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VoiSTV: voice-enabled social TV  

Microsoft Academic Search

Until recently, the TV viewing experience has not been a very social activity compared to activities on the World Wide Web. In this work, we will present a Voice-enabled Social TV system (VoiSTV) which allows users to interact, follow and monitor the online social media messages related to a TV show while watching it. Users can create, send, and reply

Bernard Renger; Junlan Feng; Ovidiu Dan; Harry Chang; Luciano Barbosa



Toxicology of upper aerodigestive tract pollutants  

SciTech Connect

The field of environmental toxicology has become quite important to the study of environmental health in human beings. The stability of the ecosystem in which we live is threatened by the nearly 5 million chemical compounds that have been synthesized worldwide, many of which have real or potentially toxic effects on the environment and on life forms. Four major groups of chemicals--metallic elements, nonmetallic elements, organic compounds and inorganic compounds--have certain agents within them that are known toxins to human beings. Some of these agents have an as yet unknown effect, whereas others have been well characterized. They can be found in the workplace, home, and outdoors, and many are unseen and odorless. In the past, most agents have been described in terms of their carcinogenic potential or major toxic effects on organ systems. It is now likely that the important characterization of some of these agents referrable to the upper aerodigestive tract should be at their receptor sites and identify the very discrete and small effects on these sites and their cumulative effects. The concept of threshold is probably an arbitrary one because to date these discrete effects have not been studied. Susceptibility on an individual basis probably varies from low to high, depending on the patient's immunologic and defense mechanisms and the existence of congenital or acquired risk factors. New attention must be given to more subtle effects on the upper aerodigestive tract (i.e., sinusitis and laryngitis) in view of the potential effects of certain toxic agents on these tissues.

Holt, G.R. (Department of Otolaryngology--Head and Neck Surgery, University of Texas Health Science Center, San Antonio (United States))



Aerodigestive Tract Burn from Ingestion of Microwaved Food  

PubMed Central

Aerodigestive tract burns represent a rare but potentially devastating injury pattern throughout the world. Although the majority of these injuries do not require intervention, these burns have the potential for poor outcomes. Traditionally this disease has been caused by superheated gases found in explosions or fire-related injury. However, as technology advances, it brings novel methods for injury that require physician awareness of potential hazards. We describe a case of laryngeal and esophageal thermal burn caused by a microwave heated food bolus.

Silberman, Michael



Concordance of Two Endoscopic Procedures for Diagnosis of Carcinoma of the Upper Aerodigestive Tract

Upper Aerodigestive Tract Lesions; Neoplasms, Oropharyngeal; Oropharyngeal Cancer; Neoplasms, Hypopharyngeal; Hypopharyngeal Cancer; Head and Neck Neoplasms; UADT Neoplasms; Carcinoma, Squamous Cell; Papilloma



Prevalence of eosinophilic esophagitis in children with refractory aerodigestive symptoms.  


IMPORTANCE Eosinophilic esophagitis (EoE) is an increasingly important diagnosis for children; it has a remarkable impact on their quality of life and can present with aerodigestive symptoms commonly evaluated by otolaryngologists. OBJECTIVES To evaluate the prevalence of EoE in children presenting to a pediatric aerodigestive clinic, to describe their presentation, and to review the role of subsequent food allergy evaluation and treatment. DESIGN Review of a prospective database. SETTING Tertiary pediatric multispecialty aerodigestive center. PATIENTS Children with aerodigestive symptoms refractory to medical treatment who underwent direct laryngoscopy with rigid or flexible bronchoscopy and esophagoscopy with or without pH probe study. MAIN OUTCOMES AND MEASURES Diagnosis of EoE. RESULTS Between 2003 and 2012, 376 of 1540 children seen in the center (mean [range] age, 4.54 [0-18.6] years; male to female ratio, 1.72:1) remained symptomatic despite medical therapy and thus underwent triple endoscopic evaluation. Of the 376 children, 14 (3.7%) were eventually diagnosed as having EoE, as defined by 15 or more eosinophils per high-power field on esophageal biopsy and either a negative pH study result or nonresponse to a trial of high-dose proton pump inhibitors. The subpopulation with EoE presented with airway symptoms and diagnoses, most commonly cough (n?=?6; 42.9%). Inflammatory subglottic stenosis due to EoE was identified in 1 patient. Of the 14 children with EoE, 6 presented with gastrointestinal symptomatology, most commonly choking or gagging. Subsequent treatment including food allergy challenge and elimination diet resulted in a clinical improvement in half of the cases identified. CONCLUSIONS AND RELEVANCE This represents the largest multispecialty clinic epidemiologic study evaluating the prevalence of EoE in children presenting not strictly with gastrointestinal symptoms but rather with aerodigestive symptoms that are frequently evaluated by pediatric otolaryngologists. Although the prevalence is low, EoE should be considered for children with appropriate symptoms in whom other medical therapies fail. PMID:24051745

Hill, Courtney A; Ramakrishna, Jyoti; Fracchia, M Shannon; Sternberg, Daniel; Ojha, Shilpa; Infusino, Scott; Hartnick, Christopher J



Upper Aerodigestive Tract Neurofunctional Mechanisms: Lifelong Evolution and Exercise  

PubMed Central

The transformation of the upper aerodigestive tract – oral cavity, pharynx and larynx – serves the functions of eating, speaking and breathing during sleeping and waking hours. These life-sustaining functions may be produced by a central neural sensorimotor system that shares certain neuroanatomic networks while maintaining separate neural functional systems and network structures. Current understanding of development, maturation, underlying neural correlates and integrative factors are discussed in light of currently available imaging modalities and recently emerging interventions. Exercise and an array of additional treatments together appear to provide promising translational pathways for evidence-based innovation, novel habilitation and rehabilitation strategies and delay, or even prevent neuromuscular decline cross-cutting functions and supporting quality of life throughout increasingly enduring lifespans.

Robbins, JoAnne



Truncation correction for VOI C-arm CT using scattered radiation  

NASA Astrophysics Data System (ADS)

In C-arm computed tomography, patient dose reduction by volume-of-interest (VOI) imaging is of increasing interest for many clinical applications. A remaining limitation of VOI imaging is the truncation artifact when reconstructing a 3D volume. It can either be cupping towards the boundaries of the field-of-view (FOV) or an incorrect offset in the Hounsfield values of the reconstructed voxels. In this paper, we present a new method for correction of truncation artifacts in a collimated scan. When axial or lateral collimation are applied, scattered radiation still reaches the detector and is recorded outside of the FOV. If the full area of the detector is read out we can use this scattered signal to estimate the truncated part of the object. We apply three processing steps: detection of the collimator edge, adjustment of the area outside the FOV, and interpolation of the collimator edge. Compared to heuristic truncation correction methods we were able to reconstruct high contrast structures like bones outside of the FOV. Inside the FOV we achieved similar reconstruction results as with water cylinder truncation correction. These preliminary results indicate that scattered radiation outside the FOV can be used to improve image quality and further research in this direction seems beneficial.

Bier, Bastian; Maier, Andreas; Hofmann, Hannes G.; Schwemmer, Chris; Xia, Yan; Struffert, Tobias; Hornegger, Joachim



Serum Protein MALDI Profiling to Distinguish Upper Aerodigestive Tract Cancer Patients From Control Subjects  

Microsoft Academic Search

Background: There are no reliable blood markers for the early detection and monitoring of aerodigestive tract tumors. Recent studies have suggested that serum protein patterns may be able to distinguish cancer patients from control subjects. Methods: We used matrix-assisted laser desorption and ionization (MALDI) mass spectroscopy to obtain serum protein patterns from patients with head and neck cancer (n 99)

David Sidransky; Rafael Irizarry; Joseph A. Califano; Xianbin Li; Hening Ren; Nicole Benoit; Li Mao



A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium  

Microsoft Academic Search

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre

James D. McKay; Therese Truong; Valerie Gaborieau; Amelie Chabrier; Shu-Chun Chuang; Graham Byrnes; David Zaridze; Oxana Shangina; Neonila Szeszenia-Dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Alexandru Bucur; Vladimir Bencko; Ivana Holcatova; Vladimir Janout; Lenka Foretova; Pagona Lagiou; Dimitrios Trichopoulos; Simone Benhamou; Christine Bouchardy; Wolfgang Ahrens; Franco Merletti; Lorenzo Richiardi; Renato Talamini; Luigi Barzan; Kristina Kjaerheim; Gary J. Macfarlane; Tatiana V. Macfarlane; Lorenzo Simonato; Cristina Canova; Antonio Agudo; Xavier Castellsagué; Ray Lowry; David I. Conway; Patricia A. McKinney; Claire M. Healy; Mary E. Toner; Ariana Znaor; Maria Paula Curado; Sergio Koifman; Ana Menezes; Victor Wünsch-Filho; José Eluf Neto; Leticia Fernández Garrote; Stefania Boccia; Gabriella Cadoni; Dario Arzani; Andrew F. Olshan; Mark C. Weissler; William K. Funkhouser; Jingchun Luo; Jan Lubi?ski; Joanna Trubicka; Marcin Lener; Dorota Oszutowska; Stephen M. Schwartz; Chu Chen; Sherianne Fish; David R. Doody; Joshua E. Muscat; Philip Lazarus; Carla J. Gallagher; Shen-Chih Chang; Zuo-Feng Zhang; Qingyi Wei; Erich M. Sturgis; Li-E Wang; Silvia Franceschi; Rolando Herrero; Karl T. Kelsey; Michael D. McClean; Carmen J. Marsit; Heather H. Nelson; Marjorie Romkes; Shama Buch; Tomoko Nukui; Shilong Zhong; Martin Lacko; Johannes J. Manni; Wilbert H. M. Peters; Rayjean J. Hung; John McLaughlin; Lars Vatten; Inger Njølstad; Gary E. Goodman; John K. Field; Triantafillos Liloglou; Paolo Vineis; Francoise Clavel-Chapelon; Domenico Palli; Rosario Tumino; Vittorio Krogh; Salvatore Panico; Carlos A. González; J. Ramón Quirós; Carmen Martínez; Carmen Navarro; Eva Ardanaz; Nerea Larrañaga; Kay-Tee Khaw; Timothy Key; H. Bas Bueno-de-Mesquita; Petra H. M. Peeters; Antonia Trichopoulou; Jakob Linseisen; Heiner Boeing; Göran Hallmans; Kim Overvad; Anne Tjønneland; Merethe Kumle; Elio Riboli; Kristjan Välk; Tõnu Voodern; Andres Metspalu; Diana Zelenika; Anne Boland; Marc Delepine; Mario Foglio; Doris Lechner; Hélène Blanché; Ivo G. Gut; Pilar Galan; Simon Heath; Mia Hashibe; Richard B. Hayes; Paolo Boffetta; Mark Lathrop; Paul Brennan



ErbB receptors in the biology and pathology of the aerodigestive tract  

SciTech Connect

The most common sites of malignancies in the aerodigestive tract include the lung, head and neck and the esophagus. Esophageal adenocarcinomas (EA), esophageal squamous cell carcinomas (ESCC), and squamous cell carcinomas of the head and neck (SCCHN) are the primary focus of this review. Traditional treatment for aerodigestive tract cancers includes primary chemoradiotherapy (CRT) or surgical resection followed by radiation (or CRT). Recent developments in treatment have focused increasingly on molecular targeting strategies including cetuximab (a monoclonal antibody against epidermal growth factor receptor (EGFR)). Cetuximab was FDA approved in 2006 for treatment of SCCHN, underscoring the importance of understanding the biology of these malignancies. EGFR is a member of the ErbB family of growth factor receptor tyrosine kinases. The major pathways activated by ErbB receptors include Ras/Raf/MAPK; PI3K/AKT; PLC{gamma} and STATs, all of which lead to the transcription of target genes that may contribute to aerodigestive tumor progression. This review explores the expression of ErbB receptors in EA, ESCC and SCCHN and the signaling pathways of EGFR in SCCHN.

Morgan, Sarah [Department of Otolaryngology, University of Pittsburgh School of Medicine, 200 Lothrop Street (United States); Suite 500, Pittsburgh, PA 15213 (United States); Grandis, Jennifer R. [Department of Otolaryngology, University of Pittsburgh School of Medicine, 200 Lothrop Street (United States); Suite 500, Pittsburgh, PA 15213 (United States)], E-mail:



Phthalates demonstrate genotoxicity on human mucosa of the upper aerodigestive tract.  


Various phthalate compounds are used as softeners and plasticizers in a wide range of plastic materials. There has been a growing concern regarding a possible health hazard to humans. The mucosa of the upper aerodigestive tract is the organ of first contact for the majority of xenobiotics, such as phthalates, entering the body. Still, there is a lack of information concerning possible carcinogenicity of phthalates in the upper aerodigestive tract. This motivated us to investigate their genotoxic effects on human epithelia: human mucosal cells derived from biopsies harvested during surgery of the oropharynx and the inferior nasal turbinate, respectively. The alkaline version of the microgel electrophoresis assay was used to detect single-strand breaks in the DNA following incubation with dibutylphthalate (DBP) and diisobutylphthalate (DiBP). DNA damage was induced by both DBP and DiBP in oropharyngeal and nasal mucosa, though the effect of DiBP was more pronounced than that of DBP. Nasal mucosa proved to be more sensitive than oropharyngeal epithelia. The results demonstrate genotoxic effects of phthalates on human mucosal cells of the upper aerodigestive tract, in contrast to earlier findings in animal models. PMID:10692222

Kleinsasser, N H; Kastenbauer, E R; Weissacher, H; Muenzenrieder, R K; Harréus, U A



Roles of Keap1-Nrf2 system in upper aerodigestive tract carcinogenesis.  


Cancers in the upper aerodigestive tract, including cancers of the tongue and the esophagus, are the third leading cause of cancer-related deaths in the world, and oxidative stress is well recognized as one of the major risk factors for carcinogenesis. The Keap1-Nrf2 system plays a critical role in cellular defense against oxidative stress, but little is known about its association with upper aerodigestive tract carcinogenesis. In this study, we examined whether loss of Nrf2-function exacerbates carcinogenesis by using an experimental carcinogenesis model that is induced by 4-nitroquinoline-1-oxide (4NQO). We found that Nrf2-knockout (Nrf2-KO) mice were more susceptible to 4NQO-induced tongue and esophageal carcinogenesis than wild-type mice, which suggests that Nrf2 is important for cancer prevention. We also examined how the suppression of Keap1 function or the induction of Nrf2 activity affected 4NQO carcinogenesis. Keap1-knockdown (Keap1-KD) mice were resistant to 4NQO-induced tongue and esophageal carcinogenesis. Importantly, no growth advantage was observed in tongue tumors in the Keap1-KD mice. These results show that the Keap1-Nrf2 system regulates an important defense mechanism against upper aerodigestive tract carcinogenesis. In addition to several important functions of Nrf2 that lead to cancer chemoprevention, we hypothesize that a mechanical defense of thickened keratin layers may also be a chemopreventive factor because thickened, stratified, squamous epithelium was found on the tongue of Keap1-KD mice. PMID:23250896

Ohkoshi, Akira; Suzuki, Takafumi; Ono, Masao; Kobayashi, Toshimitsu; Yamamoto, Masayuki



Multiple-sited amyloidosis in the upper aerodigestive tract: case report and literature review.  


There are some reports of localized amyloidosis in the larynx, an entity that corresponds to one percent of all benign tumors of this region. However, there are only two cases of amyloidosis in the Waldeyer's ring 6, 13, 14. We hereby describe a rare case of amyloidosis in areas not associated with the upper aero-digestive tract: tonsil pillar, rhinopharynx, supraglottis and glottis, without visible continuity of amyloid tissue. We will also discuss post-operative follow up with severe dysphagia. PMID:18661024

Passerotti, Gustavo Haruo; Caniello, Marcello; Hachiya, Adriana; Santoro, Patrícia P; Imamura, Rui; Tsuji, Domingos H


Geographical Variation in Surveillance Strategies After Curative-Intent Surgery for Upper Aerodigestive Tract Cancer  

Microsoft Academic Search

Background  Analysis of geographical variation in utilization of medical resources is often used to identify regions of overutilization\\u000a or underutilization.\\u000a \\u000a \\u000a \\u000a Methods  We surveyed the membership of the American Head and Neck Society regarding their recommended frequency of office visits and\\u000a 13 imaging studies and blood tests for their patients after potentially curative therapy for upper aerodigestive tract cancers.\\u000a \\u000a \\u000a \\u000a Results  Of the 1322 members

Frank E. Johnson; Michael H. Johnson; Marc F. Clemente; Randal C. Paniello; Katherine S. Virgo



Palliative treatment of AIDS-related Kaposi's sarcoma in the upper aerodigestive tract with the carbon dioxide laser  

Microsoft Academic Search

AIDS-related Kaposi's Sarcoma (KS) in the upper aerodigestive tract, although mainly asymptomatic, sometimes causes pain, bleeding or interferes with food intake and gas exchange. In trying to overcome some of the disadvantages of currently applied treatment modalities (i.e. surgery, radiotherapy and chemotherapy), the carbon dioxide laser was used to remove this vascular tumour in selected cases. Of the 16 patients

F. W. Van Der Meulen; L. J. Schot; R. J. Hadderingh; S. Bosman; M. J. C. Van Gemert



The influence of alcohol consumption on worldwide trends in mortality from upper aerodigestive tract cancers in men  

Microsoft Academic Search

STUDY OBJECTIVES: To assess current trends in male mortality from cancers of the oral cavity\\/pharynx, oesophagus, and larynx (upper aerodigestive tract cancers), and relate these to past national consumption of alcohol and smoking of cigarettes. To assess the impact of current trends in alcohol consumption and tobacco smoking on likely future rates of these cancers. DESIGN: Mortality data for cancers

G J Macfarlane; T V Macfarlane; A B Lowenfels



Rapid sequence treatment of advanced squamous cell carcinoma of the upper aerodigestive tract: A pilot study  

SciTech Connect

A review of the literature suggested that prolonged treatment time may lessen the probability of cure for patients with advanced squamous cell carcinoma of the upper aerodigestive tract. To shorten treatment time, rapid sequence treatment (RST) was devised in which chemotherapy, surgery, and irradation were administered in a total treatment time of 8 weeks. Twelve patients were treated and followed 3 years or longer. Medical complications were minor. Osteonecrosis occurred in each of the first five patients and was the only major complication of the protocol. Surgical techniques were modified, and no additional patient developed osteonecrosis. No patient developed local or regional recurrence. Two patients developed distant metastases and three other patients developed second primaries. Absolute survival was 50%. Rapid sequence treatment is an aggressive and potentially hazardous protocol that yielded encouraging results in this pilot study.

Moloy, P.J.; Moran, E.M.; Azawi, S. (Permanente Medical Group, Fresno, CA (USA))



Methionine-centered redox cycle in organs of the aero-digestive tract of young and old rats  

Microsoft Academic Search

It is commonly accepted that aging is associated with a decline in the antioxidant defense of the cell; accordingly, certain\\u000a redox enzymes are used as markers of biological senescence. To further test and specify this general concept, we studied age-related\\u000a changes in the enzymes of the methionine-centered redox cycle (MCRC) in four aero-digestive organs of rats. The levels of\\u000a cytosolic

Vladimir Vinokur; Leonid Grinberg; Eduard Berenshtein; Menachem Gross; Jackob Moskovitz; Abraham Z. Reznick; Mordechai Chevion; Ron Eliashar



Targeted expression of ornithine decarboxylase antizyme prevents upper aerodigestive tract carcinogenesis in p53-deficient mice.  


Upper aerodigestive tract (UADT) cancers of the oral cavity and esophagus are a significant global health burden, and there is an urgent need to develop relevant animal models to identify chemopreventive and therapeutic strategies to combat these diseases. Antizyme (AZ) is a multifunctional negative regulator of cellular polyamine levels, and here, we evaluate the susceptibility of keratin 5 (K5)-AZ transgenic mice to tumor models that combine chemical carcinogenesis with dietary and genetic risk factors known to influence human susceptibility to UADT cancer and promote UADT carcinogenesis in mice. First, p53(+/-) and K5-AZ/p53(+/-) (AZ/p53(+/-)) mice were placed on a zinc-deficient (ZD) or zinc-sufficient (ZS) diet and chronically exposed to 4-nitroquinoline 1-oxide. Tongue tumor incidence, multiplicity and size were substantially reduced in both ZD and ZS AZ/p53(+/-) mice compared with p53(+/-). AZ expression also reduced progression to carcinoma in situ or invasive carcinoma and decreased expression of the squamous cell carcinoma biomarkers K14, cyclooxygenase-2 and metallothionein. Next, AZ-expressing p53(+/-) and p53 null mice were placed on the ZD diet and treated with a single dose of N-nitrosomethylbenzylamine. Regardless of p53 status, forestomach (FST) tumor incidence, multiplicity and size were greatly reduced with AZ expression, which was also associated with a significant decrease in FST epithelial thickness along with reduced proliferation marker K6 and increased differentiation marker loricrin. These studies demonstrate the powerful tumor suppressive effects of targeted AZ expression in two distinct and unique mouse models and validate the polyamine metabolic pathway as a target for chemoprevention of UADT cancers. PMID:23222816

Feith, David J; Pegg, Anthony E; Fong, Louise Y Y



Diet and upper-aerodigestive tract cancer in Europe: the ARCAGE study.  


There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi-quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05-1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62-0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66-0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67-0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69-0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer. PMID:19230023

Lagiou, Pagona; Talamini, Renato; Samoli, Evangelia; Lagiou, Areti; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V; Macfarlane, Gary J; Biggs, Anne-Marie; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Lowry, Raymond J; Conway, David I; McKinney, Patricia A; Znaor, Ariana; McCartan, Bernard E; Healy, Claire M; Marron, Manuela; Hashibe, Mia; Brennan, Paul



Occupation and risk of upper aerodigestive tract cancer: the ARCAGE study.  


We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry. PMID:21671472

Richiardi, Lorenzo; Corbin, Marine; Marron, Manuela; Ahrens, Wolfgang; Pohlabeln, Hermann; Lagiou, Pagona; Minaki, Ploumitsa; Agudo, Antonio; Castellsague, Xavier; Slamova, Alena; Schejbalova, Miriam; Kjaerheim, Kristina; Barzan, Luigi; Talamini, Renato; Macfarlane, Gary J; Macfarlane, Tatiana V; Canova, Cristina; Simonato, Lorenzo; Conway, David I; McKinney, Patricia A; Sneddon, Linda; Thomson, Peter; Znaor, Ariana; Healy, Claire M; McCartan, Bernard E; Benhamou, Simone; Bouchardy, Christine; Hashibe, Mia; Brennan, Paul; Merletti, Franco



A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers  

PubMed Central

Background Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx and esophagus) in women (odds ratio (OR) =1.24, P=0.003) with little effect in men (OR=1.04, P=0.35). Methods In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. Results rs16969968 was again associated with UADT cancers in women (OR=1.21, 95% confidence interval(CI)=1.08–1.36, P=0.001) and a similar lack of observed effect in men (OR=1.02, 95%CI=0.95–1.09, P=0.66) (P-heterogeneity=0.01). In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR=1.22, 95%CI=1.12–1.34, P=7×10?6) but not males (OR=1.02, 95%CI=0.97–1.08, P=0.35) (P-heterogeneity=6×10?4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P-heterogeneity=0.86). Conclusions This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact Further research is warranted to elucidate the mechanisms underlying these observations.

Chen, Dan; Truong, Therese; Gaborieau, Valerie; Byrnes, Graham; Chabrier, Amelie; Chuang, Shu-chun; Olshan, Andrew F.; Weissler, Mark C.; Luo, Jingchun; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Franceschi, Silvia; Herrero, Rolando; Talamini, Renato; Kelsey, Karl T; Christensen, Brock; McClean, Mike; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H. M.; Lubinski, Jan; Trubicka, Joanna; Lener, Marcin; Muscat, Joshua E.; Lazarus, Philip; Wei, Qingyi; Sturgis, Erich M.; Zhang, Zuo-Feng; Chang, Shen-Chih; Wang, Renyi; Schwartz, Stephen M.; Chen, Chu; Benhamou, Simone; Lagiou, Pagona; Holcatova, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V.; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S; Conway, David I; Znaor, Ariana; Healy, Claire M.; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wunsch-Filho, Victor; Neto, Jose Eluf; Fernandez, Leticia; Boccia, Stefania; Hashibe, Mia; Hayes, Richard B.; Boffetta, Paolo; Brennan, Paul; McKay, James D.



A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium  

PubMed Central

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p?5×10?7). Two novel variants were identified, a 4q21 variant (rs1494961, p?=?1×10?8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p?=?2×10?8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p?=?5×10?8; rs1229984-ADH1B, p?=?7×10?9; and rs698-ADH1C, p?=?0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

McKay, James D.; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J.; Macfarlane, Tatiana V.; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsague, Xavier; Lowry, Ray; Conway, David I.; McKinney, Patricia A.; Healy, Claire M.; Toner, Mary E.; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wunsch-Filho, Victor; Neto, Jose Eluf; Garrote, Leticia Fernandez; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F.; Weissler, Mark C.; Funkhouser, William K.; Luo, Jingchun; Lubinski, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M.; Chen, Chu; Fish, Sherianne; Doody, David R.; Muscat, Joshua E.; Lazarus, Philip; Gallagher, Carla J.; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M.; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T.; McClean, Michael D.; Marsit, Carmen J.; Nelson, Heather H.; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J.; Peters, Wilbert H. M.; Hung, Rayjean J.; McLaughlin, John; Vatten, Lars; Nj?lstad, Inger; Goodman, Gary E.; Field, John K.; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Gonzalez, Carlos A.; Quiros, J. Ramon; Martinez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larranaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H. Bas; Peeters, Petra H. M.; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Goran; Overvad, Kim; Tj?nneland, Anne; Kumle, Merethe; Riboli, Elio; Valk, Kristjan; Voodern, Tonu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanche, Helene; Gut, Ivo G.; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B.; Boffetta, Paolo; Lathrop, Mark; Brennan, Paul



Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer.  


Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe. PMID:21684805

Anantharaman, Devasena; Marron, Manuela; Lagiou, Pagona; Samoli, Evangelia; Ahrens, Wolfgang; Pohlabeln, Hermann; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Castellsague, Xavier; Agudo, Antonio; Talamini, Renato; Barzan, Luigi; Macfarlane, Tatiana V; Tickle, Martin; Simonato, Lorenzo; Canova, Cristina; Conway, David I; McKinney, Patricia A; Thomson, Peter; Znaor, Ariana; Healy, Claire M; McCartan, Bernard E; Hashibe, Mia; Brennan, Paul; Macfarlane, Gary J



Augmentation of Radiation Response by Panitumumab in Models of Upper Aerodigestive Tract Cancer  

SciTech Connect

Purpose: To examine the interaction between panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, and radiation in head-and-neck squamous cell carcinoma and non-small-cell lung cancer cell lines and xenografts. Methods and Materials: The head-and-neck squamous cell carcinoma lines UM-SCC1 and SCC-1483, as well as the non-small-cell lung cancer line H226, were studied. Tumor xenografts in athymic nude mice were used to assess the in vivo activity of panitumumab alone and combined with radiation. In vitro assays were performed to assess the effect of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage. Results: Panitumumab increased the radiosensitivity as measured by the clonogenic survival assay. Radiation-induced epidermal growth factor receptor phosphorylation and downstream signaling through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) was inhibited by panitumumab. Panitumumab augmented radiation-induced DNA damage by 1.2-1.6-fold in each of the cell lines studied as assessed by residual {gamma}-H{sub 2}AX foci after radiation. Radiation-induced apoptosis was increased 1.4-1.9-fold by panitumumab, as evidenced by Annexin V-fluorescein isothiocyanate staining and flow cytometry. In vivo, the combination therapy of panitumumab and radiation was superior to panitumumab or radiation alone in the H226 xenografts (p = 0.01) and showed a similar trend in the SCC-1483 xenografts (p = 0.08). In vivo, immunohistochemistry demonstrated the ability of panitumumab to augment the antiproliferative and antiangiogenic effects of radiation. Conclusion: These studies have identified a favorable interaction in the combination of radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant additional pursuit.

Kruser, Tim J.; Armstrong, Eric A.; Ghia, Amol J.; Huang Shyhmin; Wheeler, Deric L. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Radinsky, Robert; Freeman, Daniel J. [Department of Oncology Research, Amgen Incorporated, Thousand Oaks, CA (United States); Harari, Paul M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)], E-mail:



Role of podoplanin expression in squamous cell carcinoma of upper aerodigestive tract.  


Podoplanin, a type-1 transmembrane glycoprotein, was originally named due to its expression in renal podocytes of rats. It was subsequently detected in a variety of normal human tissues, including lymphatic endothelium. Although podoplanin has been identified as the endogenous ligand of C-type lectin-like receptor 2 (CLEC-2) on platelets, its physiological functions and pathways remain largely unknown. A role in lymphangiogenesis has been suggested, since podoplanin-deficient mice were found to die at birth with a phenotype of dilated, malfunctioning lymphatic vessels and lymphedema. Podoplanin is invariably expressed in some tumors, such as lymphangioma, seminoma and follicular dendritic cell tumor, but tumor cell expression of podoplanin is highly variable in squamous cell carcinoma (SCC). It has been found that high podoplanin expression is associated with lymph node metastasis and poor prognosis in SCC of the upper aerodigestive tract. Now there is growing evidence that podoplanin is also involved in carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis. Additionally, animal studies confirmed some in vivo effects of podoplanin-overexpressing tumors, including formation of more tumor lymphatic vessels, larger lymph node metastases, more platelet aggregation, and more pulmonary metastases. Several recently developed anti-podoplanin antibodies, such as NZ-1, P2-0 and hP2-0, have been shown to attenuate podoplanin-induced platelet aggregation and prevent experimental hematogenous metastasis in nude mice. These antibodies may be applied in preclinical and clinical studies to evaluate the possibility of podoplanin-targeted therapy. PMID:23348382

Chuang, Wen-Yu; Chang, Yu-Sun; Yeh, Chi-Ju; Wu, Yi-Chin; Hsueh, Chuen



Augmentation of radiation response by panitumumab in models of upper aerodigestive tract cancer  

PubMed Central

Purpose In this report, we examine the interaction between panitumumab, a fully human anti-EGFR monoclonal antibody, and radiation in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines and xenografts. Methods and Materials HNSCC lines UM-SCC-1 and SCC-1483 as well as the NSCLC line H226 were studied. Tumor xenografts in athymic nude mice were utilized to assess the in vivo activity of panitumumab alone and in combination with radiation. In vitro assays were performed to assess the impact of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage. Results Panitumumab increased radiosensitivity as measured by clonogenic survival assay. Radiation-induced EGFR phosphorylation and downstream signaling through MAPK and STAT3 was inhibited by panitumumab. Panitumumab augmented radiationinduced DNA damage by 1.2–1.6-fold in each of the cell lines studied as assessed by residual ?-H2AX foci after radiation. Radiation-induced apoptosis was increased 1.4–1.9-fold by panitumumab, as evidenced by Annexin V-FITC staining and flow cytometry. In vivo, combination therapy with panitumumab and radiation was superior to panitumumab or radiation alone in H226 xenografts (p=0.01) and showed a similar trend in SCC-1483 xenografts (p=0.08). These in vivo findings correlated with immunohistochemistry examination of PCNA; panitumumab with radiation markedly reduced PCNA staining in tumor xenografts. Conclusions These studies identify a favorable interaction when combining radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant further pursuit.

