regression analysis, and adjusted for age. Between 2004 and 2012, rates of CIN2 and CIN2+ in young women aged 15-22 years in the province of British Columbia have decreased overall. After the introduction of the HPV vaccine program, the age adjusted IRR for CIN2+ for young women aged 15-17 years decreased significantly from 0.91 (95% CI: 0.86-0.98 p?

  15. CTNNB1 (β-Catenin)-altered Neoplasia: A Review Focusing on Soft Tissue Neoplasms and Parenchymal Lesions of Uncertain Histogenesis.

    PubMed

    Agaimy, Abbas; Haller, Florian

    2016-01-01

    β-catenin (CTNNB1) is a key regulatory molecule of the Wnt signaling pathway, which is important for tissue homeostasis and regulation of cell proliferation, differentiation, and function. Abnormal stabilization and nuclear accumulation of β-catenin as a consequence of missense mutations or alternative molecular mechanisms occurs at a high frequency in a variety of epithelial cancers. In mesenchymal neoplasia, the role of β-catenin has been traditionally considered limited to desmoid-type fibromatosis. However, the spectrum of β-catenin-driven (β-catenin-altered) neoplasia of mesenchymal origin has been steadily widening to include, in addition to desmoid tumors, a variety of benign and intermediate-biology neoplasms of soft tissue (intranodal palisaded myofibroblastoma), head and neck (juvenile nasopharyngeal angiofibroma and sinonasal hemangiopericytoma/glomangiopericytoma), and ovarian (microcystic stromal tumor) origin. In addition, several old and newly reported distinctive site-specific β-catenin-driven parenchymal neoplasms of uncertain histogenesis have been well characterized in recent studies, including solid-pseudopapillary neoplasm of the pancreas and its recently described ovarian counterpart, sclerosing hemangioma of lung and calcifying nested stromal-epithelial tumor of the liver. This review addresses the most relevant pathobiological and differential diagnostic aspects of β-catenin-altered neoplasms with emphasis on site-specific histologic and biological variations. In addition, the morphologic overlap and analogy as well as distinctness between these uncommon tumors will be presented and discussed. Furthermore, a note is made on association of some of these lesions with hereditary tumor syndromes, in particular with the familial adenomatous polyposis coli. PMID:26645457

  16. First-line chemotherapy in low-risk gestational trophoblastic neoplasia

    PubMed Central

    Alazzam, Mo’iad; Tidy, John; Hancock, Barry W; Osborne, Raymond; Lawrie, Theresa A

    2014-01-01

    Background This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. Objectives To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. Search methods In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review. Selection criteria For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials. Main results We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women). Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality. There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I2 = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials. Authors’ conclusions Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard. We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings. PMID:22786502

  17. Association of Combined Tobacco Smoking and Oral Contraceptive Use With Cervical Intraepithelial Neoplasia 2 or 3 in Korean Women

    PubMed Central

    Oh, Hea Young; Kim, Mi Kyung; Seo, Sang-Soo; Lee, Jae-Kwan

    2016-01-01

    Background Cigarette smoking and oral contraceptive (OC) use have been associated with cervical neoplasia, and the combination of smoking and OC use could influence cervical carcinogenesis. We aimed to assess the joint effect of smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN). Methods From a cohort of human papillomavirus-positive subjects recruited from 6 hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411 control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean age, 43 years). The risk of CIN associated with smoking and OC use on additive and multiplicative scales was estimated via multinomial logistic regression after adjustment for potential confounding factors. The relative excess risk due to interaction (RERI) and the synergy index (S) were used to evaluate the additive interaction. Results OC users (odds ratio [OR] 1.98; 95% confidence interval [CI], 1.07–3.69) and long-term OC use (≥20 months; OR 2.71; 95% CI, 1.11–6.59) had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non-OC users. Smokers and heavy smoking (≥8 cigarettes/day) were not associated with any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68–14.4; RERI/S, 3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking and long-term OC use (OR 11.5; 95% CI, 1.88–70.4; RERI/S, 9.93/18.8; P for multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no association with CIN 1 compared to combined non-smoking and non-OC use. Conclusions OC use and smoking acted synergistically to increase the risk of CIN 2 or 3 in Korean women. PMID:26441210

  18. Galaxias australes con núcleo doble

    NASA Astrophysics Data System (ADS)

    Gimeno, G.; Díaz, R.; Carranza, G.

    Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

  19. “Indefinite for Dysplasia” in Barrett's Esophagus: Inflammation and DNA Content Abnormality are Significant Predictors of Early Detection of Neoplasia

    PubMed Central

    Choi, Won-Tak; Emond, Mary J; Rabinovitch, Peter S; Ahn, Joseph; Upton, Melissa P; Westerhoff, Maria

    2015-01-01

    Background: Dysplasia arising from Barrett's esophagus precedes esophageal adenocarcinoma (EAC). Cases that are difficult to diagnose as dysplastic, especially in the setting of inflammation, may be designated “indefinite for dysplasia (IND).” Although flow cytometric analysis of DNA content has shown some promise in detecting EAC, there are few reports that have specifically evaluated the outcome of IND. Aims and methods: We analyzed a series of 96 IND patients seen at the University of Washington between 2005 and 2013 to determine the outcome of IND and to identify factors (including histologic features and DNA flow cytometric data) associated with subsequent detection of neoplasia. Results: Twenty-five percent of IND cases were found to have low-grade dysplasia, high-grade dysplasia (HGD), or EAC within 1 year, with 37% and 47% detected within 2 and 3 years, respectively. The 1-, 2-, and 3-year detection rates of HGD or EAC were 10%, 13%, and 20%, respectively. Active inflammation (hazard ratio (HR)=3.4, P=0.0005) and abnormal DNA content (HR=5.7, P=0.003) were significant risk factors of neoplasia. When active inflammation and DNA flow cytometric results were considered together, the HR for the combined markers was 18.8 (P<0.0001). The sensitivity and specificity of the combined markers for predicting detection of subsequent neoplasia within 3 years were 100% and 60%, respectively, with 100% negative and 89% positive predictive values. Conclusions: Histology with the support of DNA flow cytometry can identify a subset of IND patients who may have a higher risk for subsequent detection of neoplasia. PMID:25761942

  20. Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations

    PubMed Central

    Conner, James R.; Meserve, Emily; Pizer, Ellen; Garber, Judy; Roh, Michael; Urban, Nicole; Drescher, Charles; Quade, Bradley J.; Muto, Michael; Howitt, Brooke E.; Pearlman, Mark D.; Berkowitz, Ross S.; Horowitz, Neil; Crum, Christopher P.; Feltmate, Colleen

    2014-01-01

    Purpose This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCAm+) and determined recurrence risk. Methods We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCAm+ women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions. Results Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCAm+ cohort without neoplasia (47.8) and frequency increased with age (p<0.001). Twenty-nine BRCA m+ patients with neoplasia from three institutions were followed for a median of 5 years (1–8 yrs.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two, are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027). Conclusions Adnexal neoplasia is present in 5–6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN. PMID:24333842

  1. Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia: a case-control and immunohistochemical study

    PubMed Central

    2012-01-01

    Background Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence. Results No genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence. Conclusion From these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia. PMID:22824379

  2. The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Ng, Simpson; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2016-01-01

    We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50-70 years in a colonoscopy screening programme(2008-2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56-0.65, with sensitivities ranging from 0.04-0.44 and specificities from 0.74-0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58-0.72). The NNS (12-19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed. PMID:26838178

  3. Cervical cancer screening and treatment of cervical intraepithelial neoplasia in female sex workers using “screen and treat” approach

    PubMed Central

    Joshi, Smita; Kulkarni, Vinay; Darak, Trupti; Mahajan, Uma; Srivastava, Yogesh; Gupta, Sanjay; Krishnan, Sumitra; Mandolkar, Mahesh; Bharti, Alok Chandra

    2015-01-01

    Objective Female sex workers (FSWs) are at an increased risk of human immunodeficiency virus (HIV) as well as human papillomavirus (HPV) infections and thus have an increased risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. We evaluated the feasibility of “screen and treat approach” for cervical cancer prevention and the performance of different screening tests among FSWs. Methods Women were screened using cytology, VIA (visual inspection with acetic acid), and VILI (visual inspection with Lugol’s iodine) and underwent colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated, at the same visit. Results We screened 300 FSWs of whom 200 (66.67%) were HIV uninfected and 100 (33.34%) were HIV infected. The overall prevalence of CIN 2–3 lesions was 4.7%. But all women with CIN 2–3 lesions were HIV infected, and thus the prevalence of CIN 2–3 lesions in HIV-infected FSWs was 14/100 (14%, 95% confidence interval: 7.2–20.8). All of them screened positive by all three screening tests. Cold coagulation was well tolerated, with no appreciable side effects. Conclusion Cervical cancer prevention by “screen and treat” approach using VIA, followed by ablative treatment, in this high-risk group of women is feasible and can be implemented through various targeted intervention programs. PMID:25999765

  4. Can photodynamic therapy be the preferred treatment option for anal intraepithelial neoplasia? Initial results of a pilot study.

    PubMed

    Welbourn, Hannah; Duthie, Graeme; Powell, John; Moghissi, Keyvan

    2014-03-01

    Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over time may progress to invasive anal squamous cell carcinoma. There is no standard treatment for AIN, but one of the therapeutic options available is photodynamic therapy (PDT). There are very few published studies of the efficacy of PDT, but it has been shown to produce downgrading of high-grade dysplasia in the anal region. The aim of the study was to evaluate the role of PDT in the treatment of AIN. Fifteen patients who received anal PDT between 2004 and 2013 were identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and one had dysplasia with high-risk human papillomavirus. After a median follow-up of nineteen months, ten of these have had at least one follow-up with aceto-white staining. Six of these ten patients had a complete response to PDT, although three subsequently had some recurrence. Three further patients had a partial response to PDT. There were no major therapeutic complications. Our findings suggest that PDT is a safe and feasible treatment option for AIN, associated with reasonable response rates and relatively little morbidity. Further research into the efficacy of PDT for AIN is required. PMID:24280437

  5. Circulating Nucleic Acids in Plasma or Serum (CNAPS) as Prognostic and Predictive Markers in Patients with Solid Neoplasias

    PubMed Central

    Goebel, Georg; Zitt, Marion; Zitt, Matthias; Müller, Hannes M.

    2005-01-01

    It is now widely accepted that there is a need for the development of molecular markers of cancer that can be used for clinical prognostication and monitoring. Approximately a decade ago tumor-derived circulating nucleic acids in the plasma or serum (CNAPS) of cancer patients were introduced as a noninvasive tool for cancer detection. This review focuses on the various types of CNAPS of patients with solid neoplasias (genetic alterations in circulating DNA, microsatellites, methylated DNA, viral DNA, nucleosomes, mitochondrial DNA and cell-free mRNA) and their putative potential as prognostic or predictive parameter or even as a tool for therapy monitoring during follow-up. Additionally, this review aims to point out the difference between a prognostic and a predictive factor in patient bloodstream. However, with rapid technical improvement and well-designed studies we conclude that the next years will see CNAPS analysis integrated in the prognostication and monitoring of cancer patients, thus producing more specific treatment regimens for patients with various stages of neoplastic disease and ultimately longer survival and better quality of life. PMID:16276004

  6. Long term omeprazole therapy for reflux esophagitis: Follow-up in serum gastrin levels, EC cell hyperplasia and neoplasia

    PubMed Central

    Singh, Pankaj; Indaram, Anant; Greenberg, Ronald; Visvalingam, Vernu; Bank, Simmy

    2000-01-01

    AIM: To evaluate the long-term safety of omeprazole in patients of gastroesophageal reflux disease resistant to treatment with H2 receptor antagonist. METHODS: We prospectively followed 33 patients on omeprazole therapy for severe erosive esophagitis for 5-8 years, with periodic gastrin levels, H. pylori infection, gastric biopsies for incidence of ECL cell hyperplasia, carcinoids, gastric atrophy and neoplasia. A total 185 patient follow-up years and 137 gastric biopsies were done. RESULTS: Among the 33 patients, 36% reached their peak gastrin levels in an average of 8 mo to one year, then drifted Down slowly over 1-2 year period to just above their baseline level, 24% of the patients had a peak gastrin level above 400 ng·L-1 and one patient had a peak level above 1000 ng·L-1. One patient had a mild ECL cell hyperplasia which was self-limiting and did not show any dysplastic changes. Eighteen percent of patients were positive for H. pylori infection. The gastric biopsies did not show gastric atrophy, intestinal metaplasia or neoplastic changes. CONCLUSION: In a series of 33 patients followed for 5-8 years on omeprazole therapy for severe reflux esophagitis, we did not observe any evidence of significant ECL cell hyperplasia, gastric atrophy, intestinal metaplasia, dysplasia or neoplastic changes. PMID:11819697

  7. A lectin-based diagnostic system using circulating antibodies to detect cervical intraepithelial neoplasia and cervical cancer.

    PubMed

    Jin, Yingji; Kim, Seung Cheol; Kim, Hyoung Jin; Ju, Woong; Kim, Yun Hwan; Kim, Hong-Jin

    2016-01-01

    In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression. PMID:26358468

  8. Provocative testing for occult medullary carcinoma of the thyroid: findings in seven children with multiple endocrine neoplasia type IIa.

    PubMed

    Graham, S M; Genel, M; Touloukian, R J; Barwick, K W; Gertner, J M; Torony, C

    1987-06-01

    A rise in the serum calcitonin (CT) following provocative testing has facilitated making the diagnosis of occult medullary carcinoma of the thyroid (MCT) or C cell hyperplasia (CCH) in asymptomatic children of kindred with multiple endocrine neoplasia (MEN) type IIa. Findings were reviewed for seven children varying in age from 3 to 16 years screened at our institution between 1976 and 1986. Three had elevated basal calcitonin (S-CT). Six had significant elevation of calcitonin (delta-CT) after stimulation. Total thyroidectomy was performed in all seven. Five had MCT with bilobar involvement in three. CCH was present in all five. Two patients had no gross, microscopic, or immunohistochemical evidence of MCT or CCH. One of three had an elevated S-CT. The other had a significant delta-CT. All patients have normal postoperative S-CT and delta-CT. Our experience indicates the importance of beginning stimulation tests of affected kindred at less than 3 years of age. It appears, however, that neither elevated S-CT or positive delta-CT are perfect predictors of parafollicular cell pathology. Solitary parathyroid enlargement, second thyroid malignancy, and branchial pouch anomalies may occur with MEN IIa. One patient with MCT had a focus of papillary carcinoma. One patient with primary hyperparathyroidism had a solitary enlarged parathyroid adenoma. Additional findings were the presence of nodules of ectopic thymus in close association with the thyroid gland in three patients. PMID:2886576

  9. Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I.