Kruser, Tim J.; Armstrong, Eric A.; Ghia, Amol J.; Huang, Shyhmin; Wheeler, Deric L.; Radinsky, Robert; Freeman, Daniel J.; Harari, Paul M.



Diet, alcohol, smoking and cancer of the upper aerodigestive tract: a prospective study among Hawaii Japanese men.  


A cohort study of upper aerodigestive tract cancer was conducted among 7,995 Japanese-American men who were interviewed and examined from 1965 to 1968. Information was collected about smoking history and alcohol and dietary intake. After 24 years, 92 incident cases with histological confirmation of diagnosis were identified. Current cigarette smokers at time of examination had a 3-fold risk for upper aerodigestive tract cancer compared with never-smokers. A dose-response relationship was present with increasing amount and duration of cigarette use. Consumption of beer, wine, spirits and total alcohol was strongly associated with increased risk. Of 23 food and beverage categories, only candy/jelly/soda pop consumption had a statistically significant inverse trend. Frequent consumption of fruit was also inversely associated with this cancer. In contrast, the risk tended to be positively associated with consumption of rice, seaweed, tofu or tsukudani (a mixed dish of fish, sugar, soy sauce and seaweed), but the dose-response relationship was not statistically significant. For nutrient intake, increased calcium and fat intake decreased the risk for this cancer. PMID:7860134

Chyou, P H; Nomura, A M; Stemmermann, G N



Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay  

Microsoft Academic Search

Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and

Norbert H Kleinsasser; Barbara C Wallner; Ernst R Kastenbauer; Ruth K Muenzenrieder; Ulrich A Harréus



A functional trinucleotide repeat polymorphism in the 5'-untranslated region of the glutathione biosynthetic gene GCLC is associated with increased risk for lung and aerodigestive tract cancers.  


Glutathione (GSH), the major intracellular antioxidant, protects against cancer development by detoxifying carcinogens and free radicals and strengthening the immune system. Recently, a GAG-trinucleotide repeat polymorphism in the 5'-untranslated region of the gene for the rate-limiting enzyme for GSH biosynthesis, ?-glutamine cysteine ligase (GCL), was shown to be associated with lowered GCL activity and GSH levels in vitro and in vivo. We tested the hypothesis that this functional polymorphism in GCL is associated with the risk for lung and aerodigestive tract cancers. To this end, we conducted a case-control study that included 375 lung cancer cases, 200 aerodigestive tract cancer cases, and 537 controls. GAG repeat genotype (4, 7, 8, 9, and 10 repeat alleles) was determined by capillary electrophoresis of PCR products from the repeat region of the GCL catalytic subunit (GCLC). Odds ratios (OR) were calculated by logistic regression and adjusted for risk factors, including age, sex, body mass index, and smoking history. The GAG-7/7 genotype was associated with a 1.9-fold increased risk of lung cancer and 2.6-fold increased risk of aerodigestive tract cancer compared to the wild-type GAG-9/9 (P?aerodigestive tract cancer (OR?=?2.3, P?aerodigestive tract cancers, and further implicates a role for oxidative stress in the development of these cancers. © 2012 Wiley Periodicals, Inc. PMID:22610501

Nichenametla, Sailendra N; Muscat, Joshua E; Liao, Jason G; Lazarus, Philip; Richie, John P



Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma.  


Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the rehabilitation process, and to provide psychosocial support when needed. To our knowledge, there are no published reports in the literature dedicated to the follow-up of patients with these tumours. A comprehensive literature search for post-treatment follow-up strategies spanning from 1980 to 2012 was performed on several databases. This review focuses on malignant salivary gland tumors, soft tissue sarcomas, cutaneous squamous cell carcinomas, and sinonasal adenocarcinomas. Given the varying biological behavior and treatment-related factors and based on the literature, different recommendations are made on the follow-up of patients with the above-mentioned tumors. PMID:23100081

Digonnet, Antoine; Hamoir, Marc; Andry, Guy; Vander Poorten, Vincent; Haigentz, Missak; Langendijk, Johannes A; de Bree, Remco; Hinni, Michael L; Mendenhall, William M; Paleri, Vinidh; Rinaldo, Alessandra; Werner, Jochen A; Takes, Robert P; Ferlito, Alfio



Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study  

Microsoft Academic Search

Background: Despite several lines of evidence suggesting the biological plausibility of marijuana being carcinogenic, epidemiologic findings are inconsistent. We conducted a population-based case-control study of the association between marijuana use and the risk of lung and upper aerodigestive tract cancers in Los Angeles. Methods: Our study included 1,212 incident cancer cases and 1,040 cancer-free controls matched to cases on age,

Mia Hashibe; Hal Morgenstern; Yan Cui; Donald P. Tashkin; Zuo-Feng Zhang; Wendy Cozen; Thomas M. Mack; Sander Greenland



Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay.  


Carcinogenesis in the upper aerodigestive tract is influenced by multiple factors. Besides tobacco and alcohol consumption, specific pollutants such as phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be important in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to investigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobiotics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agents in mucosal epithelial cells and peripheral blood lymphocytes of 60 volunteers. Mucosa was harvested from larynx, oropharynx, and inferior nasal turbinates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylphthalate (DiBP), N'-nitrosodiethylamine (NDELA), benzo[a]pyrene (B[a]P), and N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG). DBP, DiBP, B[a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populations. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relatively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the upper aerodigestive tract. Further attention should be focused on intra-individual mutagen sensitivities and inter-individual genetic differences as regards susceptibility to upper aerodigestive tract cancer. PMID:10771268

Kleinsasser, N H; Wallner, B C; Kastenbauer, E R; Muenzenrieder, R K; Harréus, U A



Risk of upper aerodigestive tract cancers in a case-cohort study of autoworkers exposed to metalworking fluids  

PubMed Central

Aims: To re-examine aerodigestive cancer risk in a cohort of autoworkers exposed to metal working fluids (MWF), using improved case definition and more recently diagnosed cases. Methods: The autoworker cohort included 31 100 hourly workers alive on 1 January 1985 who worked at three automobile plants in Michigan. A case-cohort design was carried out that included incident cases of cancers of the larynx, oesophagus, and stomach, and a 10% sample of the cohort. A Cox proportional hazards model was used to estimate MWF exposure effects. The smoothing method of penalised splines was used to explore the shape of the underlying exposure-response curves. Results: The most important finding was the association between larynx cancer incidence and cumulative straight MWF exposure. The results for oesophageal cancer were less consistent. For stomach cancer there was no evidence of excess risk. Conclusion: This association between larynx cancer and straight MWF exposures was consistent with a previous finding in this cohort, providing further support for a causal relation.

Zeka, A; Eisen, E; Kriebel, D; Gore, R; Wegman, D



Prevention of upper aerodigestive tract cancer in zinc-deficient rodents: Inefficacy of genetic or pharmacological disruption of COX-2  

PubMed Central

Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced for-estomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive bio-markers COX-2, nuclear factor (NF)-? B p65 and leukotriene A4 hydrolase (LTA4H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-2?/? forestomachs displayed strong LTA4H immunostaining, indicating activation of an alter-native pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer.

Fong, Louise Y.Y.; Jiang, Yubao; Riley, Maurisa; Liu, Xianglan; Smalley, Karl J.; Guttridge, Denis C.; Farber, John L.



Risk of upper aerodigestive tract cancer and type of alcoholic beverage: a European multicenter case-control study.  


The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 %CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66 % and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95 %CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types = 0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value = 0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value = 0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT. PMID:22692594

Marron, Manuela; Boffetta, Paolo; Møller, Henrik; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Lagiou, Pagona; Lagiou, Areti; Slámová, Alena; Schejbalová, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana Victorovna; Macfarlane, Gary John; Talamini, Renato; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Biggs, Anne-Marie; Thomson, Peter; Conway, David Ian; McKinney, Patricia Ann; Znaor, Ariana; Healy, Claire Marie; McCartan, Bernard Eugene; Brennan, Paul; Hashibe, Mia



Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study.  


Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR?=?3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables. PMID:23719996

Lee, Yuan-Chin Amy; Zugna, Daniela; Richiardi, Lorenzo; Merletti, Franco; Marron, Manuela; Ahrens, Wolfgang; Pohlabeln, Hermann; Lagiou, Pagona; Trichopoulos, Dimitrios; Agudo, Antonio; Castellsague, Xavier; Betka, Jaroslav; Holcatova, Ivana; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Talamini, Renato; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Conway, David I; McKinney, Patricia A; Thomson, Peter; Znaor, Ariana; Healy, Claire M; McCartan, Bernard E; Boffetta, Paolo; Brennan, Paul; Hashibe, Mia



A high HIF-1? expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients.  


The aim of the present study was to evaluate the role of HIF-1? genetic polymorphisms and protein expression in the development of metastasis in upper aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic markers was also evaluated. Protein expression was analysed using immunohistochemistry, and RFLP analysis was used to investigate HIF-1? C1779T and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided into 2 groups according to the absence or presence of metastasis. Lymph node samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph nodes (both derived from patients with metastatic disease), and control lymph nodes, which were obtained from patients without any metastasis. The allele T was more frequently found in patients with metastatic disease. HIF-1? protein expression in the lymph nodes was increased in the presence of the T allele. Metastatic lymph nodes showed lower levels of HIF-1?, VEGFR1, and MMP-9 proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels were increased. In agreement, HIF-1? expression was correlated with MMP-9. Cox regression analysis demonstrated that higher HIF-1? and MMP-9 protein expression levels and GA and GG genotypes were associated with poor survival. Our findings show that the C1772T and G1790A polymorphisms of the HIF-1? gene are associated with increased expression of the HIF-1? protein in UADTC. The present data indicate that non-metastatic tissues express higher levels of HIF-1?, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein expression is elevated. The present study also shows that the HIF-1? G1790A polymorphism and its protein expression have an impact on the prognosis of UADTC patients. PMID:21945343

Fraga, Carlos Alberto de Carvalho; de Oliveira, Marcos Vinícius Macedo; de Oliveira, Érica Silva; Barros, Lucas Oliveira; Santos, Francis Balduino Guimarães; Gomez, Ricardo Santiago; De-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena



Early or Up-Front Radiotherapy Improved Survival of Localized Extranodal NK/T-Cell Lymphoma, Nasal-Type in the Upper Aerodigestive Tract  

SciTech Connect

Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving {>=}54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.

Huang Meijuan; Jiang Yu [Department of Biotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); State Key Laboratory of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu (China); Liu Weiping [Department of Pathology, West China Hospital, Medical School, Sichuan University, Chengdu (China); Li Zhiping [Department of Radiotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); Li Mei; Zhou Lin [Department of Biotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); Xu Yong [Department of Radiotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); Yu Chunhua [Department of Biotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); Li Qiu; Peng Feng; Liu Jiyan; Luo Feng [Department of Biotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); State Key Laboratory of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu (China); Lu You [Department of Biotherapy for Cancer, West China Hospital, Medical School, Sichuan University, Chengdu (China); State Key Laboratory of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu (China)], E-mail:



p53 mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients  

Microsoft Academic Search

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization\\u000a of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to\\u000a have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation,\\u000a we postulated

Anette Escher; Elsa Piotet; Francois Waridel; Richard Iggo; Philippe Monnier



Radiotherapy in the treatment of mucosal melanoma of the upper aerodigestive tract: Analysis of 74 cases. A Rare Cancer Network study  

SciTech Connect

Purpose: To retrospectively analyze a series of mucosal melanoma of the upper aerodigestive tract to determine the prognostic factors and contribute to understanding the role of radiotherapy in the therapeutic strategy. Methods and Materials: Seventy-four patients were analyzed. The most frequent locations were nasal and oral, in 31 patients (41.9%) and 12 patients (16.2%), respectively. Sixty-three patients (85.1%) were in Stage I, 5 (6.8%) in Stage II, and 6 (8.1%) in Stage III. Treatment consisted of surgery in 17 patients (23.0%), surgery and radiotherapy in 42 (56.8%), radiotherapy in 11 (14.9%), and chemo-immunotherapy in 4 (5.4%). Median follow-up was 20 months. Results: Local control at 3 years was 57% after surgery alone and 71% after surgery and radiotherapy. Overall and disease-free survival rates, respectively, were 41% and 31% at 3 years and 14% and 22% at 10 years. After univariate analysis, female gender, melanosis, tumor size {<=}3 cm, Stage I, postoperative radiotherapy, and complete remission were favorable prognostic factors. Stage I and melanosis were confirmed by multivariate analysis. Conclusions: Local control was improved by postoperative radiotherapy, despite survival being as poor as in other published series. Stage I and melanosis at diagnosis were the most favorable prognostic factors.

Krengli, Marco [Department of Radiation Oncology, University of Piemonte Orientale, Novara (Italy)]. E-mail:; Masini, Laura [Department of Radiation Oncology, University of Piemonte Orientale, Novara (Italy); Kaanders, Johannes [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Maingon, Philippe [Department of Radiation Oncology, Centre G. F. Leclerc, Dijon (France); Oei, Swan Bing [Department of Radiation Oncology, Dr. Bernard Verbeeten Instituut, Tilburg (Netherlands); Zouhair, Abderrahim [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Ozyar, Enis [Department of Radiation Oncology, Hacettepe University Medical School, Ankara (Turkey); Roelandts, Martine [Department of Radiation Oncology, Institut Jules Bordet, Bruxelles (Belgium); Amichetti, Maurizio [Department of Radiation Oncology, Ospedale Oncologico A. Businco, Cagliari (Italy); Bosset, Mathieu [Department of Radiation Oncology, Centre Hospitalier Universitaire de Besancon, Besancon (France); Mirimanoff, Rene-Olivier [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland)



Putative EPHX1 Enzyme Activity Is Related with Risk of Lung and Upper Aerodigestive Tract Cancers: A Comprehensive Meta-Analysis  

PubMed Central

Background EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers. Methodology/Principal Findings A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR?=?0.88, 95%CI?=?0.80–0.96) and UADT cancers (OR?=?0.86, 95%CI?=?0.77–0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR?=?1.18, 95%CI?=?1.04–1.33) but not of UADT cancers (OR?=?1.05, 95%CI?=?0.93–1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR?=?0.83, 95%CI?=?0.75–0.93) whereas high EPHX1 activity increased risk of the cancers (OR?=?1.20, 95%CI?=?0.98–1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR?=?0.77/0.85 for smokers/nonsmokers; high activity allele R: OR?=?1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR?=?0.73/0.88 for smokers/nonsmokers; putative high activity: OR?=?1.02/0.93 for smokers/ nonsmokers). Conclusions/Significance Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk.

Qu, Xinshun; Zhu, Jiadong; Li, Lin; Ring, Brian Z.; Su, Li



Lung and Upper Aerodigestive Cancer

Conducts and supports research on the prevention and early detection of head and neck and lung cancers. Clinical trials and the evaluation of new agents, surrogate biomarkers, and new technologies to identify premalignant lesions are developed and supported. Funding


Reflux and aerodigestive tract diseases.  


Gastroesophageal reflux disease can present with a wide variety of extraesophageal symptoms. In particular, the type of disease characterized predominately by laryngopharyngeal reflux may be difficult to diagnose because of the absence of regurgitation or heartburn. The available battery of diagnostic tools is often insufficient to confirm a diagnosis of reflux, so the diagnosis is often made by elimination. In many cases, treatment with proton pump inhibitors will relieve symptoms and respiratory complications, despite the persistence of non-acidic reflux. Such treatment is often employed to "confirm" the diagnosis, as measured by patient response. Many diseases have been related to this condition in the literature. The authors review knowledge about these manifestations and their relationship with refluxed gastric content. Physiopathology, symptoms and treatment are reviewed in order to clarify our understanding of laryngopharyngeal reflux diseases and related manifestations. PMID:22773190

Coca-Pelaz, Andrés; Rodrigo, Juan P; Paccagnella, Daniela; Takes, Robert P; Rinaldo, Alessandra; Silver, Carl E; Woolgar, Julia A; Hinni, Michael L; Ferlito, Alfio



The nature of the Ailao Shan-Red River (ASRR) shear zone: Constraints from structural, microstructural and fabric analyses of metamorphic rocks from the Diancang Shan, Ailao Shan and Day Nui Con Voi massifs  

NASA Astrophysics Data System (ADS)

The structural geology, timing of shearing, and tectonic implications of the ASRR shear zone, one of the most striking lineaments in Southeast Asia, have been the topics of extensive studies over the past few decades. The Xuelong Shan (XLS), Diancang Shan (DCS), Ailao Shan (ALS) and Day Nui Con Voi (DNCV) metamorphic massifs along the shear zone have preserved important information on its structural and tectonic evolution. Our field structural analysis, detailed microstructural and fabric analysis, as well as the quartz, sillimanite and garnet fabric studies of the sheared rocks from the massifs demonstrate the dominant roles of three deformation episodes during Cenozoic tectonic evolution in the shear zone. Among the contrasting structural and microstructural associations in the shear zone, D2 structures, which were formed at the brittle to ductile transition during large-scale left-lateral shearing in the second deformation episode, predominate over the structural styles of the other two deformation episodes. Discrete micro-shear zones with intensive grain size reduction compose the characteristic structural style of D2 deformation. In addition, several types of folds (early shearing folds, F21, and late-shearing folds, F22) were formed in the sheared rocks, including discrete to distributed mylonitic foliation, stretching lineation and shear fabrics (e.g., mica fish, domino structures, as well as sigma and delta fabrics). A sequence of microstructures from syn-kinematic magmatic flow, high-temperature solid-state deformation, to brittle-ductile shearing is well-preserved in the syn-kinematic leucocratic intrusions. Deformation structures from the first episode (D1) are characterized by F1 folds and distributed foliations (S1) in rocks due to pure shearing at high temperatures. They are preserved in weakly sheared (D2) rocks along the eastern margin of the ALS belt or in certain low-strain tectonic enclaves within the shear zone. Furthermore, semi-brittle deformation structures, such as hot striae and discrete retrogression zones, are attributed to normal-slip shearing in the third deformation episode (D3), which was probably locally active, along the eastern flank of the DCS range, for example.There are four quartz c-axis fabric patterns in the mylonitic rocks, including type A point maxima, type B Y point maxima with crossed girdles superimposition, type C quadrant maxima, as well as type D point and quadrant maxima combination. They are consistent with microscopic observations of microstructures of high-temperature pure shearing, low-temperature simple shearing and their superimposition. Integrated microstructural analysis and fabric thermometer studies provide information on both high temperature (up to 750 °C) and dominant low-temperature (300-600 °C) deformations of quartz grains in different rock types. Sillimanite and garnet fabrics, especially the latter, were primarily formed at the peak metamorphism during high-temperature pure shearing.The above structural, microstructural and fabric associations were generated in the tectonic framework of the Indian-Eurasian collision. The low-temperature microstructures and fabrics are attributed to left-lateral shearing along the ASRR shear zone from 27 to 21 Ma during the southeastward extrusion of the Indochina block, which postdated high-temperature deformation at the peak metamorphism during the collision.

Liu, Junlai; Tang, Yuan; Tran, My-Dung; Cao, Shuyun; Zhao, Li; Zhang, Zhaochong; Zhao, Zhidan; Chen, Wen



Glutathione S-transferase M1 or T1 null genotype as a risk factor for developing multiple primary neoplasms in the upper aero-digestive tract, in Indian males using tobacco.  


In this study conducted amongst Indian male tobacco users with upper aero-digestive tract (UADT) squamous carcinoma, 30 patients with multiple primary neoplasms (MPN) were compared with 28 age and sex matched patients with a single primary neoplasm (SPN) for various environmental factors (form of tobacco use, alcohol, radiotherapy for index cancer) and genetic parameters (family history of UADT cancers and GSTT1/GSTM1 genotype). The GSTM1/T1 null genotype, seen in 60% patients with MPN versus 33% patients with SPN (P=0.03) had an odds ratio of 3.7 [CI=1.14-11.99; P=0.03] for developing MPN. Tobacco use in the form of smoking with or without chewing, as opposed to only chewing, and regular alcohol intake were the two other factors with almost three fold increased risk for the development of MPN, although, the effect was not statistically significant. All three patients with a family history of UADT cancer developed MPN, suggesting an inherited predisposition. PMID:14662420

Jhavar, Sameer; Sarin, Rajiv; Mulherkar, Rita; Benner, Axel; Agarwal, Jai Prakash; Dinshaw, Ketayun



Evaluation with mTHPC of early squamous cell carcinomas of the cheek pouch mucosa of Golden Syrian hamsters as a model for clinical PDT of early cancers in the upper aerodigestive tract, the esophag  

NASA Astrophysics Data System (ADS)

Golden Syrian hamsters are evaluated as an animal model for light induced fluorescence (LIF) photodetection and phototherapy of early squamous cell carcinomas of the upper aerodigestive tract, the esophagus, and the traecheo-bronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12-DMBA. For phototherapeutic experiments on the animals we utilized meso-(tetrahydoxyphenyl) chlorin (mTHPC). This drug is currently in phase I and II clinical trials for ENT patients presenting superficial `early' squamous cell carcinomas. By means of LIF we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer with laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for testing new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical PDT.

Glanzmann, Thomas; Theumann, Jean-Francois; Forrer, Martin; Braichotte, Daniel; Wagnieres, Georges; van den Bergh, Hubert; Andrejevic, Snezana; Savary, Jean-Francois; Monnier, Philippe



An Integrated Digital Campus Delivers ROI and VOI  

ERIC Educational Resources Information Center

|Five years ago, North Shore Community College (NSCC) encountered rising enrollments in the face of lagging state funding. The addition of two new campuses stretched NSCC thin as it attempted to provide administrative and academic services across five (more recently consolidated to four) locations. Its students increasingly struggled to balance…

Forsstrom, Jan; Ham, Gary



Pratique d'apprentissage en ligne aux etudes superieures (Online Learning for Higher Education).  

ERIC Educational Resources Information Center

Online learning requires new approaches to teaching and learning. At the University of Montreal, 28 graduate students in education and adult students specializing in educational technology attended an experimental distance education course. Students identified advantages and disadvantages of online learning/teaching and reflected on how the course…

Marchand, Louise



L'enseignement superieur tunisien: Enjeux et avenir (Higher Education in Tunisia: Challenges and Opportunities).  

ERIC Educational Resources Information Center

This report presents findings of a study of higher education in Tunisia. It finds that higher education in Tunisia is a largely effective and well-performing system. However, it notes an expected doubling of enrollment over the next 10 years which will create obstacles that prevent it from playing the role expected of it by a society and economy…

World Bank, Washington, DC.


From "Ecoles Superieures de Commerce" to "Management Schools": Transformations and Continuity in French Business Schools  

ERIC Educational Resources Information Center

Part of the national system of grandes Ecoles, French Business schools have known radical changes since the 1980s, notably in size, and have become more attractive to students both at a national and an international level. As a consequence, the French elitist system has been questioned by the competition of foreign--especially Anglo-Saxon--models.…

Blanchard, Marianne



Le francais fonde sur la competence, Superieur (Competency Based French, Superior).  

ERIC Educational Resources Information Center

This instructional guide in French is intended for training Peace Corps volunteers serving in the Central African Republic. It includes 35 topical units at the superior level, each consisting of briefly stated competency objectives and a number of brief, related situational texts. Unit topics include: explaining how to do something; explaining…

Dimanche, Maurice


Les voies de signalisation intracellulaire : de nouvelles cibles thérapeutiques dans la polyarthrite rhumatoïde  

Microsoft Academic Search

Biotherapies and other new treatments introduced over the last few years have considerably enriched the therapeutic armamentarium for rheumatoid arthritis. Nevertheless, primary refractoriness or secondary escape phenomenon may occur, indicating a need for identifying new treatment targets. Promising candidates can be found among compounds involved in signal transduction pathways, most notably protein kinases (mitogen-activated protein kinase [MAPK] and phosphatidylinositol-3 protein

Jacques Morel; Francis Berenbaum



Des voies nouvelles pour l'apprentissage des langues (New Paths for the Teaching of Languages).  

ERIC Educational Resources Information Center

Trends in second-language instruction in higher education are noted, including growth in establishment of university-based language resource centers for both students and teachers, competency-based teaching and certification, and a French initiative to promote instruction in less commonly taught European languages such as Dutch, Greek, and Irish.…

Olivieri, Claude



MRI-PET Correlation in Three Dimensions Using a Volume-of-Interest (VOI) Atlas  

Microsoft Academic Search

Summary: Quantitative interpretation of functional images (PET or SPECT) is hampered by poor spatial resolution, low counting statistics, and, for many tracers, low contrast between different brain structures of interest. Furthermore, normal tracer distributions can be severely disrupted by such gross pathologies as stroke, tumor, and dementia. Hence, the complementary anatomical information provided by CT or MRI is essential for

A. C. Evans; S. Marrett; J. Torrescorzo; S. Ku; L. Collins



Chimiothérapie systémique des cancers avancés des voies biliaires: actualités et perspectives  

Microsoft Academic Search

\\u000a Abstract  Biliary tract cancers, with fewer than 2,000 new cases per year in France, must be regarded as orphan tumors. There is currently\\u000a no evidence of the benefit of neoadjuvant or adjuvant chemotherapy and\\/or radiotherapy in resectable biliary tract cancers.\\u000a In unresectable disease, best supportive care is the mainstay of treatment, especially effective biliary drainage. Gemcitabinecisplatin\\u000a combination (GEMCIS regimen) is the

D. Malka; V. Boige; M. Ducreux



Tinkering with tenure: the community land trust experiment in Voi, Kenya  

Microsoft Academic Search

Projects to secure land rights for the urban poor have been implemented in Sub-Saharan Africa for over 30 years. A recurrent issue in such projects is the provision of sustainable land tenure for beneficiaries. Commonly, individual titles with restrictions on resale have been used. Despite these, recipients often sell their land rights to more affluent city dwellers exacerbating the growth

Ellen M. Bassett



L'informel dans la formation des enseignants: Le cas de l'Institut Superieur Pedagogique de Bukavu (Zaïre)  

NASA Astrophysics Data System (ADS)

This article deals with the crucial question of teacher training in an attempt to explore the activities and means which are developed by students, future teachers, in order to acquire the required competence. To reach that objective, the authors designed a research instrument, a questionnaire, which they submitted to a group of students at the Institut Supérieur Pédagogique in Bukavu, Zaire. The results demonstrate that the activities in which students engage when confronted with learning tasks, play an important role in determining what they learn. In fact, besides the normal activities foreseen by the curriculum, students make serious use, during their professional training, of resources which are frequently unsuspected by their instructors. The discussion of these results has led the authors to formulate propositions which may improve the theory and practice of teacher training.

Magabe, M.; Bapolisi, B.; Lokombe, K.



Inventory of Research into Higher Education in Canada = Inventaire des recherches sur l'enseignement superieur au Canada.  

ERIC Educational Resources Information Center

|Information is provided in English and French on research projects concerned with postsecondary education in Canada. Approximately 250 current or recently completed projects reported by researchers in universities, community colleges, educational organizations, and government departments and agencies are described. The projects, which are entered…

Houwing, J. F., Ed.; Kristjanson, A. M., Ed.


Intraoperative Consultation (IOC) in Mucosal Lesions of the Upper Aerodigestive Tract  

Microsoft Academic Search

Intraoperative consultation (frozen section) plays an important part in the treatment of the head and neck cancer patient.\\u000a The appropriate use of intraoperative consultations (frozen sections) usually results in a definitive diagnosis with immediate\\u000a therapeutic impact while the patient is in the operating room. Among the determinations made by frozen section analysis include\\u000a the evaluation of adequacy of surgical margins

Bruce M. Wenig



Toys in the upper aerodigestive tract: Evidence on their risk as emerging from the ESFBI study  

Microsoft Academic Search

ObjectiveForeign body inhalation\\/aspiration or ingestion is a relatively common event in young children and, despite many efforts made in several Countries to reach acceptable safety levels for products devoted to children, small toys or toy parts are frequently mentioned among risky foreign bodies. The aim of the present study is to characterize the risk of complications and prolonged hospitalization due

Francesca Foltran; Dario Gregori; Desiderio Passàli; Luisa Bellussi; Giuseppe Caruso; Francesco Maria Passàli; Giulio Cesare Passàli



Glycemic index and load and risk of upper aero-digestive tract neoplasms (Italy)  

Microsoft Academic Search

Background: The ability of dietary carbohydrates to affect blood glucose and insulin levels by dietary carbohydrates is best measured by the glycemic index (GI) and glycemic load (GL) which have been directly associated with risk of several chronic conditions, including cancer. Patients and methods: Three case–control studies were conducted between 1992 and 2000 in Italy. The first one included 598

Livia S. A. Augustin; Silvano Gallus; Silvia Franceschi; Eva Negri; David J. A. Jenkins; Cyril W. C. Kendall; Luigino Dal Maso; Renato Talamini; Carlo La Vecchia



Migration of a fish bone from the upper aerodigestive tract to the skin of the neck: A case report.  