    PubMed

    Mignon, M; Ruszniewski, P; Podevin, P; Sabbagh, L; Cadiot, G; Rigaud, D; Bonfils, S

    1993-01-01

    The difficult and controversial diagnostic and therapeutic management of patients having gastrinoma or insulinoma with multiple endocrine neoplasia type I (MEN-I) has been discussed by reference to the literature and a personal series of 45 gastrinoma/MEN-I patients followed consecutively at Bichat Hospital. In both gastrinoma/ and insulinoma/MEN-I patients, anatomic distribution and morphology of tumoral process(es) are usually multiple, diffuse, of small size, and associated with endocrine cell hyperplasia and even nesidioblastosis. These features enhance the difficulty of tumor localization and eradication. Despite the dramatic development of modern medical imagery and surgical experience, the real possibility, on a long-term basis, of curing the patients from their disease remains limited, especially in the gastrinoma/MEN-I patients. In the latter group, according to our experience, persistence or recurrence of the disease after surgery is usual, and metachronous hepatic metastasis development is frequently observed when the follow-up is long enough. Patients with liver metastases, however, seem to undergo a more indolent course than sporadic gastrinoma cases. In insulinoma/MEN-I patients, removal of the functionally dominant islet cell area(s) is essential. Various preoperative and intraoperative localization techniques allow efficacious selective pancreatic surgery in many cases. The latter refinements and the promises of long-acting somatostatin analogs, if confirmed, might restrict to exceptional circumstances the indication of near-total or total pancreatectomy. PMID:8103251

  10. An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

    PubMed

    Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

    2014-01-01

    Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

  11. RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma.

    PubMed

    Krampitz, Geoffrey W; Norton, Jeffrey A

    2014-07-01

    The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto-oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at-risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto-oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto-oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2. PMID:24699901

  12. Epigenetic inactivation of the candidate tumor suppressor USP44 is a frequent and early event in colorectal neoplasia

    PubMed Central

    Sloane, Mathew A; Wong, Jason WH; Perera, Dilmi; Nunez, Andrea C; Pimanda, John E; Hawkins, Nicholas J; Sieber, Oliver M; Bourke, Michael J; Hesson, Luke B; Ward, Robyn L

    2014-01-01

    In mouse models, loss of the candidate tumor suppressor gene Ubiquitin Specific Protease 44 (USP44) is associated with aneuploidy and cancer. USP44 is also transcriptionally silenced in human cancers. Here we investigated the molecular mechanism of USP44 silencing and whether this correlated with aneuploidy in colorectal adenomas. DNA methylation at the USP44 CpG island (CGI) promoter was measured using combined bisulfite restriction analysis (COBRA) in colorectal cancer (CRC) cell lines (n = 18), and with COBRA and bisulfite sequencing in colorectal adenomas (n = 89) and matched normal colonic mucosa (n = 51). The USP44 CGI was hypermethylated in all CRC cell lines, in most colorectal adenomas (79 of 89, 89%) but rarely in normal mucosa samples (3 of 51, 6%). USP44 expression was also compared between normal mucosa and paired hypermethylated adenomas in six patients using qRT-PCR. Hypermethylation of the USP44 CGI in adenomas was associated with a 1.8 to 5.5-fold reduction in expression compared with paired normal mucosa. Treatment of CRC cell lines with the DNA hypomethylating agent decitabine resulted in a 14 to 270-fold increase in USP44 expression. Whole genome SNP array data showed that gain or loss of individual chromosomes occurred in adenomas, but hypermethylation did not correlate with more aneuploidy. In summary, our data shows that USP44 is epigenetically inactivated in colorectal adenomas, but this alone is not sufficient to cause aneuploidy in colorectal neoplasia. PMID:24837038

  13. Symptomatic Improvement in Human Papillomavirus-Induced Epithelial Neoplasia by Specific Targeting of the CXCR4 Chemokine Receptor.

    PubMed

    Meuris, Floriane; Gaudin, Françoise; Aknin, Marie-Laure; Hémon, Patrice; Berrebi, Dominique; Bachelerie, Françoise

    2016-02-01

    Human papillomavirus (HPV) infection is estimated to be the causal agent in 5% of all human cancers and is the leading cause of genital warts, which is the most common sexually transmitted viral disease. Currently, there are no medications to treat HPV infection, and therapeutic strategies primarily target HPV-related cancer rather than viral infection. HPV infection has severe effects on patients who display selective susceptibility to the virus in the context of primary immunodeficiencies, such as the warts, hypogammaglobulinemia, infections, and myelokathexis syndrome, which is caused by dysfunctions of CXCR4, the receptor for the CXCL12 chemokine. In this study we showed in a transgenic mouse model of HPV-induced epidermal neoplasia the beneficial effects of Cxcl12/Cxcr4 pathway blockade with the selective CXCR4 antagonist AMD3100. Daily treatment with AMD3100 for 28 days potently reduced the abnormal ear epidermal thickening in all mice. This effect was associated with reductions in keratinocyte hyperproliferation and immune cell infiltration, both of which are linked to neoplastic progression. Moreover, we observed the abnormal coordinate expression of Cxcl12 and p16INK4a (a surrogate marker of HPV-induced cancers) in dysplastic epidermal keratinocytes, which was inhibited by AMD3100 treatment. These results provide strong evidence for the therapeutic potential of CXCL12/CXCR4 pathway blockade in HPV-induced pathogenesis. PMID:26967480

  14. An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

    PubMed Central

    Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

    2014-01-01

    Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

  15. Thymic and Bronchial Carcinoid Tumors in Multiple Endocrine Neoplasia Type 1: The Mayo Clinic Experience from 1977 to 2013.

    PubMed

    Singh Ospina, Naykky; Thompson, Geoffrey B; C Nichols, Francis; Cassivi, Stephen D; Young, William F

    2015-12-01

    The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0% (n = 7) and of BC 4.9% (n = 17). The majority of the patients with BC were men (61%) diagnosed on routine screening (77%) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43% died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior. PMID:26070346

  16. Disseminated neoplasia in flat oysters Ostrea edulis from Galicia (NW Spain): occurrence, ultrastructural aspects and relationship with bonamiosis.

    PubMed

    da Silva, Patricia Mirella; Fuentes, José; Villalba, Antonio

    2011-05-01

    Disseminated neoplasia (DN) was one of the most important pathological conditions found in cultured flat oysters (Ostrea edulis) from different geographical origins grow in Galicia (NW Spain), during a two years selective breeding programme to produce oysters less susceptible to bonamiosis. Histological characteristics observed in oysters affected by DN included intense infiltration of connective tissue of various organs (gills, stomach, digestive gland and gonad) by large undifferentiated cells, with a large nucleus and a high nucleus-to-cytoplasm ratio. The main ultrastructural features were predominance of euchromatin over heterochromatin that was arrayed in small clumps in the nucleus, prominent granular nucleolus, swollen mitochondria with few cristae and high number of free ribosomes in the cytoplasm. A seasonal pattern of DN prevalence was detected, with higher values in spring-summer, but there were no significant differences between geographic origins or families within these origins. However, the intensity of the disease was significantly different between origins; oysters originating outside of Galicia (particularly those originating from Ireland) were more susceptible to develop advanced DN. DN (8%) and bonamiosis (4.9%) were found concurrently in oysters. The nature and significance of this association warrants more investigation to determine its importance, if any. PMID:21236261

  17. Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

    PubMed Central

    Isidro, Raymond A; Cruz, Myrella L; Isidro, Angel A; Baez, Axel; Arroyo, Axel; González-Marqués, William A; González-Keelan, Carmen; Torres, Esther A; Appleyard, Caroline B

    2015-01-01

    AIM: To determine the expression of neurokinin-1 receptor (NK-1R), phosphorylated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (Cox-2), and vitamin D receptor (VDR) in normal, inflammatory bowel disease (IBD), and colorectal neoplasia tissues from Puerto Ricans. METHODS: Tissues from patients with IBD, colitis-associated colorectal cancer (CAC), sporadic dysplasia, and sporadic colorectal cancer (CRC), as well as normal controls, were identified at several centers in Puerto Rico. Archival formalin-fixed, paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R, pEGFR, Cox-2, and VDR. Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a 4-point scale that assessed intensity of staining. Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia, in addition to the areas of cancer, within each tissue. Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test. The mean scores for normal tissues and tissues with IBD, dysplasia, CRC, and CAC were calculated and statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test. Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient. Data are presented as mean ± SE. RESULTS: On average, patients with IBD were younger (34.60 ± 5.81) than normal (63.20 ± 6.13, P < 0.01), sporadic dysplasia (68.80 ± 4.42, P < 0.01), sporadic cancer (74.80 ± 4.91, P < 0.001), and CAC (57.50 ± 5.11, P < 0.05) patients. NK-1R in cancer tissue (sporadic CRC, 1.73 ± 0.34; CAC, 1.57 ± 0.53) and sporadic dysplasia (2.00 ± 0.45) were higher than in normal tissues (0.73 ± 0.19). pEGFR was significantly increased in sporadic CRC (1.53 ± 0.43) and CAC (2.25 ± 0.47) when compared to normal tissue (0.07 ± 0.25, P < 0.05, P < 0.001, respectively). Cox-2 was significantly increased in sporadic colorectal cancer (2.20 ± 0.23 vs 0.80 ± 0.37 for normal tissues, P < 0.05). In comparison to normal (2.80 ± 0.13) and CAC (2.50 ± 0.33) tissues, VDR was significantly decreased in sporadic dysplasia (0.00 ± 0.00, P < 0.001 vs normal, P < 0.001 vs CAC) and sporadic CRC (0.47 ± 0.23, P < 0.001 vs normal, P < 0.001 vs CAC). VDR levels negatively correlated with NK-1R (r = -0.48) and pEGFR (r = -0.56) in normal, IBD, sporadic dysplasia and sporadic CRC tissue, but not in CAC. CONCLUSION: Immunohistochemical NK-1R and pEGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia. VDR immunoreactivity can distinguish CAC from sporadic cancer. PMID:25684939

  18. Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms

    PubMed Central

    Chen, Bing-Qing; Xue, Ying-Ben; Liu, Jia-Ren; Yang, Yan-Mei; Zheng, Yu-Mei; Wang, Xuan-Lin; Liu, Rui-Hai

    2003-01-01

    AIM: To explore the inhibition of conjugated linoleic acid isomers in different purity (75% purity c9, t11-, 98% purity c9, t11- and 98% purity t10,c12-CLA) on the formation of forestomach neoplasm and cheopreventive mechanisms. METHODS: Forestomach neoplasm model induced by B (a) P in KunMing mice was established. The numbers of tumor and diameter of each tumor in forestomach were counted; the mice plasma malondialdehyde (MDA) were measured by TBARS assay; TUNEL assay was used to analyze the apoptosis in forestomach neoplasia and the expression of MEK-1, ERK-1, MKP-1 protein in forestomach neoplasm were studied by Western Blotting assay. RESULTS: The incidence of neoplasm in B (a) P group, 75% purity c9,t11-CLA group, 98% purity c9,t11-CLA group and 98% purity t10,c12-CLA group was 100%, 75.0% (P > 0.05), 69.2% (P < 0.05) and 53.8% (P < 0.05) respectively and the effect of two CLA isomers in 98% purity on forestomach neoplasia was significant; CLA showed no influence on the average tumor numbers in tumor-bearing mouse, but significantly decreased the tumor size, the tumor average diameter of mice in 75% purity c9,t11-CLA group, 98% purity c9,t11-CLA group and 98% purity t10,c12-CLA group was 0.157 ± 0.047 cm, 0.127 ± 0.038 cm and 0.128 ± 0.077 cm (P < 0.05) and 0.216 ± 0.088 cm in B (a) P group; CLA could also significantly increase the apoptosis cell numbers by 144.00 ± 20.31, 153.75 ± 23.25, 157.25 ± 15.95 (P < 0.05) in 75% purity c9,t11-CLA group, 98% purity c9,t11-CLA group and 98% purity t10,c12-CLA group (30.88 ± 3.72 in BP group); but there were no significant differences between the effects of 75% purity c9,t11-CLA and two isomers in 98% purity on tumor size and apoptotic cell numbers; the plasma levels of MDA in were increased by 75% purity c9,t11-CLA, 98% purity c9,t11-CLA and 98% purity t10,c12-CLA. The 75% purity c9,t11-CLA showed stronger inhibition; CLA could also inhibit the expression of ERK-1 protein and promote the expression of MKP-1 protein, however no influence of CLA on MEK-1 protein was observed. CONCLUSION: Two isomers in 98% purity show stronger inhibition on carcinogenesis. However, the inhibitory mechanisms of CLA on carcinogenesis is complicated, which may be due to the increased mice plasma MDA, the inducing apoptosis in tumor tissues. And the effect of CLA on the expression of ERK-1 and MKP-1 may be one of the mechanisms of the inhibition of CLA on the tumor. PMID:12508349

  19. Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial.

    PubMed

    Capodice, Jillian L; Gorroochurn, Prakash; Cammack, A Sam; Eric, Goluboff; McKiernan, James M; Benson, Mitchell C; Stone, Brian A; Katz, Aaron E

    2009-01-01

    Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP. PMID:19476738

  20. Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization

    PubMed Central

    Haffner, Michael C; Weier, Christopher; Xu, Meng Meng; Vaghasia, Ajay; Gürel, Bora; Gümüşkaya, Berrak; Esopi, David M; Fedor, Helen; Tan, Hsueh-Li; Kulac, Ibrahim; Hicks, Jessica; Isaacs, William B; Lotan, Tamara L; Nelson, William G; Yegnasubramanian, Srinivasan; De Marzo, Angelo M

    2015-01-01

    Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2–ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for intraductal carcinoma adjacent to invasive adenocarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification. PMID:26331372

  1. Altered membrane lipid composition and functional parameters of circulating cells in cockles (Cerastoderma edule) affected by disseminated neoplasia.