We describe an unusual case of a migratory foreign body (fish bone) in the neck of a 45-year-old woman. The 2.1-cm bone migrated from the esophagus and traversed through the entire soft tissue of the neck, and it almost extruded through the skin of the neck. With the patient under local anesthesia, the foreign body was easily extracted through an incision over the skin. PMID:23975496

Sinha, Ramanuj; Sen, Indranil; Saha, Jayanta; Mukherjee, Ankur; Guha, Ruma



Toys in the upper aerodigestive tract: new evidence on their risk as emerging from the ESFBI study  

Microsoft Academic Search

Rationale and aimForeign body (FB) inhalation\\/aspiration or ingestion are relatively common events in young children and, despite many efforts made in several countries to reach acceptable safety levels for products devoted to children, small toys or toy parts are frequently mentioned among risky FBs. The aim of the present study is to characterise the risk of complications and prolonged hospitalisation

F Foltran; P Berchialla; D Gregori; A Pitkranta; I Slapak; J Jakubkov; L Bellussi; D Passali



A simplified method for the routine culture of normal oral epithelial (NOE) cells from upper aerodigestive tract mucosa  

Microsoft Academic Search

A method has been established for the routine culture for normal oral epithelial (NOE) cells based on simple methodology and commercially available materials. Normal mucosa was obtained from surgical resections of cancer patients, oropharyngeal mucosa, or pediatric tonsillectomies, anterior tonsillar pillar. NOE cells were allowed to outgrow using explant outgrowth techniques on whole mucosa or the dispased epithelial component. Outgrowth

Li Xu; Stimson P. Schantz; David Edelstein; Peter G. Sacks



Genetic susceptibility to multiple primary neoplasms in the upper aero-digestive tract: genotype score and phenotype correlation.  


Early detection and treatment of head and neck cancer has led to increased patient survival. However such patients are at a high risk for multiple primary neoplasm(s) (MPN). In order to study the genetic susceptibility to MPN, 22 candidate SNPs were genotyped based on which a distinctive Genotype Score was created using Additive, Dominant and Recessive models. Using lymphoblastoid cell lines (LCLs) generated from these individuals, the Genotype Score was correlated with carcinogen sensitivity in vitro. LCLs from MPN patients exhibited significantly higher Genotype Score and showed resistance to genotoxic agents compared to matched controls. This report demonstrates quantitative assessment of cumulative effect of gene polymorphisms and its correlation with carcinogen sensitivity for predicting susceptibility to MPN. PMID:23348701

Hussain, Tabish; Kotnis, Ashwin; Sarin, Rajiv; Mulherkar, Rita



Phonematic Recognition by Linear Prediction: Experiment Reconnaissance Phonemique Par Prediction Lineaire. L'Experience de l'Ecole Nationale Superieure des Telecommunications (E.N.S.T.).  

National Technical Information Service (NTIS)

The recognition of speech signals analyzed by linear prediction is introduced. The principle of the channel adapted vocoder (CAV) is outlined. The learning of each channel model and adaptation to the speaker are discussed. A method stemming from the canon...

L. Miclet Y. Grenier J. Leroux



Une experience de collaboration entre la BBC et des etablissements d'enseignement superieur britanniques (Collaboration Experiences between BBC and Some British Higher Education Institutions).  

ERIC Educational Resources Information Center

|Describes the BBC French language program and the activities that have resulted from BBC's collaboration with institutions such as the Brighton Polytechnic. These activites include the organization of intensive courses, the publication of instructional materials for teachers, and the development of correspondence studies. (MES)|

Hill, Brian



SPS 91 - Power from space; Proceedings of the 2nd International Symposium, Ecole Superieure d'Electricite, Gif-sur-Yvette, France, Aug. 27-30, 1991  

NASA Astrophysics Data System (ADS)

Various papers on the concept of Solar Power Satellites (SPS) are presented. The general topics addressed include: global energy issues; SPS demonstration projects; extraterrestrial materials; power generation, conversion, and storage; environmental issues; development strategies.


A New Way for Multidimensional Medical Data Management: Volume of Interest (VOI)Based Retrieval of Medical Images With Visual and Functional Features  

Microsoft Academic Search

The advances in digital medical imaging and storage in integrated databases are resulting in growing demands for efficient image retrieval and management. Content-based image retrieval (CBIR) refers to the retrieval of images from a database, using the visual features derived from the information in the image, and has become an attractive approach to managing large medical image archives. In conventional

Jinman Kim; Weidong Cai; Dagan Feng; Hao Wu



WindVOiCe, a Self-Reporting Survey: Adverse Health Effects, Industrial Wind Turbines, and the Need for Vigilance Monitoring  

ERIC Educational Resources Information Center

|Industrial wind turbines have been operating in many parts of the globe. Anecdotal reports of perceived adverse health effects relating to industrial wind turbines have been published in the media and on the Internet. Based on these reports, indications were that some residents perceived they were experiencing adverse health effects. The purpose…

Krogh, Carmen M. E.; Gillis, Lorrie; Kouwen, Nicholas; Aramini, Jeff




Microsoft Academic Search

RESUME : La détection des bovins infectés excréteurs est un point critique pour l'évaluation des risques de transmission de l'infection par Coxiella burnetii entre bovins et des bovins à l'Homme. Coxiella burnetii est excrétée chez les ruminants dans les produits de la parturition, mais aussi dans les fèces, le sperme, l'urine, le mucus vaginal et le lait. Cependant, la valeur

François Beaudeau; Raphaël Guatteo; Henri Seegers


Development and evaluation of an automated atlas-based image analysis method for microPET studies of the rat brain  

Microsoft Academic Search

An automated method for placement of 3D rat brain atlas-derived volumes of interest (VOIs) onto PET studies has been designed and evaluated. VOIs representing major structures of the rat brain were defined on a set of digitized cryosectioned images of the rat brain. For VOI placement, each PET study was registered with a synthetic PET target constructed from the VOI

Daniel J Rubins; William P Melega; Goran Lacan; Alain Plenevaux; Andre Luxen; Simon R Cherry



Biology of and Novel Therapeutic Approaches for Epithelial Cancers of the Aerodigestive Tract. Proceedings of a Conference. Held in Steamboat Springs, Colorado on April 1-7, 1991.  

National Technical Information Service (NTIS)

The Journal of the National Cancer Institute Monograph offers a synthesis of recent data into molecular models of tumor genesis and progression with discussions of diagnostic, prognostic, and therapeutic applications of these studies.

D. C. Ihde



Discordant p53 Gene Mutations in Primary Head and Neck Cancers and Corresponding Second Primary Cancers of the Upper Aerodigestive Tract1  

Microsoft Academic Search

Patients with primary head and neck malignancies have a 3-7% yearly incidence of second primary cancers. It is thought that these second pri mary cancers arise independently following exposure to a common car cinogen by a process that has been called field cancerization. Since mu tations in the p53 tumor suppressor gene represent a genetic alteration occurring during the evolution

Kyung Y. Chung; Tapas Mukhopadhyay; Jhingook Kim; Alan Casson; Jae Y. Ro; Helmuth Goepfert; Waun K. Hong; Jack A. Roth


Scale-up Approach in CATI Surveys for Estimating the Number of Foreign Body Injuries in the Aero-digestive Tract in Children  

PubMed Central

Foreign body injuries are a well-known threat to children due to the high risk of ingestion of small objects and choking. In order to depict the epidemiological framework of such injuries, data are mostly available for hospitalizations and partially for emergency room visits. The hidden part of the phenomenon consisting of minor self-resolved injuries is still unknown. The purpose of this paper is to provide an estimate of the overall burden of such injuries in children in Italy. Our paper proposes the use of the scale up technique to overcome most of the pitfalls of classical techniques in the estimation of the number of children aged 0–14 that suffered a foreign body injury in 2004. Our results, based on a CATI survey on 1,081 women, show that the estimated number of children under 15 years that incurred in a foreign body injury was 15,829 (95% CI: 14,376–17,282), of these 12,844 were treated in hospital or in emergency department (95% CI: 11,535–14,153). The scale-up method in conjunction with a CATI survey provides a reliable estimate of the size of hard-to-count populations as those of injured children at lower costs with respect to classical sampling schemes.

Snidero, Silvia; Soriani, Nicola; Baldi, Ileana; Zobec, Federica; Berchialla, Paola; Gregori, Dario



Le Francais au Zaire: Langue "superieure" et chances de "survie" dans un pays africain (French in Zaire: The Language of Prestige and Its Odds for Survival in an African Country).  

ERIC Educational Resources Information Center

Factors affecting the survival or decline of French in Zaire are examined, including its social, cultural, and political status, the history of other European languages established in Africa, and the influences of intercultural needs and ethnic identity on the continued use of French. (Author/MSE)

ya Rubango, Nyunda



Highlighting the Impacts of North-South Research Collaboration among Canadian and Southern Higher Education Partners (Principaux impacts des collaborations de recherche Nord-Sud entre les partenaires des etablissements d'enseignement superieur du Canada et du Sud)  

ERIC Educational Resources Information Center

|The Association of Universities and Colleges of Canada (AUCC) felt it was timely to create an academic forum in which university researchers have the opportunity to engage with their peers and relevant stakeholders and document the impacts of their North-South research collaboration in a peer-reviewed publication. The Association achieved this by…

Association of Universities and Colleges of Canada, 2006



L'E.A.P. ou l'anglais enseigne dans les etudes superieures. Un guide pour le debutant (E.A.P. or English for Academic Purposes: A Guide for the Beginner).  

ERIC Educational Resources Information Center

Addresses those readers who are not familiar with EAP, offering an introductory discussion of its objectives and methods, in two parts. Devotes the first part to the needs that justify an EAP approach, and the second to its methodology, with particular attention to interdisciplinary, task-oriented instruction. Societe Nouvelle Didier Erudition, 40…

Roe, Peter J.



From Higher Education to Employment. Volume IV: Portugal, United Kingdom, Sweden, Switzerland = De l'enseignement superieur a l'emploi. Volume IV: Portugal, Royaume-Uni, Suede, Suisse.  

ERIC Educational Resources Information Center

|This volume reports on the flow of graduates from higher education into working life in Portugal, the United Kingdom, Sweden and Switzerland. Chapters for each nation were contributed by national experts in that field. The first section of the report, on Portugal, contains two papers. The first, written in English, discusses recent changes in the…

Organisation for Economic Cooperation and Development, Paris (France).


Highlighting the Impacts of North-South Research Collaboration among Canadian and Southern Higher Education Partners (Principaux impacts des collaborations de recherche Nord-Sud entre les partenaires des etablissements d'enseignement superieur du Canada et du Sud)  

ERIC Educational Resources Information Center

The Association of Universities and Colleges of Canada (AUCC) felt it was timely to create an academic forum in which university researchers have the opportunity to engage with their peers and relevant stakeholders and document the impacts of their North-South research collaboration in a peer-reviewed publication. The Association achieved this by…

Association of Universities and Colleges of Canada, 2006



Est-ce que l'enseignement superieur chez les jeunes femmes a considerablement reduit l'ecart entre les sexes en matiere d'emploi et de revenu?  

Microsoft Academic Search

Les jeunes femmes ont gagne enormement de terrain par rapport aux hommes du meme age en ce qui concerne le niveau de scolarite atteint dans les annees 1990. L'objectif de cette etude est d'evaluer le role que joue le niveau de scolarite, qui va rapidement en augmentant, des jeunes femmes quant a leur place relative sur le marche du travail.

Marc Coulombe Simon Frenette



EDUCAFRICA, December 1986. Special Issue: Case Studies on Higher Education in Africa. Special Volume 1=EDUCAFRICA, Decembre 1986. Etudes de cas sur L'Enseignement Superieur en Afrique, Tome 1.  

ERIC Educational Resources Information Center

Case studies of the development of higher education in 17 African countries are presented. Eleven of the case studies are written in French, and six are in English. The country reports that are in English are as follows: Cameroon, Ethiopia, Lesotho, Malawi, Sierra Leone, and Tanzania. The country reports in French are: Benin, Burkina Faso,…




From Higher Education To Employment. Volume II: Canada, Denmark, Spain, United States = De l'enseignement superieur a l'emploi. Volume II: Canada, Danemark, Expagne, Etats-Unis.  

ERIC Educational Resources Information Center

This volume presents reports on the flows of graduates from higher education and on their entry into working life in Canada, Denmark, Spain and the United States. Each paper is written according to detailed guidelines designed to assemble information from many sources, to reflect the state of the art, and to illustrate a variety of approaches,…

Organisation for Economic Cooperation and Development, Paris (France).


Programs and Projects

Programs and Projects Lung and Upper Aerodigestive Cancers Research Group Research Portfolio Search the NCI-Funded Research Portfolio for projects supported by the Lung and Upper Aerodigestive Cancer Research Group. Use the Advanced Search to choose Division


2008 Research Highlights

Alcohol, a known risk factor for upper aerodigestive cancers, is metabolized by several enzymes, including alcohol dehydrogenase (ADH). The genes in the ADH pathway are important candidate genes for aerodigestive cancers.


Contrast-to-noise ratio improvement in volume-of-interest cone beam breast CT  

NASA Astrophysics Data System (ADS)

In this study, we demonstrated the contrast-to-noise ratio (CNR) improvement in breast cone beam CT (CBCT) using the volume-of-interest (VOI) scanning technique. In VOI breast CBCT, the breast is first scanned at a low exposure level. A pre-selected VOI is then scanned at a higher exposure level with collimated x-rays. The two image sets are combined together to reconstruct high quality 3-D images of the VOI. A flat panel detector based system was built to demonstrate and investigate the CNR improvement in VOI breast CBCT. The CNRs of the 8 plastic cones (Teflon, Delrin, polycarbonate, Lucite, solid water, high density polystyrene, nylon and polystyrene) in a breast phantom were measured in images obtained with the VOI CBCT technique and compared to those measured in standard full field CBCT images. CNRs in VOI CBCT images were found to be higher than those in regular CBCT images in all plastic cones. The mean glandular doses (MGDs) from the combination of a high exposure VOI scan and a low exposure full-field scan was estimated to be similar to that from regular full-field scan at standard exposure level. The VOI CBCT technique allows a VOI to be imaged with enhanced image quality with an MGD similar to that from regular CBCT technique.

Shen, Youtao; Liu, Xinming; Lai, Chao-Jen; Zhong, Yuncheng; Yi, Ying; You, Zhicheng; Wang, Tianpeng; Shaw, Chris C.



Local Speed Functions in Level Set Based Vessel Segmentation  

Microsoft Academic Search

\\u000a A new segmentation scheme is proposed for 3D vascular tree delineation in CTA data sets, which has two essential features.\\u000a First, the segmentation is carried out locally in a small volume of interest (VOI), second, a global topology estimation is\\u000a made to initialize a new VOI. The use of local VOI allows that parameter settings for the level set speed

Rashindra Manniesing; Wiro J. Niessen



Value of information in virtual patient performance evaluations.  


The American Board of Family Medicine (ABFM) uses virtual patients (VP) in Maintenance of Certification. User queries might be evaluated by calculating diagnostic value of information (VOI). Typical primary care queries address concerns far beyond efficient diagnosis. We identify practical constraints on VOI scoring in simulations of primary care practice. We imagine a Bayesian physician as the ideal candidate for VOI scoring. Bayesian physicians require an explicit decision making perspective and many local data. PMID:18998811

Sumner, Walton; Hagen, Michael D



Four-dimensional volume-of-interest reconstruction for cone-beam computed tomography-guided radiation therapy  

SciTech Connect

Purpose: Data sufficiency are a major problem in four-dimensional cone-beam computed tomography (4D-CBCT) on linear accelerator-integrated scanners for image-guided radiotherapy. Scan times must be in the range of 4-6 min to avoid undersampling artifacts. Various image reconstruction algorithms have been proposed to accommodate undersampled data acquisitions, but these algorithms are computationally expensive, may require long reconstruction times, and may require algorithm parameters to be optimized. The authors present a novel reconstruction method, 4D volume-of-interest (4D-VOI) reconstruction which suppresses undersampling artifacts and resolves lung tumor motion for undersampled 1-min scans. The 4D-VOI reconstruction is much less computationally expensive than other 4D-CBCT algorithms. Methods: The 4D-VOI method uses respiration-correlated projection data to reconstruct a four-dimensional (4D) image inside a VOI containing the moving tumor, and uncorrelated projection data to reconstruct a three-dimensional (3D) image outside the VOI. Anatomical motion is resolved inside the VOI and blurred outside the VOI. The authors acquired a 1-min. scan of an anthropomorphic chest phantom containing a moving water-filled sphere. The authors also used previously acquired 1-min scans for two lung cancer patients who had received CBCT-guided radiation therapy. The same raw data were used to test and compare the 4D-VOI reconstruction with the standard 4D reconstruction and the McKinnon-Bates (MB) reconstruction algorithms. Results: Both the 4D-VOI and the MB reconstructions suppress nearly all the streak artifacts compared with the standard 4D reconstruction, but the 4D-VOI has 3-8 times greater contrast-to-noise ratio than the MB reconstruction. In the dynamic chest phantom study, the 4D-VOI and the standard 4D reconstructions both resolved a moving sphere with an 18 mm displacement. The 4D-VOI reconstruction shows a motion blur of only 3 mm, whereas the MB reconstruction shows a motion blur of 13 mm. With graphics processing unit hardware used to accelerate computations, the 4D-VOI reconstruction required a 40-s reconstruction time. Conclusions: 4D-VOI reconstruction effectively reduces undersampling artifacts and resolves lung tumor motion in 4D-CBCT. The 4D-VOI reconstruction is computationally inexpensive compared with more sophisticated iterative algorithms. Compared with these algorithms, our 4D-VOI reconstruction is an attractive alternative in 4D-CBCT for reconstructing target motion without generating numerous streak artifacts.

Ahmad, Moiz; Balter, Peter; Pan, Tinsu [Department of Imaging Physics, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030 (United States)



High resolution dual detector volume-of-interest cone beam breast CT - Demonstration with a bench top system  

SciTech Connect

Purpose: In this study, we used a small field high resolution detector in conjunction with a full field flat panel detector to implement and investigate the dual detector volume-of-interest (VOI) cone beam breast computed tomography (CBCT) technique on a bench-top system. The potential of using this technique to image small calcifications without increasing the overall dose to the breast was demonstrated. Significant reduction of scatter components in the high resolution projection image data of the VOI was also shown. Methods: With the regular flat panel based CBCT technique, exposures were made at 80 kVp to generate an air kerma of 6 mGys at the isocenter. With the dual detector VOI CBCT technique, a high resolution small field CMOS detector was used to scan a cylindrical VOI (2.5 cm in diameter and height, 4.5 cm off-center) with collimated x-rays at four times of regular exposure level. A flat panel detector was used for full field scan with low x-ray exposures at half of the regular exposure level. The low exposure full field image data were used to fill in the truncated space in the VOI scan data and generate a complete projection image set. The Feldkamp-Davis-Kress (FDK) filtered backprojection algorithm was used to reconstruct high resolution images for the VOI. Two scanning techniques, one breast centered and the other VOI centered, were implemented and investigated. Paraffin cylinders with embedded thin aluminum (Al) wires were imaged and used in conjunction with optically stimulated luminescence (OSL) dose measurements to demonstrate the ability of this technique to image small calcifications without increasing the mean glandular dose (MGD). Results: Using exposures that produce an air kerma of 6 mGys at the isocenter, the regular CBCT technique was able to resolve the cross-sections of Al wires as thin as 254 {mu}m in diameter in the phantom. For the specific VOI studied, by increasing the exposure level by a factor of 4 for the VOI scan and reducing the exposure level by a factor of 2 for the full filed scan, the dual-detector CBCT technique was able to resolve the cross-sections of Al wires as thin as 152 {mu}m in diameter. The CNR evaluated for the entire Al wire cross-section was found to be improved from 5.5 in regular CBCT to 14.4 and 16.8 with the breast centered and VOI centered scanning techniques, respectively. Even inside VOI center, the VOI scan resulted in significant dose saving with the dose reduced by a factor of 1.6 at the VOI center. Dose saving outside the VOI was substantial with the dose reduced by a factor of 7.3 and 7.8 at the breast center for the breast centered and VOI centered scans, respectively, when compared to full field scan at the same exposure level. The differences between the two dual detector techniques in terms of dose saving and scatter reduction were small with VOI scan at 4x exposure level and full field scan at 0.5x exposure level. The MGDs were only 94% of that from the regular CBCT scan. Conclusions: For the specific VOI studied, the dual detector VOI CBCT technique has the potential to provide high quality images inside the VOI with MGD similar to or even lower than that of full field breast CBCT. It was also found that our results were compromised by the use of inadequate detectors for the VOI scan. An appropriately selected detector would better optimize the image quality improvement that can be achieved with the VOI CBCT technique.

Shen Youtao; Yi Ying; Zhong Yuncheng; Lai Chaojen; Liu Xinming; You Zhicheng; Ge Shuaiping; Wang Tianpeng; Shaw, Chris C. [Department of Imaging Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 (United States)



High resolution dual detector volume-of-interest cone beam breast CT--Demonstration with a bench top system  

PubMed Central

Purpose: In this study, we used a small field high resolution detector in conjunction with a full field flat panel detector to implement and investigate the dual detector volume-of-interest (VOI) cone beam breast computed tomography (CBCT) technique on a bench-top system. The potential of using this technique to image small calcifications without increasing the overall dose to the breast was demonstrated. Significant reduction of scatter components in the high resolution projection image data of the VOI was also shown. Methods: With the regular flat panel based CBCT technique, exposures were made at 80 kVp to generate an air kerma of 6 mGys at the isocenter. With the dual detector VOI CBCT technique, a high resolution small field CMOS detector was used to scan a cylindrical VOI (2.5 cm in diameter and height, 4.5 cm off-center) with collimated x-rays at four times of regular exposure level. A flat panel detector was used for full field scan with low x-ray exposures at half of the regular exposure level. The low exposure full field image data were used to fill in the truncated space in the VOI scan data and generate a complete projection image set. The Feldkamp-Davis-Kress (FDK) filtered backprojection algorithm was used to reconstruct high resolution images for the VOI. Two scanning techniques, one breast centered and the other VOI centered, were implemented and investigated. Paraffin cylinders with embedded thin aluminum (Al) wires were imaged and used in conjunction with optically stimulated luminescence (OSL) dose measurements to demonstrate the ability of this technique to image small calcifications without increasing the mean glandular dose (MGD). Results: Using exposures that produce an air kerma of 6 mGys at the isocenter, the regular CBCT technique was able to resolve the cross-sections of Al wires as thin as 254 ?m in diameter in the phantom. For the specific VOI studied, by increasing the exposure level by a factor of 4 for the VOI scan and reducing the exposure level by a factor of 2 for the full filed scan, the dual-detector CBCT technique was able to resolve the cross-sections of Al wires as thin as 152 ?m in diameter. The CNR evaluated for the entire Al wire cross-section was found to be improved from 5.5 in regular CBCT to 14.4 and 16.8 with the breast centered and VOI centered scanning techniques, respectively. Even inside VOI center, the VOI scan resulted in significant dose saving with the dose reduced by a factor of 1.6 at the VOI center. Dose saving outside the VOI was substantial with the dose reduced by a factor of 7.3 and 7.8 at the breast center for the breast centered and VOI centered scans, respectively, when compared to full field scan at the same exposure level. The differences between the two dual detector techniques in terms of dose saving and scatter reduction were small with VOI scan at 4×?exposure level and full field scan at 0.5×?exposure level. The MGDs were only 94% of that from the regular CBCT scan. Conclusions: For the specific VOI studied, the dual detector VOI CBCT technique has the potential to provide high quality images inside the VOI with MGD similar to or even lower than that of full field breast CBCT. It was also found that our results were compromised by the use of inadequate detectors for the VOI scan. An appropriately selected detector would better optimize the image quality improvement that can be achieved with the VOI CBCT technique.

Shen, Youtao; Yi, Ying; Zhong, Yuncheng; Lai, Chao-Jen; Liu, Xinming; You, Zhicheng; Ge, Shuaiping; Wang, Tianpeng; Shaw, Chris C.



A Value of Information approach to data quality objectives for the Hanford high-level waste tanks  

Microsoft Academic Search

This report summarizes a Pacific Northwest Laboratory review of the organic-nitrate reaction safety issue in the Hanford single-shell tanks. This study employed a decision analytic method known as Value of Information (VOI). VOI analysis is a special form of decision analysis that has an information collection alternative as one of the initial decision choices. This type of decision analysis, therefore

T. W. Wood; V. L. Hunter; J. W. Ulvila



Quantification of F-18 FDG PET Images in Temporal Lobe Epilepsy Patients Using Probabilistic Brain Atlas  

Microsoft Academic Search

A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). It is a good frame for calculating volume of interest (VOI) in many fields of brain images. After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices

Keon Wook Kang; Dong Soo Lee; Jae Hun Cho; Jae Sung Lee; Jeong Seok Yeo; Sang Kun Lee; June-Key Chung; Myung Chul Lee



Effects of computing parameters and measurement locations on the estimation of 3D NPS in non-stationary MDCT images.  


The goal of this study was to investigate the impact of computing parameters and the location of volumes of interest (VOI) on the calculation of 3D noise power spectrum (NPS) in order to determine an optimal set of computing parameters and propose a robust method for evaluating the noise properties of imaging systems. Noise stationarity in noise volumes acquired with a water phantom on a 128-MDCT and a 320-MDCT scanner were analyzed in the spatial domain in order to define locally stationary VOIs. The influence of the computing parameters in the 3D NPS measurement: the sampling distances bx,y,z and the VOI lengths Lx,y,z, the number of VOIs NVOI and the structured noise were investigated to minimize measurement errors. The effect of the VOI locations on the NPS was also investigated. Results showed that the noise (standard deviation) varies more in the r-direction (phantom radius) than z-direction plane. A 25 × 25 × 40 mm(3) VOI associated with DFOV = 200 mm (Lx,y,z = 64, bx,y = 0.391 mm with 512 × 512 matrix) and a first-order detrending method to reduce structured noise led to an accurate NPS estimation. NPS estimated from off centered small VOIs had a directional dependency contrary to NPS obtained from large VOIs located in the center of the volume or from small VOIs located on a concentric circle. This showed that the VOI size and location play a major role in the determination of NPS when images are not stationary. This study emphasizes the need for consistent measurement methods to assess and compare image quality in CT. PMID:22858431

Miéville, Frédéric A; Bolard, Gregory; Bulling, Shelley; Gudinchet, François; Bochud, François O; Verdun, François R



Funding Opportunities

Funding Opportunities Funding Related Resources DCP Funding Resources NCI Grant Application and Review Process Lung and Upper Aerodigestive Cancer Research Portfolio Search the NCI-Funded Research Portfolio for projects supported by the Division of


Head and Neck Cancer  


... found: Upper aerodigestive tract. This includes the lips, tongue, mouth, throat, and voice box (larynx). Of all ... inside the mouth or on the lip or tongue. You may have a sore throat that doesn' ...


Flexible fibreoptic rhinolaryngoscopy. Results of 338 consecutive examinations.  


Flexible fibreoptic rhinolaryngoscopy has been shown to be an accurate, reliable, inexpensive and safe method of examining the upper aero-digestive tract (Lancer and Moir, 1985). The results of 338 consecutive examinations are reported. PMID:4020274

Lancer, J M; Jones, A S



The flexible fibreoptic rhinolaryngoscope.  


An accurate, reliable, inexpensive and safe method for the examination of the upper aero-digestive tract is described. Its efficacy is evaluated retrospectively on 250 patients over an 18-month period. PMID:4020273

Lancer, J M; Moir, A A



28 CFR 91.63 - Preparing an Environmental Impact Statement  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Preparing an Environmental Impact Statement 91.63 Section 91.63...CORRECTIONAL FACILITIES Environmental Impact Review Procedures for VOI/TIS Grant...91.63 Preparing an Environmental Impact Statement (a) Initial...



28 CFR 91.57 - Actions that normally require the preparation of an environmental impact statement.  

Code of Federal Regulations, 2013 CFR

...require the preparation of an environmental impact statement. 91.57 Section 91.57...CORRECTIONAL FACILITIES Environmental Impact Review Procedures for VOI/TIS Grant...require the preparation of an environmental impact statement. Significant...



28 CFR 91.68 - Compliance with other Federal environmental statutes, regulations and executive orders.  

Code of Federal Regulations, 2013 CFR

...CORRECTIONAL FACILITIES Environmental Impact Review Procedures for VOI...where applicable, to the environmental impact analysis requirements of...example, one category of environmental impacts that must be addressed...



Effects of rigid and non-rigid image registration on test-retest variability of quantitative [18F]FDG PET/CT studies  

PubMed Central

Background [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) is a valuable tool for monitoring response to therapy in oncology. In longitudinal studies, however, patients are not scanned in exactly the same position. Rigid and non-rigid image registration can be applied in order to reuse baseline volumes of interest (VOI) on consecutive studies of the same patient. The purpose of this study was to investigate the impact of various image registration strategies on standardized uptake value (SUV) and metabolic volume test-retest variability (TRT). Methods Test-retest whole-body [18F]FDG PET/CT scans were collected retrospectively for 11 subjects with advanced gastrointestinal malignancies (colorectal carcinoma). Rigid and non-rigid image registration techniques with various degrees of locality were applied to PET, CT, and non-attenuation corrected PET (NAC) data. VOI were drawn independently on both test and retest scans. VOI drawn on test scans were projected onto retest scans and the overlap between projected VOI and manually drawn retest VOI was quantified using the Dice similarity coefficient (DSC). In addition, absolute (unsigned) differences in TRT of SUVmax, SUVmean, metabolic volume and total lesion glycolysis (TLG) were calculated in on one hand the test VOI and on the other hand the retest VOI and projected VOI. Reference values were obtained by delineating VOIs on both scans separately. Results Non-rigid PET registration showed the best performance (median DSC: 0.82, other methods: 0.71-0.81). Compared with the reference, none of the registration types showed significant absolute differences in TRT of SUVmax, SUVmean and TLG (p > 0.05). Only for absolute TRT of metabolic volume, significant lower values (p < 0.05) were observed for all registration strategies when compared to delineating VOIs separately, except for non-rigid PET registrations (p = 0.1). Non-rigid PET registration provided good volume TRT (7.7%) that was smaller than the reference (16%). Conclusion In particular, non-rigid PET image registration showed good performance similar to delineating VOI on both scans separately, and with smaller TRT in metabolic volume estimates.



From dysphonia to dysphoria: Mokken scaling shows a strong, reliable hierarchy of voice symptoms in the Voice Symptom Scale questionnaire  

Microsoft Academic Search

Symptoms of hoarseness (dysphonia) are common and often associated with psychological distress. The Voice Symptom Scale (VoiSS) is a 30-item self-completed questionnaire concerning voice and throat symptoms. Psychometric and clinical studies on the VoiSS show that it has good reliability and validity, and a clear factorial structure. The present article presents a further advance in voice measurement from the patient's

Ian J. Deary; Janet A. Wilson; Paul N. Carding; Kenneth MacKenzie; Roger Watson



Value of information in virtual patients portraying pharyngitis.  


The American Board of Family Medicine (ABFM) uses virtual patients (VP) in Maintenance of Certification. Theoretically, the ABFM could score users on the value of information (VOI) in their queries. Pharyngitis, a prototypical primary care topic, appears practically intractable to VOI scoring. Problems include conflicting goals of various stakeholders and strong regional and temporal variability in disease characteristics. Nevertheless, the analysis yielded insights that may shift, or validate, the ABFM's selection of scoring criteria. PMID:18998813

Sumner, Walton; Hagen, Michael D



Improved Regional Activity Quantitation in Nuclear Medicine Using a New Approach to Correct for Tissue Partial Volume and Spillover Effects  

Microsoft Academic Search

We have developed a new method of compensating for effects of partial volume and spillover in dual-modality imaging. The approach requires segmentation of just a few tissue types within a small volume-of-interest (VOI) surrounding a lesion; the algorithm estimates simultaneously, from projection data, the activity concentration within each segmented tissue inside the VOI. Measured emission projections were fitted to the

Stephen C. Moore; Sudeepti Southekal; Mi-Ae Park; Sarah J. McQuaid; Marie Foley Kijewski; Stefan P. Muller



Teaching with "Voix et Images de France"  

ERIC Educational Resources Information Center

|A report on the classroom use of Voix et Images de France," the French text prepared by the Centre de Recherche et d'Etude pourla Diffusion du Francais (CREDIF) at the Ecole Normale Superieure de Saint-Cloud in France. (FB)|

Marrow, G. D.



School Safety in France.  

ERIC Educational Resources Information Center

|Describes the "Observatoire national de la securite des etablissements scolaires et d'enseignement superieur," a national agency established by the French government in 1995 to ensure safety in schools and colleges. Its annual reports, drawn up in conjunction with experts, are sent out to government, public authorities, and any stakeholders with…

PEB Exchange, 2003



A Prestigious Image: Advantage or Obstacle in Attracting Candidates to French Elite Higher Education?  

ERIC Educational Resources Information Center

One hundred and twenty students successful at entering four of the most famous French "grandes ecoles" ("Ecole Normale Superieure" Ulm, Polytechnique, HEC, Sciences Po) were questioned about their institution's image. We focus on how the prestige of these institutions in the French society played a role in students' attraction and contributed to…

Draelants, Hugues



The Normative Effects of Higher Education Policy in France  

ERIC Educational Resources Information Center

This student survey was a response to the French youth unrest in 2005 and 2006. It considers the degree to which French higher and secondary education institutions create social cohesion. Focusing on three distinct higher-education institutions: "L'institut d'etudes politiques de Paris" (Sciences Po), "Ecole Normale Superieure," Paris 8, and a…

Langan, Elise



A Prestigious Image: Advantage or Obstacle in Attracting Candidates to French Elite Higher Education?  

ERIC Educational Resources Information Center

|One hundred and twenty students successful at entering four of the most famous French "grandes ecoles" ("Ecole Normale Superieure" Ulm, Polytechnique, HEC, Sciences Po) were questioned about their institution's image. We focus on how the prestige of these institutions in the French society played a role in students' attraction and contributed to…

Draelants, Hugues



The Normative Effects of Higher Education Policy in France  

ERIC Educational Resources Information Center

|This student survey was a response to the French youth unrest in 2005 and 2006. It considers the degree to which French higher and secondary education institutions create social cohesion. Focusing on three distinct higher-education institutions: "L'institut d'etudes politiques de Paris" (Sciences Po), "Ecole Normale Superieure," Paris 8, and a…

Langan, Elise



Melodie: A Code for Risk Assessment of Waste Repositories in Deep Geological Formations.  

National Technical Information Service (NTIS)

In order to perform the safety evaluation of nuclear waste repositories, a global model, called MELODIE, is currently developed at the CEA/IPSN, in collaboration with order CEA teams and non-CEA like ENSMP (Ecole Nationale Superieure des Mines de Paris). ...

J. Lewi M. J. Mejon-Goula A. Cernes P. Goblet



Conceptual Integration of Hybridization by Algerian Students Intending to Teach Physical Sciences  

ERIC Educational Resources Information Center

|This work aims to assess the difficulties encountered by students of the Ecole Normale Superieure of Kouba (Algeria) intending to teach physical science in the integration of the hybridization of atomic orbitals. It is a concept that they should use in describing the formation of molecular orbitals ([sigma] and [pi]) in organic chemistry and gaps…

Salah, Hazzi; Dumon, Alain



The Idea of a Normal University in the 21st Century  

ERIC Educational Resources Information Center

|The establishment of normal colleges and universities is an important component of building a modern country, which possesses different value ethos with the universities. The emergence of the Ecole Normale Superieure in Paris and the local normal schools has set a new model for teacher education around the world and promoted values and knowledge…

Hayhoe, Ruth; Li, Jun



Teaching with "Voix et Images de France"  

ERIC Educational Resources Information Center

A report on the classroom use of Voix et Images de France," the French text prepared by the Centre de Recherche et d'Etude pourla Diffusion du Francais (CREDIF) at the Ecole Normale Superieure de Saint-Cloud in France. (FB)

Marrow, G. D.



Voxel-Based Analysis of 11C-PIB Scans for Diagnosing Alzheimer's Disease  

PubMed Central

The positron emission tomography (PET) radioligand N-methyl-11C-2-(4-methylaminophenyl)-6-hydroxybenzothiazole (also known as 11C-6-OH-BTA-1 or 11C-PIB) binds to amyloid-? (A?), which accumulates pathologically in Alzheimer's disease (AD). Although 11C-PIB accumulation is greater in patients with AD than in healthy controls at a group level, the optimal method for discriminating between these 2 groups has, to our knowledge, not been established. We assessed the use of data-determined standardized voxels of interest (VOIs) to improve the classification capability of 11C-PIB scans on patients with AD. Methods A total of 16 controls and 14 AD age-matched patients were recruited. All subjects underwent a 11C-PIB scan and structural MRI. Binding potential (a measure of amyloid burden) was calculated for each voxel using the Logan graphical method with cerebellar gray matter as the reference region. Voxel maps were then partial-volume corrected and spatially normalized by MRI onto a standardized template. The subjects were divided into 2 cohorts. The first cohort (control, 12; AD, 9) was used for statistical parametric mapping analysis and delineation of data-based VOIs. These VOIs were tested in the second cohort (control, 4; AD, 5) of subjects. Results Statistical parametric mapping analysis revealed significant differences between control and AD groups. The VOI map determined from the first cohort resulted in complete separation between the control and the AD subjects in the second cohort (P < 0.02). Binding potential values based on this VOI were in the same range as other reported individual and mean cortical VOI results. Conclusion A standardized VOI template that is optimized for control or AD group discrimination provides excellent separation of control and AD subjects on the basis of 11C-PIB uptake. This VOI template can serve as a potential replacement for manual VOI delineation and can eventually be fully automated, facilitating potential use in a clinical setting. To facilitate independent analysis and validation with more and a broader variety of subjects, this VOI template and the software for processing will be made available through the Internet.

Mikhno, Arthur; Devanand, Davangere; Pelton, Gregory; Cuasay, Katrina; Gunn, Roger; Upton, Neil; Lai, Robert Y.; Libri, Vincenzo; Mann, J. John; Parsey, Ramin V.



Completeness map evaluation demonstrated with candidate next-generation cardiac CT architectures  

SciTech Connect

Purpose: In this report, the authors introduce the general concept of the completeness map, as a means to evaluate the completeness of data acquired by a given CT system design (architecture and scan mode). They illustrate the utility of completeness map by applying the completeness map concept to a number of candidate CT system designs, as part of a study to advance the state-of-the-art in cardiac CT. Methods: In order to optimally reconstruct a point within a volume of interest (VOI), the Radon transform on all possible planes through that point should be measured. The authors quantified the extent to which this ideal condition is satisfied for the entire image volume. They first determined a Radon completeness number for each point in the VOI, as the percentage of possible planes that is actually measured. A completeness map is then defined as a 3D matrix of the completeness numbers for the entire VOI. The authors proposed algorithms to analyze the projection datasets in Radon space and compute the completeness number for a fixed point and apply these algorithms to various architectures and scan modes that they are evaluating. In this report, the authors consider four selected candidate architectures, operating with different scan modes, for a total of five system design alternatives. Each of these alternatives is evaluated using completeness map. Results: If the detector size and cone angle are large enough to cover the entire cardiac VOI, a single-source circular scan can have {>=}99% completeness over the entire VOI. However, only the central z-slice can be exactly reconstructed, which corresponds to 100% completeness. For a typical single-source architecture, if the detector is limited to an axial dimension of 40 mm, a helical scan needs about five rotations to form an exact reconstruction region covering the cardiac VOI, while a triple-source helical scan only requires two rotations, leading to a 2.5x improvement in temporal resolution. If the source and detector of an inverse-geometry (IGCT) system have the same axial extent, and the spacing of source points in the axial and transaxial directions is sufficiently small, the IGCT can also form an exact reconstruction region for the cardiac VOI. If the VOI can be covered by the x-ray beam in any view, a composite-circling scan can generate an exact reconstruction region covering the VOI. Conclusions: The completeness map evaluation provides useful information for selecting the next-generation cardiac CT system design. The proposed completeness map method provides a practical tool for analyzing complex scanning trajectories, where the theoretical image quality for some complex system designs is impossible to predict, without yet-undeveloped reconstruction algorithms.

Liu Baodong; Bennett, James; Wang Ge; De Man, Bruno; Zeng Kai; Yin Zhye; Fitzgerald, Paul; Yu Hengyong [Department of Radiology, Division of Radiologic Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, 27157 (United States) and Biomedical Imaging Division, VT-WFU School of Biomedical Engineering and Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157 (United States); Biomedical Imaging Division, VT-WFU School of Biomedical Engineering and Sciences, Virginia Tech., Blacksburg, Virginia 24061 (United States); Biomedical Imaging Division, VT-WFU School of Biomedical Engineering and Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157 (United States) and Biomedical Imaging Division, VT-WFU School of Biomedical Engineering and Sciences, Virginia Tech., Blacksburg, Virginia 24061 (United States); CT Systems and Applications Laboratory, GE Global Research, Niskayuna, New York 12309 (United States); Department of Radiology, Division of Radiologic Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157 (United States) and Biomedical Imaging Division, VT-WFU School of Biomedical Engineering and Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157 (United States)



Water Experiments Related To The "Von Karman Sodium" Dynamo Project  

NASA Astrophysics Data System (ADS)

The purpose of the "Von Karman Sodium" (V.K.S.) experiment is to study the "Dynamo Effect," namely the spontaneous generation of magnetic field in a flow of electrically conducting fluid. The device has been built at CEA / Cadarache, in collaboration with CEA / Saclay, Ecole Normale Superieure de Lyon and Ecole Normale Superieure de Paris. It consists of a cylindrical vessel, filled with liquid Sodium, in which two coaxial rotating disks induce a Von-Karman type flow. Several experimental runs have taken place since June 2000. In order to optimize the V.K.S. set-up, a half-scale water prototype has also been built. It has allowed us to measure mean velocity profiles, as well as pressure fluctuations and mechanical power dissipation. We have observed that under certain circumstances the mean component of the turbulent flow can undergo a global bifurcation.

Marie, L.; Bourgoin, M.; Petrelis, F.; Roy, J.; Burguete, J.; Chiffaudel, A.; Daviaud, F.; Fauve, S.; Odier, P.; Pinton, J.-F.



A technique for manual definition of an irregular volume of interest in single photon emission computed tomography  

NASA Astrophysics Data System (ADS)

A technique is described for manually outlining a volume of interest (VOI) in a three-dimensional SPECT dataset. Regions of interest (ROIs) are drawn on three orthogonal maximum intensity projections. Image masks based on these ROIs are backprojected through the image volume and the resultant 3D dataset is segmented to produce the VOI. The technique has been successfully applied in the exclusion of unwanted areas of activity adjacent to the brain when segmenting the organ in SPECT imaging using HMPAO. An example of its use for segmentation in tumour imaging is also presented. The technique is of value for applications involving semi-automatic VOI definition in SPECT.

Fleming, J. S.; Kemp, P. M.; Bolt, L.



Application of value of information of tank waste characterization: A new paradigm for defining tank waste characterization requirements  

SciTech Connect

This report presents the rationale for adopting a recommended characterization strategy that uses a risk-based decision-making framework for managing the Tank Waste Characterization program at Hanford. The risk-management/value-of-information (VOI) strategy that is illustrated explicitly links each information-gathering activity to its cost and provides a mechanism to ensure that characterization funds are spent where they can produce the largest reduction in risk. The approach was developed by tailoring well-known decision analysis techniques to specific tank waste characterization applications. This report illustrates how VOI calculations are performed and demonstrates that the VOI approach can definitely be used for real Tank Waste Remediation System (TWRS) characterization problems.

Fassbender, L.L.; Brewster, M.E.; Brothers, A.J. [and others



Diminution de l'avantage des immigrants en matiere de propriete : analyse de cycle de vie de la baisse de fortunes et de l'evolution de l'accession a la propriete chez les immigrants de Montreal, Toronto et Vancouver, 1981 a 2001  

Microsoft Academic Search

Par le passe, les familles d'immigrants en age de travailler dans les grandes agglomerations urbaines du Canada presentaient des taux de propriete de l'habitation superieurs a ceux de la population de souche. Ces 20 dernieres annees cependant, l'avantage est passe a la population de souche a cause tant d'une baisse des taux d'immigration que d'une hausse des taux de propriete

Michael Haan



Fast shape-directed landmark-based deep gray matter segmentation for quantification of iron deposition  

NASA Astrophysics Data System (ADS)

This paper introduces image processing methods to automatically detect the 3D volume-of-interest (VOI) and 2D region-of-interest (ROI) for deep gray matter organs (thalamus, globus pallidus, putamen, and caudate nucleus) of patients with suspected iron deposition from MR dual echo images. Prior to the VOI and ROI detection, cerebrospinal fluid (CSF) region is segmented by a clustering algorithm. For the segmentation, we automatically determine the cluster centers with the mean shift algorithm that can quickly identify the modes of a distribution. After the identification of the modes, we employ the K-Harmonic means clustering algorithm to segment the volumetric MR data into CSF and non-CSF. Having the CSF mask and observing that the frontal lobe of the lateral ventricle has more consistent shape accross age and pathological abnormalities, we propose a shape-directed landmark detection algorithm to detect the VOI in a speedy manner. The proposed landmark detection algorithm utilizes a novel shape model of the front lobe of the lateral ventricle for the slices where thalamus, globus pallidus, putamen, and caudate nucleus are expected to appear. After this step, for each slice in the VOI, we use horizontal and vertical projections of the CSF map to detect the approximate locations of the relevant organs to define the ROI. We demonstrate the robustness of the proposed VOI and ROI localization algorithms to pathologies, including severe amounts of iron accumulation as well as white matter lesions, and anatomical variations. The proposed algorithms achieved very high detection accuracy, 100% in the VOI detection , over a large set of a challenging MR dataset.

Ekin, Ahmet; Jasinschi, Radu; van der Grond, Jeroen; van Buchem, Mark A.; van Muiswinkel, Arianne



Methodological considerations for analyzing trabecular architecture: an example from the primate hand  

PubMed Central

Micro-computed tomographic analyses of trabecular bone architecture have been used to clarify the link between positional behavior and skeletal anatomy in primates. However, there are methodological decisions associated with quantifying and comparing trabecular anatomy across taxa that vary greatly in body size and morphology that can affect characterizations of trabecular architecture, such as choice of the volume of interest (VOI) size and location. The potential effects of these decisions may be amplified in small, irregular-shaped bones of the hands and feet that have more complex external morphology and more heterogeneous trabecular structure compared to, for example, the spherical epiphysis of the femoral head. In this study we investigate the effects of changes in VOI size and location on standard trabecular parameters in two bones of the hand, the capitate and third metacarpal, in a diverse sample of nonhuman primates that vary greatly in morphology, body mass and positional behavior. Results demonstrate that changes in VOI location and, to a lesser extent, changes in VOI size had a dramatic affect on many trabecular parameters, especially trabecular connectivity and structure (rods vs. plates), degree of anisotropy, and the primary orientation of the trabeculae. Although previous research has shown that some trabecular parameters are susceptible to slight variations in methodology (e.g. VOI location, scan resolution), this study provides a quantification of these effects in hand bones of a diverse sample of primates. An a priori understanding of the inherent biases created by the choice of VOI size and particularly location is critical to robust trabecular analysis and functional interpretation, especially in small bones with complex arthroses.

Kivell, Tracy L; Skinner, Matthew M; Lazenby, Richard; Hublin, Jean-Jacques



Pulmonary airways tree segmentation from CT examinations using adaptive volume of interest  

NASA Astrophysics Data System (ADS)

Airways tree segmentation is an important step in quantitatively assessing the severity of and changes in several lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. It can also be used in guiding bronchoscopy. The purpose of this study is to develop an automated scheme for segmenting the airways tree structure depicted on chest CT examinations. After lung volume segmentation, the scheme defines the first cylinder-like volume of interest (VOI) using a series of images depicting the trachea. The scheme then iteratively defines and adds subsequent VOIs using a region growing algorithm combined with adaptively determined thresholds in order to trace possible sections of airways located inside the combined VOI in question. The airway tree segmentation process is automatically terminated after the scheme assesses all defined VOIs in the iteratively assembled VOI list. In this preliminary study, ten CT examinations with 1.25mm section thickness and two different CT image reconstruction kernels ("bone" and "standard") were selected and used to test the proposed airways tree segmentation scheme. The experiment results showed that (1) adopting this approach affectively prevented the scheme from infiltrating into the parenchyma, (2) the proposed method reasonably accurately segmented the airways trees with lower false positive identification rate as compared with other previously reported schemes that are based on 2-D image segmentation and data analyses, and (3) the proposed adaptive, iterative threshold selection method for the region growing step in each identified VOI enables the scheme to segment the airways trees reliably to the 4th generation in this limited dataset with successful segmentation up to the 5th generation in a fraction of the airways tree branches.

Park, Sang Cheol; Kim, Won Pil; Zheng, Bin; Leader, Joseph K.; Pu, Jiantao; Tan, Jun; Gur, David



Sensitivity to Prior and Reliability Measurements for Value of Geophysical Information  

NASA Astrophysics Data System (ADS)

To ensure the sustainability of groundwater resources, actions that require spatial decisions may need to be taken although much spatial uncertainty about the aquifer flow properties exists. Geophysical data may be critical to reduce this uncertainty but may be too expensive. Therefore, the value of information (VOI) of such data needs to be assessed before proceeding with the actual survey. We present an example where the decision is whether existing contaminant sources must be relocated by identifying critical surface recharge locations. Hence assessing the aquifer vulnerability is critical. From decision analysis theory, VOI equals value with information minus the prior value. Estimating VOI requires several components. The prior geological uncertainty and a measure for information reliability are two components crucial in the VOI metric. The goal of this work is to assess the sensitivity of VOI to these two components. To address the prior geological uncertainty realistically, multiple-point geostatistical algorithms (ie snesim) stochastically model the patterns of the interpreted geological depositional system (represented by the training image). For this example study, geological concepts for glacial buried valleys are used to develop training images of the valleys. Since properties such as valley width, length and direction are not well known, many possible alternative training images can be built. To assess the most important geological components impacting aquifer vulnerability, we apply a novel distance-based clustering technique to rank the various geological factors. Secondly, to compute VOI, a measure of reliability for the proposed geophysical measurement is needed. For this example, three types of datasets collected in Denmark (in a buried valley system) are used: transient electromagnetic (TEM), DC resistivity and driller’s log. Bayesian calibration is performed to obtain likelihood and posterior functions of electrical resistivity and lithology. Monte Carlo simulation then generate many posterior probabilities of sand or clay occurring. To assess the impact of the geophysical data on aquifer vulnerability, one set of models is constrained to the geophysical surveys, another set is not. The real data set demonstrates a decent electrical resistivity contrast between the two lithologies (sand/clay). However, valley locations may not entirely consist of sand. Thus, another set of soft probabilities is generated from alternative electrical resistivity-lithology likelihood. The two calibrations demonstrate the sensitivity of the VOI measurement to different electrical resistivity contrasts. The work here ensures that the VOI is robust by evaluating the prior geological uncertainty modeling and including several reliability measures.

Trainor, W. J.; Caers, J.; Mukerji, T.



Teleconsultation in otolaryngology: Live versus store and forward consultations  

Microsoft Academic Search

Objective: To evaluate the relative strengths and weaknesses of interactive and delayed teleconsultations in otolaryngology. Setting: Ambulatory clinic at an urban tertiary care facility. Subjects: Forty-five adult patients with known or suspected upper aerodigestive tract pathology. Intervention: Patients were interviewed by an otolaryngology chief resident (CR) using a standardized protocol; the results were presented to a board-certified otolaryngologist present locally




Cytology vs molecular analysis for the detection of head and neck squamous cell carcinoma in oesopharyngeal brush samples: a prospective study in 56 patients  

Microsoft Academic Search

Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of 56 patients with a known unique head and neck squamous cell carcinoma (HNSCC) and

S Temam; M Trassard; G Leroux; J Bosq; B Luboinski; G Lenoir; J Bénard; F Janot



Association of aldehyde dehydrogenase 2gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients  

Microsoft Academic Search

BACKGROUNDMultiple occurrences of oesophageal dysplasia are frequently observed in head and neck cancer patients, and closely associated with alcohol consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an important role in the carcinogenesis of the upper aerodigestive tract.AIMTo investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3, alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with

M Muto; Y Hitomi; A Ohtsu; S Ebihara; S Yoshida; H Esumi



Relation between age and head and neck cancer recurrence after surgery: A multivariate analysis  

Microsoft Academic Search

Recent reports have described an increase in squamous cell carcinoma of the upper aerodigestive tract in young adults. As the preponderance of epidemiologic data exists for the population between 50 and 70 years of age, controversy has developed regarding the clinical course of head and neck cancer in youth. Some authors advocate more aggressive management, calling attention to the lack




Dental considerations in management of head and neck cancer  

SciTech Connect

The successful management of patients with squamous cell cancer of the aerodigestive tract requires a multispecialty team. Cooperation among these individuals will ensure that the patient has the best possible chance for a favorable outcome. The role of the dentist as a member of this team is discussed.

Hurst, P.S.



If You Continue To Smoke, We May Have a Problem: Smoking's Effects on Plastic Surgery  

Microsoft Academic Search

smoking causes various aero-digestive neoplasms, some cardiovascular diseases, respiratory pathologies, and cardiovascular disorders. surgeons have observed an association between impaired wound healing and smoking. in plastic surgery, cigarette smoking should be forbidden before and after surgery to prevent poor surgical results. in this retrospective study, we presented four major complications related with continuous smoking immediately after surgery. although we have

Tayfun Aköz; Mithat Akan; Serkan Yildirim



Feeding & Motor Functioning: Start at the Hips to Get to the Lips  

ERIC Educational Resources Information Center

Swallowing is one of the most complex movement patterns that people must use accurately throughout the day and night from the time they are born. These movement patterns are very closely integrated with breathing and movement of food through the aerodigestive tract. Malalignment or dysfunction in any part of these integrated patterns and systems…

Donato, Jessica; Fox, Cathy; Mormon, Johnnie; Mormon, Mike



Genetic Evidence for an Independent Origin of Multiple Preneoplastic and Neoplastic Lung Lesions1  

Microsoft Academic Search

Patients with a primary cancer in the lung or in the upper aerodigestive tract have an increased risk of developing synchronous or metachronous second primary lung tumors. This phenomenon has been related to the chronic exposure of the bronchial tree to carcinogens through a so-called \\

Cabriella Sozzi; Monica Miozzo; Ugo Pastorino; Silvana Pilotti; Rosangela Donghi; Monica Giarola; Laura De Gregorio; Giacomo Manenti; Paolo Radice; Fabiola Minoletti; Giuseppe Della Porta; Marco A. Pierotti


Esophagopharyngeal distribution of refluxed gastric acid in patients with reflux laryngitis  

Microsoft Academic Search

Background & Aims A variety of otolaryngological abnormalities have been attributed to the contact of gastroesophageal refluxate with respective structures of the aerodigestive tract. The aim of this study was to determine and compare the pharyngoesophageal distribution of gastric acid refluxate between patients with proven laryngitis attributed clinically to gastroesophageal reflux and three control groups. Methods An ambulatory 24-hour simultaneous

Reza Shaker; Mary Milbrath; Junlong Ren; Robert Toohill; Walter J. Hogan; Qun Li; Candy L. Hofmann



Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage  

Microsoft Academic Search

Factors that contribute to an increased prevalence of squamous cell carcinoma of the upper aerodigestive tract among young adults in the United States remain unknown. A potential etiologic factor may relate to a genetically controlled sensitivity to environmental carcinogens. This study, therefore, examined 20 young adult patients who had squamous cell carcinoma for mutagen-induced chromosome sensitivity. Lymphocytes from respective patients

S. P. Schantz; T. C. Hsu; N. Ainslie; R. P. Moser



Correlation between Initial and Early Follow-Up CT Perfusion Parameters with Endoscopic Tumor Response in Patients with Advanced Squamous Cell Carcinomas of the Oropharynx Treated with Organ-Preservation Therapy  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Current organ-preservation regimens for upper aerodigestive tract squamous cell carcinoma (SCCA) require endoscopic procedures under general anesthesia to evaluate the tumor response. The purpose of our study was to determine whether CT perfusion (CTP) parameters correlate with response to induction chemotherapy as assessed by endoscopy under general anesthesia. METHODS: Nine patients with advanced (stage 3 or 4)

D. Gandhi; D. B. Chepeha; T. Miller; R. C. Carlos; C. R. Bradford; R. Karamchandani; F. Worden; A. Eisbruch; T. N. Teknos; G. T. Wolf; S. K. Mukherji


Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database.  


Familial aggregation of cervical cancer has been demonstrated previously, however aggregation of other human papillomavirus-associated anogenital, upper aerodigestive tract and skin cancers has not been fully characterized. The Swedish Family-Cancer Database, which contains reliable data on cancer incidence and nuclear family linkages for all residents of Sweden between 1958 and 2004, was used to calculate standardized incidence ratios (SIR) and 95% confidence intervals for offspring site-specific cancer risks according to site-specific cancer in sibling and parental probands. Offspring cancer risk was significantly increased when either a sibling or parent was affected at the same site for penile squamous cell carcinoma (SCC, SIR = 7.54), cervical adenocarcinoma (AC, SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR = 1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and upper aerodigestive tract SCC (SIR = 1.57). Significant aggregation on the order of 2-fold between anogenital cancers at different sites or histologies was also observed. In situ cervical SCC risk in offspring was strongly influenced by siblings affected with oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR = 1.84). Familial skin SCC was largely unassociated with anogenital or upper aerodigestive tract cancer risk in offspring. These data suggest that common host factors exist among individuals affected with anogenital and upper aerodigestive tract cancers. PMID:18074353

Hussain, Shehnaz K; Sundquist, Jan; Hemminki, Kari



Feeding & Motor Functioning: Start at the Hips to Get to the Lips  

ERIC Educational Resources Information Center

|Swallowing is one of the most complex movement patterns that people must use accurately throughout the day and night from the time they are born. These movement patterns are very closely integrated with breathing and movement of food through the aerodigestive tract. Malalignment or dysfunction in any part of these integrated patterns and systems…

Donato, Jessica; Fox, Cathy; Mormon, Johnnie; Mormon, Mike




Technology Transfer Automated Retrieval System (TEKTRAN)

A number of epidemiological studies have indicated that long-term and excessive alcohol consumption is a significant risk factor for upper aerodigestive tract cancers and liver cancer. High alcohol consumption also increases the risk for other types of cancer, such as colorectal, lung and breast. In...



Technology Transfer Automated Retrieval System (TEKTRAN)

Chronic alcohol consumption is a major risk factor for cancer of upper aero-digestive tract (oro-pharynx, hypopharynx, larynx and oesophagus), the liver, the colo-rectum and the breast. Evidence was accumulated that acetaldehyde is predominantly responsible for alcohol-associated carcinogenesis. Ac...


An audit of Bjork flap tracheostomies in head and neck plastic surgery  

Microsoft Academic Search

Patients undergoing head and neck surgery for malignancy especially resection of parts of the upper aerodigestive tracts need a secure airway intra- and postoperatively. A tracheostomy is an effective method of achieving this objective. In our unit the Bjork flap technique' has been the preferred type of tracheostomy. Ninety-five consecutive Bjork flap tracheostomies performed by one surgeon preceding major head

C. M. Malata; I. T. H. Foo; K. H. Simpson; A. G. Batchelor



Dietary Zinc Modulation of COX2 Expression and Lingual and Esophageal Carcinogenesis in Rats  

Microsoft Academic Search

Background: Cancer of the upper aerodigestive tract, includ- ing esophageal and tongue carcinomas, is a major cause of cancer deaths worldwide. Esophageal and tongue cancers have both been associated with dietary zinc deficiency (ZD), and cyclooxygenase (COX-2) is often overexpressed in these cancers. Using rat models, we examined whether zinc regu- lates COX-2 expression in these cancers. Method: Expression of

Louise Y. Y. Fong; Liang Zhang; Yubao Jiang; John L. Farber



Autologous embedded foreign body of mobile tongue  

Microsoft Academic Search

Foreign bodies of upper aerodigestive tract are common otorhinolarygological emergencies. The foreign bodies of mobile tongue\\u000a are however very rare and there are only limited case reports in literature. The case of a young female with an autologous\\u000a foreign body mobile tongue with unusual presentation is presented.