    PubMed

    Le Grand, Fabienne; Soudant, Philippe; Marty, Yanic; Le Goïc, Nelly; Kraffe, Edouard

    2013-01-01

    Membrane lipid composition and morpho-functional parameters were investigated in circulating cells of the edible cockle (Cerastoderma edule) affected by disseminated neoplasia (neoplastic cells) and compared to those from healthy cockles (hemocytes). Membrane sterol levels, phospholipid (PL) class and subclass proportions and their respective fatty acid (FA) compositions were determined. Morpho-functional parameters were evaluated through total hemocyte count (THC), mortality rate, phagocytosis ability and reactive oxygen species (ROS) production. Both morpho-functional parameters and lipid composition were profoundly affected in neoplastic cells. These dedifferentiated cells displayed higher THC (5×), mortality rate (3×) and ROS production with addition of carbonyl cyanide m-chloro phenylhydrazone (1.7×) but lower phagocytosis ability (½×), than unaffected hemocytes. Total PL amounts were higher in neoplastic cells than in hemocytes (12.3 and 5.1 nmol×10(-6) cells, respectively). However, sterols and a particular subclass of PL (plasmalogens; 1-alkenyl-2-acyl PL) were present in similar amounts in both cell type membranes. This led to a two times lower proportion of these membrane lipid constituents in neoplastic cells when compared to hemocytes (20.5% vs. 42.1% of sterols in total membrane lipids and 21.7% vs. 44.2% of plasmalogens among total PL, respectively). Proportions of non-methylene interrupted FA- and 20:1n-11-plasmalogen molecular species were the most impacted in neoplastic cells when compared to hemocytes (?× and ¼×, respectively). These changes in response to this leukemia-like disease in bivalves highlight the specific imbalance of plasmalogens and sterols in neoplastic cells, in comparison to the greater stability of other membrane lipid components. PMID:23333874

  2. A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia.

    PubMed

    Odenike, Olatoyosi; Halpern, Anna; Godley, Lucy A; Madzo, Jozef; Karrison, Theodore; Green, Margaret; Fulton, Noreen; Mattison, Ryan J; Yee, Karen W L; Bennett, Meghan; Koval, Gregory; Malnassy, Gregory; Larson, Richard A; Ratain, Mark J; Stock, Wendy

    2015-04-01

    Background We hypothesized that targeting two mechanisms of epigenetic silencing would be additive or synergistic with regard to expression of specific target genes. The primary objective of the study was to establish the maximum tolerated dose (MTD) of belinostat in combination with a fixed dose of azacitidine (AZA). Methods In Part A of the study, patients received a fixed dose of AZA, with escalating doses of belinostat given on the same days 1-5, in a 28 day cycle. Part B was designed to evaluate the relative contribution of belinostat to the combination based on analysis of pharmacodynamic markers, and incorporated a design in which patients were randomized during cycle 1 to AZA alone, or the combination, at the maximally tolerated dose of belinostat. Results 56 patients with myeloid neoplasia were enrolled. Dose escalation was feasible in part A, up to 1000 mg/m(2) dose level of belinostat. In Part B, 18 patients were assessable for quantitative analysis of specific target genes. At day 5 of therapy, MDR1 was significantly up-regulated in the belinostat/AZA arm compared with AZA alone arm (p = 0.0023). There were 18 responses among the 56 patients. Conclusions The combination of belinostat and AZA is feasible and associated with clinical activity. The recommended phase II dose is 1000 mg/m(2) of belinostat plus 75 mg/m(2) of AZA on days 1-5, every 28 days. Upregulation in MDR1 was observed in the combination arm at day 5 compared with the AZA alone arm, suggesting a relative biologic contribution of belinostat to the combination. PMID:25483416

  3. Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia

    PubMed Central

    Wang, Hansong; Yamamoto, Jennifer F.; Caberto, Christian; Saltzman, Barbara; Decker, Robert; Vogt, Thomas M.; Yokochi, Lance; Chanock, Stephen; Wilkens, Lynne R.; Le Marchand, Loïc

    2011-01-01

    Animal work implicates chemical carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to the development of colorectal cancer (CRC). The epidemiologic evidence, however, remains inconsistent possibly due to intra-individual variation in bioactivation of these compounds. We conducted a case–control study of colorectal adenoma (914 cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans, European Americans and Native Hawaiians to investigate the association of genetic variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR and ARNT) identified through sequencing with risk of colorectal neoplasia, as well as their interactions with smoking and intakes of red meat and HAAs. The A allele for ARNT rs12410394 was significantly inversely associated with CRC [odds ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes: 1.00, 0.66 (0.48–0.89), 0.54 (0.37–0.78), Ptrend = 0.0008] after multiple comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated with CRC, where each copy of the T allele was associated with reduced risk (OR: 0.72, 95% CI: 0.58–0.88, Ptrend = 0.0017). No heterogeneity of genetic effects across racial/ethnic groups was detected. In addition, no significant interaction was observed after adjusting for multiple testing between genetic variants and pack-years of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC. PMID:21081473

  4. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study.

    PubMed

    Holl, Katsiaryna; Nowakowski, Andrzej M; Powell, Ned; McCluggage, W Glenn; Pirog, Edyta C; Collas De Souza, Sabrina; Tjalma, Wiebren A; Rosenlund, Mats; Fiander, Alison; Castro Sánchez, Maria; Damaskou, Vasileia; Joura, Elmar A; Kirschner, Benny; Koiss, Robert; O'Leary, John; Quint, Wim; Reich, Olaf; Torné, Aureli; Wells, Michael; Rob, Lukas; Kolomiets, Larisa; Molijn, Anco; Savicheva, Alevtina; Shipitsyna, Elena; Rosillon, Dominique; Jenkins, David

    2015-12-15

    Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type-distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV-positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual-type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear-cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric-type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV-positive ADC. There were variations in HPV prevalence and ADC type-distribution by country. Age at diagnosis differed by ADC subtype, with usual-type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV-positive ADC cases were younger than HPV-negative ADC. The six years difference in median age for women with AIS compared to those with usual-type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45-positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV. PMID:26096203

  5. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    SciTech Connect

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck

    2013-10-11

    Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

  6. An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.

    PubMed

    Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-05-01

    PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

  7. Long term cumulative incidence of cervical intraepithelial neoplasia grade 3 or worse after abnormal cytology: Impact of HIV infection

    PubMed Central

    Massad, L. Stewart; Pierce, Christopher B.; Minkoff, Howard; Watts, D. Heather; Darragh, Teresa M.; Sanchez-Keeland, Lorraine; Wright, Rodney L.; Colie, Christine; D’Souza, Gypsyamber

    2013-01-01

    To estimate the long term cumulative risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+ after an abnormal cervical Pap test and to assess the effect of HIV infection on that risk. Participants in the Women’s Interagency HIV Study were followed semiannually for up to 10 years. Pap tests were categorized according to the 1991 Bethesda system. Colposcopy was prescribed within six months of any abnormality. Risk for biopsy-confirmed CIN3 or worse after abnormal cytology and at least 12 months follow-up was assessed using Kaplan-Meier curves and compared using log-rank tests. Risk for CIN2 or worse was also assessed, since CIN2 is the threshold for treatment. After a median of 3 years of observation, 1,947 (85%) women subsequently presented for colposcopy (1571 [81%] HIV seropositive, 376 [19%] seronegative). CIN2 or worse was found in 329 (21%) of HIV seropositive and 42 (11%) seronegative women. CIN3 or worse was found in 141 (9%) of seropositive and 22 (6%) seronegative women. In multivariable analysis, after controlling for cytology grade HIV seropositive women had an increased risk for CIN2 or worse (H.R. 1.66, 95% C.I 1.15, 2.45) but higher risk for CIN3 or worse did not reach significance (H.R. 1.33, 95% C.I. 0.79, 2.34).HIV seropositive women with abnormal Paps face a marginally increased and long-term risk for cervical disease compared to HIV seronegative women, but most women with ASCUS and LSIL Pap results do not develop CIN2 or worse despite years of observation. PMID:24170366

  8. Risk Factors for the Presence of Anal Intraepithelial Neoplasia in HIV+ Men Who Have Sex with Men

    PubMed Central

    Richel, Olivier; De Vries, Henry J. C.; Dijkgraaf, Marcel G. W.; Van Noesel, Carel J. M.; Prins, Jan M.

    2013-01-01

    Objective Anal Intraepithelial Neoplasia (AIN) is present in the majority of HIV+ men who have sex with men (MSM) and routine AIN-screening is subject of discussion. In this study we analysed a wide range of potential risk factors for AIN in order to target screening programs. Methods We screened 311 HIV+ MSM by high resolution anoscopy, with biopsies of suspect lesions. HIV-parameters, previous sexual transmitted infections (STI’s), anal pathology, sexual practices and substance use were analysed in relation to AIN by uni- and multivariable logistic regression. Results AIN (any grade) was found in 175/311 MSM (56%), high grade (HG)AIN in 30%. In the univariable analysis, years since HIV diagnosis, years of antiretroviral therapy (cART) and anal XTC use decreased AIN risk, while a history of anogenital warts and use of GHB (?-hydroxybutyric acid) increased this risk. In the multivariable analysis three parameters remained significant: years of cART (OR=0.92 per year, p=0.003), anal XTC use (OR=0.10, p=0.002) and GHB use (OR=2.60, p=0.003). No parameters were significantly associated with HGAIN, but there was a trend towards increased risk with anal enema use prior to sex (>50 times ever; p=0.07) and with a history of AIN (p=0.06). CD4 count, STI’s, anal pathology, smoking, number of sex partners and anal fisting were not associated with (HG)AIN. Conclusion GHB use increases the risk for AIN, while duration of cART and anal XTC use are negatively correlated with AIN. Given the high prevalence of AIN in HIV+ MSM, these associations are not helpful to guide a screening program. PMID:24367625

  9. Inhibition of BMP signaling in P-Cadherin positive hair progenitor cells leads to trichofolliculoma-like hair follicle neoplasias

    PubMed Central

    2011-01-01

    Background Skin stem cells contribute to all three major lineages of epidermal appendages, i.e., the epidermis, the hair follicle, and the sebaceous gland. In hair follicles, highly proliferative committed progenitor cells, called matrix cells, are located at the base of the follicle in the hair bulb. The differentiation of these early progenitor cells leads to specification of a central hair shaft surrounded by an inner root sheath (IRS) and a companion layer. Multiple signaling molecules, including bone morphogenetic proteins (BMPs), have been implicated in this process. Methods To further probe the contribution of BMP signaling to hair follicle development and maintenance we employed a transgenic mouse that expresses the BMP inhibitor, Noggin, to disrupt BMP signaling specifically in subset of hair follicle progenitors under the control of neuron specific enolase (Nse) promoter. We then studied the skin tumor phenotypes of the transgenic mice through histology, immunohistochemistry and Western Blotting to delineate the underlying mechanisms. Double transgenic mice expressing BMP as well as noggin under control of the Nse promoter were used to rescue the skin tumor phenotypes. Results We found that the transgene is expressed specifically in a subpopulation of P-cadherin positive progenitor cells in Nse-Noggin mice. Blocking BMP signaling in this cell population led to benign hair follicle-derived neoplasias resembling human trichofolliculomas, associated with down-regulation of E-cadherin expression and dynamic regulation of CD44. Conclusions These observations further define a critical role for BMP signaling in maintaining the homeostasis of hair follicles, and suggest that dysregulation of BMP signaling in hair follicle progenitors may contribute to human trichofolliculoma. PMID:22168923

  10. Evaluation of HPV Infection and Smoking Status Impacts on Cell Proliferation in Epithelial Layers of Cervical Neoplasia

    PubMed Central

    Guillaud, Martial; Buys, Timon P. H.; Carraro, Anita; Korbelik, Jagoda; Follen, Michele; Scheurer, Michael; Storthz, Karen Adler; van Niekerk, Dirk; MacAulay, Calum E.

    2014-01-01

    Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n?=?196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n?=?261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ?50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy. PMID:25210770

  11. Effects of Referral Bias on Estimates of Anal Intraepithelial Neoplasia Progression and Regression Rates in a 3-State Markov Model

    PubMed Central

    Mathews, William Christopher; Cachay, Edward Rafael; Agmas, Wollelaw; Jackson, Christopher

    2015-01-01

    Abstract The study aim is to compare anal intraepithelial neoplasia (AIN) progression and regression rates in a cytology inception cohort to estimates based on the subcohort referred for ?1 high-resolution anoscopies (HRAs). A cytology-based retrospective cohort was assembled including the anal cytology histories and invasive anal cancer (IAC) outcomes of all HIV-infected adults under care between 2001 and 2012. A 3-state Markov model (400, and to have HSIL at baseline and thereafter. They also had more anal cytology examinations (median 6 vs 3) and longer follow-up (median 5.5 vs 3.6 years). State transition rates were overestimated in the HRA subcohort relative to inception cohort, but the degree of discordance varied by transition: for

  12. VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop

    SciTech Connect

    Gonzalez-Moreno, Oscar; Lecanda, Jon; Green, Jeffrey E.; Segura, Victor; Catena, Raul; Serrano, Diego; Calvo, Alfonso

    2010-02-15

    Vascular endothelial growth factor (VEGF) is overexpressed during the transition from prostate intraepithelial neoplasia (PIN) to invasive carcinoma. We have mimicked such a process in vitro using the PIN-like C3(1)/Tag-derived Pr-111 cell line, which expresses low levels of VEGF and exhibits very low tumorigenicity in vivo. Elevated expression of VEGF164 in Pr-111 cells led to a significant increase in tumorigenicity, invasiveness, proliferation rates and angiogenesis. Moreover, VEGF164 induced strong changes in cell morphology and cell transcriptome through an autocrine mechanism, with changes in TGF-beta1- and cytoskeleton-related pathways, among others. Further analysis of VEGF-overexpressing Pr-111 cells or following exogenous addition of recombinant VEGF shows acquisition of epithelial-mesenchymal transition (EMT) features, with an increased expression of mesenchymal markers, such as N-cadherin, Snail1, Snail2 (Slug) and vimentin, and a decrease in E-cadherin. Administration of VEGF led to changes in TGF-beta1 signaling, including reduction of Smad7 (TGF-beta inhibitory Smad), increase in TGF-betaR-II, and translocation of phospho-Smad3 to the nucleus. Our results suggest that increased expression of VEGF in malignant cells during the transition from PIN to invasive carcinoma leads to EMT through an autocrine loop, which would promote tumor cell invasion and motility. Therapeutic blockade of VEGF/TGF-beta1 in PIN lesions might impair not only tumor angiogenesis, but also the early dissemination of malignant cells outside the epithelial layer.

  13. Lack of commensal flora in H. pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia

    PubMed Central

    Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.

    2010-01-01

    Background & Aims Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. Methods We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Results Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Conclusions Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice. PMID:20950613

  14. An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

    PubMed Central

    Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-01-01

    SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

  15. Subtype Distribution of Human Papillomavirus in HIV-Infected Women With Cervical Intraepithelial Neoplasia Stages 2 and 3 in Botswana

    PubMed Central

    Ramogola-Masire, Doreen; McGrath, Cindy M.; Barnhart, Kurt T.; Friedman, Harvey M.; Zetola, Nicola M.

    2013-01-01

    Summary Human papillomavirus (HPV) vaccines containing types 16 and 18 are likely to be effective in preventing cervical cancer associated with these HPV types. No information currently exists in Botswana concerning the HPV types causing precancerous or cancerous lesions. Our goal was to determine the prevalence of HPV types associated with precancerous cervical intraepithelial neoplasia (CIN) stages 2 and 3 in HIV-infected women in Gaborone, Botswana. HIV-infected women referred to our clinic with high-grade intraepithelial lesion on the Pap smear were enrolled in the study. HPV typing was only performed if the histopathology results showed CIN stage 2 or 3 disease using linear array genotyping (CE-IVD, Roche Diagnostics).One hundred HIV-infected women were identified with CIN stages 2 or 3 between August 11, 2009 and September 29, 2010. Eighty-two of 100 women enrolled had coinfection by multiple HPV subtypes (range, 2 to 12). Of the remaining 18 women, 14 were infected with a single high-risk subtype and 4 had no HPV detected. Overall, 92 (92%) women were infected with at least 1 high-risk HPV subtype, and 56 were coinfected with more than 1 high-risk HPV type (range, 2 to 5). Fifty-one (51%) women had HPV subtypes 16, 18, or both. HPV 16 and 18 are the most common types in HIV-infected women with CIN 2 or 3 in Gaborone, Botswana, suggesting that the implementation of HPV vaccination programs could have a significant impact on the reduction of cervical cancer incidence. However, given the relative lack of knowledge on the natural history of cervical cancer in HIV-infected women and the significant prevalence of infection and coinfection with other high-risk HPV types in our sample, the true impact and cost-effectiveness of such vaccination programs need to be evaluated. PMID:21979597

  16. Genital Warts and Vulvar Intraepithelial Neoplasia: Natural History and Effects of Treatment and Human Immunodeficiency Virus Infection

    PubMed Central

    Massad, L. Stewart; Xie, Xianhong; Darragh, Teresa; Minkoff, Howard; Levine, Alexandra M.; Watts, D. Heather; Wright, Rodney L.; D’Souza, Gypsyamber; Colie, Christine; Strickler, Howard D.

    2011-01-01

    Objective To describe the natural history of genital warts and vulvar intraepithelial neoplasia (VIN) in women with human immunodeficiency virus (HIV). Methods A cohort of 2,791 HIV infected and 953 uninfected women followed for up to 13 years had genital examinations at 6-month intervals, with biopsy for lesions suspicious for VIN. Results The prevalence of warts was 4.4% (5.3% for HIV seropositive women and 1.9% for seronegative women, P < 0.0001). The cumulative incidence of warts was 33% (95% C.I. 30, 36%) in HIV seropositive and 9% (95% C.I. 6, 12%) in seronegative women (P < 0.0001). In multivariable analysis, lower CD4 lymphocyte count, younger age, and current smoking were strongly associated with risk for incident warts. Among 501 HIV seropositive and 43 seronegative women, warts regressed in 410 (82%) seropositive and 41 (95%) seronegative women (P = 0.02), most in the first year after diagnosis. In multivariable analysis, regression was negatively associated with HIV status and lower CD4 count as well as older age. Incident VIN of any grade occurred more frequently among HIV seropositive than seronegative women: 0.42 (0.33 – 0.53) vs 0.07 (0.02 – 0.18)/100 person-years (P < 0.0001). VIN2+ was found in 58 women (55 with and 3 without HIV, P < 0.001). Two women with HIV developed stage IB squamous cell vulvar cancers. Conclusion While genital warts and VIN are more common among HIV seropositive than seronegative women, wart regression is common even in women with HIV, and cancers are infrequent. PMID:21934446

  17. The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants

    PubMed Central

    Wong, Martin C. S.; Ching, Jessica Y. L.; Ng, Simpson; Lam, Thomas Y. T.; Luk, Arthur K. C.; Wong, Sunny H.; Ng, Siew C.; Ng, Simon S. M.; Wu, Justin C. Y.; Chan, Francis K. L.; Sung, Joseph J. Y.

    2016-01-01

    We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50–70 years in a colonoscopy screening programme(2008–2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56–0.65, with sensitivities ranging from 0.04–0.44 and specificities from 0.74–0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58–0.72). The NNS (12–19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed. PMID:26838178

  18. Prospective multicenter evaluation of fecal tumor pyruvate kinase type M2 (M2-PK) as a screening biomarker for colorectal neoplasia.

    PubMed

    Shastri, Yogesh M; Naumann, Marc; Oremek, Gerhard M; Hanisch, Ernst; Rösch, Wolfgang; Mössner, Joachim; Caspary, Wolfgang F; Stein, Jürgen M

    2006-12-01

    Proliferating cells, particularly the tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2-PK. It's a direct target of several oncoproteins; the determination of fecal tumor pyruvate kinase type M2 (M2-PK) might be another promising tool for colorectal cancer (CRC) screening. In this study, we have evaluated fecal M2-PK as a screening biomarker for colorectal neoplasia. It was compared against fecal occult blood (FOB) and colonoscopy. Three hundred and seventeen consecutive subjects from 4 different centers were included. Stool specimens were collected before purgation, processed appropriately and were tested for FOB and quantitatively analyzed for M2-PK. Colonoscopies were performed by experienced endoscopists who were unaware of fecal assay results. At cutoff value of 4 U/ml, fecal M2-PK assay had a sensitivity, specificity, PPV and NPV of 81.1, 86.7, 71.1 and 61.9% respectively for diagnosing CRC whereas FOBT showed a sensitivity of 36.5%, specificity of 92.2%, PPV of 72.9% and NPV of 71.5% for CRC. Such low specificity of fecal M2-PK will lead to unacceptably high number of false positives if it is used for mass CRC screening, leading to unindicated colonoscopies with its associated inconveniences, risks and costs. CRC screening test must have high specificity; a high sensitivity is not as vital. To conclude, M2-PK was found to be a poor screening biomarker for CR neoplasia in a subject population at above average risk based on its prospective comparison with colonoscopy. These marginal performance characteristics do not permit its use as a screening tool for CR neoplasia in present clinical settings. PMID:16929517

  19. The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential.

    PubMed

    Renaud, Florence; Mariette, Christophe; Vincent, Audrey; Wacrenier, Agnès; Maunoury, Vincent; Leclerc, Julie; Coppin, Lucie; Crépin, Michel; Van Seuningen, Isabelle; Leteurtre, Emmanuelle; Buisine, Marie-Pierre

    2016-03-15

    The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention. PMID:26476272

  20. Epithelial neoplasia coincides with exacerbated injury and fibrotic response in the lungs of Gprc5a-knockout mice following silica exposure

    PubMed Central

    Zhong, Shuangshuang; Song, Hongyong; Sun, Beibei; Zhou, Binhua P.; Deng, Jiong; Han, Baohui

    2015-01-01

    Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a−/− mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a−/− mouse model following silica exposure. Intra-tracheal administration of fine silica particles in Gprc5a−/− mice resulted in more severe lung injury and pulmonary inflammation than in wild-type mice. Moreover, an enhanced fibrogenic response, including EMT-like characteristics, was induced in the lungs of Gprc5a−/− mice compared to those from wild-type ones. Importantly, increased hyperplasia or neoplasia coincided with silica-induced tissue injury and fibrogenic response in lungs from Gprc5a−/− mice. Consistently, expression of MMP9, TGFβ1 and EGFR was significantly increased in lungs from silica-treated Gprc5a−/− mice compared to those untreated or wild-type ones. These results suggest that, the process of tissue repair coincides with tissue damages; whereas persistent tissue damages leads to abnormal repair or neoplasia. Thus, silica-induced pulmonary inflammation and injury contribute to increased neoplasia development in lungs from Gprc5a−/− mouse model. PMID:26447616

  1. Association between biomarkers of obesity and risk of high-grade prostatic intraepithelial neoplasia and prostate cancer--evidence of effect modification by prostate size.

    PubMed

    Fowke, Jay H; Motley, Saundra; Dai, Qi; Concepcion, Raoul; Barocas, Daniel A

    2013-01-28

    Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC. PMID:23079532

  2. Calcium Intake and Ion Transporter Genetic Polymorphisms Interact in Human Colorectal Neoplasia Risk in a 2-Phase Study123

    PubMed Central

    Zhu, Xiangzhu; Liang, Ji; Shrubsole, Martha J.; Ness, Reid M.; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Wiese, Dawn; Zhang, Bing; Smalley, Walter E.; Edwards, Todd L.; Giovannucci, Edward; Zheng, Wei; Dai, Qi

    2014-01-01

    Background: The kidney-specific sodium-potassium-chloride cotransporter (NKCC2) protein encoded by solute carrier family 12 member 1 (SLC12A1) is the direct downstream effector of the inward-rectifier potassium channel (ROMK) encoded by potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), both of which are critical for calcium reabsorption in the kidney. Objective: We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. Methods: We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. Results: In phase I, we identified 5 single-nucleotide polymorphisms (SNPs) that significantly interacted with calcium intake in adenoma risk. In phase II, rs2855798 in KCNJ1 was replicated. In combined analysis of phases I and II, the P values for interactions between calcium intake and rs2855798 were 1 × 10?4 for all adenoma and 5 × 10?3 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with no variant allele but was significantly associated with a 41% reduced adenoma risk among those who carried at least 1 variant allele in KCNJ1. The corresponding reduction in risk of multiple or advanced adenomas was 52% among those with at least 1 variant allele. The P values for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 × 10?5 for adenoma and 9.9 × 10?5 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with nonvariant alleles in 2 genes but was significantly associated with a 34% reduced adenoma risk among those who carried a variant allele in 1 of the genes. The corresponding reduction in risk of multiple or advanced adenomas was 64% among those with variant alleles in both genes. Conclusion: These findings, if confirmed, will be critical for the development of personalized prevention strategies for colorectal cancer. PMID:25165391

  3. Prevalence of Advanced Colorectal Neoplasia in Whites and Blacks Undergoing Screening Colonoscopy in a Safety Net Hospital

    PubMed Central

    Schroy, Paul C.; Coe, Alison; Chen, Clara A.; O’Brien, Michael J.; Heeren, Timothy C.

    2014-01-01

    Background Blacks are more likely than whites to be diagnosed with colorectal cancer and die of their disease. The extent to which genetic or biologic factors versus disparities in screening rates explain this variance remains controversial. Objective To define the prevalence and location of presymptomatic advanced colorectal neoplasia (ACN) among whites and blacks undergoing screening colonoscopy controlling for other epidemiologic determinants of risk. Design Cross-sectional survey between March 22, 2005 and January 31, 2012. Setting Urban, open-access, academic, safety net hospital in Massachusetts. Participants Asymptomatic, average-risk whites (n=1172) and blacks (n=1681) 50 to 79 years of age presenting for screening colonoscopy. Measurements Adjusted prevalence and location of ACN, defined as a tubular adenoma ? 10 mm in size, any adenoma with villous features or high-grade dysplasia, any dysplastic serrated lesion, or invasive cancer. Results The prevalence of ACN was higher among whites than blacks (6.8% vs. 5.0%; P=0.039) but varied by sex (white versus black men, 9.3% vs. 5.7%; white vs. black women, 3.5% vs. 4.3%; P for interaction =0.034). After controlling for exposure to multiple risk factors, black men were 41% less likely than white men (adjusted odds ratio [aOR], 0.59; 95% confidence intervals [CI], 0.39–0.89) to have ACN; conversely, no significant differences were observed for women (aOR, 1.32; 95% CI, 0.73–2.40). Among individuals with ACN, blacks a higher percentage of proximal disease (52% vs. 39%) after adjustment for age and sex (P=0.055). Limitations Single institution study; inadequate statistical power for subgroup analyses; recall bias. Conclusions Black men are less likely than white men to have ACN at screening colonoscopy in a safety net health care setting. These findings suggest that disparities in access to screening and differential exposure to modifiable risk factors rather than genetic or biologic factors are largely responsible for the higher incidence of CRC among black men. Genetic or biologic factors, however may explain the predilection for proximal disease. Primary Funding Source National Cancer Institute PMID:23817700

  4. A Blood Test for Methylated BCAT1 and IKZF1 vs. a Fecal Immunochemical Test for Detection of Colorectal Neoplasia

    PubMed Central

    Symonds, Erin L; Pedersen, Susanne K; Baker, Rohan T; Murray, David H; Gaur, Snigdha; Cole, Stephen R; Gopalsamy, Geetha; Mangira, Dileep; LaPointe, Lawrence C; Young, Graeme P

    2016-01-01

    Objectives: To compare the performance of a new blood test for colorectal cancer (CRC) to an established fecal immunochemical test (FIT) in a study population with the full range of neoplastic and non-neoplastic pathologies encountered in the colon and rectum. Methods: Volunteers were asked to complete a FIT prior to colonoscopy. Blood was collected after bowel preparation but prior to colonoscopy, and plasma was assayed for the presence of methylated BCAT1 and IKZF1 DNA using a multiplex real-time PCR assay. Sensitivity and specificity estimates for the blood test were calculated from true- and false-positive rates for neoplasia and compared with FIT at a range of fecal hemoglobin (Hb) concentration positivity thresholds. Results: In total, 1,381 volunteers (median age 64 years; 49% male) completed both tests prior to colonoscopy. Estimated sensitivity of the BCAT1/IKZF1 blood test for CRC was 62% (41/66; 95% confidence interval 49–74%) with a specificity of 92% (1207/1315; 90–93%). FIT returned the same specificity at a cutoff of 60 μg Hb/g, at which its corresponding sensitivity for cancer was 64% (42/66; 51–75%). In the range of commonly used FIT cutoffs, respective cancer sensitivity and specificity estimates with FIT were: 59% (46–71%) and 93% (92–95%) at 80 μg Hb/g, and 79% (67–88%) and 81% (78–83%) at 10 μg Hb/g. Although estimated sensitivities were not significantly different between the two tests for any stage of cancer, FIT showed a significantly higher sensitivity for advanced adenoma at the lower cutoffs. Specificity of FIT, but not of the BCAT1/IKZF1 blood test, deteriorated substantially in people with overt blood in the feces. When combining FIT (cutoff 10 μg Hb/g) with the BCAT1/IKZF1 blood test, sensitivity for cancer was 89% (79–96%) at 74% (72–77%) specificity. Conclusions: A test based on detection of methylated BCAT1/IKZF1 DNA in blood has comparable sensitivity but better specificity for CRC than FIT at the commonly used positivity threshold of 10 μg Hb/g. Further evaluation of the new test relative to FIT in the population screening context is now required to fully understand the potential advantages and disadvantages of these biomarkers in screening. PMID:26765125

  5. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe.