Rohit Verma; Kapil Sikka; A. Thakar



Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double-blind, placebo-controlled pilot study in intensive care unit patients  

Microsoft Academic Search

INTRODUCTION: Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of ventilator-associated pneumonia in intensive care units. However, antibiotic use in selective decontamination protocols is controversial. The purpose of this study was to investigate the effect of oral administration of a probiotic, namely Lactobacillus, on gastric and respiratory tract

Christiane Forestier; Dominique Guelon; Valérie Cluytens; Thierry Gillart; Jacques Sirot; Christophe De Champs



Head and Neck Cancer: Meeting Summary and Research Opportunities  

Microsoft Academic Search

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant neoplasm arising in the mucosa of the upper aerodigestive tract. Nearly two thirds of patients present with advanced (stage III and IV) disease. Fifty percent of HNSCC patients die of their disease, and 5% of HNSCC patients per year will develop additional second primary tumors. Currently used therapeutic

Jennifer R. Grandis; Jennifer A. Pietenpol; Joel S. Greenberger; Richard A. Pelroy; Suresh Mohla



The treatment of advanced sinonasal malignancies with pre-operative intra-arterial cisplatin and concurrent radiation  

Microsoft Academic Search

Introduction: Malignancies of the nasal and paranasal sinuses are uncommon tumors, accounting for only 3% of all aerodigestive tract neoplasms. Despite advances in surgical techniques and continued evolution of adjuvant therapies, the 5-year mortality remains unusually high at greater than 50%. In 1996, we begin utilizing a novel strategy in the treatment of advanced sinonasal carcinomas. This consisted of neoadjuvant

L. Madison Michael II; Jeffrey M. Sorenson; Sandeep Samant; Jon H. Robertson



EDITORIAL Etiology of the Mutational Spectrum of ras Genes in Human Carcinomas  

Microsoft Academic Search

Among the many human behaviors that are associated with increased risk of malignancy, the smoking of tobacco has the most incontrovertible epidemiologic evidence linking it to ma- lignancies of the upper aerodigestive and urinary systems. Sus- tained by nicotine addiction, tobacco smokers inhale a complex mixture of more than 60 known or suspected carcinogens, in- cluding polyaromatic hydrocarbons (PAHs), nitrosamines,

Michael J. Kelley; Susan J. Littman


The value of animal test information in environmental control decisions  

Microsoft Academic Search

Value of information (VOI) analytic techniques are used to evaluate the benefit of performing animal bioassays to provide information about the cancer potency of specific chemical compounds. These tools allow the identification of the conditions in which the cost of reducing uncertainty about potency, by performing a subchronic or chronic bioassay, is justified by the benefit of having improved information

Alison C. Taylor; John S. Evans; Thomas E. McKone



Assessment of systematic errors in the calibration of SPECT systems for I-131 dosimetry estimations in radio-immunotherapy  

Microsoft Academic Search

In radioimmunotherapy, SPECT has a potentially important role in dosimetry estimates for the critical organ systems and target tumor(s). The ability to quantitate activity, within a tomographic plane, has been addressed for low photon energy. However, the practical problems in calibrating SPECT systems for measuring activity in volume sources include the uncertainties associated with: a) selecting volumes of interest (VOI)

L. P. Clarke; C. B. Saw; L. Leong; A. Heal; G. Sfakianakis; F. Ashkar; A. Serafini



Apparatus and method for processing an ultrasound image  

US Patent & Trademark Office Database

The present invention relates to an apparatus for processing an ultrasound image of a target object including a periodically moving object, including: an ROI setting unit for setting regions of interest (ROIs) to each of frames constituting ultrasound volume data acquired from a target object; a VOI setting unit for selecting a predetermined number of first reference frames from the ultrasound volume data and setting a predetermined number of volumes of interest (VOIs) by combining ROIs of the first reference frames with ROIs of frames adjacent to the reference frames; a motion compensating unit for processing the VOIs to compensate a motion of the target object; a correlation coefficient curve calculating unit for calculating a correlation coefficient curve for a predetermined interval at each VOI; a period setting unit for setting a moving period of the moving object based on the correlation coefficient curve in the volume data; and an ultrasound volume data reconstructing unit for reconstructing the ultrasound volume data based on the moving period.

Kim; Nam Chul (Daegu, KR); Kim; Sang Hyun (Busan, KR); Kwak; Jong In (Daegu, KR); Choi; Do Young (Seoul, KR); Kwon; Eui Chul (Seoul, KR)



3D Monte Carlo model of optical transport in laser-irradiated cutaneous vascular malformations  

NASA Astrophysics Data System (ADS)

We have developed a three-dimensional Monte Carlo (MC) model of optical transport in skin and applied it to analysis of port wine stain treatment with sequential laser irradiation and intermittent cryogen spray cooling. Our MC model extends the approaches of the popular multi-layer model by Wang et al.1 to three dimensions, thus allowing treatment of skin inclusions with more complex geometries and arbitrary irradiation patterns. To overcome the obvious drawbacks of either "escape" or "mirror" boundary conditions at the lateral boundaries of the finely discretized volume of interest (VOI), photons exiting the VOI are propagated in laterally infinite tissue layers with appropriate optical properties, until they loose all their energy, escape into the air, or return to the VOI, but the energy deposition outside of the VOI is not computed and recorded. After discussing the selection of tissue parameters, we apply the model to analysis of blood photocoagulation and collateral thermal damage in treatment of port wine stain (PWS) lesions with sequential laser irradiation and intermittent cryogen spray cooling.

Majaron, Boris; Milani?, Matija; Jia, Wangcun; Nelson, J. S.



Emotional Experiences of Youth Sport Parents I: Anger  

Microsoft Academic Search

Although there is general agreement that some sideline behavior at youth sport events is problematic (Goldstein & Iso-Ahola, 2008), the reasons why parent spectators sometimes act inappropriately are not well understood. Given that the most problematic behaviors appear to be motivated by anger (Omli & LaVoi, 2009), the purpose of this study is to identify sources of anger from the

Jens Omli; Nicole M. LaVoi



Parkinson's disease prediction using diffusion-based atlas approach  

Microsoft Academic Search

We study Parkinson's disease (PD) using an automatic specialized diffusion-based atlas. A total of 47 subjects, among who 22 patients diagnosed clinically with PD and 25 control cases, underwent DTI imaging. The EPIs have lower resolution but provide essential anisotropy information for the fiber tracking process. The two volumes of interest (VOI) represented by the Substantia Nigra and the Putamen

Roxana O. Teodorescu; Daniel Racoceanu; Nicolas Smit; Vladimir I. Cretu; Eng K. Tan; Ling L. Chan



A new source of volatile organoiodine compounds in surface seawater  

NASA Astrophysics Data System (ADS)

Volatile organoiodine compounds (VOIs) are the main carrier of iodine from the oceans to the atmosphere. We have identified a novel, sea-surface source of the short-lived VOIs CH2I2, CHClI2 and CHI3 in a series of laboratory experiments. These compounds were formed when seawater, collected during winter in the North Sea, was exposed to ambient levels of ozone. The VOIs are produced from the reaction of marine dissolved organic matter with hypoiodous acid/molecular iodine, which are formed at the sea surface when ozone reacts with dissolved iodide. The same three VOIs were formed when we incubated seawater of different productivity levels with molecular iodine during a cruise in the tropical Atlantic Ocean. We suggest that the presence of dissolved iodide, dissolved organic matter and ozone can lead to the sea-surface production of CH2I2, CHClI2 and CHI3. As such, this process could provide a ubiquitous source of iodine to the marine atmosphere.

Martino, Manuela; Mills, Graham P.; Woeltjen, Janina; Liss, Peter S.



Improving initial polyp candidate extraction for CT colonography  

NASA Astrophysics Data System (ADS)

Reducing the number of false positives (FPs) as much as possible is a challenging task for computer-aided detection (CAD) of colonic polyps. As part of a typical CAD pipeline, an accurate and robust process for segmenting initial polyp candidates (IPCs) will significantly benefit the successive FP reduction procedures, such as feature-based classification of false and true positives (TPs). In this study, we introduce an improved scheme for segmenting IPCs. It consists of two main components. One is geodesic distance-based merging, which merges suspicious patches (SPs) for IPCs. Based on the merged SPs, another component, called convex dilation, grows each SP beyond the inner surface of the colon wall to form a volume of interest (VOI) for that IPC, so that the inner border of the VOI beyond the colon inner surface could be segmented as convex, as expected. The IPC segmentation strategy was evaluated using a database of 50 patient studies, which include 100 scans at supine and prone positions with 84 polyps and masses sized from 6 to 35 mm. The presented IPC segmentation strategy (or VOI extraction method) demonstrated improvements, in terms of having no undesirably merged true polyp and providing more helpful mean and variance of the image intensities rooted from the extracted VOI for classification of the TPs and FPs, over two other VOI extraction methods (i.e. the conventional method of Nappi and Yoshida (2003 Med. Phys. 30 1592-601) and our previous method (Zhu et al 2009 Cancer Manag. Res. 1 1-13). At a by-polyp sensitivity of 0.90, these three methods generated the FP rate (number of FPs per scan) of 4.78 (new method), 6.37 (Nappi) and 7.01 (Zhu) respectively.

Zhu, Hongbin; Fan, Yi; Lu, Hongbing; Liang, Zhengrong



The impact of 3D volume of interest definition on accuracy and precision of activity estimation in quantitative SPECT and planar processing methods  

NASA Astrophysics Data System (ADS)

Accurate and precise estimation of organ activities is essential for treatment planning in targeted radionuclide therapy. We have previously evaluated the impact of processing methodology, statistical noise and variability in activity distribution and anatomy on the accuracy and precision of organ activity estimates obtained with quantitative SPECT (QSPECT) and planar (QPlanar) processing. Another important factor impacting the accuracy and precision of organ activity estimates is accuracy of and variability in the definition of organ regions of interest (ROI) or volumes of interest (VOI). The goal of this work was thus to systematically study the effects of VOI definition on the reliability of activity estimates. To this end, we performed Monte Carlo simulation studies using randomly perturbed and shifted VOIs to assess the impact on organ activity estimates. The 3D NCAT phantom was used with activities that modeled clinically observed 111In ibritumomab tiuxetan distributions. In order to study the errors resulting from misdefinitions due to manual segmentation errors, VOIs of the liver and left kidney were first manually defined. Each control point was then randomly perturbed to one of the nearest or next-nearest voxels in three ways: with no, inward or outward directional bias, resulting in random perturbation, erosion or dilation, respectively, of the VOIs. In order to study the errors resulting from the misregistration of VOIs, as would happen, e.g. in the case where the VOIs were defined using a misregistered anatomical image, the reconstructed SPECT images or projections were shifted by amounts ranging from -1 to 1 voxels in increments of with 0.1 voxels in both the transaxial and axial directions. The activity estimates from the shifted reconstructions or projections were compared to those from the originals, and average errors were computed for the QSPECT and QPlanar methods, respectively. For misregistration, errors in organ activity estimations were linear in the shift for both the QSPECT and QPlanar methods. QPlanar was less sensitive to object definition perturbations than QSPECT, especially for dilation and erosion cases. Up to 1 voxel misregistration or misdefinition resulted in up to 8% error in organ activity estimates, with the largest errors for small or low uptake organs. Both types of VOI definition errors produced larger errors in activity estimates for a small and low uptake organs (i.e. -7.5% to 5.3% for the left kidney) than for a large and high uptake organ (i.e. -2.9% to 2.1% for the liver). We observed that misregistration generally had larger effects than misdefinition, with errors ranging from -7.2% to 8.4%. The different imaging methods evaluated responded differently to the errors from misregistration and misdefinition. We found that QSPECT was more sensitive to misdefinition errors, but less sensitive to misregistration errors, as compared to the QPlanar method. Thus, sensitivity to VOI definition errors should be an important criterion in evaluating quantitative imaging methods.

He, Bin; Frey, Eric C.



The cosmological microwave background radiation, cosmic and superconducting strings  

NASA Astrophysics Data System (ADS)

We study different kinds of anisotropies and distortions in the cosmological background radiation due to cosmic and superconducting strings: (i) temperature angular anisotropy by loop decay into gravitational waves and (ii) spectral distortions due to electromagnetic energy emission. We relate distortions produced by loops indifferent epochs of their evolution. We confront these predictions with observations, in particular with the submillimeter excess recently observed by the Nagoya-Berkeley experiment. This allows us to place constraints both of the string parameter G? and on the parameters governing loop evolution. UA 336 Laboratoire Associé au CNRS, Observatoire de Meudon et Ecole Normale Superieure, 24 reu Lhomond, F-75231 Paris Cedex 05, France.

Sanchez, N.; Signore, M.



Absorption coefficient of luminescent bodies in the emission band  

NASA Astrophysics Data System (ADS)

Einstein's theory associating the coefficients of absorption, induced emission and spontaneous emission cannot be applied to luminescent systems, because the radiative transitions occur with the absorption or emission of phonons. It may be generalised to include luminescent systems by the use of a hollow sphere whose internal walls are covered with a substance irradiated by a Wood lamp, placed at the centre of the sphere. From this we determine the absorption coefficient of the luminescent substance in the emission band. Work performed in part at Groupe de Physique du Solide de l'Ecole Normale Superieure.

Alexic', A.; Nikoli?, K.; Buri?, J.; Magnant, D.; de La Garanderie, H. Payen



Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden  

PubMed Central

Background Smaller hippocampal volumes in major depressive disorder (MDD) have been linked with earlier onset, previous recurrences and treatment refractoriness. The aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden. Methods Glutamate/glutamine (Glx), N-acetylaspartate (NAA) and choline (Cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 T magnetic resonance spectroscopy scanner. Voxels were placed in the head of the right and left hippocampus. We controlled for systematic differences resulting from volume-of-interest (VOI) tissue composition and total hippocampal volume. Results Our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. Patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of Glx and NAA than controls, especially in the right hippocampal region (p ? 0.025). Diminished levels of Glx were correlated with longer illness duration (left VOI r = ?0.34, p = 0.01). By contrast, Cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19% higher; all p ? 0.025) and were consistently related to longer illness duration (right VOI r = 0.30, p = 0.028; left VOI r = 0.38, p = 0.004) and more previous episodes (right VOI r = 0.46, p = 0.001; left VOI r = 0.44, p = 0.001). Limitations The cross-sectional design and the inclusion of treated patients are the main limitations of the study. Conclusion Our results support that metabolite alterations within the hippocampus are more pronounced in patients with a clinical evolution characterized by recurrences and/or chronicity and add further evidence to the potential deleterious effects of stress and depression on this region.

de Diego-Adelino, Javier; Portella, Maria J.; Gomez-Anson, Beatriz; Lopez-Moruelo, Olga; Serra-Blasco, Maria; Vives, Yolanda; Puigdemont, Dolors; Perez-Egea, Rosario; Alvarez, Enric; Perez, Victor



Native cellular fluorescence and its application to cancer prevention.  

PubMed Central

Native cellular fluorescence (NCF) represents the innate capacity of tissues to absorb and emit light of specified wavelengths. Recent advances in optical engineering and computer technology have provided the, opportunity to measure NCF characteristics of various tissues in vivo. This report will briefly review the current status of NCF analysis of various neoplastic tissues. The status of investigations involving the upper aerodigestive tract will be discussed. Though initial results demonstrate that neoplastic tissues can be discriminated from normal mucosa by NCF analysis, the biologic basis of this difference remains uncertain. This report will also emphasize that the ability to screen for cancer in aerodigestive mucosa may be enhanced through the assessment of multiple emission and excitation wavelengths. The true nature of the cellular fluorophores responsible for these mucosal spectral characteristics should be more fully defined in coming years.

Schantz, S P; Savage, H E; Sacks, P; Alfano, R R



CRCHD - CRCHD Research - Principal Investigator: Joseph Califano, M.D.

Dr. Joseph Califano is a Professor in the Department of Otolaryngology-Head and Neck Surgery and Oncology, Johns Hopkins Medical Institutions in Baltimore, Maryland. He is an active head and neck surgeon who treats tumors of the oral cavity, larynx, pharynx, neck, skull base, salivary glands, thyroid cancer, premalignant conditions of the upper aerodigestive tract, unknown primary head and neck squamous cell carcinoma, advance skin cancer, and melanoma.


Long-term Outcomes of Reversal of Laryngotracheal Separation  

Microsoft Academic Search

The aim of this study was to evaluate the long-term outcomes of the reversal of laryngotracheal separation (LTS) in patients\\u000a who underwent extensive resection of tumors located in the upper aerodigestive tract. We performed a retrospective analysis\\u000a of the medical records of eight patients who had LTS reversal. The operation was successful in six patients who were followed\\u000a up for

Orlando B. ZocrattoPaulo; Paulo R. Savassi-Rocha; Rafael M. Paixão



Structural Displacements in Normal Swallowing: A Videofluoroscopic Study  

Microsoft Academic Search

.   Dynamic videofluoroscopic swallow studies were performed on 60 normal adult volunteers to establish normative data for displacement\\u000a of upper aerodigestive tract structures during deglutition. Variables evaluated included hyoid bone displacement, larynx-to-hyoid\\u000a bone approximation, pharyngeal constriction, and the extent of pharyngoesophageal sphincter (PES) opening during liquid swallows\\u000a of 1, 3, and 20 cc. Results showed direct relationships between bolus size

Rebecca J. Leonard; Katherine A. Kendall; Sue McKenzie; Maria Inês Gonçalves; Alice Walker



Intra-arterial chemoradiation for T3-4 oral cavity cancer: Treatment outcomes in comparison to oropharyngeal and hypopharyngeal carcinoma  

Microsoft Academic Search

BACKGROUND: Surgery followed by radiotherapy is the standard of care for resectable locally advanced oral cavity squamous cell carcinoma (SCC). We report the treatment outcomes of patients with T3-T4 SCC of the oral cavity treated with chemoradiation, an alternative approach. PATIENTS AND METHODS: From a series of 240 patients with stage III-IV carcinoma of the upper aerodigestive tract who were

Ilana Doweck; K Thomas Robbins; Sandeep Samant; Francisco Vieira



Iatrogenic Migration of an Impacted Pharyngeal Foreign Body of the Hypopharynx to the Prevertebral Space  

PubMed Central

Impaction of foreign bodies in the upper aerodigestive tract is commonly encountered in ENT practice. The present paper describes an iatrogenic complication with migration of an impacted foreign body (chicken bone) of the hypopharynx into the prevertebral space, after unsuccessful attempt of endoscopic removal. The foreign body was visualized with cervical CT scan lying extraluminally between the major vessels of the neck. An open surgical procedure with neck exploration was necessary for the definite treatment.

Hajiioannou, Jiannis; Kousoulis, Panagiotis; Florou, Vassiliki; Stavrianou, Eleni



Fluorometric analysis for neoplasm diagnostics and localization  

NASA Astrophysics Data System (ADS)

The paper presents methods of laser-induced fluorescence with the use of endo- and exogenous dyes for diagnosis of early tumors of aerodigestive tracts, colons, bladder, GYN, and skin, as well as a review of equipment developed during laboratory examination, construction of diagnostic instruments and clinical use of fluorometric methods with application of various devices, from simple fluorometers to sophisticated endoscopic spectra-analyzers.

Kwasny, Miroslaw; Mierczyk, Zygmunt



Alcohol, Altered Protein Homeostasis, and Cancer  

Microsoft Academic Search

\\u000a Epidemiological studies provide convincing evidence that alcohol consumption is an etiological inducer of human cancers originated\\u000a primarily in the upper aerodigestive tract, liver, colorectum and female breast, while association is suggested for cancers\\u000a of the lung and pancreas. The underlying mechanism of alcohol induced tumorigenesis is incompletely understood, but plausible\\u000a hypotheses suggest mechanisms that are intimately intertwined with alcohol metabolism

András Orosz


Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants  

Microsoft Academic Search

The complexity of carcinogenesis in squamous cell cancer (SCC) of the upper aerodigestive tract requires examining environmental\\u000a risk factors, including mutagen sensitivities to xenobiotics. Three environmental, occupational, and habitual pollutants –\\u000a dibutylphthalate (DBP), diisobutylphthalate (DiBP), and N?nitrosodiethylamine (NDELA) – were submitted to genotoxicity testing on mucosal biopsy specimens of tumor and nontumor patients\\u000a in vitro. The single-cell microgel electrophoresis (Comet)

Norbert H. Kleinsasser; Herbert Weissacher; Ernst R. Kastenbauer; Peter Dirschedl; Barbara C. Wallner; Ulrich A. Harréus



Expectoration of a bullet after gunshot wound to the chest  

PubMed Central

Over the last century, only four cases have been published of patients sustaining gunshot wounds to the chest, managed nonoperatively, who eventually expectorated the bullet. We report the case of a hemodynamically stable 24-year-old male whose bullet was found in the left pulmonary hilum on admission computed tomography (CT) scan. Further workup revealed no obvious aerodigestive injury. Shortly after extubation, he expectorated the bullet onto the floor. Little is known about how to manage these stable, yet challenging patients.

Rhodes, Stancie C.; Gupta, Surupa S.



Impression technique for nonosseous free-tissue transfer reconstruction after cranioorbitomaxillary resection: A clinical report  

Microsoft Academic Search

The use of vascularized free-tissue transfers has given the head and neck surgeon the ability to offer enhanced oncologic therapy with less risk of exposing vital structures to the aerodigestive tract. Resulting free-flap tissue consistencies and contours inhibit the successful use of routine impression techniques.The technique described in this clinical report uses a previously reported procedure to obtain an accurate

Herman B Dumbridgue; Michael R Arcuri; Gerry F Funk; William E LaVelle



January 29-31, 2003: 7th EDRN Steering Committee Meeting

The Early Detection Research Network Steering Committee meeting is devoted to discuss and conduct reviews of the network's research, collaborations, data sharing and dissemination, the network infrastructure, management, enrolment of associate members. Specific discussions will be conducted by the network collaborative group meetings (Breast and Gynecologic Cancers; G.I. and Other Associated Cancers; Lung and Upper Aerodigestive Cancers; Prostate and Urologic Cancers) and the data management and coordination center. This meeting has a special emphasis on validation and discovery studies.


Stomal seeding of head and neck cancer by percutaneous endoscopic gastrostomy tube placement  

Microsoft Academic Search

Background: Percutaneous endoscopic gastrostomy (PEG) tubes have replaced nasogastric tubes and Stamm gastrostomy tubes as a preferred\\u000a means of feeding for patients with head and neck cancers, as recommended by the results of large series. A patient with stomal\\u000a seeding of squamous cell carcinoma of the upper aerodigestive tract by PEG placement was reported. A review of literature\\u000a was performed.

Derek S. Lee; Mirseyed A. Mohit-Tabatabai; Benjamin F. Rush; Charles Levine



HPV Status and second primary tumours in Oropharyngeal Squamous Cell Carcinoma  

PubMed Central

Introductions The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCCs) is rising in developed nations. Studies have shown that these virally mediated tumours are epidemiologically, clinically, and biologically different than other head and neck squamous cell carcinomas and traditional concepts of field cancerization may not apply to HPV-related oropharyngeal cancer. Objective The purpose of this study was to evaluate the rate of second primary tumors and the diagnostic yield of field cancerization work up in the upper aerodigestive tract in patients with HPV-related and HPV-unrelated oropharyngeal squamous cell carcinoma. Design Retrospective review. Setting Tertiary cancer care centers in Alberta. Methods Retrospective review of 406 patients diagnosed with OPSCC in Alberta between 2005 and 2009. HPV-status of tumours was determined by tissue microarray using immunohistochemistry staining for p16. Main outcome measures Primary outcome: incidence of upper aerodigestive tract second primary tumours in p16-positive versus p16-negative OPSCC. Secondary outcomes: diagnostic yield of traditional field cancerization work-up in p16-positive versus negative patients. Results The overall rate of SPTs was 7.4% (30/406). The incidence rate of SPTs was significantly lower in p16-positive patients (0.7 per 100 patient-yrs vs. 8.5 in p16-negative, p < 0.0001). Field cancerization work-up for synchronous lesions in the upper aerodigestive tract, including panendoscopy and whole-body PET-CT, had decreased diagnostic yield in p16-positive patients (2.8% vs. 10.2% in HPV-negative patients, p=0.02). Conclusions Patients with HPV-related OPSCC, who are non-smokers have decreased risk of developing second primary tumours in the upper aerodigestive tract and have low yield on field cancerization work-up. This study provides further evidence that virally mediated OPSCC are distinct and may benefit from alternate diagnostic pathways.



Pediatric laryngeal cancer with 5-year follow up: case report.  


Larynx cancer is the commonest malignancy of upper aerodigestive tract. However, laryngeal cancer is extremely rare in childhood since these tumors are generally not suspected in the differential diagnosis of hoarseness, dysphagia and/or progressive airway obstruction in children; diagnosis can be made relatively late. In this report we would like to present a case of advanced stage pediatric laryngeal carcinoma who was treated with chemoradiotherapy and remained well on her 5-year follow-up. PMID:23673162

Olgun, Yuksel; Erdag, Taner Kemal; Aydin, Barbaros; Mutafoglu, Kamer; Ozer, Erdener; Ikiz, Ahmet Omer; Akman, Fadime



Chemoprevention of head and neck cancer  

Microsoft Academic Search

Squamous cell carcinoma of the head and neck is the most common epithelial neoplasm of the upper aerodigestive tract and represents\\u000a a major health concern in the United States and worldwide. Invasive squamous cell carcinoma is the end result of a multiyear,\\u000a multistep process of accumulation of genetic and phenotypic damage. Chemoprevention is defined as the use of pharmacologic\\u000a or

Katrina Y. Glover; Vali A. Papadimitrakopoulou



Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study  

Microsoft Academic Search

CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage. We report a large case-control study of a non-functional variant that had previously been expected to increase cancer rates. Four thousand and fifteen cancer patients (2250 lung, 811 squamous upper aero-digestive and 954 kidney) and 3052

Paul Brennan; James McKay; Lee Moore; David Zaridze; Anush Mukeria; Neonilia Szeszenia-Dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Wong-Ho Chow; Nathanial Rothman; Amelie Chabrier; Valerie Gaborieau; Fabrice Odefrey; Melissa Southey; Mia Hashibe; Janet Hall; Paolo Boffetta; Julian Peto; Richard Peto; R. J. Hung



Laser Resistance of Endotracheal Tubes I: Experimental Results of a Compound Tube in Comparison to a Metallic Tube  

Microsoft Academic Search

.  Laser-induced ignition of endotracheal tubes is a serious problem in CO2 laser surgery of the upper aerodigestive tract. A new tube built of composite materials with a foam at its surface is protected\\u000a by vaporisation of water from the wet foam. This tube and a flexible metallic tube of stainless steel were tested experimentally\\u000a against the radiation of various lasers

H.-J. Foth



Risk factors and genetic susceptibility  

Microsoft Academic Search

\\u000a Upper aerodigestive tract (oral cavity, pharyngeal, and laryngeal) cancers are sentinel diseases of exposure to tobacco and\\u000a alcohol, and thus can be considered the paradigm of environmentally induced disease. The fact that only a fraction of exposed\\u000a individuals develop these cancers suggests interindividual differences in susceptibility to these environmental insults. In\\u000a fact, heritable differences in susceptibility may be identified at

Margaret R. Spitz


Unsupervised tumour segmentation in PET using local and global intensity-fitting active surface and alpha matting.  


This paper proposes an unsupervised tumour segmentation approach for PET data. The method computes the volumes of interest (VOIs) with sub-voxel precision by considering the limited image resolution and partial volume effects. First, an improved anisotropic diffusion filter is used to remove image noise. A hierarchical local and global intensity active surface modelling scheme is then applied to segment VOIs, followed by an alpha matting step to further refine the segmentation boundary. The proposed method is validated on real PET images of head-and-neck cancer patients with ground truth provided by human experts, as well as custom-designed phantom PET images with objective ground truth. Experimental results show that our method outperforms previous automatic approaches in terms of segmentation accuracy. PMID:24034745

Zeng, Ziming; Wang, Jue; Tiddeman, Bernie; Zwiggelaar, Reyer



Optical biopsy fiber-based fluorescence spectroscopy instrumentation  

NASA Astrophysics Data System (ADS)

Native fluorescence spectroscopy of biomolecules has emerged as a new modality to the medical community in characterizing the various physiological conditions of tissues. In the past several years, many groups have been working to introduce the spectroscopic methods to diagnose cancer. Researchers have successfully used native fluorescence to distinguish cancerous from normal tissue samples in rat and human tissue. We have developed three generations of instruments, called the CD-scan, CD-ratiometer and CD-map, to allow the medical community to use optics for diagnosing tissue. Using ultraviolet excitation and emission spectral measurements on both normal and cancerous tissue of the breast, gynecology, colon, and aerodigestive tract can be separated. For example, from emission intensities at 340 nm to 440 nm (300 nm excitation), a statistically consistent difference between malignant tissue and normal or benign tissue is observed. In order to utilize optical biopsy techniques in a clinical setting, the CD-scan instrument was developed, which allows for rapid and reliable in-vitro and in-vivo florescence measurements of the aerodigestive tract with high accuracy. The instrumentation employs high sensitivity detection techniques which allows for lamp excitation, small diameter optical fiber probes; the higher spatial resolution afforded by the small diameter probes can increase the ability to detect smaller tumors. The fiber optic probes allow for usage in the aerodigestive tract, cervix and colon. Needle based fiber probes have been developed for in-vivo detection of breast cancer.

Katz, Al; Ganesan, S.; Yang, Yuan-Long; Tang, Gui C.; Budansky, Y.; Celmer, Edward J.; Savage, Howard E.; Schantz, Stimson P.; Alfano, Robert R.