    PubMed

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf; Powell, Ned; Nowakowski, Andrzej M; Kirschner, Benny; Koiss, Robert; O'Leary, John; Joura, Elmar A; Rosenlund, Mats; Colau, Brigitte; Schledermann, Doris; Kukk, Kersti; Damaskou, Vasileia; Repanti, Maria; Vladareanu, Radu; Kolomiets, Larisa; Savicheva, Alevtina; Shipitsyna, Elena; Ordi, Jaume; Molijn, Anco; Quint, Wim; Raillard, Alice; Rosillon, Dominique; De Souza, Sabrina Collas; Jenkins, David; Holl, Katsiaryna

    2013-02-15

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions. PMID:22752992

  6. Factors Associated with Colposcopy-Histopathology Confirmed Cervical Intraepithelial Neoplasia among HIV-Infected Women from Rio De Janeiro, Brazil

    PubMed Central

    de Andrade, Angela Cristina Vasconcelos; Luz, Paula Mendes; Velasque, Luciane; Veloso, Valdiléa Gonçalves; Moreira, Ronaldo I.; Russomano, Fabio; Chicarino-Coelho, Janice; Pires, Elaine; Levi, José Eduardo; Grinsztejn, Beatriz; Friedman, Ruth Khalili

    2011-01-01

    Introduction Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. Results The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ?35 years (aPR ?=? 3.22 95%CI 1.23–8.39), current tobacco use (aPR ?=? 3.69 95%CI 1.54–8.78), nadir CD4 T-cell count <350 cells/mm3 when compared to ? 350 cells/mm3 (aPR ?=? 6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR ?=? 2.68 95%CI 0.99–7.24). Discussion Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of women. PMID:21479179

  7. Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

    PubMed Central

    Yoshikawa, Hiroyuki

    2016-01-01

    Objective We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Methods Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. Results The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). Conclusion Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins. PMID:26463429

  8. Comparison of Seven Tests for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears: the Predictors 2 Study

    PubMed Central

    Mesher, David; Cadman, Louise; Austin, Janet; Ashdown-Barr, Lesley; Ho, Linda; Terry, George; Liddle, Stuart; Young, Martin; Stoler, Mark; McCarthy, Julie; Wright, Corrina; Bergeron, Christine; Soutter, W. P; Lyons, Deirdre; Cuzick, Jack

    2012-01-01

    High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16INK4a cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16INK4a cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting. PMID:22422852

  9. Association of stem-like cells in gender-specific chemoprevention against intestinal neoplasia in MIN mouse

    PubMed Central

    Gandhi, Seema R; Tiwari, Ashish K; Kunte, Dhananjay P; De la Cruz, Mart Angelo; Stypula, Yolanda; Gibson, Tina; Brasky, Jeffrey; Backman, Vadim; Wali, Ramesh K; Roy, Hemant K

    2013-01-01

    This study was undertaken to examine gender sensitivity and chemopreventive responsiveness of celecoxib on intestinal stem-like cells as biomarker of colon carcinogenesis, using the MIN mouse model. Male and female MIN mice (6–7 weeks old) were randomized to either control diet or to one supplemented with celecoxib (1500 ppm). The animals were euthanized ten weeks later and the intestines were flushed and opened longitudinally to assess tumor count. Small intestinal segments were formalin fixed and tissue sections were subjected to immunohistochemical evaluation of DCAMKL1, a known marker of stem-like cells. We found that in animals receiving control (AIN 76A diet) alone, female MIN mice had higher polyp count than that of males (52.32±13.89 vs. 35.43±16.05; p<0.0005). However, compared to control diet groups, celecoxib supplementation caused a larger reduction in the number of polyps in females than their male cohorts (6.38±1.43 vs. 12.83±6.74; a reduction of 88% in females to 64% in males). Significant differences (p=0.013) were observed in the number of DCAMKL1 stained cells in the crypts of the wildtype (WT) (10.01 ± 1.07 stem cells per high powered field; HPF) compared to the MIN mice (24.15 ± 8.08 stem cells per HPF), illustrating increased stem-like cells in animals that are more prone to neoplasia. DCAMKL1 labeled stem-like cells were equal in number in the male and female groups receiving the control AIN 76A diet alone (females= 25.73 stem-like cells/HPF); males= 24.15 stem-like cells/HPF). However females showed a greater reduction in the number of DCAMKL1 labeled stem like cells with the celecoxib supplementation than the males (16.63±4.23 vs. 21.56±9.06; a reduction of 35.4% in females to 10.7% in males). We conclude that a higher number of stem-like cells in the uninvolved mucosa paralleled tumorigenesis and mirrored greater chemopreventive responsiveness of female MIN mice to males. PMID:21769438

  10. Multiple Endocrine Neoplasia Syndromes

    MedlinePLUS

    ... ALL NEWS > Resources First Aid Videos Figures Images Audio Pronunciations The One-Page Manual of Health Quizzes ... ALL NEWS > Resources First Aid Videos Figures Images Audio Pronunciations The One-Page Manual of Health Quizzes ...

  11. Multiple Endocrine Neoplasia Syndromes

    MedlinePLUS

    ... gland The thyroid gland (less often affected) The adrenal glands (less often affected) Almost all people with multiple ... of pituitary tumors produce corticotropin , which overstimulates the adrenal glands, leading to high levels of corticosteroid hormones and ...

  12. Serrated Colorectal Neoplasia.

    PubMed

    Snover, Dale C; Batts, Kenneth P

    2010-06-01

    Until very recently, there was general acceptance in the pathology community that all serrated lesions of the colon and rectum without overt cytologic dysplasia were hyperplastic polyps and had no malignant potential. Although there are still several unanswered questions in regard to the relationship between the various serrated lesions, there is a better understanding of the relationship of sessile serrated adenoma to carcinoma. This article discusses hyperplastic polyps, sessile serrated adenoma, traditional serrated adenoma, mixed polyps, and serrated lesions in such conditions as idiopathic inflammatory bowel disease and mechanical trauma. The major focus of the content is on diagnostic features of these lesions. PMID:26839130

  13. Asbestos exposure and neoplasia

    SciTech Connect

    Selikoff, I.J.; Churg, J.; Hammond, E.C.

    1984-07-06

    Builiding trades insulation workers have relatively light, intermittent, exposure to asbestos. Of 632 insulation workers, who entered the trade before 1943 and were traced through 1962, forty-five died of cancer of the lung or pleura, whereas only 6.6 such deaths were expected. Three of the pleural tumors were mesotheliomas; there was also one peritoneal mesothelioma. Four mesotheliomas in a total of 255 deaths is an exceedingly high incidence for such a rare tumor. In addition, an unexpectedly large number of men died of cancer of the stomach, colon, or rectum (29 compared with 9.4 expected). Other cancers were not increased; 20.5 were expected, 21 occurred. Twelve men died of asbestosis. This landmark article appeared originally in this journal 188:22-26, 1964.

  14. Prevalence of high-risk human papillomavirus and cervical intraepithelial neoplasias in a previously unscreened population--a pooled analysis from three studies.

    PubMed

    Basu, Partha; Mittal, Srabani; Bhaumik, Suchismita; Mandal, Shyam Sunder; Samaddar, Anusree; Ray, Chinmayi; Siddiqi, Maqsood; Biswas, Jaydip; Sankaranarayanan, Rengaswamy

    2013-04-01

    Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening. PMID:22907663

  15. Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings

    NASA Astrophysics Data System (ADS)

    Yamal, Jose-Miguel; Zewdie, Getie A.; Cox, Dennis D.; Neely Atkinson, E.; Cantor, Scott B.; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P. H.; Follen, Michele

    2012-04-01

    Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training.

  16. Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus

    PubMed Central

    Hendry, William J.; Hariri, Hussam Y.; Alwis, Imala D.; Gunewardena, Sumedha S.; Hendry, Isabel R.

    2014-01-01

    Neonatal treatment of hamsters with diethylstilbestrol (DES) induces uterine hyperplasia/dysplasia/neoplasia (endometrial adenocarcinoma) in adult animals. We subsequently determined that the neonatal DES exposure event directly and permanently disrupts the developing hamster uterus (initiation stage) so that it responds abnormally when it is stimulated with estrogen in adulthood (promotion stage). To identify candidate molecular elements involved in progression of the disruption/neoplastic process, we performed: 1) immunoblot analyses and 2) microarray profiling (Affymetrix Gene Chip System) on sets of uterine protein and RNA extracts, respectively, and 3) immunohistochemical analysis on uterine sections; all from both initiation stage and promotion stage groups of animals. Here we report that: 1) progression of the neonatal DES-induced hyperplasia/dysplasia/neoplasia phenomenon in the hamster uterus involves a wide spectrum of specific gene expression alterations and 2) the gene products involved and their manner of altered expression differ dramatically during the initiation vs. promotion stages of the phenomenon. Particularly interesting changes included members in the functional categories of nuclear receptors (progesterone receptor), cell-cell interactions (E-cadherin, connexins), cytokine action (IRF-1, Stat5A), growth factor action (IRS-1), extracellular matrix component (tenascin-C), transcription factors (Nrf2, Sp1), and multi-functional nuclear protein (SAFB1). PMID:25242112

  17. ProEx(™) C is a useful ancillary study for grading anal intraepithelial neoplasia alone and in combination with other biomarkers.

    PubMed

    Larson, Brent K; Mohanty, Sambit K; Wu, Julie M; Bose, Shikha; Walts, Ann E

    2016-03-01

    Anal intraepithelial neoplasia (AIN) is a precursor to invasive anal squamous cell carcinoma. Histologic evaluation is hampered by intra- and interobserver variability. Various biomarkers have been investigated to improve the accuracy and reproducibility of diagnosis and grading, but interpretation can be challenging. ProEx(™) C is an antibody cocktail for proteins upregulated in cervical intraepithelial neoplasia. This study investigated ProEx(™) C's role alone and with p16 and Ki-67 in the diagnosis and grading of AIN. Sixty-seven anal tissue samples (22 AIN I, 25 AIN II/III, and 20 non-dysplastic) were stained for ProEx(™) C, Ki-67, and p16. Staining patterns were recorded and correlated with morphologic diagnoses. Considering AIN II/III vs I, full-thickness ProEx(™) C staining was more frequent in AIN II/III (p = 0.0373), and showed the highest sensitivity of the biomarkers. In combination with Ki-67, sensitivity was lower, but specificity for AIN II/III rose to 83%. For differentiating non-dysplasia from AIN I, negative ProEx(™) C staining correlated with non-dysplasia (p < 0.0001) and had the highest sensitivity (90%). In combination with Ki-67, sensitivity dropped to 80%, but specificity was high (96%). ProEx(™) C is useful for diagnosing and grading AIN, performing as well or better than other markers at identifying AIN II/III and non-dysplastic epithelium. PMID:26590011

  18. Cryospray ablation using pressurized CO2 for ablation of Barrett’s esophagus with early neoplasia: early termination of a prospective series

    PubMed Central

    Verbeek, Romy E.; Vleggaar, Frank P.; ten Kate, Fiebo J.; van Baal, Jantine W. P. M.; Siersema, Peter D.

    2015-01-01

    Background: Cryotherapy is a relatively novel ablation modality for the endoscopic ablation of Barrett’s esophagus (BE). Data on the use of pressurized carbon dioxide (CO2) gas for cryoablation are scarce. Study aim: To determine the efficacy and safety of cryospray ablation using pressurized CO2 gas in the treatment of BE with early neoplasia. Methods: In this prospective single center case series, we aimed to include 30 patients with BE and early neoplasia. Nodular neoplastic lesions were treated with endoscopic mucosal resection (EMR). Residual BE mucosa was treated with cryospray ablation every 4 weeks until the complete BE segment was eliminated or up to seven treatment sessions. If no reduction of the BE segment was observed after two subsequent treatment sessions, cryoablation was terminated. Patients were contacted at days 1 and 4 post-treatment to evaluate the level of discomfort. Endoscopic and histologic follow-up evaluations were performed up to 24 months post-treatment. Results: After the inclusion of 10 patients, insufficient effect of cryoablation was observed, resulting in early termination of the study. In total, seven patients with intramucosal carcinoma (IMC) and three with high grade dysplasia (HGD) were included. Prior EMR was performed in nine patients. A median of 2.5 (IQR 2.0?–?4.0) cryoablation sessions were performed. At 6 months of follow-up, complete eradication of intestinal metaplasia was observed in 11?% (1?/9; one patient died, not treatment or disease related) of the patients and complete eradication of dysplasia in 44?% (4?/9). In three patients, HGD or IMC was detected during follow-up, and was endoscopically treated. Apart from a gastric perforation as a result of gastric distension caused by CO2 gas during the first treatment, cryospray treatments were well tolerated. Conclusion: After a short learning curve, cryoablation using CO2 gas was found to be a safe and well tolerated treatment modality. However, in our experience, the efficacy of CO2 cryoablation combined with EMR for nodular lesions is disappointing for the treatment of BE associated neoplasia. PMID:26135648

  19. Zinc finger arrays binding human papillomavirus types 16 and 18 genomic DNA: precursors of gene-therapeutics for in-situ reversal of associated cervical neoplasia

    PubMed Central

    2012-01-01

    Background Human papillomavirus (HPV) types 16 and 18 are the high-risk, sexually transmitted infectious causes of most cervical intraepithelial neoplasias (CIN) or cancers. While efficacious vaccines to reduce the sexual acquisition of these high-risk HPVs have recently been introduced, no virus-targeted therapies exist for those already exposed and infected. Considering the oncogenic role of the transforming (E6 and E7) genes of high-risk HPVs in the slow pathogenesis of cervical cancer, we hypothesize that timely disruption or abolition of HPV genome expression within pre-cancerous lesions identified at screening may reverse neoplasia. We aimed to derive model zinc finger nucleases (ZFNs) for mutagenesis of the genomes of two high-risk HPV (types 16 & 18). Methods and results Using ZiFiT software and the complete genomes of HPV types16 and 18, we computationally generated the consensus amino acid sequences of the DNA-binding domains (F1, F2, & F3) of (i) 296 & 327 contextually unpaired (or single) three zinc-finger arrays (sZFAs) and (ii) 9 & 13 contextually paired (left and right) three- zinc-finger arrays (pZFAs) that bind genomic DNA of HPV-types 16 and 18 respectively, inclusive of the E7 gene (s/pZFAHpV/E7). In the absence of contextually paired three-zinc-finger arrays (pZFAs) that bind DNA corresponding to the genomic context of the E6 gene of either HPV type, we derived the DNA binding domains of another set of 9 & 14 contextually unpaired E6 gene-binding ZFAs (sZFAE6) to aid the future quest for paired ZFAs to target E6 gene sequences in both HPV types studied (pZFAE6). This paper presents models for (i) synthesis of hybrid ZFNs that cleave within the genomic DNA of either HPV type, by linking the gene sequences of the DNA-cleavage domain of the FokI endonuclease FN to the gene sequences of a member of the paired-HPV-binding ZFAs (pZFAHpV/E7 + FN), and (ii) delivery of the same into precancerous lesions using HPV-derived viral plasmids or vectors. Conclusions With further optimization, these model ZFNs offer the opportunity to induce target-mutagenesis and gene-therapeutic reversal of cervical neoplasia associated with HPV types 16 & 18. PMID:22840184

  20. Different DNA methylation pattern of HPV16, HPV18 and HPV51 genomes in asymptomatic HPV infection as compared to cervical neoplasia.

    PubMed

    Simanaviciene, Vaida; Popendikyte, Violeta; Gudleviciene, Zivile; Zvirbliene, Aurelija

    2015-10-01

    Epigenetic alterations of human papillomavirus (HPV) genome play an important role in virus life cycle and carcinogenic progression. The aim of the current study was to investigate the correlation between the grade of cervical pathology and DNA methylation status within the L1 gene and the long control region (LCR) of HPV16, HPV18 and HPV51. HPV genomes were analyzed using bisulfite DNA modification procedure with the subsequent amplification of target DNA regions and sequencing. A collection of 202 cervical specimens was analyzed: 157 HPV16-positive specimens, 21 HPV18-positive specimens and 24 HPV51-positive specimens. This study revealed that methylation of CpG was significantly more prevalent in L1 gene as compared to LCR region of all three studied HPV types and the degree of DNA methylation level correlated with the severity of cervical neoplasia. An increased DNA methylation level of HPV16 promoter region in case of cervical cancer was determined. PMID:26119875

  1. Multiple therapeutic and preventive effects of 3,3′-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

    PubMed Central

    Zhang, William Weiben; Feng, Zhenqing; Narod, Steven A.

    2014-01-01

    Abstract Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross. These vegetables are an abundant source of dietary phytochemicals, including glucosinolates and their hydrolysis products such as indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM). By 2013, the total number of natural glucosinolates that have been documented is estimated to be 132. Recently, cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer, antiviral infections, human sex hormone regulation, and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia (HGPIN). DIM is a hydrolysis product of glucosinolates and has been used in various trials. This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN. PMID:25332705

  2. Low Discrepancy Between Tissue Biopsy Plus Magnifying Endoscopy With Narrow-Band Imaging and Endoscopic Resection in the Diagnosis of Gastric Epithelial Neoplasia (STROBE)

    PubMed Central

    Zhang, Qiang; Lian, Zhou Yang; Chen, Zhen Yu; Wang, Zhen; di Chen, Chu; An, Sheng li; Gong, Wei; Zhi, Fa chao; de Liu, Si

    2015-01-01

    Abstract Tissue biopsy is often not very accurate for the diagnosis of gastric epithelial neoplasia (GEN), and the results differ notably from endoscopic resection (ER) in terms of the pathological diagnosis. The aims of this study were to evaluate the diagnostic performances of biopsy, magnifying endoscopy with narrow-band imaging (ME-NBI), and biopsy plus ME-NBI for GEN. This study retrospectively analyzed 101 cases diagnosed as GEN using ER samples. The discrepancies between biopsy and ER, as well as between biopsy plus ME-NBI and ER in the diagnosis of GEN were evaluated. Factors that contributed to such discrepancies were analyzed. The sensitivity and specificity of biopsy and ME-NBI for the diagnosis of high-grade neoplasia (HGN) were determined. The discrepancy in the pathological diagnosis between biopsy and ER was 39.6% for GEN and 54.2% for HGN. The discrepancy between biopsy combined with ME-NBI and ER was 15.9% for GEN and 10.2% for HGN. Factors that undermined the diagnostic accuracy of biopsy included the lesion size (?10?mm, odds ratio [OR] 1; 10–20?mm, OR 0.2, 95% confidence interval [CI] 0.1–0.7; >20?mm, OR 0.5, 95% CI 0.1–2.1, P?=?0.03) and the number of biopsy fragments (OR 0.6, 95% CI 0.5–0.8, P?=?0.001). The sensitivity and specificity for HGN were 45.8% (33.7%–58.3%) and 100% (87.5%–100%) for biopsy, and 88.1% (77.5%–94.1%) and 92.9% (81.0%–97.5%) for ME-NBI, respectively. In conclusion, biopsy-based diagnoses for GEN should be interpreted with caution. Biopsy combined with ME-NBI can contribute to the diagnosis of GEN, which improves diagnostic consistency with pathological result of ER specimens. PMID:26166094

  3. Low Discrepancy Between Tissue Biopsy Plus Magnifying Endoscopy With Narrow-Band Imaging and Endoscopic Resection in the Diagnosis of Gastric Epithelial Neoplasia (STROBE).

    PubMed

    Zhang, Qiang; Lian, Zhou Yang; Chen, Zhen Yu; Wang, Zhen; di Chen, Chu; An, Sheng Li; Gong, Wei; Zhi, Fa Chao; de Liu, Si

    2015-07-01

    Tissue biopsy is often not very accurate for the diagnosis of gastric epithelial neoplasia (GEN), and the results differ notably from endoscopic resection (ER) in terms of the pathological diagnosis. The aims of this study were to evaluate the diagnostic performances of biopsy, magnifying endoscopy with narrow-band imaging (ME-NBI), and biopsy plus ME-NBI for GEN.This study retrospectively analyzed 101 cases diagnosed as GEN using ER samples. The discrepancies between biopsy and ER, as well as between biopsy plus ME-NBI and ER in the diagnosis of GEN were evaluated. Factors that contributed to such discrepancies were analyzed. The sensitivity and specificity of biopsy and ME-NBI for the diagnosis of high-grade neoplasia (HGN) were determined.The discrepancy in the pathological diagnosis between biopsy and ER was 39.6% for GEN and 54.2% for HGN. The discrepancy between biopsy combined with ME-NBI and ER was 15.9% for GEN and 10.2% for HGN. Factors that undermined the diagnostic accuracy of biopsy included the lesion size (?10?mm, odds ratio [OR] 1; 10-20?mm, OR 0.2, 95% confidence interval [CI] 0.1-0.7; >20?mm, OR 0.5, 95% CI 0.1-2.1, P?=?0.03) and the number of biopsy fragments (OR 0.6, 95% CI 0.5-0.8, P?=?0.001). The sensitivity and specificity for HGN were 45.8% (33.7%-58.3%) and 100% (87.5%-100%) for biopsy, and 88.1% (77.5%-94.1%) and 92.9% (81.0%-97.5%) for ME-NBI, respectively.In conclusion, biopsy-based diagnoses for GEN should be interpreted with caution. Biopsy combined with ME-NBI can contribute to the diagnosis of GEN, which improves diagnostic consistency with pathological result of ER specimens. PMID:26166094

  4. Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers.

    PubMed

    Yokoyama, Akira; Mizukami, Takeshi; Yokoyama, Tetsuji

    2015-01-01

    Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (?180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV?106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia. PMID:25427912

  5. Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

    PubMed Central

    Hall, Michael J; Innocent, Julie; Rybak, Christina; Veloski, Colleen; Scott, Walter J; Wu, Hong; Ridge, John A; Hoffman, John P; Borghaei, Hossein; Turaka, Aruna; Daly, Mary B

    2015-01-01

    Introduction Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described. PMID:25733923

  6. Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience

    PubMed Central

    Ortiz-Fernández-Sordo, J; Sami, S; Mansilla-Vivar, R; De Caestecker, J; Cole, A; Ragunath, K

    2016-01-01

    Objective Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. Design This study was conducted as part of the service evaluation audit. Setting Tertiary referral centre. Patients All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. Interventions All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. Results Fifty patients were analysed; median age 73?years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). Conclusions In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high-incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise.

  7. Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia.

    PubMed

    Lucena, Adriana A S; Guimarães, Mírian Viviane M B; Michelin, Márcia A; Lodi, Cláudia T C; Lima, Maria Inês M; Murta, Eddie Fernando Candido; Melo, Victor Hugo

    2016-01-01

    Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV-seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross-sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, P<0.04). Considering CIN degree (CIN 1 and CIN 2/3), the HIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (P<0.018) and 54.5% (P<0.0048). The HIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1. PMID:26545568

  8. Importance of universal mismatch repair protein immunohistochemistry in patients with sebaceous neoplasia as an initial screening tool for Muir-Torre syndrome.

    PubMed

    Jessup, Chad J; Redston, Mark; Tilton, Erin; Reimann, Julie D R

    2016-03-01

    Muir-Torre syndrome, a Lynch syndrome variant, is characterized by sebaceous neoplasia plus one or more malignancies, typically colon cancer. The significance of DNA mismatch repair (MMR) deficiency detection by immunohistochemistry (IHC) in colorectal carcinomas is well established and is recommended as a screening tool for Lynch syndrome in newly diagnosed colorectal carcinomas. In comparison, literature on IHC application to detect MMR proteins (MLH1, MSH2, MSH6, and PMS2) in sebaceous neoplasia has been less studied and has been derived almost exclusively from tertiary care centers. Herein we describe the largest series to date characterizing MMR deficiency in sebaceous neoplasms, as well as the relative frequencies of each deficiency. Two hundred sixteen consecutive sebaceous neoplasms (216 patients) were analyzed from a community practice setting (133 sebaceous adenomas, 68 sebaceomas, 15 sebaceous carcinomas). One hundred forty-three were MMR deficient (66%), of which 90 were MSH2/MSH6 deficient (63%), 27 MLH1/PMS2 deficient (19%), 22 MSH6 deficient (15%), and 4 PMS2 deficient (3%). MMR deficiency was significantly associated with site, with tumors off of the head and neck more likely to be MMR deficient (specificity 96%). In contrast to prior reports, no significant trend in MMR-deficient versus -nondeficient tumors was seen in age at presentation (median age, 68 versus 66), tumor-infiltrating lymphocytes, or tumor type. Given the low sensitivity of age < 60 years (30%), location off of the head and neck (41%), or presence of tumor-infiltrating lymphocytes (29%) in MMR deficiency detection, IHC screening programs should test all sebaceous neoplasms for MMR deficiency, regardless of their clinicopathological features. PMID:26826402

  9. Endoscopic Mucosal Resection Results in Change of Histologic Diagnosis in Barrett’s Esophagus Patients with Visible and Flat Neoplasia: A Multicenter Cohort Study

    PubMed Central

    Wani, Sachin; Abrams, Julian; Edmundowicz, Steven A.; Gaddam, Srinivas; Hovis, Christine E.; Green, Daniel; Gupta, Neil; Higbee, April; Bansal, Ajay; Rastogi, Amit; Early, Dayna; Lightdale, Charles J.

    2015-01-01

    Background There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett’s esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. Aim To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. Methods In this multicenter outcomes project, patients with Barrett’s-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. Results One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). Conclusions EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET. PMID:23633158

  10. A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E δ-tocotrienol in Patients with Pancreatic Ductal Neoplasia

    PubMed Central

    Springett, Gregory M.; Husain, Kazim; Neuger, Anthony; Centeno, Barbara; Chen, Dung-Tsa; Hutchinson, Tai Z.; Lush, Richard M.; Sebti, Saïd; Malafa, Mokenge P.

    2015-01-01

    Background Vitamin E δ-tocotrienol (VEDT), a natural vitamin E from plants, has shown anti-neoplastic and chemoprevention activity in preclinical models of pancreatic cancer. Here, we investigated VEDT in patients with pancreatic ductal neoplasia in a window-of-opportunity preoperative clinical trial to assess its safety, tolerability, pharmacokinetics, and apoptotic activity. Methods Patients received oral VEDT at escalating doses (from 200 to 3200 mg) daily for 13 days before surgery and one dose on the day of surgery. Dose escalation followed a three-plus-three trial design. Our primary endpoints were safety, VEDT pharmacokinetics, and monitoring of VEDT-induced neoplastic cell apoptosis (ClinicalTrials.gov number NCT00985777). Findings In 25 treated patients, no dose-limiting toxicity was encountered; thus no maximum-tolerated dose was reached. One patient had a drug-related adverse event (diarrhea) at a 3200-mg daily dose level. The effective half-life of VEDT was ~ 4 h. VEDT concentrations in plasma and exposure profiles were quite variable but reached levels that are bioactive in preclinical models. Biological activity, defined as significant induction of apoptosis in neoplastic cells as measured by increased cleaved caspase-3 levels, was seen in the majority of patients at the 400-mg to 1600-mg daily dose levels. Interpretation VEDT from 200 to 1600 mg daily taken orally for 2 weeks before pancreatic surgery was well tolerated, reached bioactive levels in blood, and significantly induced apoptosis in the neoplastic cells of patients with pancreatic ductal neoplasia. These promising results warrant further clinical investigation of VEDT for chemoprevention and/or therapy of pancreatic cancer. PMID:26844278

  11. Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model1

    PubMed Central

    Kelavkar, Uddhav P; Parwani, Anil V; Shappell, Scott B; Martin, W David

    2006-01-01

    Abstract The incidence and mortality of prostate cancer (PCa) vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1), which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN), and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM) models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP)]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt), FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC), and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN) according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN). In summary, targeted overexpression of h15-LO-1 (a gene overexpressed in human PCa and HGPIN) to mouse prostate is sufficient to promote epithelial proliferation and mPIN development. These results support 15-LO-1 as having a role in prostate tumor initiation and as an early target for dietary or other prevention strategies. The FLiMP mouse model should also be useful in crosses with other GEM models to further define the combinations of molecular alterations necessary for PCa progression. PMID:16820097

  12. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    PubMed Central

    Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC. PMID:24386251

  13. Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project.

    PubMed

    Herrero, R; Schiffman, M H; Bratti, C; Hildesheim, A; Balmaceda, I; Sherman, M E; Greenberg, M; Cárdenas, F; Gómez, V; Helgesen, K; Morales, J; Hutchinson, M; Mango, L; Alfaro, M; Potischman, N W; Wacholder, S; Swanson, C; Brinton, L A

    1997-05-01

    This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented. PMID:9180057

  14. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  15. Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry

    PubMed Central

    Haidry, R J; Butt, M A; Dunn, J M; Gupta, A; Lipman, G; Smart, H L; Bhandari, P; Smith, L; Willert, R; Fullarton, G; Di Pietro, M; Gordon, C; Penman, I; Barr, H; Patel, P; Kapoor, N; Hoare, J; Narayanasamy, R; Ang, Y; Veitch, A; Ragunath, K; Novelli, M; Lovat, L B

    2015-01-01

    Background Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. Methods We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12?months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008–2010 and 2011–2013). Durability of successful treatment and progression to OAC were also evaluated. Results 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12?months is not significantly different (3.6% vs 2.1%, p=0.51). Conclusions Clinical outcomes for BE neoplasia have improved significantly over the past 6?years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2–4% at 1?year in these high-risk patients. Trial registration number ISRCTN93069556. PMID:25539672

  16. Laser capture microdissection–reduced representation bisulfite sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse

    PubMed Central

    Schillebeeckx, Maximiliaan; Schrade, Anja; Löbs, Ann-Kathrin; Pihlajoki, Marjut; Wilson, David B.; Mitra, Robi D.

    2013-01-01

    DNA methylation is a mechanism for long-term transcriptional regulation and is required for normal cellular differentiation. Failure to properly establish or maintain DNA methylation patterns leads to cell dysfunction and diseases such as cancer. Identifying DNA methylation signatures in complex tissues can be challenging owing to inaccurate cell enrichment methods and low DNA yields. We have developed a technique called laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) for the multiplexed interrogation of the DNA methylation status of cytosine–guanine dinucleotide islands and promoters. LCM-RRBS accurately and reproducibly profiles genome-wide methylation of DNA extracted from microdissected fresh frozen or formalin-fixed paraffin-embedded tissue samples. To demonstrate the utility of LCM-RRBS, we characterized changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Compared with adjacent normal tissue, the adrenocortical tumors showed reproducible gains and losses of DNA methylation at genes involved in cell differentiation and organ development. LCM-RRBS is a rapid, cost-effective, and sensitive technique for analyzing DNA methylation in heterogeneous tissues and will facilitate the investigation of DNA methylation in cancer and organ development. PMID:23589626

  17. High expression of astrocyte elevated gene-1 (AEG-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer

    PubMed Central

    2013-01-01

    Background Astrocyte elevated gene-1(AEG-1) plays an important role in the development and progression of certain types of human cancers. However, the expression dynamics of AEG-1 in cervical cancer and its clinical/prognostic significance are unclear. Method In present study, the methods of tissue microarrays (TMA) and immunohistochemistry (IHC) were utilized to investigate AEG-1 expression in cervical intraepithelial neoplasia (CIN) and cervical cancer. Receiver operating characteristic (ROC) curve analysis, χ2 test, Kaplan-Meier plots, and multivariate Cox regression analysis were used to analyze the data. Results The expression level of AEG-1 was increased from CIN I to CIN III. High expression of AEG-1 could be observed in 61.1% (55/90) of cervical cancer. Moreover, high expression of AEG-1 correlated with tumor size and lymph node metastasis (all P <0.05). More importantly, high expression of AEG-1 was closely associated with cervical cancer patient shortened survival time as evidenced by univariate and multivariate analysis (P <0.05). Conclusions Our data suggest for the first time that high expression of AEG-1 is associated significantly with progression of cervical cancer. AEG-1 overexpression, as examined by IHC, has the potential to be used as an immunomarker to predict prognosis of cervical cancer patients. PMID:24256614

  18. A Simple Laparoscopic Procedure to Restore a Normal Vaginal Length After Colpohysterectomy With Large Upper Colpectomy for Cervical and/or Vaginal Neoplasia.