Plexus splanchniques: Conceptions actuelles sur les activités ganglionnaires et médullo-surrénales  

Microsoft Academic Search

Résumé 1.Cet exposé est surtout basé sur des recherches personnelles réalisées à l'aide de technique de «plexus solaire» et de «surrénale» vogués in situ.2.Les expériences rapportées poursuivies sous une forme analytique dans des conditions pourtant aussi physiologiques que possible, permettent de préciser diverses données sur la transmission synaptique ganglionnaire sur les relais disposés sur les voies vasomotrices splanchniques, sur l'action

J. Malméjac



A Monte Carlo investigation of dual-energy-window scatter correction for volume-of-interest quantification in 99Tcm SPECT  

Microsoft Academic Search

Using Monte Carlo simulation of 99Tcm single-photon-emission computed tomography (SPECT), the authors investigate the effects of tissue-background activity, tumour location, patient size, uncertainty of energy windows, and definition of tumour region on the accuracy of quantification. The dual-energy-window method of correction for Compton scattering is employed and the multiplier which yields correct activity for the volume-of-interest (VOI) as a whole

Jian-Qiao Luo; K. F. Koral; M. Ljungberg; C. E. Floyd Jr.; R. J. Jaszczak



Les multiples emplois ?imatinib dans les tumeurs solides  

Microsoft Academic Search

?imatinib mésylate (STI-571) est un inhibiteur sélectif des tyrosines kinases KIT, Platelet-Derived Growth Factor Receptors (PDGFRs), BCR-ABL, ABL, c-FMS et ARG (1). ?imatinib est une petite molécule orale qui agit par inhibition compétitive avec le site de fixation de ?ATP dans la kinase,\\u000a inhibant de ce fait ?activité de la kinase et bloquant ?activation des voies de la transduction du

F. Duffaud; A. Le Cesne


Anatomophysiologie des algies pudendales  

Microsoft Academic Search

Résumé  Les algies pudendales sont périnéales de type tronculaire et somatique. Elles siègent dans le territoire du nerf atteint et\\u000a sont positionnelles, ce qui évoque un phénomène de compression lors de la position assise. L’anatomophysiologie de ces douleurs\\u000a met l’accent sur plusieurs items: a) définition et innervation du périnée; b) étude du parcours des voies de la douleur; étude\\u000a des structures

R. Robert; Y. Beaudic; O. Hamel; M. Khalfallah; J.-J. Labat; T. Riant



Partial volume effect estimation and correction in the aortic vascular wall in PET imaging.  


We evaluated the impact of partial volume effect (PVE) in the assessment of arterial diseases with (18)FDG PET. An anthropomorphic digital phantom enabling the modeling of aorta related diseases like atherosclerosis and arteritis was used. Based on this phantom, we performed GATE Monte Carlo simulations to produce realistic PET images with a known organ segmentation and ground truth activity values. Images corresponding to 15 different activity-concentration ratios between the aortic wall and the blood and to 7 different wall thicknesses were generated. Using the PET images, we compared the theoretical wall-to-blood activity-concentration ratios (WBRs) with the measured WBRs obtained with five measurement methods: (1) measurement made by a physician (Expert), (2) automated measurement supposed to mimic the physician measurements (Max), (3) simple correction based on a recovery coefficient (Max-RC), (4) measurement based on an ideal VOI segmentation (Mean-VOI) and (5) measurement corrected for PVE using an ideal geometric transfer matrix (GTM) method. We found that Mean-VOI WBRs values were strongly affected by PVE. WBRs obtained by the physician measurement, by the Max method and by the Max-RC method were more accurate than WBRs obtained with the Mean-VOI approach. However Expert, Max and Max-RC WBRs strongly depended on the wall thickness. Only the GTM corrected WBRs did not depend on the wall thickness. Using the GTM method, we obtained more reproducible ratio values that could be compared across wall thickness. Yet, the feasibility of the implementation of a GTM-like method on real data remains to be studied. PMID:24099932

Burg, S; Dupas, A; Stute, S; Dieudonné, A; Huet, P; Le Guludec, D; Buvat, I




Microsoft Academic Search

SUMMARY The energetic cost of generating muscular force was studied by measuring the energetic cost of carrying loads in rats, dogs, humans, and horses for loads ranging between 7 and 27% of body mass. Oxygen consumption increased in direct proportion to mass supported by the muscles, i.e. %jJ?°i= I-OI±S.D. ± 0-017, mL\\/m where VOi< L is the oxygen consumption of



Obstruction of the lumen of new endotracheal tubes  

Microsoft Academic Search

\\u000a RéSUMé  Les photos ci-contre montrent un tube endotrachéal à ballonet, un tube neuf No. 10 oral. Ce tube a été placé dans la trachée\\u000a d’un homme complètement paralysé et Ton a constaté une obstruction presque complète des voies respiratoires. Nous avons examiné\\u000a un autre tube et avons trouvé dans sa lumière le même matériel caoutchouté. Ce matériel nous a paru être

F. A. Walton



Homicide and Medical Science: Is There a Relationship? 1  

Microsoft Academic Search

Les taux de criminaliteviolente demeurent eleves aux Etats-Unis comme au Canada. Or, certains chercheurs ont posel'hypothese qu'il existerait un ecart entre l'evolution du taux de voies de fait graves (ainsi que de crimes violents en general) et du taux d'homicides, evolution qui s'expliquerait par la baisse des taux de mortaliteala suite d'un traumatisme. Par ailleurs, l'approche axee sur l'analyse de

Martin A. Andresen



Partial volume effect estimation and correction in the aortic vascular wall in PET imaging  

NASA Astrophysics Data System (ADS)

We evaluated the impact of partial volume effect (PVE) in the assessment of arterial diseases with 18FDG PET. An anthropomorphic digital phantom enabling the modeling of aorta related diseases like atherosclerosis and arteritis was used. Based on this phantom, we performed GATE Monte Carlo simulations to produce realistic PET images with a known organ segmentation and ground truth activity values. Images corresponding to 15 different activity-concentration ratios between the aortic wall and the blood and to 7 different wall thicknesses were generated. Using the PET images, we compared the theoretical wall-to-blood activity-concentration ratios (WBRs) with the measured WBRs obtained with five measurement methods: (1) measurement made by a physician (Expert), (2) automated measurement supposed to mimic the physician measurements (Max), (3) simple correction based on a recovery coefficient (Max-RC), (4) measurement based on an ideal VOI segmentation (Mean-VOI) and (5) measurement corrected for PVE using an ideal geometric transfer matrix (GTM) method. We found that Mean-VOI WBRs values were strongly affected by PVE. WBRs obtained by the physician measurement, by the Max method and by the Max-RC method were more accurate than WBRs obtained with the Mean-VOI approach. However Expert, Max and Max-RC WBRs strongly depended on the wall thickness. Only the GTM corrected WBRs did not depend on the wall thickness. Using the GTM method, we obtained more reproducible ratio values that could be compared across wall thickness. Yet, the feasibility of the implementation of a GTM-like method on real data remains to be studied.

Burg, S.; Dupas, A.; Stute, S.; Dieudonné, A.; Huet, P.; Le Guludec, D.; Buvat, I.



Self-preservation as a foundation of rational behavior under risk  

Microsoft Academic Search

This paper derives an expected utility theorem from the principle of self-preservation thus providing a new interpretation of the notion of rationality underlying the voi~ Neumann- Morgenstern theory. Self-preservation is defined as the maximiTation of the probability of survival in a finite horizon model where in each period the decision maker must choose a risky prospect from a feasible set

Edi Karni; David Schmeidler



Simulation modeling to derive the value-of-information for risky animal disease-import decisions  

Microsoft Academic Search

Simulation modeling can be used in aiding decision-makers in deciding when to invest in additional research and when the risky animal disease-import decision should go forward. Simulation modeling to evaluate value-of-information (VOI) techniques provides a robust, objective and transparent framework for assisting decision-makers in making risky animal and animal product decisions.In this analysis, the hypothetical risk from poultry disease in

W. Terry Disney; Mark A. Peters



Regional age-related effects in the monkey brain measured with 1H magnetic resonance spectroscopy  

PubMed Central

The rhesus monkey is a useful model for examining age-related effects on the brain, because of the extensive neuroanatomical homology between the monkey and the human brain, the tight control for neurological diseases as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses. Here, proton magnetic resonance spectroscopy (1H-MRS) was used together with high resolution anatomical MRI images to carefully assess regional concentrations of brain metabolites in a group of 20 rhesus monkeys. In an anterior volume of interest (VOI) that covered frontal and prefrontal areas, significant positive correlations of myo-inositol and of total creatine concentrations with age were detected, whereas N-acetyl aspartate (NAA) and choline compounds (Cho) were not significantly correlated with age. In an occipito-parietal VOI, all metabolites showed no statistically significant age-dependent trend. Strong correlations were found between NAA concentration and gray matter fraction in the VOIs as well as between choline compounds and white matter fraction.

Ronen, Itamar; Fan, Xiaoying; Schettler, Steve; Jain, Sahil; Murray, Donna; Kim, Dae-Shik; Killiany, Ronald; Rosene, Douglas



Dietary Flavonoid Intake and Smoking-Related Cancer Risk: A Meta-Analysis  

PubMed Central

Purpose To systematically investigate the effects of dietary flavonoids and flavonoid subclasses on the risk of smoking-related cancer in observational studies. Methods Summary estimates and corresponding standard errors were calculated using the multivariate-adjusted odds ratio (OR) or relative risk (RR) and 95% CI of selected studies and weighted by the inverse variance. Results A total of 35 studies, including 19 case-controls (9,525 cases and 15,835 controls) and 15 cohort studies (988,082 subjects and 8,161 cases), were retrieved for the meta-analysis. Total dietary flavonoids and most of the flavonoid subclasses were inversely associated with smoking-related cancer risk (OR: 0.82, 95% CI: 0.72-0.93). In subgroup analyses by cancer site, significant associations were observed in aerodigestive tract and lung cancers. Total dietary flavonoid intake was significantly associated with aerodigestive tract cancer risk (OR: 0.67, 95% CI: 0.54-0.83) marginally associated with lung cancer risk (OR: 0.84, 95% CI: 0.71-1.00). Subgroup analyses by smoking status showed significantly different results. The intake of total flavonoids, flavonols, flavones, and flavanones, as well as the flavonols quercetin and kaempferol was significantly associated with decreased risk of smoking-related cancer in smokers, whereas no association was observed in non-smokers, except for flavanones. In meta-analysis for the effect of subclasses of dietary flavonoids by cancer type, aerodigestive tract cancer was inversely associated with most flavonoid subclasses. Conclusion The protective effects of flavonoids on smoking-related cancer risk varied across studies, but the overall results indicated that intake of dietary flavonoids, especially flavonols, was inversely associated with smoking-related cancer risk. The protective effects of flavonoids on smoking-related cancer risk were more prominent in smokers.

Woo, Hae Dong; Kim, Jeongseon



SubMIR - a submillimeter and IR observations database  

NASA Astrophysics Data System (ADS)

We have built the first submillimeter and IR observations database of the Laboratoire de Radioastronomie-Ecole Normale Superieure de Paris-LERMA (Observatoire de Paris) which contains already more than 1000 submm/mm spectra and several IR maps of nearby galaxies (D<10Mpc) from Bayet et al. 2004, 2005a, 2005b, 2006; Gerin & Phillips 1998, 2000. It has been developed to gather, classify and make available all the submm, mm, IR observations collected these last years and obtained not only for the nearby galaxies but also for more distant objects. SubMIR interacts and completes the already existing databases such as NED, ADS, SIMBAD, etc... Presently, the test periods are almost finished and we hope to open SubMIR very soon to the large astrophysical community. In this poster, we present the way the database works.

Bayet, E.; Rabasse, J. F.; Gerin, M.



Journees 2010: New challenges for reference systems and numerical standards in astronomy  

NASA Astrophysics Data System (ADS)

The Journees 2010 "Systemes de reference spatio-temporels", with the sub-title "New challenges for reference systems and numerical standards in astronomy", were organized from 20 to 22 September 2010 at Paris Observatory and Ecole Normale Superieure in Paris, France. The scientific programme was focused on the issues related to the recent developments and new challenges in astronomical space and time reference systems and their relativistic aspects, astrometric catalogs, Earth orientation, astronomical constants and numerical standards, planetary ephemerides and modern astrometry. There have been presentations and discussions related to the IAU Division 1 commissions and IAU Working Group "Numerical Standards for Fundamental astronomy" (NSFA); there has been a special session for presenting the latest developments in the solar system ephemerides and comparing details in those ephemerides.

Capitaine, Nicole



Rhinolith in the fossa of Rosenmuller--a hidden stone.  


This is a case report of an 80-year-old woman who presented to the ENT services with multiple non-specific upper aerodigestive tract symptoms. Despite extensive investigation and treatment, her symptoms remained unalleviated with significant impact on the psychological morbidity. During a routine flexible nasoendoscopy for worsening globus pharnygis, a mass was noted in the right Rosenmüller's fossa, where the Eustachian tube leaves the lateral wall of the nasopharynx. A CT scan showed this to be a 10 mm calcified entity within the right Eustachian tube. It was subsequently removed under local anaesthesia providing much relief to the patient. Histology showed this mass to be a rhinolith. PMID:22715230

Shilston, J; Foo, S H; Oko, M



Rhinolith in the fossa of Rosenm?ller - a hidden stone  

PubMed Central

This is a case report of an 80-year-old woman who presented to the ENT services with multiple non-specific upper aerodigestive tract symptoms. Despite extensive investigation and treatment, her symptoms remained unalleviated with significant impact on the psychological morbidity. During a routine flexible nasoendoscopy for worsening globus pharnygis, a mass was noted in the right Rosenmüller's fossa, where the Eustachian tube leaves the lateral wall of the nasopharynx. A CT scan showed this to be a 10 mm calcified entity within the right Eustachian tube. It was subsequently removed under local anaesthesia providing much relief to the patient. Histology showed this mass to be a rhinolith.

Shilston, J; Foo, S H; Oko, M



An unusual nasopharyngeal foreign body with unusual presentation as nasal regurgitation and change in voice.  


Upper aerodigestive tract may harbour foreign bodies such as sponges, grains, toy parts, stones, paper, insects, cotton, etc. These objects may go undetected for days or even weeks. A metallic foreign body after being inhaled and ultimately being lodged in the nasopharynx is a rare entity. We report a case of an unusual nasopharyngeal foreign body (metallic bolt) presenting with symptoms of nasal regurgitation and change in voice in a 2-year boy. The foreign body was diagnosed by X-ray skull lateral view including nasopharynx and was removed under general anaesthesia. PMID:23884977

Kumar, Sunil; Singh, Devendra Bahadur; Singh, Abhishek Bahadur



Pseudovascular adenoid squamous cell carcinoma of oral cavity: A mimicker of angiosarcoma  

PubMed Central

Pseudovascular adenoid squamous cell carcinoma (PASCC) is an uncommon histological variant of squamous cell carcinoma that can mimic vascular neoplasms, particularly angiosarcoma, in its morphologic characteristics. PASCC has been reported in the head and neck, as well as in the other organs such as the breast, lungs, urinary bladder, vulva, and uterine cervix. Only two cases of PASCC arising from the upper aerodigestive tract have been reported so far. We report a case of PASCC of oral cavity in a 40-year-old man, which mimicked an angiosarcoma initially. Immunohistochemical analysis led to a conclusive diagnosis of PASCC.

Vidyavathi, K; Prasad, CSBR; Kumar, Harendra ML; Deo, RP



Diagnosis of pancreatic plasmacytoma by endoscopic ultrasound-fine needle aspiration.  


Plasmacytoma presents more frequently in middle age men with aerodigestive tract involvement, especially in the head and the neck. Gastrointestinal tract involvement is uncommon, but the organ most commonly involved is the stomach. We report the first case in the literature in which final diagnosis was made by fine- needle aspiration biopsy guided by endoscopic ultrasound with adequate sample for pathologic analysis. The treatment of this entity is systemic chemotherapy but its effectiveness is limited. Plasmacytoma should be taken into account in differential diagnosis of pancreatic masses. PMID:20959192

Artifon, E L A; Okawa, L; Baba, E R; Moura, E G H; Sakai, P; Savides, T J



Fuzzy hidden Markov chains segmentation for volume determination and quantitation in PET  

PubMed Central

Accurate volume of interest (VOI) estimation in PET is crucial in different oncology applications such as response to therapy evaluation and radiotherapy treatment planning. The objective of our study was to evaluate the performance of the proposed algorithm for automatic lesion volume delineation; namely the Fuzzy Hidden Markov Chains (FHMC), with that of current state of the art in clinical practice threshold based techniques. As the classical Hidden Markov Chain (HMC) algorithm, FHMC takes into account noise, voxel’s intensity and spatial correlation, in order to classify a voxel as background or functional VOI. However the novelty of the fuzzy model consists of the inclusion of an estimation of imprecision, which should subsequently lead to a better modelling of the “fuzzy” nature of the object on interest boundaries in emission tomography data. The performance of the algorithms has been assessed on both simulated and acquired datasets of the IEC phantom, covering a large range of spherical lesion sizes (from 10 to 37mm), contrast ratios (4:1 and 8:1) and image noise levels. Both lesion activity recovery and VOI determination tasks were assessed in reconstructed images using two different voxel sizes (8mm3 and 64mm3). In order to account for both the functional volume location and its size, the concept of % classification errors was introduced in the evaluation of volume segmentation using the simulated datasets. Results reveal that FHMC performs substantially better than the threshold based methodology for functional volume determination or activity concentration recovery considering a contrast ratio of 4:1 and lesion sizes of <28mm. Furthermore differences between classification and volume estimation errors evaluated were smaller for the segmented volumes provided by the FHMC algorithm. Finally, the performance of the automatic algorithms was less susceptible to image noise levels in comparison to the threshold based techniques. The analysis of both simulated and acquired datasets led to similar results and conclusions as far as the performance of segmentation algorithms under evaluation is concerned.

Hatt, Mathieu; Lamare, Frederic; Boussion, Nicolas; Roux, Christian; Turzo, Alexandre; Cheze-Lerest, Catherine; Jarritt, Peter; Carson, Kathryn; Salzenstein, Fabien; Collet, Christophe; Visvikis, Dimitris



Three-dimensional image registration of MR proximal femur images for the analysis of trabecular bone parameters  

NASA Astrophysics Data System (ADS)

This study investigated the feasibility of automatic image registration of MR high-spatial resolution proximal femur trabecular bone images as well as the effects of gray-level interpolation and volume of interest (VOI) misalignment on MR-derived trabecular bone structure parameters. For six subjects, a baseline scan and a follow-up scan of the proximal femur were acquired on the same day. An automatic image registration technique, based on mutual information, utilized a baseline and a follow-up scan to compute transform parameters that aligned the two images. These parameters were subsequently used to transform the follow-up image with three different gray-level interpolators. Nearest neighbor interpolation and b-spline approximation did not significantly alter bone parameters, while linear interpolation significantly modified bone parameters (p<0.01). Improvement in image alignment due to the automatic registration was determined by visually inspecting difference images and 3D renderings. This work demonstrates the first application of automatic registration, without prior segmentation, of high-spatial resolution trabecular bone MR images of the proximal femur. Additionally, effects due to imprecise analysis volume alignment are investigated. Inherent heterogeneity in trabecular bone structure and imprecise positioning of the VOI along the slice (A/P) direction resulted in significant changes in bone parameters (p<0.01). Results suggest that automatic mutual information registration using nearest-neighbor gray-level interpolation to transform the final image ensures VOI alignment between baseline and follow-up images and does not compromise the integrity of MR-derived trabecular bone parameters.

Blumenfeld, Janet; Studholme, Colin; Carballido-Gamio, Julio; Link, Thomas M.; Majumdar, Sharmila



Effect of denoising on supervised lung parenchymal clusters  

NASA Astrophysics Data System (ADS)

Denoising is a critical preconditioning step for quantitative analysis of medical images. Despite promises for more consistent diagnosis, denoising techniques are seldom explored in clinical settings. While this may be attributed to the esoteric nature of the parameter sensitve algorithms, lack of quantitative measures on their ecacy to enhance the clinical decision making is a primary cause of physician apathy. This paper addresses this issue by exploring the eect of denoising on the integrity of supervised lung parenchymal clusters. Multiple Volumes of Interests (VOIs) were selected across multiple high resolution CT scans to represent samples of dierent patterns (normal, emphysema, ground glass, honey combing and reticular). The VOIs were labeled through consensus of four radiologists. The original datasets were ltered by multiple denoising techniques (median ltering, anisotropic diusion, bilateral ltering and non-local means) and the corresponding ltered VOIs were extracted. Plurality of cluster indices based on multiple histogram-based pair-wise similarity measures were used to assess the quality of supervised clusters in the original and ltered space. The resultant rank orders were analyzed using the Borda criteria to nd the denoising-similarity measure combination that has the best cluster quality. Our exhaustive analyis reveals (a) for a number of similarity measures, the cluster quality is inferior in the ltered space; and (b) for measures that benet from denoising, a simple median ltering outperforms non-local means and bilateral ltering. Our study suggests the need to judiciously choose, if required, a denoising technique that does not deteriorate the integrity of supervised clusters.

Jayamani, Padmapriya; Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Bartholmai, Brian J.; Robb, Richard A.



Cardiac imaging using a four-segment slant-hole collimator  

SciTech Connect

The main objective of this paper is to evaluate four segmentslant-hole (FSSH) SPECT for cardiac imaging. FSSH is a slant-holecollimator that is divided into four segments and arranged such that thephotons from the volume of interest (VOI)are projected four times forevery location of the detector. These multiple projections help toimprove the sensitivity of the photons from the VOI by a factor4(cos(sigma))3, where is the slant angle of the collimator. Anotheradvantage of FSSH SPECT is a reduction in the total scan time, since agantry rotation of pi-2sigma is sufficient to satisfy Orlov's condition.That means, for a slant angle of 30 degrees, a gantry rotation of 120degrees is sufficient to satisfy Orlov's condition and obtain a completedataset. In this paper, we evaluate and compare the reconstructed imagesobtained using an FSSH collimator, for a gantry rotation of 180 degreesand 120 degrees, with those obtained from a parallel-hole (PH) SPECTsystem using a 180 degree acquisition. The reconstructed images from thethree imaging geometries were compared in terms of average image noise,contrast, and percentage error, for seven different clinical count levelsand for multiple noise realizations in each case. The increase insensitivity of the FSSH system was found to translate into a proportionaldecrease in statistical noise for voxels in the VOI of the reconstructedimages. Finally, a physical phantom study was performed using a prototypeFSSH collimator. Our findings show that FSSH collimators have thepotential of being the collimator of choice for cardiac SPECT imaging.Though we explore the potential of FSSH collimators for cardiac imagingin this paper, the concept can be extended for imaging other organs suchas the breasts, kidney, and brain.

Bal, G.; DiBella, E.V.R.; Gullberg, G.T.; Zeng, G.L.



Micro-morphologic changes around biophysically-stimulated titanium implants in ovariectomized rats  

PubMed Central

Background Osteoporosis may present a risk factor in achievement of osseointegration because of its impact on bone remodeling properties of skeletal phsiology. The purpose of this study was to evaluate micro-morphological changes in bone around titanium implants exposed to mechanical and electrical-energy in osteoporotic rats. Methods Fifteen 12-week old sprague-dowley rats were ovariectomized to develop osteoporosis. After 8 weeks of healing period, two titanium implants were bilaterally placed in the proximal metaphyses of tibia. The animals were randomly divided into a control group and biophysically-stimulated two test groups with five animals in each group. In the first test group, a pulsed electromagnetic field (PEMF) stimulation was administrated at a 0.2 mT 4 h/day, whereas the second group received low-magnitude high-frequency mechanical vibration (MECHVIB) at 50 Hz 14 min/day. Following completion of two week treatment period, all animals were sacrificed. Bone sites including implants were sectioned, removed en bloc and analyzed using a microCT unit. Relative bone volume and bone micro-structural parameters were evaluated for 144 ?m wide peri-implant volume of interest (VOI). Results Mean relative bone volume in the peri-implant VOI around implants PEMF and MECHVIB was significantly higher than of those in control (P < .05). Differences in trabecular-thickness and -separation around implants in all groups were similar (P > .05) while the difference in trabecular-number among test and control groups was significant in all VOIs (P < .05). Conclusion Biophysical stimulation remarkably enhances bone volume around titanium implants placed in osteoporotic rats. Low-magnitude high-frequency MECHVIB is more effective than PEMF on bone healing in terms of relative bone volume.

Akca, Kivanc; Sarac, Ebru; Baysal, Ugur; Fanuscu, Mete; Chang, Ting-Ling; Cehreli, Murat



Automated volume of interest delineation and rendering of cone beam CT images in interventional cardiology  

NASA Astrophysics Data System (ADS)

Interventional C-arm systems allow the efficient acquisition of 3D cone beam CT images. They can be used for intervention planning, navigation, and outcome assessment. We present a fast and completely automated volume of interest (VOI) delineation for cardiac interventions, covering the whole visceral cavity including mediastinum and lungs but leaving out rib-cage and spine. The problem is addressed in a model based approach. The procedure has been evaluated on 22 patient cases and achieves an average surface error below 2mm. The method is able to cope with varying image intensities, varying truncations due to the limited reconstruction volume, and partially with heavy metal and motion artifacts.

Lorenz, Cristian; Schäfer, Dirk; Eshuis, Peter; Carroll, John; Grass, Michael



ESA's Venus Express to reach final destination  

NASA Astrophysics Data System (ADS)

First step: catching Venus To begin to explore our Earth’s hot and hazy sister planet, Venus Express must complete a critical first step, the most challenging one following launch. This involves a set of complex operations and manoeuvres that will inject the spacecraft into orbit. The Venus Orbit Insertion (VOI) manoeuvre allows the spacecraft to reduce its speed relative to Venus, so that it can be captured by the planet’s gravitation. The manoeuvre is a critical one which must proceed at precisely the right place and time. The VOI phase officially started on 4 April and will not be completed until 13 April. It is split into three main sub-phases. The first consists in preparing or initialising the spacecraft for the actual capture manoeuvre so as to avoid the risk of the spacecraft going into safe mode, should parameters unrelated to VOI go off-range. The capture manoeuvre itself consists of a main-engine burn lasting about 50 minutes on the morning of 11 April starting at 09:17 (Central European Summer Time). This is the second main VOI sub-phase. The final sub-phase will be restoring all spacecraft functions, notably resuming communications with Earth and uplinking the commands to be executed during the preliminary ‘capture’ orbit. Orbital capture is controlled by an automatic sequence of predefined commands, uploaded to the spacecraft four days prior to VOI. This sequence is the minimum set needed to perform the main-engine burn. All spacecraft operations are controlled and commanded by the ground control team located at ESA’s European Spacecraft Operations Centre (ESOC) in Darmstadt, Germany. Timeeline of major VOI events (some times subject to change) 4 Aprilacecraft transmitter connected to low gain antenna is switched on. During its interplanetary cruise and during the scientific part of the mission to come, Venus Express communicates with Earth by means of its two high gain antennas. However, during the orbit capture phase (11 April), these two antennas become unusable because of the spacecraft’s required orientation at that time. The low gain antenna, carrying a feeble but instantly recognisable signal, will be transmitting throughout all VOI manoeuvres. This will allow ground controllers to monitor the velocity change during the burn, using NASA’s Deep Space Network’s 70-metre antenna near Madrid, Spain. No other means of communication with the Earth is possible during the capture burn. 5 and 9 April, targeting control manoeuvres. Two time slots are available to adjust course if needed. Given the high accuracy of the course correction performed end of March, Venus Express is currently on the right trajectory for a successful capture into orbit and it is therefore unlikely that either of these two extra slots will be required. 10 to 11 April, final preparations for VOI manoeuvre. 24 to 12 hours before VOI, spacecraft controllers will command Venus Express into its final configuration for the burn. Over the final 12 hours, they will monitor its status, ready to deal with any contingencies requiring last-minute trajectory correction or any revising of the main-engine burn duration. 11 April, 08:03 (CEST), ‘slew’ manoeuvre. This manoeuvre lasts about half an hour and rotates Venus Express so that the main engine faces the direction of motion. Thanks to this, the burn will slow down (rather than accelerate) the spacecraft. 11 April, 09:17 (CEST), main-engine burn starts. A few minutes after firing of the spacecraft thrusters to make sure the propellant settles in the feed lines to the main engine, the latter will begin its 50-minute long burn, ending at 10:07. This thrust will reduce the initial velocity of 29 000 kilometres per hour (in relation to Venus) by 15 percent, allowing capture. Venus Express will settle into its preliminary, elongated nine-day orbit. On capture, it will be at about 120 million kilometres from the Earth and, at its nearest point, within 400 km of the surface of Venus. During the burn, at 09:45 (CEST), Venus Express will disappear behind the planet and will not be visi



Segmentation of pulmonary nodules in three-dimensional CT images by use of a spiral-scanning technique  

SciTech Connect

Accurate segmentation of pulmonary nodules in computed tomography (CT) is an important and difficult task for computer-aided diagnosis of lung cancer. Therefore, the authors developed a novel automated method for accurate segmentation of nodules in three-dimensional (3D) CT. First, a volume of interest (VOI) was determined at the location of a nodule. To simplify nodule segmentation, the 3D VOI was transformed into a two-dimensional (2D) image by use of a key 'spiral-scanning' technique, in which a number of radial lines originating from the center of the VOI spirally scanned the VOI from the 'north pole' to the 'south pole'. The voxels scanned by the radial lines provided a transformed 2D image. Because the surface of a nodule in the 3D image became a curve in the transformed 2D image, the spiral-scanning technique considerably simplified the segmentation method and enabled reliable segmentation results to be obtained. A dynamic programming technique was employed to delineate the 'optimal' outline of a nodule in the 2D image, which corresponded to the surface of the nodule in the 3D image. The optimal outline was then transformed back into 3D image space to provide the surface of the nodule. An overlap between nodule regions provided by computer and by the radiologists was employed as a performance metric for evaluating the segmentation method. The database included two Lung Imaging Database Consortium (LIDC) data sets that contained 23 and 86 CT scans, respectively, with 23 and 73 nodules that were 3 mm or larger in diameter. For the two data sets, six and four radiologists manually delineated the outlines of the nodules as reference standards in a performance evaluation for nodule segmentation. The segmentation method was trained on the first and was tested on the second LIDC data sets. The mean overlap values were 66% and 64% for the nodules in the first and second LIDC data sets, respectively, which represented a higher performance level than those of two existing segmentation methods that were also evaluated by use of the LIDC data sets. The segmentation method provided relatively reliable results for pulmonary nodule segmentation and would be useful for lung cancer quantification, detection, and diagnosis.