    PubMed

    Leblanc, Eric; Bresson, Lucie; Merlot, Benjamin; Puga, Marco; Kridelka, Frederic; Tsunoda, Audrey; Narducci, Fabrice

    2016-01-01

    Colpohysterectomy is sometimes associated with a large upper colpectomy resulting in a shortened vagina, potentially impacting sexual function. We report on a preliminary experience of a laparoscopic colpoplasty to restore a normal vaginal length. Patients with shortened vaginas after a laparoscopic colpohysterectomy were considered for a laparoscopic modified Davydov's procedure to create a new vaginal vault using the peritoneum of the rectum and bladder. From 2010 to 2014, 8 patients were offered this procedure, after informed preoperative consent. Indications were 2 extensive recurrent vaginal intraepithelial neoplasias grade 3 and 6 radical hysterectomies for cervical cancer. Mean vaginal length before surgery was 3.8 cm (standard deviation, 1.6). Median operative time was 50 minutes (range, 45-90). Blood loss was minimal (50-100 mL). No perioperative complications occurred. Median vaginal length at discharge was 11.3 cm (range, 9-13). Sexual intercourse could be resumed around 10 weeks after surgery. At a median follow-up of 33.8 months (range, 2.4-51.3), 6 patients remained sexually active but 2 had stopped. Although this experience is small, this laparoscopic modified Davydov's procedure seems to be an effective procedure, adaptable to each patient's anatomy. If the initial postoperative regular self-dilatation is carefully observed, vaginal patency is durably restored and enables normal sexual function. PMID:26299773

  19. Clinical data and characterization of the liver conditional mouse model exclude neoplasia as a non-neurological manifestation associated with Friedreich’s ataxia

    PubMed Central

    Martelli, Alain; Friedman, Lisa S.; Reutenauer, Laurence; Messaddeq, Nadia; Perlman, Susan L.; Lynch, David R.; Fedosov, Kathrin; Schulz, Jörg B.; Pandolfo, Massimo; Puccio, Hélène

    2012-01-01

    SUMMARY Friedreich’s ataxia (FRDA) is the most common hereditary ataxia in the caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia, hypertrophic cardiomyopathy and increased incidence of diabetes. FRDA is caused by impaired expression of the FXN gene coding for the mitochondrial protein frataxin. During the past ten years, the development of mouse models of FRDA has allowed better understanding of the pathophysiology of the disease. Among the mouse models of FRDA, the liver conditional mouse model pointed to a tumor suppressor activity of frataxin leading to the hypothesis that individuals with FRDA might be predisposed to cancer. In the present work, we investigated the presence and the incidence of neoplasia in the largest FRDA patient cohorts from the USA, Australia and Europe. As no predisposition to cancer could be observed in both cohorts, we revisited the phenotype of the liver conditional mouse model. Our results show that frataxin-deficient livers developed early mitochondriopathy, iron-sulfur cluster deficits and intramitochondrial dense deposits, classical hallmarks observed in frataxin-deficient tissues and cells. With age, a minority of mice developed structures similar to the ones previously associated with tumor formation. However, these peripheral structures contained dying, frataxin-deficient hepatocytes, whereas the inner liver structure was composed of a pool of frataxin-positive cells, due to inefficient Cre-mediated recombination of the Fxn gene, that contributed to regeneration of a functional liver. Together, our data demonstrate that frataxin deficiency and tumorigenesis are not associated. PMID:22736457

  20. 5th International ACC Symposium: The New Genetics of Benign Adrenocortical Neoplasia: Hyperplasias, Adenomas, and Their Implications for Progression into Cancer.

    PubMed

    Kirschner, Lawrence S; Stratakis, Constantine A

    2016-02-01

    Genetic tools for the analysis of human tumors have developed rapidly over the past 20 years. Adrenocortical neoplasms have been subject to multiple analyses using these new genetic tools. Analysis of adrenocortical carcinomas (ACCs) has been complicated by the fact that these tumors tend to exhibit multiple somatic abnormalities, so that identifying driver mutations is complex task. In contrast, benign adrenocortical neoplasms have proven to be a fertile ground for the identification of the genetic causes of adrenocortical adenomas, as well as a variety of adrenocortical hyperplasia. Analysis of cortisol-producing adrenocortical adenomas has revealed alterations leading to enhanced signaling through the cAMP-dependent protein kinase (PKA) pathway. In contrast, macronodular cortisol-producing neoplasias have been shown to result from mutations in the ARMC5 gene, whose function is not yet quite so clear. In contrast, adrenal tumors resulting in excess production of the blood pressure hormone aldosterone almost always result from abnormalities of calcium handling, both in single adenomas and in bilateral hyperplasias. In both cases, there is elevation of a signaling pathway responsible both for hormone secretion and for gland growth and maintenance, thus confirming the linkage of these two output of cellular physiology. The connection between the benign hyperplasia observed in these states and adrenocortical carcinogenesis is not nearly as clear, although genetic studies are beginning to elucidate the relationship between benign and malignant tumors of this gland. PMID:26684645

  1. A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families

    SciTech Connect

    Marsh, D.J.; Andrew, S.; Richardson, A.L.

    1994-09-15

    Multiple endocrine neoplasia type 2A (MEN2A) and familial medullary thyroid carcinoma (FMTC) are autosomal dominant inherited cancer syndromes with incomplete penetrance. Following the identification of mutations in the RET proto-oncogene that segregate with the disease phenotype in MEN2A, MEN2B, and FMTC, genetic screening of individuals with mutations in RET may be performed. The authors have employed restriction endonuclease digestion of polymerase chain reaction products as an alternative to sequence analysis for rapid identification of mutant gene carriers in families in which MEN2A and RMTC are segregating. Twenty-one Australasian MEN2A and FMTC families have been screened for mutations in a cysteine-rich region of the RET proto-oncogene. Seven independent mutations were identified in key individuals in 16 of these families. The authors have identified a mutation in codon 620, 2053 T {r_arrow}C (Cys620Arg), and two mutations in codon 634 of exon 11 of RET, 2095 T {r_arrow} C (Cys634Arg) and 2096 G {r_arrow} A (Cys634Tyr), all three of which were present in both MEN2A and FMTC families. 7 refs., 1 fig., 1 tab.

  2. Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

    PubMed Central

    Certad, Gabriela; Creusy, Colette; Ngouanesavanh, Tramy; Guyot, Karine; Gantois, Nausicaa; Mouray, Anthony; Chassat, Thierry; Flament, Nicolas; Fleurisse, Laurence; Pinon, Anthony; Delhaes, Laurence; Dei-Cas, Eduardo

    2010-01-01

    We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (106–107) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duodenum of some animals. Interestingly, SCID mice (6/6) inoculated with 105–107 oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI. PMID:20134002

  3. Development of Cryptosporidium parvum-induced gastrointestinal neoplasia in severe combined immunodeficiency (SCID) mice: severity of lesions is correlated with infection intensity.

    PubMed

    Certad, Gabriela; Creusy, Colette; Ngouanesavanh, Tramy; Guyot, Karine; Gantois, Nausicaa; Mouray, Anthony; Chassat, Thierry; Flament, Nicolas; Fleurisse, Laurence; Pinon, Anthony; Delhaes, Laurence; Dei-Cas, Eduardo

    2010-02-01

    We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (10(6)-10(7)) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duodenum of some animals. Interestingly, SCID mice (6/6) inoculated with 10(5)-10(7) oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI. PMID:20134002

  4. A study of the lifetime occurrence of neoplasia and breed differences in a cohort of German Shepherd Dogs and Belgian Malinois military working dogs that died in 1992.

    PubMed

    Peterson, M R; Frommelt, R A; Dunn, D G

    2000-01-01

    The population of U.S. Department of Defense military working dogs provides an opportunity to study the lifetime occurrence of neoplasia in 2 breeds of dogs--the German Shepherd Dog and the Belgian Malinois. Medical records were reviewed for all dogs that died or were euthanized in 1992 (135 German Shepherd Dogs and 106 Belgian Malinois). Histologically confirmed neoplasms were recorded. More than 30% of both breeds (41 German Shepherd Dogs and 33 Belgian Malinois) developed at least 1 primary neoplasm during their lives, with 10% developing more than 1 neoplasm. Nearly 57% of the neoplasms were benign, and approximately 43% were malignant. German Shepherd Dogs lived 9.7 years, on average, and Belgian Malinois lived 7.9 years, on average. Of the dogs that developed any neoplasm, Belgian Malinois had a mean age at 1st diagnosis that was 1.1 years younger and a mean age at 1st diagnosis of malignancy that was 1.7 years younger than those in German Shepherd Dogs. The risk of a malignancy being the cause of death or euthanasia of a Belgian Malinois was 4.21 times the risk in German Shepherd Dogs (95% CI: 1.32, 13.47). Seminoma was the malignancy that occurred most frequently. Hemangioma was the benign neoplasm that occurred most frequently. Veterinarians identified masses clinically at equal rates in both groups. PMID:10772484

  5. Spectral classifier design with ensemble classifiers and misclassification-rejection: application to elastic-scattering spectroscopy for detection of colonic neoplasia

    NASA Astrophysics Data System (ADS)

    Rodriguez-Diaz, Eladio; Castanon, David A.; Singh, Satish K.; Bigio, Irving J.

    2011-06-01

    Optical spectroscopy has shown potential as a real-time, in vivo, diagnostic tool for identifying neoplasia during endoscopy. We present the development of a diagnostic algorithm to classify elastic-scattering spectroscopy (ESS) spectra as either neoplastic or non-neoplastic. The algorithm is based on pattern recognition methods, including ensemble classifiers, in which members of the ensemble are trained on different regions of the ESS spectrum, and misclassification-rejection, where the algorithm identifies and refrains from classifying samples that are at higher risk of being misclassified. These ``rejected'' samples can be reexamined by simply repositioning the probe to obtain additional optical readings or ultimately by sending the polyp for histopathological assessment, as per standard practice. Prospective validation using separate training and testing sets result in a baseline performance of sensitivity = .83, specificity = .79, using the standard framework of feature extraction (principal component analysis) followed by classification (with linear support vector machines). With the developed algorithm, performance improves to Se ~ 0.90, Sp ~ 0.90, at a cost of rejecting 20-33% of the samples. These results are on par with a panel of expert pathologists. For colonoscopic prevention of colorectal cancer, our system could reduce biopsy risk and cost, obviate retrieval of non-neoplastic polyps, decrease procedure time, and improve assessment of cancer risk.

  6. AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia

    PubMed Central

    Norris, A.M.; Gore, A.; Balboni, A.; Young, A.; Longnecker, D.S.; Korc, M.

    2012-01-01

    The mechanisms controlling expression of the putative oncogene AGR2 in pancreatic ductal adenocarcinoma (PDAC) are not well understood. We now show that AGR2 is a TGF-?-responsive gene in human pancreatic cancer cells, whose down-regulation is SMAD4-dependent. We also provide evidence supporting a role for AGR2 as an ER-chaperone for the cancer-associated mucin, MUC1. AGR2 is both sufficient and required for MUC1 expression in pancreatic cancer cells. Furthermore, AGR2 is co-expressed with MUC1 in mouse pancreatic intraepithelial neoplasia (mPanIN)-like lesions and in the cancer cells of four distinct genetically engineered mouse models of PDAC. We also show that Pdx1-Cre/LSL-KrasG12D/Smad4lox/lox mice heterozygous for Agr2 exhibit a delay in mPanIN initiation and progression to PDAC. It is proposed that loss of Smad4 may convert TGF-? from a tumor suppressor to a tumor promoter by causing the up-regulation of AGR2, which then leads to increased MUC1 expression, at which point both AGR2 and MUC1 facilitate mPanIN initiation and progression to PDAC. PMID:22945649

  7. Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization.

    PubMed

    Gosvig, Camilla F; Huusom, Lene D; Andersen, Klaus K; Duun-Henriksen, Anne Katrine; Frederiksen, Kirsten; Iftner, Angelika; Svare, Edith; Iftner, Thomas; Kjaer, Susanne K

    2015-12-15

    Little research has been conducted on the long-term value of human papillomavirus (HPV) testing after conization. We investigated whether cytology adds to the value of a negative HPV test for long-term prediction of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In addition, we compared risk of CIN2+ following a negative HPV test in women after conization with that in women from the general population. During 2002-2005, 667 women treated for CIN2+ were tested for HPV and cytology 46 months after conization. Only HPV-negative women were included. Women participating in routine screening were age-matched with post-conization HPV-negative women, leaving 13,230 and 477 women, respectively, for analysis. By linkage to the Pathology Data Bank, we identified all cases of CIN2+ by December 2013. The 3-, 5-, 8- and 10-year risks for CIN2+ were 0.7, 0.9, 2.8 and 5.7% after a negative HPV test and 0.5, 0.8, 2.9 and 6.1% in HPV and cytology-negative women. HPV-negative women in the general population had similar 3-year and 5-year risks of 0.4 and 1.0%; thereafter, they had lower risks of 1.9% at 8 years and 2.7% at 10 years. Our results indicate that HPV testing may be used as a test of cure after conization. In the first 5 years after testing, the risk for CIN2+ of women who were HPV-negative at 34 months after conization was similar to that of HPV-negative women in the general population. After 67 years, however, women who have undergone conization may be at higher risk for CIN2+. PMID:26139420

  8. In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology

    PubMed Central

    van Seters, M; Kate, F J W ten; van Beurden, M; Verheijen, R H M; Meijer, C J L M; Burger, M P M; Helmerhorst, T J M

    2007-01-01

    Background Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. Aim To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. Methods Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. Results Twenty?seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n?=?10), VIN 2 (n?=?11) and VIN 3 (n?=?6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow?up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. Conclusions VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high?grade VIN. PMID:16714399

  9. The canonical NF-kappaB pathway is required for formation of luminal mammary neoplasias and is activated in the mammary progenitor population.

    PubMed

    Pratt, M A C; Tibbo, E; Robertson, S J; Jansson, D; Hurst, K; Perez-Iratxeta, C; Lau, R; Niu, M Y

    2009-07-30

    The role of the canonical NF-kappaB pathway in mammary tumorigenesis was investigated using a transgenic (TG) mouse expressing a dominant-negative inhibitor of kappaB (IkappaBalpha(SR (S32A/S36A))) in the mammary gland under the control of the mouse mammary tumor virus promoter (MMTV). TG and control mice were subjected to a chemical carcinogenesis protocol. Hyperkeratinized squamous metaplasias (cytokeratin-6+/p63+) sometimes with a basaloid island component, were found in both TG and control mice whereas luminal (cytokeratin-19+/MUC1+) ErbB2+ papillary and adenomatous lesions developed almost exclusively in control mice. p65/RelA- and NF-kappaB DNA-binding activity were detected in mammary luminal lesions, but rarely in squamous metaplasias. Analysis of NF-kappaB family proteins and target genes using microarray data from a cohort of human mammary tumors revealed the expression of a canonical NF-kappaB pathway, but not non-canonical pathway proteins in HER2+ luminal cancers. HER2+ tumors also showed differential regulation of specific NF-kappaB target genes relative to basal and ER+ luminal cancers. Isolation of mammary cell populations enriched for stem and progenitor cell characteristics from an NF-kappaB-EGFP reporter mouse by fluorescence-activated cell sorting demonstrated that luminal progenitors contain activated NF-kappaB whereas the mammary stem cell-enriched population, does not. Together these data suggest that the canonical NF-kappaB pathway is active in normal luminal progenitor cells before transformation and is required for the formation of mammary luminal-type epithelial neoplasias. PMID:19483731

  10. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    PubMed

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2015-09-01

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here. PMID:25227285

  11. The pattern of CD44 and matrix metalloproteinase 9 expression is a useful predictor of ulcerative colitis-associated dysplasia and neoplasia.