Wang Jiahui; Engelmann, Roger; Li Qiang [Department of Radiology, MC2026, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637 (United States)



The effect of volume-of-interest misregistration on quantitative planar activity and dose estimation  

NASA Astrophysics Data System (ADS)

In targeted radionuclide therapy (TRT), dose estimation is essential for treatment planning and tumor dose response studies. Dose estimates are typically based on a time series of whole-body conjugate view planar or SPECT scans of the patient acquired after administration of a planning dose. Quantifying the activity in the organs from these studies is an essential part of dose estimation. The quantitative planar (QPlanar) processing method involves accurate compensation for image degrading factors and correction for organ and background overlap via the combination of computational models of the image formation process and 3D volumes of interest defining the organs to be quantified. When the organ VOIs are accurately defined, the method intrinsically compensates for attenuation, scatter and partial volume effects, as well as overlap with other organs and the background. However, alignment between the 3D organ volume of interest (VOIs) used in QPlanar processing and the true organ projections in the planar images is required. The aim of this research was to study the effects of VOI misregistration on the accuracy and precision of organ activity estimates obtained using the QPlanar method. In this work, we modeled the degree of residual misregistration that would be expected after an automated registration procedure by randomly misaligning 3D SPECT/CT images, from which the VOI information was derived, and planar images. Mutual information-based image registration was used to align the realistic simulated 3D SPECT images with the 2D planar images. The residual image misregistration was used to simulate realistic levels of misregistration and allow investigation of the effects of misregistration on the accuracy and precision of the QPlanar method. We observed that accurate registration is especially important for small organs or ones with low activity concentrations compared to neighboring organs. In addition, residual misregistration gave rise to a loss of precision in the activity estimates that was on the order of the loss of precision due to Poisson noise in the projection data. These results serve as a lower bound on the effects of misregistration on the accuracy and precision of QPlanar activity estimate and demonstrate that misregistration errors must be taken into account when assessing the overall precision of organ dose estimates.

Song, N.; He, B.; Frey, E. C.



Risk estimation and value-of-information analysis for three proposed genetic screening programs for chronic beryllium disease prevention  

SciTech Connect

Genetic differences (polymorphisms) among members of a population are thought to influence susceptibility to various environmental exposures. In practice, however, this information is rarely incorporated into quantitative risk assessment and risk management. The authors describe an analytic framework for predicting the risk reduction and value-of-information (VOI) resulting from specific risk management applications of genetic biomarkers, and they apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leukocyte Antigen gene variant, HLA-DP{beta}1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity ({approximately}94%) but low specificity ({approximately}70%) with respect to CBD among individuals occupationally exposed to respirable beryllium. The expected postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothetical cohort with 1% baseline CBD prevalence. VOI analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed CBD intervention programs based on the genetic susceptibility test. For the example cohort the expected net VOI per beryllium worker for genetically based testing and intervention is $13,000, $1,800, and $5,100, respectively, based on a health valuation of $1.45 million per CBD case avoided. VOI results for alternative CBD valuations are also presented. Despite large parameter uncertainty, probabilistic analysis predicts generally positive utility for each of the three evaluated programs when avoidance of a CBD case is valued at $1 million or higher. Although the utility of a proposed risk management program may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consider serious social, legal, and ethical factors.

Bartell, S.M.; Ponce, R.A.; Takaro, T.K.; Zerbe, R.O.; Omenn, G.S.; Faustman, E.M.



Pulmonary nodule registration in serial CT scans based on rib anatomy and nodule template matching.  


An automated method is being developed in order to identify corresponding nodules in serial thoracic CT scans for interval change analysis. The method uses the rib centerlines as the reference for initial nodule registration. A spatially adaptive rib segmentation method first locates the regions where the ribs join the spine, which define the starting locations for rib tracking. Each rib is tracked and locally segmented by expectation-maximization. The ribs are automatically labeled, and the centerlines are estimated using skeletonization. For a given nodule in the source scan, the closest three ribs are identified. A three-dimensional (3D) rigid affine transformation guided by simplex optimization aligns the centerlines of each of the three rib pairs in the source and target CT volumes. Automatically defined control points along the centerlines of the three ribs in the source scan and the registered ribs in the target scan are used to guide an initial registration using a second 3D rigid affine transformation. A search volume of interest (VOI) is then located in the target scan. Nodule candidate locations within the search VOI are identified as regions with high Hessian responses. The initial registration is refined by searching for the maximum cross-correlation between the nodule template from the source scan and the candidate locations. The method was evaluated on 48 CT scans from 20 patients. Experienced radiologists identified 101 pairs of corresponding nodules. Three metrics were used for performance evaluation. The first metric was the Euclidean distance between the nodule centers identified by the radiologist and the computer registration, the second metric was a volume overlap measure between the nodule VOIs identified by the radiologist and the computer registration, and the third metric was the hit rate, which measures the fraction of nodules whose centroid computed by the computer registration in the target scan falls within the VOI identified by the radiologist. The average Euclidean distance error was 2.7 +/- 3.3 mm. Only two pairs had an error larger than 10 mm. The average volume overlap measure was 0.71 +/- 0.24. Eighty-three of the 101 pairs had ratios larger than 0.5, and only two pairs had no overlap. The final hit rate was 93/101. PMID:17500464

Shi, Jiazheng; Sahiner, Berkman; Chan, Heang-Ping; Hadjiiski, Lubomir; Zhou, Chuan; Cascade, Philip N; Bogot, Naama; Kazerooni, Ella A; Wu, Yi-Ta; Wei, Jun



Complete remission after first-line radio-chemotherapy as predictor of survival in extranodal NK/T cell lymphoma  

PubMed Central

Background Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors. Methods Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80?% of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20?% extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). Results For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84?% vs. 10?% for combined CT?+?radiation therapy (RT), respectively), while for early-stage disease, 50?% of patients received the combination of CT?+?RT and 50?% CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39?% and 33?%. Complete remission (CR) rates were significantly higher when using CT?+?RT (90?%) versus CT alone (33?%) (p?



Changes in Socioeconomic Inequalities in Cancer Mortality Rates Among French Men Between 1968 and 1996  

PubMed Central

Objectives. We investigated changes in socioeconomic inequalities in cancer mortality rates among men in France between 1968 and 1996. Methods. We used a representative sample of 1% of the French population and studied 4 periods (1968–1974, 1975–1981, 1982–1988, and 1990–1996). Causes of death were obtained by direct linkage with the French national death registry. The socioeconomic position of men aged 35 to 59 years was measured by using the occupational class reported at the time of the census at the beginning of each period. Analyses were conducted for all cancers and specifically for lung, upper aerodigestive tract, esophageal, colorectal, and other cancers. Results. In all analyses, we observed socioeconomic inequalities during the 4 periods considered; the inequalities increased between the first and the last period. Most of the total increase occurred between 1968 and 1981, and inequalities remained stable thereafter. Inequalities were larger when men out of the labor force were included in the analysis. The strongest increase in socioeconomic inequalities over time was observed for upper aerodigestive tract cancer. Conclusions. Although cancer mortality rates have decreased, substantial socioeconomic inequalities in cancer mortality among men remain.

Menvielle, Gwenn; Leclerc, Annette; Chastang, Jean-Francois; Melchior, Maria; Luce, Daniele



Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis.  

PubMed Central

Individuals with one aerodigestive tract malignancy have a high incidence of second primary aerodigestive tumors. The mechanism for this field effect has not been determined. We studied an individual with widespread dysplastic changes in the respiratory epithelium but no overt carcinoma. The entire tracheobronchial tree obtained at autopsy was embedded in paraffin, and bronchial epithelial cells were isolated by microdissection. DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identical point mutation consisting of a G:C to T:A transversion in codon 245 was identified in bronchial epithelium from 7 of 10 sites in both lungs. Epithelium at sites containing the p53 mutation was morphologically abnormal, exhibiting squamous metaplasia and mild to moderate atypia. No invasive tumor was found in the tracheobronchial tree or any other location. Cells from peripheral blood, kidney, liver, and lymph node exhibited no abnormality in the p53 gene. The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.

Franklin, W A; Gazdar, A F; Haney, J; Wistuba, I I; La Rosa, F G; Kennedy, T; Ritchey, D M; Miller, Y E



Hematoporphyrin-mediated photodynamic therapy for treatment of head and neck cancer: clinical update 1996  

NASA Astrophysics Data System (ADS)

From 1983 to 1996 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 55 of 56 patients treated with hematoporphyrin-derivative or PHOTOFRIN-mediated photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial 'condemned mucosa' or 'field cancerization' of the oral cavity and larynx (7 cases); (2) Stage III/IV head and neck cancer (25 cases); (3) mucocutaneous AIDS-associated Kaposi's sarcoma of the upper aerodigestive tract and non AIDS-related Kaposi's sarcoma of the lower extremity (15 cases); (4) recurrent laryngotracheal papillomatosis (3 cases); (5) severe dysplasia/adenocarcinoma or squamous cell carcinoma in situ in Barrett's esophagus (4 cases); (6) partial or completely obstructing terminal esophageal cancer (9 cases). At the time of this report, HPD-PDT produced complete responses in 24 patients (follow up 6 months to 9 years) with 'field cancerization' (CIS, T1N0M0) of the oral cavity and larynx (6 cases), adenocarcinoma in situ in Barrett's esophagus (3 cases), mucocutaneous Kaposi's sarcoma (12 cases), obstructing esophageal carcinoma (1 case), and stage IV squamous cell carcinoma of the nasopharynx (1 case), and radiation therapy or solar-induced basal cell/squamous cell carcinomas (2 cases). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck cancer are reviewed in this article.

Schweitzer, Vanessa G.



ICA based automatic segmentation of dynamic H(2)(15)O cardiac PET images.  


In this study, we applied an iterative independent component analysis (ICA) method for the separation of cardiac tissue components (myocardium, right, and left ventricle) from dynamic positron emission tomography (PET) images. Previous phantom and animal studies have shown that ICA separation extracts the cardiac structures accurately. Our goal in this study was to investigate the methodology with human studies. The ICA separated cardiac structures were used to calculate the myocardial perfusion in two different cases: 1) the regions of interest were drawn manually on the ICA separated component images and 2) the volumes of interest (VOI) were automatically segmented from the component images. For the whole myocardium, the perfusion values of 25 rest and six drug-induced stress studies obtained with these methods were compared to the values from the manually drawn regions of interest on differential images. The separation of the rest and stress studies using ICA-based methods was successful in all cases. The visualization of the cardiac structures from H (2) (15) O PET studies was improved with the ICA separation. Also, the automatic segmentation of the VOI seemed to be feasible. PMID:19273031

Margadán-Méndez, Margarita; Juslin, Anu; Nesterov, Sergey V; Kalliokoski, Kari; Knuuti, Juhani; Ruotsalainen, Ulla



Iterative image reconstruction in helical cone-beam x-ray CT using a stored system matrix approach  

NASA Astrophysics Data System (ADS)

We present a stored system matrix (SM) approach for iterative x-ray CT image reconstruction with helical cone-beam geometry. Because of the symmetry of a helical source trajectory, it is sufficient to calculate and store the SM entries for one transaxial slice only and for all source positions illuminating the slice. This is made possible by (1) selecting the reconstruction slice thickness to be an integer multiple of the source translation per projection view, and (2) discretizing the 3D reconstruction volume on a rotated stack of slices. Using the proposed method, the memory requirement for reconstructing a full field-of-view of clinical scanners is manageable on current computing platforms. The same storage principle can be generalized and applied to volume-of-interest (VOI) image reconstruction for helical cone-beam CT. In this case, the stored SM entries correspond to a partial- or full-ring region on one transaxial slice, and for all source positions illuminating the ring. The size and location of the ring depend on the size and the location of the VOI and the scan geometry. We demonstrate by both computer simulations and clinical patient data the speed and efficacy of iterative image reconstruction using the stored SM approach.

Xu, Jingyan; Tsui, Benjamin M. W.



Optimising the reward of appraisal drilling  

SciTech Connect

Management of the uncertainties associated with the development of a hydrocarbon resource is essential to minimize economic risk. In many instances these uncertainties can only be reduced by appraisal drilling. This presentation illustrates the efforts being made to manage uncertainty by determining its impact on overall project profitability. The Value of Information (VOI) approach is described. VOI aims at quantifying the benefits of appraisal by determining its economic reward in terms of its contribution to a development plan which is economically robust over the uncertainty range. Appraisal drilling costs can be reduced by combining appraisal and development objectives in one well. The growing use of horizontal drilling technology has resulted in novel approaches to appraisal. As examples, in the Osprey and Brent Fields (UK North Sea) wells were designed to satisfy both appraisal and development objectives. In Osprey, a well was drilled from a central production platform to provide water injection support in a satellite structure while at the same time appraising the saddle area between the two structures. In Brent, horizontal wells are used to appraise and develop the so called slump blocks, characterized by being highly faulted and compartmentalized. Another increasingly common application of horizontal wells is for the flank appraisal of hydrocarbon bearing structure. Examples from the Rabi Field (Gabon) and Batan Field (Nigeria) show how appraisal was achieved by extending the reach of horizontal development wells from the central core of the structures.

Gdula, J.



Detection of Amide and Aromatic Proton Resonances of Human Brain Metabolites Using Localized Correlated Spectroscopy Combined with Two Different Water Suppression Schemes.  


The purpose of the study was to demonstrate the J-coupling connectivity network between the amide, aliphatic, and aromatic proton resonances of metabolites in human brain using two-dimensional (2D) localized correlated spectroscopy (L-COSY). Two different global water suppression techniques were combined with L-COSY, one before and another after localizing the volume of interest (VOI). Phantom solutions containing several cerebral metabolites at physiological concentrations were evaluated initially for sequence optimization. Nine healthy volunteers were scanned using a 3T whole body MRI scanner. The VOI for 2D L-COSY was placed in the right occipital white/gray matter region. The 2D cross and diagonal peak volumes were measured for several metabolites such as N-acetyl aspartate (NAA), creatine (Cr), free choline (Ch), glutamate/glutamine (Glx), aspartate (Asp), myo-inositol (mI), GABA, glutathione (GSH), phosphocholine (PCh), phosphoethanolamine (PE), tyrosine (Tyr), lactate (Lac), macromolecules (MM) and homocarnosine (Car). Using the pre-water suppression technique with L-COSY, the above mentioned metabolites were clearly identifiable and the relative ratios of metabolites were calculated. In addition to detecting multitude of aliphatic resonances in the high field region, we have demonstrated that the amide and aromatic resonances can also be detected using 2D L-COSY by pre water suppression more reliably than the post-water suppression. PMID:21546981

Nagarajan, Rajakumar; Ramadan, Saadallah; Thomas, M Albert



Assessing the value of information for long-term structural health monitoring  

NASA Astrophysics Data System (ADS)

In the field of Structural Health Monitoring, tests and sensing systems are intended as tools providing diagnoses, which allow the operator of the facility to develop an efficient maintenance plan or to require extraordinary measures on a structure. The effectiveness of these systems depends directly on their capability to guide towards the most optimal decision for the prevailing circumstances, avoiding mistakes and wastes of resources. Though this is well known, most studies only address the accuracy of the information gained from sensors without discussing economic criteria. Other studies evaluate these criteria separately, with only marginal or heuristic connection with the outcomes of the monitoring system. The concept of "Value of Information" (VoI) provides a rational basis to rank measuring systems according to a utility-based metric, which fully includes the decision-making process affected by the monitoring campaign. This framework allows, for example, an explicit assessment of the economical justifiability of adopting a sensor depending on its precision. In this paper we outline the framework for assessing the VoI, as applicable to the ranking of competitive measuring systems. We present the basic concepts involved, highlight issues related to monitoring of civil structures, address the problem of non-linearity of the cost-to-utility mapping, and introduce an approximate Monte Carlo approach suitable for the implementation of time-consuming predictive models.

Pozzi, Matteo; der Kiureghian, Armen



Ultrasonic diaphragm tracking for cardiac interventional navigation on 3D motion compensated static roadmaps  

NASA Astrophysics Data System (ADS)

In this paper, a novel approach to cardiac interventional navigation on 3D motion-compensated static roadmaps is presented. Current coronary interventions, e.g. percutaneous transluminal coronary angioplasties, are performed using 2D X-ray fluoroscopy. This comes along with well-known drawbacks like radiation exposure, use of contrast agent, and limited visualization, e.g. overlap and foreshortening, due to projection imaging. In the presented approach, the interventional device, i.e. the catheter, is tracked using an electromagnetic tracking system (MTS). Therefore, the catheters position is mapped into a static 3D image of the volume of interest (VOI) by means of an affine registration. In order to compensate for respiratory motion of the catheter with respect to the static image, a parameterized affine motion model is used which is driven by a respiratory sensor signal. This signal is derived from ultrasonic diaphragm tracking. The motion compensation for the heartbeat is done using ECG-gating. The methods are validated using a heart- and diaphragm-phantom. The mean displacement of the catheter due to the simulated organ motion decreases from approximately 9 mm to 1.3 mm. This result indicates that the proposed method is able to reconstruct the catheter position within the VOI accurately and that it can help to overcome drawbacks of current interventional procedures.

Timinger, Holger; Kruger, Sascha; Dietmayer, Klaus; Borgert, Joern



Automated cloud tracking system for the Akatsuki Venus Climate Orbiter data  

NASA Astrophysics Data System (ADS)

Japanese Venus Climate Orbiter, Akatsuki, is cruising to approach to Venus again although its first Venus orbital insertion (VOI) has been failed. At present, we focus on the next opportunity of VOI and the following scientific observations.We have constructed an automated cloud tracking system for processing data obtained by Akatsuki in the present study. In this system, correction of the pointing of the satellite is essentially important for improving accuracy of the cloud motion vectors derived using the cloud tracking. Attitude errors of the satellite are reduced by fitting an ellipse to limb of an imaged Venus disk. Next, longitude-latitude distributions of brightness (cloud patterns) are calculated to make it easy to derive the cloud motion vectors. The grid points are distributed at regular intervals in the longitude-latitude coordinate. After applying the solar zenith correction and a highpass filter to the derived longitude-latitude distributions of brightness, the cloud features are tracked using pairs of images. As a result, we obtain cloud motion vectors on longitude-latitude grid points equally spaced. These entire processes are pipelined and automated, and are applied to all data obtained by combinations of cameras and filters onboard Akatsuki. It is shown by several tests that the cloud motion vectors are determined with a sufficient accuracy. We expect that longitude-latitude data sets created by the automated cloud tracking system will contribute to the Venus meteorology.

Ogohara, Kazunori; Kouyama, Toru; Yamamoto, Hiroki; Sato, Naoki; Takagi, Masahiro; Imamura, Takeshi



Information-theoretic approach for automated white matter fiber tracts reconstruction.  


Fiber tracking is the most popular technique for creating white matter connectivity maps from diffusion tensor imaging (DTI). This approach requires a seeding process which is challenging because it is not clear how and where the seeds have to be placed. On the other hand, to enhance the interpretation of fiber maps, segmentation and clustering techniques are applied to organize fibers into anatomical structures. In this paper, we propose a new approach to automatically obtain bundles of fibers grouped into anatomical regions. This method applies an information-theoretic split-and-merge algorithm that considers fractional anisotropy and fiber orientation information to automatically segment white matter into volumes of interest (VOIs) of similar FA and eigenvector orientation. For each VOI, a number of planes and seeds is automatically placed in order to create the fiber bundles. The proposed approach avoids the need for the user to define seeding or selection regions. The whole process requires less than a minute and minimal user interaction. The agreement between the automated and manual approaches has been measured for 10 tracts in a DTI brain atlas and found to be almost perfect (kappa >?0.8) and substantial (kappa >?0.6). This method has also been evaluated on real DTI data considering 5 tracts. Agreement was substantial (kappa >?0.6) in most of the cases. PMID:22467471

Prados, Ferran; Boada, Imma; Feixas, Miquel; Prats-Galino, Alberto; Blasco, Gerard; Puig, Josep; Pedraza, Salvador



A New Method to Evaluate Volumetric Changes in Sinus Augmentation Procedure.  


BACKGROUND: In sinus augmentation procedure, the assessment of volume changes of grafted materials is important both in the clinical practice and in dental research to evaluate the features of filling materials. PURPOSE: In this study, we assessed the repeatability of a new method proposed to evaluate volumetric changes following sinus lift augmentation procedure. MATERIALS AND METHODS: In 10 patients, maxillary sinus augmentation procedure with simultaneous implant placement was performed. Maxillary cone beam computer tomographies were taken 1 week after surgery (T1) and 6 months after surgery (T2). At each evaluation the gap inside the implant between the fixture and the bottom of the screw was used as reference point (Rp), and a standardized volume of interest (VOI) centered on the Rp was selected. Masks were chosen to select the graft and bone tissue within the VOI; the volume at T1, T2, and the difference of volume between T1 and T2 were computed. Expert and non-expert operators performed the analysis. Method errors were computed. RESULTS: The error of the method was 1% for both intra-operator and inter-operator measurements. Tissue contraction at T2 was 19?±?4% of the total initial volume. CONCLUSIONS: The standardization of the method allows to obtain repeatable measurements. PMID:23509966

Dellavia, Claudia; Speroni, Stefano; Pellegrini, Gaia; Gatto, Alessandra; Maiorana, Carlo



Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion.  


Chronic cerebral hypoperfusion (CCH) causes neurodegeneration which contributes to the cognitive impairment. This study utilized a modified rat model with CCH to investigate cerebral blood flow (CBF) and hippocampal metabolic changes. CBF was measured by laser Doppler flowmetry. Various metabolic ratios were evaluated from selective volumes of interest (VOI) in left hippocampal regions using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). The ultrastructural changes with special respect to ribosomes in rat hippocampal CA1 neurons were studied by electron microscopy. CBF decreased immediately after CCH and remained reduced significantly at 1 day and 3 months postoperatively. (1)H-MRS revealed that CCH led to a significant decrease of N-acetyl aspartate/creatine (NAA/Cr) ratio in the hippocampal VOI in the model rats compared with the sham-operated control rats. However, no changes of myo-inositol/Cr, choline/Cr and glutamate and glutamine/Cr ratios between the model and control groups were observed. Under electron microscopy, most rosette-shaped polyribosomes were relatively evenly distributed in the hippocampal CA1 neuronal cytoplasms of the control rats. After CCH, most ribosomes were clumped into large abnormal aggregates in the model rats. Our data suggests that both permanent decrease of CBF and reduction of NAA/Cr ratio in the hippocampal regions may be related to the cognitive deficits in rats with CCH. PMID:23111782

Jian, Hai; Yi-Fang, Wu; Qi, Lin; Xiao-Song, Huang; Gui-Yun, Zhang



Scalable active learning for multiclass image classification.  


Machine learning techniques for computer vision applications like object recognition, scene classification, etc., require a large number of training samples for satisfactory performance. Especially when classification is to be performed over many categories, providing enough training samples for each category is infeasible. This paper describes new ideas in multiclass active learning to deal with the training bottleneck, making it easier to train large multiclass image classification systems. First, we propose a new interaction modality for training which requires only yes-no type binary feedback instead of a precise category label. The modality is especially powerful in the presence of hundreds of categories. For the proposed modality, we develop a Value-of-Information (VOI) algorithm that chooses informative queries while also considering user annotation cost. Second, we propose an active selection measure that works with many categories and is extremely fast to compute. This measure is employed to perform a fast seed search before computing VOI, resulting in an algorithm that scales linearly with dataset size. Third, we use locality sensitive hashing to provide a very fast approximation to active learning, which gives sublinear time scaling, allowing application to very large datasets. The approximation provides up to two orders of magnitude speedups with little loss in accuracy. Thorough empirical evaluation of classification accuracy, noise sensitivity, imbalanced data, and computational performance on a diverse set of image datasets demonstrates the strengths of the proposed algorithms. PMID:22997129

Joshi, Ajay J; Porikli, Fatih; Papanikolopoulos, Nikolaos P



High Resolution Multi-Detector CT Aided Tissue Analysis and Quantification of Lung Fibrosis  

PubMed Central

Rational and Objectives Volumetric high-resolution scans can be acquired of the lungs with multi-detector CT (MDCT). Such scans have potential to facilitate useful visualization, characterization, and quantification of the extent of diffuse lung diseases, such as Usual Interstitial Pneumonitis or Idiopathic Pulmonary Fibrosis (UIP/IPF). There is a need to objectify, standardize and improve the accuracy and repeatability of pulmonary disease characterization and quantification from such scans. This paper presents a novel texture analysis approach toward classification and quantification of various pathologies present in lungs with UIP/IPF. The approach integrates a texture matching method with histogram feature analysis. Materials and Methods Patients with moderate UIP/IPF were scanned on a Lightspeed 8-detector GE CT scanner (140kVp, 250mAs). Images were reconstructed with 1.25mm slice thickness in a high-frequency sparing algorithm (BONE) with 50% overlap and a 512 × 512 axial matrix, (0.625 mm3 voxels). Eighteen scans were used in this study. Each dataset is pre-processed which includes segmentation of the lungs and the broncho-vascular trees. Two types of analysis were performed, first an analysis of independent volume of interests (VOIs) and second an analysis of whole lung datasets. 1.) Fourteen of the eighteen scans were used to create a database of independent 15×15×15 cubic voxel VOIs. The VOIs were selected by experts as having greater than 70% of the defined class. The database was composed of the following: Honeycombing (# of VOIs 337), Reticular (130), Ground glass (148), Normal (240), and Emphysema (54). This database was used to develop our algorithm. Three progressively challenging classification experiments were designed to test our algorithm. All three experiments were performed using a 10-fold cross validation method for error estimation. Experiment 1 consisted of a two class discrimination: Normal and Abnormal. Experiment 2 consisted of a four class discrimination: Normal, Reticular, Honeycombing, and Emphysema. Experiment 3 consisted of a five class discrimination: Normal, Ground glass, Reticular, Honeycombing, and Emphysema. 2.) The remaining four scans were used to further test the algorithm on new data in the context of a whole lung analysis. Each of the four datasets was manually segmented by three experts. These datasets included Normal, Reticular and Honeycombing regions and did not include Ground glass or Emphysema. The accuracy of the classification algorithm was then compared with results from experts. Results Independent VOIs: 1.) Two class discrimination problem (sensitivity, specificity): Normal versus Abnormal (92.96%,93.78%). 2.) Four class discrimination problem: Normal (92%,95%), Reticular (86%,87%), Honeycombing (74%,98%), and Emphysema (93%,98%). 3.) Five class discrimination problem: Normal(92%,95%), Ground glass (75%,89%), Reticular (22%,92%), Honeycombing (74%,91%), and Emphysema (94%,98%). Whole lung datasets: 1.) William's Index shows that algorithm classification of lungs agrees with the experts as well as the experts agree with themselves. 2.) Student-T test between overlap measures of algorithm and expert (AE) and expert and expert (EE) : Normal (t=-1.20, p = 0.230), Reticular (t=-1.44, p = 0.155), Honeycombing (t=-3.15, p = 0.003). 3.) Lung Volumes Intra-class correlation: Dataset 1 (ICC = 0.9984, F = 0.0007); Dataset 2 (ICC = 0.9559, F = 0); Dataset 3 (ICC = 0.8623, F= 0.0015); Dataset 4 (ICC = 0.7807, F = 0.0136). Conclusions We have demonstrated that our novel method is computationally efficient and produces results comparable to expert radiologic judgment. It is effective in the classification of normal versus abnormal tissue and performs as well as the experts in distinguishing among typical pathologies present in lungs with UIP/IPF. The continuing development of quantitative metrics will improve quantification of disease and provide objective measures of disease progression.

Zavaletta, Vanessa A.; Bartholmai, Brian J.; Robb, Richard A



Structure crustale et anomalies du champ de gravite dans l'est du Canada  

NASA Astrophysics Data System (ADS)

Cette these presente les resultats d'etudes gravimetriques menees dans le Bouclier canadien. Les mesures du champ de gravite recoltees le long et a proximite de divers transects Lithoprobe y sont interpretees. Chacun des chapitres de cette these est un article publie ou soumis. Le premier article presente l'interpretation gravimetrique le long de la ligne sismique 52 de Lithoprobe, dans la province de Grenville. A l'echelle regionale, la modelisation de l'anomalie de Bouguer invoque un amincissement crustal au sud du front de Grenville sous le terrane allochtone du reservoir Cabonga. Cet amincissement, localise au niveau de la croute inferieure, peut etre associe a une extension post-orogenique. Le modele gravimetrique a aussi permis de mettre en evidence des caracteristiques majeures non revelees par les donnees sismiques, telle que la zone de contact subverticale entre les terranes du reservoir de Cabonga et du reservoir Dozois. La rampe de Baskatong representerait une discontinuite majeure le long de laquelle, les terranes proterozoiques furent accretes. Par ailleurs, un modele de l'anomalie residuelle, dans la partie nord du profil, met en evidence trois corps gabbroiques peu profonds. Le second article presente des modeles crustaux du nord de la province du Superieur a la lumiere de nouvelles donnees de gravite recoltees le long d'un transect traversant les sous-provinces de Nemiscau et La Grande. L'interpretation de l'anomalie de Bouguer pour le nord de l'Abitibi et l'Opatica, invoque un epaississement crustal. Pour les sous-provinces de Nemiscau et La Grande, l'interpretation gravimetrique invoque une densite de la croute superieure plus elevee qu'en Abitibi et en Opatica. Un leger epaississement crustal est observe dans la sous-province de La Grande. Des sequences supracrustales mafiques sont aussi mises en evidence a l'extremite nord du profil dans la sous-province de La Grande. La signature gravimetrique associee a la variation laterale de densite et les evidences de terrain indiquent un pendage vers le nord des principales frontieres tectoniques. Le troisieme chapitre fait l'objet d'une etude du champ de pesanteur au dessus de la region de la baie d'Ungava a partir de donnees satellite et de nouvelles donnees recoltees le long de la cote sud de la baie. Un leve gravimetrique partant de la baie aux Feuilles, dans la province du Superieur, traversant l'Orogene du Nouveau Quebec (ONQ), et finissant pres de la riviere George dans le craton de Rae, a ete realise. L'interpretation des donnees acquises a permis de fournir des modeles de densite. Ces modeles mettent en evidence un epaississement crustal sous l'ONQ et un amincissement sous le terrane de Kuujjuaq, a l'est de l'orogene. Alors que plus a l'est, dans le craton de Rae, une anomalie negative de quelques dix milligals est correlee avec les extensions vers le nord de la zone de cisaillement de la riviere George (ZCRG) et du batholite de De Pas. L'orientation des structures sur les modeles de gravite suggere un chevauchement du craton de Rae au dessus de l'ONQ. (Abstract shortened by UMI.)