    PubMed

    AbdElazeem, Marwa A; El-Sayed, Mona

    2015-12-01

    Ulcerative colitis (UC)-associated neoplasia presumably evolves through a chronic inflammation-dysplasia-adenocarcinoma sequence in which a corporation of several factors takes place. The grade of dysplasia is important in further development of colorectal cancer. CD44 is a cell adhesion molecule and acts as a docking receptor for matrix metalloproteinase 9 (MMP-9). The aims of this study are to assess UC-associated dysplasia and to distinguish regenerative changes from premalignant ones through detecting pattern of CD44 and MMP-9 expression in different UC lesions. Fifty-four samples of UC and UC-associated carcinoma were collected and examined for the immunohistochemical expression of CD44 and MMP-9 in the colon mucosa. Correlation between their expression and the severity of dysplasia were also statistically analyzed. Homogenous membranous staining pattern of CD44 was detected in all cases of regenerative atypia (negative for dysplasia) and most of indefinite for dysplasia (IND) cases, whereas most dysplastic (low-grade and high-grade dysplasia) cases showed irregular staining pattern. CD44 expression pattern was significantly correlated with grade of dysplasia in UC (P = .0001); on the other hand, MMP-9 expression was significantly increased in the dysplastic and neoplastic cases than in nondysplastic cases (regenerative atypia and IND) (P = .0001). Significant correlation was found between irregular CD44 staining pattern and MMP-9 expression (P = .0001). Irregular staining pattern of CD44 together with increased MMP-9 expression in UC-associated dysplasia predicts advanced disease and aids in the differentiation of regenerative atypia from UC-associated dysplasia as well as grading of IND cases. PMID:26420348

  12. Multiple cores of high grade prostatic intraepithelial neoplasia and any core of atypia on first biopsy are significant predictor for cancer detection at a repeat biopsy

    PubMed Central

    Kim, Tae Sun; Ko, Kwang Jin; Shin, Seung Jea; Ryoo, Hyun Soo; Song, Wan; Sung, Hyun Hwan; Han, Deok Hyun; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Kyu Sung; Lee, Sung Won; Lee, Hyun Moo; Choi, Han Yong

    2015-01-01

    Purpose To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. Materials and Methods We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. Results A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). Conclusions Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients. PMID:26682019

  13. Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice.

    PubMed

    Stadthagen, Gustavo; Tehler, Disa; Høyland-Kroghsbo, Nina Molin; Wen, Jiayu; Krogh, Anders; Jensen, Klaus T; Santoni-Rugiu, Eric; Engelholm, Lars H; Lund, Anders H

    2013-10-01

    miRNAs are small regulatory RNAs that, due to their considerable potential to target a wide range of mRNAs, are implicated in essentially all biological process, including cancer. miR-10a is particularly interesting considering its conserved location in the Hox cluster of developmental regulators. A role for this microRNA has been described in developmental regulation as well as for various cancers. However, previous miR-10a studies are exclusively based on transient knockdowns of this miRNA and to extensively study miR-10a loss we have generated a miR-10a knock out mouse. Here we show that, in the Apc(min) mouse model of intestinal neoplasia, female miR-10a deficient mice develop significantly more adenomas than miR-10(+/+) and male controls. We further found that Lpo is extensively upregulated in the intestinal epithelium of mice deprived of miR-10a. Using in vitro assays, we demonstrate that the primary miR-10a target KLF4 can upregulate transcription of Lpo, whereas siRNA knockdown of KLF4 reduces LPO levels in HCT-116 cells. Furthermore, Klf4 is upregulated in the intestines of miR-10a knockout mice. Lpo has previously been shown to have the capacity to oxidize estrogens into potent depurinating mutagens, creating an instable genomic environment that can cause initiation of cancer. Therefore, we postulate that Lpo upregulation in the intestinal epithelium of miR-10a deficient mice together with the predominant abundance of estrogens in female animals mainly accounts for the sex-related cancer phenotype we observed. This suggests that miR-10a could be used as a potent diagnostic marker for discovering groups of women that are at high risk of developing colorectal carcinoma, which today is one of the leading causes of cancer-related deaths. PMID:24204315

  14. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance.

    PubMed

    Xu, Xiao-Xian; Zhou, Jian-Song; Yuan, Shu-Hui; Yu, Hua; Lou, Han-Mei

    2015-09-01

    Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine. PMID:26404339

  15. Positive Selection for New Disease Mutations in the Human Germline: Evidence from the Heritable Cancer Syndrome Multiple Endocrine Neoplasia Type 2B

    PubMed Central

    Calabrese, Peter; Arnheim, Norman

    2012-01-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a highly aggressive thyroid cancer syndrome. Since almost all sporadic cases are caused by the same nucleotide substitution in the RET proto-oncogene, the calculated disease incidence is 100–200 times greater than would be expected based on the genome average mutation frequency. In order to determine whether this increased incidence is due to an elevated mutation rate at this position (true mutation hot spot) or a selective advantage conferred on mutated spermatogonial stem cells, we studied the spatial distribution of the mutation in 14 human testes. In donors aged 36–68, mutations were clustered with small regions of each testis having mutation frequencies several orders of magnitude greater than the rest of the testis. In donors aged 19–23 mutations were almost non-existent, demonstrating that clusters in middle-aged donors grew during adulthood. Computational analysis showed that germline selection is the only plausible explanation. Testes of men aged 75–80 were heterogeneous with some like middle-aged and others like younger testes. Incorporating data on age-dependent death of spermatogonial stem cells explains the results from all age groups. Germline selection also explains MEN2B's male mutation bias and paternal age effect. Our discovery focuses attention on MEN2B as a model for understanding the genetic and biochemical basis of germline selection. Since RET function in mouse spermatogonial stem cells has been extensively studied, we are able to suggest that the MEN2B mutation provides a selective advantage by altering the PI3K/AKT and SFK signaling pathways. Mutations that are preferred in the germline but reduce the fitness of offspring increase the population's mutational load. Our approach is useful for studying other disease mutations with similar characteristics and could uncover additional germline selection pathways or identify true mutation hot spots. PMID:22359510

  16. Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

    PubMed

    Clifford, Gary M; Franceschi, Silvia; Keiser, Olivia; Schöni-Affolter, Franziska; Lise, Mauro; Dehler, Silvia; Levi, Fabio; Mousavi, Mohsen; Bouchardy, Christine; Wolfensberger, Aline; Darling, Katharine E; Staehelin, Cornelia; Bertisch, Barbara; Kuenzli, Esther; Bernasconi, Enos; Pawlita, Michael; Egger, Matthias

    2016-04-01

    HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer. PMID:26537763

  17. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance

    PubMed Central

    Xu, Xiao-Xian; Zhou, Jian-Song; Yuan, Shu-Hui; Yu, Hua; Lou, Han-Mei

    2015-01-01

    Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine. PMID:26404339

  18. PTCH 1 staining of pancreatic neuroendocrine tumor (PNET) samples from patients with and without multiple endocrine neoplasia (MEN-1) syndrome reveals a potential therapeutic target.

    PubMed

    Gurung, Buddha; Hua, Xianxin; Runske, Melissa; Bennett, Bonita; LiVolsi, Virginia; Roses, Robert; Fraker, Douglas A; Metz, David C

    2015-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur sporadically or develop in association with well-recognized hereditary syndromes, particularly multiple endocrine neoplasia type 1 (MEN-1). We previously demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We hypothesized that the HH signaling pathway is similarly upregulated in human PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh and archival PNET specimens to examine whether human sporadic and MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and correlated the results with clinical and demographic factors of the study cohort. PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of 5 MEN-1 patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). Nine of 16 patients with metastatic disease stained for PTCH1 as compared with zero of 3 with localized disease only (p = 0.21). No demographic or clinical features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up regulation, is detectable in both primary and metastatic tumors in more than 50% of PNET patients. Although no clinical or demographic factors predict PTCH1 positivity and PTCH1 positivity does not predict clinical outcome, the frequency of expression alone indicates that perturbation of this pathway with agents such as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future clinical trials. PMID:25482929

  19. Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats.

    PubMed Central

    Hard, G C; Rodgers, I S; Baetcke, K P; Richards, W L; McGaughy, R E; Valcovic, L R

    1993-01-01

    This review paper examines the relationship between chemicals inducing excessive accumulation of alpha 2u-globulin (alpha 2u-g) (CIGA) in hyaline droplets in male rat kidneys and the subsequent development of nephrotoxicity and renal tubule neoplasia in the male rat. This dose-responsive hyaline droplet accumulation distinguishes CIGA carcinogens from classical renal carcinogens. CIGA carcinogens also do not appear to react with DNA and are generally negative in short-term tests for genotoxicity, CIGA or their metabolites bind specifically, but reversibly, to male rat alpha 2u-g. The resulting complex appears to be more resistant to hydrolytic degradation in the proximal tubule than native, unbound alpha 2u-g. Single cell necrosis of the tubule epithelium, with associated granular cast formation and papillary mineralization, is followed by sustained regenerative tubule cell proliferation, foci of tubule hyperplasia in the convoluted proximal tubules, and renal tubule tumors. Although structurally similar proteins have been detected in other species, including humans, renal lesions characteristic of alpha 2u-g nephropathy have not been observed. Epidemiologic investigation has not specifically examined the CIGA hypothesis for humans. Based on cancer bioassays, hormone manipulation studies, investigations in an alpha 2u-g-deficient strain of rat, and other laboratory data, an increased proliferative response caused by chemically induced cytotoxicity appears to play a role in the development of renal tubule tumors in male rats. Thus, it is reasonable to suggest that the renal effects induced in male rats by chemicals causing alpha 2u-g accumulation are unlikely to occur in humans. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. PMID:7686485

  20. MspI restriction fragment length polymorphism at the glycoprotein hormone alpha-subunit locus. Association of certain genotypes with neoplasia.

    PubMed

    Cox, G S; Cosgrove, D E; Haas, M J; Stiles, W; McIntosh, D G

    1997-10-01

    A restriction fragment length polymorphism (RFLP) in the human glycoprotein hormone common alpha-subunit gene has been identified and partially characterized in normal lymphocytes and placentae, established tumor cell lines, and tumor biopsy samples. High molecular weight DNA was digested with the restriction endonuclease MspI, separated by electrophoresis in agarose gels, transferred to nylon membranes by the method of Southern, and hybridized to 32P-labeled human chorionic gonadotropin alpha-subunit cDNA. After autoradiography, bands were detected at 5.3, 3.3, 2.1, 1.6, 0.8 and 0.6 kbp. Presence of the 5.3, 3.3 and 0.6 kbp bands was invariant and uninformative. Patterns missing the 0.8 kbp band and both the 2.1 and 1.6 kbp bands are consistent with separate alleles that occur in placental and lymphocyte DNA with frequencies of 0.44 (15/34) and 0.06 (2/34), respectively. Presence of all three bands (2.1, 1.6 and 0.8 kbp) is indicative of heterozygosity, occurring at a frequency of 0.50 (17/34). Additional restriction patterns, not yet observed in DNA isolated from term placentae or circulating lymphocytes, were detected in DNA obtained from tumor cell lines and fresh tumor tissues at frequencies of 0.79 (15/19) and 0.59 (10/17), respectively. Thus, particular alpha-subunit genotypes are disproportionately represented in tumor-derived DNA, occurring at frequencies 10- to 13-times higher than would be predicted from their occurrence in normal tissue. Paired normal and tumor tissues from the same individual exhibited identical hybridization patterns, suggesting that this RFLP may be representative of a predisposition toward a variety of neoplasias rather than indicative of a change in DNA structure at or near this locus as a result of tumor development. PMID:9375796

  1. High-dose-rate Intracavitary Radiotherapy in the Management of Cervical Intraepithelial Neoplasia 3 and Carcinoma In Situ Presenting With Poor Histologic Factors After Undergoing Excisional Procedures

    SciTech Connect

    Kim, Yong Bae; Kim, Young Tae; Cho, Nam Hoon; Koom, Woong Sub; Kim, Sunghoon; Kim, Sang Wun; Nam, Eun Ji; Kim, Gwi Eon

    2012-09-01

    Purpose: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. Methods and Materials: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%). All patients were treated with HDR-ICR using Co{sup 60} or Ir{sup 192} at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. Results: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. Conclusions: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.

  2. Use of Image-Guided Stereotactic Body Radiation Therapy in Lieu of Intracavitary Brachytherapy for the Treatment of Inoperable Endometrial Neoplasia

    SciTech Connect

    Kemmerer, Eric; Hernandez, Enrique; Ferriss, James S.; Valakh, Vladimir; Miyamoto, Curtis; Li, Shidong; Micaily, Bizhan

    2013-01-01

    Purpose: Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. Methods and Materials: We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median of 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction Multiplication-Sign 5). Results: The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. Conclusion: In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.

  3. Lower Risk of Cervical Intraepithelial Neoplasia in Women with High Plasma Folate and Sufficient Vitamin B12 in the Post-Folic Acid Fortification Era

    PubMed Central

    Piyathilake, Chandrika J.; Macaluso, Maurizio; Alvarez, Ronald D.; Bell, Walter C.; Heimburger, Douglas C.; Partridge, Edward E.

    2016-01-01

    The purpose of this study was to determine the influence of plasma folate and vitamin B12 concentrations on cervical cancer risk in the U.S. after the folic acid fortification era. The study included 376 premenopausal women of childbearing age who tested positive for infections with high-risk (HR) human papillomaviruses (HPVs) and were diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN 2+, cases) or ≤CIN 1 (noncases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified plasma folate concentrations combined with plasma B12 concentrations as the independent predictors of primary interest, adjusting for age, race, education, smoking, parity, number of lifetime male sexual partners, use of contraceptives, waist circumference, physical activity, healthy eating index, and circulating concentrations of vitamins A, C, tocopherol, and total carotene. Women with supraphysiologic concentrations of plasma folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (≥200.6 pg/mL) had 70% lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma folate of ≤19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. Our results do not corroborate the concern that supraphysiologic plasma folate concentrations seen in the post-U.S. folic acid fortification era increase the risk of CIN in premenopausal women of childbearing age. In fact, higher folate is associated with significantly lower risk of CIN, especially when vitamin B12 is sufficient, demonstrating the importance of vitamin B12 in the high-folate environment created by the folic acid fortification program. PMID:19542191

  4. Adjunctive HPV in-situ hybridization (ISH) assay as an aid in the diagnosis of cervical intraepithelial