Telmat, Hamid


Le changement comme tradition dans la recherche et la formation a la recherche en biotechnologie et en peripherie Etude de cas en sciences de la sante, sciences naturelles et genie  

NASA Astrophysics Data System (ADS)

Le champ de la recherche scientifique et de la formation a la recherche est traverse depuis quelques dizaines d'annees par plusieurs courants et discours associes au changement, mais peu de travaux empiriques permettent de comprendre ce qui change concretement. C'est la contribution originale de cette these au champ de l'education, plus specifiquement a l'etude sociologique de l'enseignement superieur ou sont concentrees les activites liees a la triade thematique du programme doctoral dans lequel elle a ete produite : recherche, formation et pratique. L'enquete-terrain a ete realisee en 2009 et 2010 aupres de 808 repondants affilies a 60 etablissements au Quebec et a produit un vaste materiau de nature mixte (donnees quantitatives et qualitatives). Un portrait de la nebuleuse biotechnologique qui touche les secteurs des sciences de la sante, des sciences naturelles et du genie a ete realise. Ce domaine concerne des dizaines de disciplines et se revele de nature transdisciplinaire, mais les pratiques n'y sont pas davantage marquees par le changement que celles d'autres domaines connexes. Les dynamiques sociales ont fait l'objet d'analyses comparatives dans quatre contextes: le choix des programmes, des objets et des methodes, le financement, la diffusion et la planification de la carriere. Les resultats indiquent que les echanges entre les agents traditionnellement situes au coeur des activites de recherche dominent ces dynamiques dans tous les contextes etudies. L'etude des representations au fondement des pratiques a revele l'existence de trois ecoles de pensee qui coexistent dans le champ scientifique: academique, pragmatique et economiste. Ces ecoles permettent de categoriser les agents en fonction des zones de fractures qui marquent leurs oppositions tout en identifiant ce qu'ils ont en commun. Les representations et les pratiques liees a la formation temoignent d'un habitus plutot homogene, alors que les contradictions semblent plus souvent ancrees dans des luttes universitaires que scientifiques, concentrees sur la negociation du capital scientifique, symbolique et economique en jeu dans la formation doctorale, dans les carrieres auxquelles elle mene, et dans les qualites du titre de Ph.D. Au final, la confusion entre des logiques opposees peut etre reduite en reinterpretant le changement comme tradition du champ scientifique. Mots-cles Sociologie, education, enseignement superieur, science et technologie, biotechnologie, formation doctorale, champ scientifique, reseaux sociaux

Bourque, Claude Julie


Analysis of real-time reservoir monitoring : reservoirs, strategies, & modeling.  

SciTech Connect

The project objective was to detail better ways to assess and exploit intelligent oil and gas field information through improved modeling, sensor technology, and process control to increase ultimate recovery of domestic hydrocarbons. To meet this objective we investigated the use of permanent downhole sensors systems (Smart Wells) whose data is fed real-time into computational reservoir models that are integrated with optimized production control systems. The project utilized a three-pronged approach (1) a value of information analysis to address the economic advantages, (2) reservoir simulation modeling and control optimization to prove the capability, and (3) evaluation of new generation sensor packaging to survive the borehole environment for long periods of time. The Value of Information (VOI) decision tree method was developed and used to assess the economic advantage of using the proposed technology; the VOI demonstrated the increased subsurface resolution through additional sensor data. Our findings show that the VOI studies are a practical means of ascertaining the value associated with a technology, in this case application of sensors to production. The procedure acknowledges the uncertainty in predictions but nevertheless assigns monetary value to the predictions. The best aspect of the procedure is that it builds consensus within interdisciplinary teams The reservoir simulation and modeling aspect of the project was developed to show the capability of exploiting sensor information both for reservoir characterization and to optimize control of the production system. Our findings indicate history matching is improved as more information is added to the objective function, clearly indicating that sensor information can help in reducing the uncertainty associated with reservoir characterization. Additional findings and approaches used are described in detail within the report. The next generation sensors aspect of the project evaluated sensors and packaging survivability issues. Our findings indicate that packaging represents the most significant technical challenge associated with application of sensors in the downhole environment for long periods (5+ years) of time. These issues are described in detail within the report. The impact of successful reservoir monitoring programs and coincident improved reservoir management is measured by the production of additional oil and gas volumes from existing reservoirs, revitalization of nearly depleted reservoirs, possible re-establishment of already abandoned reservoirs, and improved economics for all cases. Smart Well monitoring provides the means to understand how a reservoir process is developing and to provide active reservoir management. At the same time it also provides data for developing high-fidelity simulation models. This work has been a joint effort with Sandia National Laboratories and UT-Austin's Bureau of Economic Geology, Department of Petroleum and Geosystems Engineering, and the Institute of Computational and Engineering Mathematics.

Mani, Seethambal S.; van Bloemen Waanders, Bart Gustaaf; Cooper, Scott Patrick; Jakaboski, Blake Elaine; Normann, Randy Allen; Jennings, Jim (University of Texas at Austin, Austin, TX); Gilbert, Bob (University of Texas at Austin, Austin, TX); Lake, Larry W. (University of Texas at Austin, Austin, TX); Weiss, Chester Joseph; Lorenz, John Clay; Elbring, Gregory Jay; Wheeler, Mary Fanett (University of Texas at Austin, Austin, TX); Thomas, Sunil G. (University of Texas at Austin, Austin, TX); Rightley, Michael J.; Rodriguez, Adolfo (University of Texas at Austin, Austin, TX); Klie, Hector (University of Texas at Austin, Austin, TX); Banchs, Rafael (University of Texas at Austin, Austin, TX); Nunez, Emilio J. (University of Texas at Austin, Austin, TX); Jablonowski, Chris (University of Texas at Austin, Austin, TX)



EQPlanar: A Maximum-Likelihood Method for Accurate Organ Activity Estimation from Whole Body Planar Projections  

PubMed Central

Optimizing targeted radionuclide therapy (TRT) requires patient-specific estimation of organ doses. The organ doses are estimated from quantitative nuclear medicine imaging studies, many of which involve planar wholebody scans. We have previously developed the Quantitative Planar (QPlanar) processing method and demonstrated its ability to provide more accurate activity estimates than conventional geometric-mean based planar (CPlanar) processing methods using physical phantom and simulation studies. The QPlanar method uses the maximum likelihood-expectation maximization (ML-EM) algorithm, 3D organ VOIs, and rigorous models of physical image degrading factors to estimate organ activities. However, the QPlanar method requires alignment between the 3D organ VOIs and the 2D planar projections and assumes uniform activity distribution in each VOI. This makes application to patients challenging. As a result, in this paper we propose an extended QPlanar (EQPlanar) method that provides independent-organ rigid registration and includes multiple background regions. We have validated this method using both Monte Carlo simulation and patient data. In the simulation study, we evaluated the precision and accuracy of the method in comparison to the original QPlanar method. For the patient studies, we compared organ activity estimates at 24 hours after injection with those from conventional geometric mean based planar quantification using a 24 hour post-injection quantitative SPECT reconstruction as the gold standard. We also compared the goodness of fit of the measured and estimated projections obtained from EQPlanar method to those from the original method at 4 other time points where gold standard data was not available. In the simulation study, more accurate activity estimates were provided by the EQPlanar method for all the organs at all the time points compared with the QPlanar method. Based on the patient data, we concluded that the EQPlanar method provided a substantial increase in accuracy of organ activity estimates from 24 hr planar images compared to the CPlanar using 24 hr SPECT as the golden standard. For other time points, where no golden standard is available, better agreement between estimated and measured projections was observed by using EQPlanar method compared to the QPlanar method. This phenomenon is consistent with the improvement in goodness of fit seen in both simulation data and 24 hr patient data. Therefore, this indicates the improved reliability of organ activity estimates obtained though EQPlanar method.

Song, N.; He, B.; Wahl, R. L.; Frey, E. C.



Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer  

PubMed Central

Purpose To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation. Methods and materials Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC. To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter. Results The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40?minutes for prostate, and about 20?minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma). Conclusions From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.



Ferret thoracic anatomy by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (18F-FDG PET/CT) imaging.  


The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with (18)F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of (18)F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUV(Max)] 8.60, mean standardized uptake value [SUV(Mean)] 5.42), thymus (SUV(Max) 3.86, SUV(Mean) 2.59), liver (SUV(Max) 1.37, SUV(Mean) 0.99), right lung (SUV(Max) 0.92, SUV(Mean) 0.56), and left lung (SUV(Max) 0.88, SUV(Mean) 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of (18)F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that (18)F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging features and uptake measurements with and without respiratory gating as well as with intraperitoneal and intravenous (18)F-FDG injections. (18)F-FDG PET and CT can be a valuable resource for the in vivo tracking of disease progression in future studies that employ the ferret model. PMID:23382267

Wu, Albert; Zheng, Huaiyu; Kraenzle, Jennifer; Biller, Ashley; Vanover, Carol D; Proctor, Mary; Sherwood, Leslie; Steffen, Marlene; Ng, Chin; Mollura, Daniel J; Jonsson, Colleen B



Dosimetric effects of manual cone-beam CT (CBCT) matching for spinal radiosurgery: our experience.  


Radiosurgical treatment of cranial or extracranial targets demands accurate positioning of the isocenter at the beam and table isocenter, and immobilization of the target during treatment. For spinal radiosurgery, the standard approach involves matching of cone-beam CT (CBCT) in-room images with the planning CT (pCT) to determine translation and yaw corrections. The purpose of this study was to assess the accuracy of these techniques compared to advanced automatching using mutual information metrics, with consideration given to volume of interest (VOI) and optimizing translations and rotations in all axes. The dosimetric consequences of our current standard matching techniques were also evaluated. Ten consecutive spinal radiosurgery patients treated in the last year were subjected to analysis. For purposes of this analysis, the automatch using mutual information and a VOI was considered to create "the true isocenter" for positioning the patients. Review of the imaging from this automatch confirmed perfect superimposition of the two datasets within the VOI. Matching the CBCT to the pCT using the automatch allowed assessment of the rotations which had been previously ignored. Recalculation of the dose volume histogram was undertaken for each patient, assuming displacement of the true isocenter to the treated isocenter. Comparisons between the delivered doses and the intended doses were made. The mean absolute lateral/vertical/longitudinal translations and vector displacement between the manual CBCT-pCT matching isocenter and the true isocenter were 0.13, -0.05, and -0.39 mm, with a minimum and maximum individual pixel vector shift of 3.2 and 8.94 mm. The mean pitch, yaw, and roll correction for automatch was -0.30°, 0.25°, and 0.97° with a maximum of 1.65°, 2.92°, and 1.43°. Four of ten patients had a significant change in the coverage of the tumor due to lack of correction of translational and rotational errors. The largest errors were observed in patients with small and irregular target volumes. Our initial results show that precise positioning for spinal radiosurgery cannot be accomplished with manual pCT-CBCT matching without a clinical strategy to compensate for rotations. In the absence of this, significant underdosing of the tumor may occur. PMID:21844858

Schreibmann, Eduard; Fox, Tim; Crocker, Ian



Extramedullary Plasmacytoma of the Nasal Cavity Report of Three Cases With Review of the Literature  

PubMed Central

Extramedullary plasmacytoma is a rare neoplasm characterized by monoclonal proliferation of plasma cells. Most lesions occur in the head and neck, primarily in the upper aerodigestive tract. The nasal cavity and nasal septum are the most common sites of occurrence. In this report, three patients admitted in our clinic with history of nasal obstruction and/or epistaxis. Patients were diagnosed with extramedullary plasmacytoma and mass were completely excised. This entity usually occurred in 5th-6th decade of life. One of our patients, a young man, was completely asymptomatic and following a paroxysm of coughing, a polypoid mass was expectorated. The clinical and histopathologic findings of plasmacytoma are discussed. In order to exclude systemic involvement, systematic approach using clinical, laboratory, and radiologic investigations was performed. Extramedullary plasmacytoma of the nasal cavity is rare and should be considered in the differential diagnosis of nasal cavity masses especially in young age group.

Ashraf, Mohamad Javad; Azarpira, Negar; Khademi, Bighan; Abedi, Elham; Hakimzadeh, Afsoon; Valibeigi, Bita



Extramedullary plasmocytoma relapsing at differents sites: an unusual presentation.  


Extramedullary plasmacytoma (EMP) is an uncommon plasma cell neoplasm results from plasma cell proliferation and consists of monoclonal plasmacytic infiltration, without bone marrow involvement and any other systemic characteristics of multiple myeloma. EMP accounts for 3% of all plasma cell neoplasms and approximately 80% to 90% of EMP involve submucosa of the upper aerodigestive, while scrotal, dermis and retroperitoneal infiltration are very rare. There are no consensus guidelines for treatment, but EMP is highly radiosensitive, surgery may be considered for some sites, but 11 at 30% can progress in multiple myeloma. We report here an exceptional case of recurrent EMP in much localization. It's about a man 72 years old with initially testicular plasmocytoma who generalized the plasmacytic infiltration after 16 months in skin and progressively in mediastinal and retroperitoneal plasmacytoma, without any medullar and bone involvement. PMID:23560117

Ahnach, Maryame; Marouan, Sofia; Rachid, Mohamed; Madani, Abdellah; Quessar, Asmaa; Benchekroun, Said; Quachouh, Meryem



Pathogenesis and therapeutic intervention of oral submucous fibrosis.  


Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize on the molecular changes taking place in OSF and possible therapeutic interventions. PMID:23946584

Yoithapprabhunath, Thukanaykanpalayam Ragunathan; Maheswaran, Thangadurai; Dineshshankar, Janardhanam; Anusushanth, Abraham; Sindhuja, Pandian; Sitra, Govindasamy



Pathogenesis and therapeutic intervention of oral submucous fibrosis  

PubMed Central

Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize on the molecular changes taking place in OSF and possible therapeutic interventions.

Yoithapprabhunath, Thukanaykanpalayam Ragunathan; Maheswaran, Thangadurai; Dineshshankar, Janardhanam; Anusushanth, Abraham; Sindhuja, Pandian; Sitra, Govindasamy



Salivary mRNA targets for cancer diagnostics  

PubMed Central

Head and neck squamous cell carcinoma (HNSCC) affects almost 1 million people worldwide per year. Despite therapeutic advances the overall survival rate remains low because diagnosis often occurs only at advanced stages with poor prognosis. Like in most cancers, the implementation of an early detection scheme would have a positive impact on this disease. Similarly, as oral cancer has a very high recurrence rate, the early identification of recurrence or second primary tumors is an important challenge. HNSCC detection is currently based on expert clinical examination of the upper aerodigestive tract and histologic analysis of suspicious areas, but it may be undetectable in hidden sites, and unfortunately visual screening for oral lesions is an often neglected part of dental healthcare. Our group is actively pursuing the assembly of a toolbox for the molecular analysis of oral fluid. Here we present our current status utilizing the salivary transcriptome for oral cancer diagnostics.

Zimmermann, Bernhard G.; Wong, David T.



Transoral laser microsurgery for early laryngeal cancer.  


The decision to treat patients suffering from glottic cancer with either radiotherapy or surgery is both complex and controversial. Transoral laser microsurgery is a surgical technique that offers an attractive alternative therapy for laryngeal cancer. In addition to excellent oncologic outcomes and organ preservation, the benefits of transoral laser microsurgery include low morbidity and mortality, shorter periods of hospitalization and exceptional functional results. As the evidence base for the effectiveness of laser surgery grows, transoral laser microsurgery has become established as a valid surgical option for the treatment of early laryngeal cancer. In this article we examine the surgical technique and discuss the oncologic and functional outcomes of transoral laser microsurgery. Furthermore, we offer a vision of the future of endoscopic laser surgery for the management of cancer of the larynx and the upper aerodigestive tract. PMID:20214514

Grant, David G; Repanos, Costa; Malpas, Gemma; Salassa, John R; Hinni, Michael L



Management of venous malformations.  


Venous malformations (VMs) frequently occur in the head and neck with a predilection for the parotid gland, submandibular triangle, buccal space, muscles of mastication, lips, and upper aerodigestive tract. They are composed of congenitally disrupted ectatic veins with inappropriate connections and tubular channels. Because VMs have poorly defined boundaries and a tendency to infiltrate normal tissue, they require calculated treatment decisions in the effort to preserve surrounding architecture. Sclerotherapy, surgical excision, neodymium:yttrium aluminum garnet laser therapy, or a combination of these modalities is employed in the management of VMs. Although many small VMs can be cured, the objective is often to control the disease with periodic therapy. Location, size, and proximity to vital structures dictate the type of therapy chosen. Vigilance with long-term follow up is important. This review outlines current diagnostic and therapeutic approaches to simple and extensive cervicofacial VMs. PMID:23188688

Richter, Gresham T; Braswell, Leah



Malignant fibrous histiocytoma/undifferentiated high-grade pleomorphic sarcoma of the maxillary sinus : report of a case and review of the literature.  


Malignant fibrous histiocytoma (MFH) also known as undifferentiated high-grade pleomorphic sarcoma (UHPS) is a soft tissue sarcoma, composed of undifferentiated mesenchymal tumors possessed fibrohistiocytic morphology without definite true histiocytic differentiation. Head and neck localization is very rare, showing an incidence ranging from 4 % to 10 % in different series of investigations. The most frequent involved sites in UHPS are the neck and parotid, followed by the scalp, face, anterior skull base and orbit. Upper aerodigestive tract, lateral skull base and ear are rare locations. The incidence of the lymphatic metastases is also rare. The aim of this article is to report a case of UHPS in the maxillary sinus with palatal, orbital and ethmoidal involvement, with lymphatic metastasis and its surgical treatment. In addition, we review the literature of similar cases of the past 12 years. PMID:23812657

Vuity, Drazsen; Bogdan, Sandor; Csurgay, Katalin; Sapi, Zoltan; Nemeth, Zsolt



Voluminous Extracardiac Adult Rhabdomyoma of the Neck: A Case Presentation  

PubMed Central

Introduction. Rhabdomyomas of the head and neck are exceptionally rare benign mesenchymal tumors. Rare cases have been reported to involve other sites of the body including the head and neck regions. Case Presentation. We report a case of voluminous extracardiac adult rhabdomyoma affecting adult patients and initially seen as slowly growing, indolent neoplasms. The patient is a seventy-year old male Italian patient. Conclusion. Adult extracardiac rhabdomyoma is a rare benign tumor that may present with symptoms that vary from aerodigestive tract obstruction to remaining asymptomatic for many years. Although histology is very characteristic, several differential diagnoses have to be considered. To our knowledge, this is the first case of voluminous adult-type symptomless rhabdomyoma.

Maglio, Riccardo; Francesco, Scicchitano; Paolo, Magistri; Stefano, Valabrega; Francesco, D'Angelo; Giovanni, Ramacciato



Basaloid squamous cell carcinoma of oral cavity with incongruent clinical course.  


Basaloid squamous cell carcinoma (BSCC) is a rare variant of SCC having a marked predilection for the upper aerodigestive tract. It is regarded as a high-grade tumour with increased propensity for metastasis to distant sites. The histological hallmark of BSCC is its dimorphic pattern of presentation with a characteristic basal cell component associated with squamous component. We report two cases of BSCC on the buccal mucosa and gingiva, respectively, with the former presenting as a primary lesion in a patient without a positive history of tobacco and alcohol use and the latter present as a seemingly metachronous development from carcinoma lung. The proliferative index of the two diverse yet similar entities was assessed by Ki-67 labelling index (LI) and the association of human papillomavirus (HPV) was detected with p16 monoclonal antibody. The intrinsically aggressive behaviour of BSCC and its association with HPV is highlighted. PMID:24051147

Patel, Pratik Nalinbhai; Mutalik, Vimi Sunil; Rehani, Shweta; Radhakrishnan, Raghu



Second primary squamous cell carcinoma arising in cutaneous flap reconstructions of two head and neck cancer patients  

PubMed Central

Early complications of myocutaneous flap transfers following surgical eradication of head and neck tumors have been extensively described. However, knowledge concerning long-term complications of these techniques remains limited. We report the cases of two patients with a prior history of squamous cell carcinoma of the head and neck (HNSCC), who developed a second primary SCC on the cutaneous surface of their flaps, years after reconstruction. Interestingly, it seems that the well-known risk of a second primary SCC in patients with previous head and neck carcinoma also applies to foreign tissues implanted within the area at risk. Given the important expansion of these interventions, this type of complication may become more frequent in the future. Therefore, long-term follow-up of patients previously treated for HNSCC not only requires careful evaluation of the normal mucosa of the upper aero-digestive tract, but also of the cutaneous surface of the flap used for reconstruction.

Monnier, Yan; Pasche, Philippe; Monnier, Philippe



Multiple Cancers of the Head and Neck  

PubMed Central

ABSTRACT Multiple head and neck cancers are not rare entities and according to studies in the literature, their incidence is increasing. The emergence of multiple cancers is explained by the phenomenon of "field cancerization". Patients with cancer of the upper digestive and respiratory tract develop most often a second malignancy, usually in the upper aero-digestive tract and among them, those with larynx cancer ranks first among patients with multiple cancers. In the literature and in practice, we met rare combination of multiple cancers, associations that appear to be "random", cannot be explained by any of the hypotheses developed: exposure to carcinogens, genetic susceptibility, and immunodeficiency or cancer treatments after index tumor. Follow-up of patients who have had a head and neck cancer and periodic control are important for early detection of multiple cancers.

HEROIU (CATALOIU), Adriana-Daniela; DANCIU, Cezara Elisabeta; POPESCU, Cristian Radu



An Unusual Localization of a Pleomorphic Adenoma in the Rhinopharynx  

PubMed Central

Pleomorphic adenoma is the most common benign tumor of the parotid glands. Rarely it may arise from minor salivary glands of the upper aerodigestive tract. A 57-year-old woman was admitted at our institution presenting with nasal obstruction. Endoscopic evaluation revealed a pedicled mass in the rhinopharynx. After radiological examination, we opted for a transnasal endoscopic-assisted excision of the mass under general anaesthesia. Histological evaluation deponed for pleomorphic adenoma with clear surgical margins. No endoscopic evidence of local recurrence has been shown after 48 months of followup. In the literature, few cases of pleomorphic adenoma arising in the rhinopharynx have been reported. The introduction of endoscopy, as shown by our experience, leads to important benefits in the identification, treatment, and followup of such rhinopharyngeal benign tumors.

Pagella, Fabio; Chu, Francesco; Pusateri, Alessandro; Matti, Elina



Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage  

SciTech Connect

Factors that contribute to an increased prevalence of squamous cell carcinoma of the upper aerodigestive tract among young adults in the United States remain unknown. A potential etiologic factor may relate to a genetically controlled sensitivity to environmental carcinogens. This study, therefore, examined 20 young adult patients who had squamous cell carcinoma for mutagen-induced chromosome sensitivity. Lymphocytes from respective patients were cultured, exposed to the clastogen bleomycin, arrested during metaphase, and examined quantitatively for chromosome breakage. The young adult population with squamous cell carcinoma expressed a significantly increased number of bleomycin-induced chromosome breaks per cell. Furthermore, among the study patients, chromosome sensitivity was most apparent in the non-tobacco users and in patients less than 30 years of age. The expression of such chromosome fragility following mutagen exposure should be considered in epidemiologic studies that intend to define risk factors for development of head and neck cancer.

Schantz, S.P.; Hsu, T.C.; Ainslie, N.; Moser, R.P. (Univ. of Texas M.D. Anderson Cancer Center, Houston (USA))



Ingestion of caustic cosmetic products.  


Twelve children over a 6-year period (1985 to 1991) underwent aerodigestive tract endoscopy after ingestion of lye-containing cosmetic products. All children were less than 2 years of age and had facial and/or oral cavity burns. Eleven of these patients ingested alkaline hair products such as "activators" or "relaxers." Endoscopy revealed pharyngeal burns in five patients but no laryngeal or esophageal burns in any patient. Erythema of the esophageal mucosa was seen in one patient. One patient ingested a solution used in fingernail decorating. This patient sustained extensive superficial burns of the pharynx, larynx, and esophagus and required intubation and admission to the intensive care unit. No long-term sequelae developed. Cosmetic products containing caustic chemicals represent a significant health risk to small children, especially because child-proof packaging is not standard for these products. PMID:8247560

Stenson, K; Gruber, B



Quality of life in relation to upper and lower respiratory conditions among retired 9\\/11-exposed firefighters with pulmonary disability  

Microsoft Academic Search

Purpose  To examine health-related quality of life (HRQoL) and World Trade Center (WTC) cough syndrome conditions in male firefighters\\u000a who retired due to a 9\\/11-related pulmonary disability.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  From 3\\/1\\/2008 to 1\\/31\\/2009, we contacted 275 disability-retired firefighters and compared their HRQoL and current aerodigestive\\u000a conditions to those from WTC-exposed non-disabled retired and active firefighters. Relationships between HRQoL and explanatory\\u000a variable(s) were examined

Amy Berninger; Mayris P. Webber; Jessica Weakley; Jackson Gustave; Rachel Zeig-Owens; Roy Lee; Fairouz Al-Othman; Hillel W. Cohen; Kerry Kelly; David J. Prezant



Pictorial essay: Salivary gland imaging  

PubMed Central

Salivary glands are the first organs of digestion secreting their digestive juices into the oral cavity. Parotid, submandibular, and sublingual glands are the major paired salivary glands in the decreasing order of their size. In addition, multiple small minor salivary glands are noted randomly distributed in the upper aerodigestive tract, including paranasal sinuses and parapharyngeal spaces. The imaging is directed to the major salivary glands. Commonly used imaging methods include plain radiography and conventional sialography. Recently, high-resolution ultrasonography (HRUS) is being increasingly used for targeted salivary gland imaging. However, the advent of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionized the imaging of salivary glands. This article illustrates the role of imaging in evaluating the variegated disease pattern of the major salivary glands.

Rastogi, Rajul; Bhargava, Sumeet; Mallarajapatna, Govindarajan Janardan; Singh, Sudhir Kumar



Molecular Pathology of Head and Neck Cancer: Implications for Diagnosis, Prognosis, and Treatment  

PubMed Central

The prototypic head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract, demonstrates squamous differentiation microscopically, involves older men with a long history of cigarette smoking and alcohol consumption, and is treated by multimodality therapy. HNSCC has long been regarded as a uniform disease process requiring a methodical and unwavering therapeutic approach. Divergence in epidemiologic trends among HNSCCs arising from different anatomic sites has introduced a view that, morphologic repetition aside, head and neck cancers form a heterogeneous group. This view has been supported at the molecular genetic level. A more complete understanding of the molecular genetics of head and neck cancer is providing new insights into long-held but poorly comprehended concepts such as field cancerization and is introducing various biomarkers with potential application for diagnosing, staging, monitoring, and prognosticating HNSCC.

Pai, Sara I.; Westra, William H.



Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma  

PubMed Central

Background Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. Objective This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.

Mohd Bakri, Marina; Mohd Hussaini, Haizal; Rachel Holmes, Ann; David Cannon, Richard; Mary Rich, Alison



[Medical handicap and otorhinolaryngologic foreign bodies about 4 original cases].  


The multiple variant of aero-digestive foreign bodies' pathology determine many complex aspects with regard to their physiopathology, nature, and their location. The presence of a medical handicap or any particular condition could increase morbidity and expose to major risks. We are reporting here about 4 cases including an esophagus foreign body in a leprosies patient, an esophago-gastric case in a mental disorder patient, and two laryngeal-tracheal-bronchial cases during epileptic episodes. From the rarity of such accidents in an adult to their happening during a loss of consciousness or a delirious state, the clinical history is always missing. The symptoms are atypical and may misguide. The classical penetration syndrome cannot be reported. Only a clinical examination carefully conducted and completed with targeted para clinical examinations can help make early diagnosis. Endoscopy of the Esophagus on one hand, and endoscopy of the trachea and lungs on the other hand were used to extract these foreign bodies. PMID:21435999

Timbo, S K; Keita, M A; Doumbia-Singare, K; Togola-Konipo, F; Traore, L; Guindo, B; Soumaoro, S; Ag Mohamed, A



Extramedullary plasmocytoma relapsing at differents sites: an unusual presentation  

PubMed Central

Extramedullary plasmacytoma (EMP) is an uncommon plasma cell neoplasm results from plasma cell proliferation and consists of monoclonal plasmacytic infiltration, without bone marrow involvement and any other systemic characteristics of multiple myeloma. EMP accounts for 3% of all plasma cell neoplasms and approximately 80% to 90% of EMP involve submucosa of the upper aerodigestive, while scrotal, dermis and retroperitoneal infiltration are very rare. There are no consensus guidelines for treatment, but EMP is highly radiosensitive, surgery may be considered for some sites, but 11 at 30% can progress in multiple myeloma. We report here an exceptional case of recurrent EMP in much localization. It's about a man 72 years old with initially testicular plasmocytoma who generalized the plasmacytic infiltration after 16 months in skin and progressively in mediastinal and retroperitoneal plasmacytoma, without any medullar and bone involvement.

Ahnach, Maryame; Marouan, Sofia; Rachid, Mohamed; Madani, Abdellah; Quessar, Asmaa; Benchekroun, Said; Quachouh, Meryem



Acute sinusitis.  


Sinusitis is a common patient complaint that carries with it a large economic burden. It is one of the most common reasons patients visit their primary care physician. Acute bacterial rhinosinusitis (ABRS) can be distinguished from other forms of rhinosinusitis based on symptom duration of <4 weeks in a patient with purulent rhinorrhea associated with facial pain or pressure. Native upper aerodigestive tract bacteria are the most common etiologic agents. Treatment of ABRS is targeted primarily at symptom improvement. Amoxicillin can be used based on the clinical scenario and patient comorbidities. Computed tomographic scans are reserved for complicated presentations or when there is concern for intracranial extension or other complications. A systematic approach to ABRS will allow for improved patient quality of life and a decreased overall economic burden of this common entity. PMID:24096952

Feldt, Brent; Dion, Gregory R; Weitzel, Erik K; McMains, Kevin C



CT-clinical approach to patients with symptoms related to the V, VII, IX-XII cranial nerves and cervical sympathetics  

SciTech Connect

Forty-three patients who had signs and symptoms possibly related to the extracranial course of cranial nerves V, VII, IX, X-XII, and the cervical sympathetics were examined prospectively using high resolution CT to obtain images of thin sections during rapid drip infusion of contrast material. Anatomic areas in the scan protocols included the posterior fossa, cavernous and paranasal sinuses, skull base, temporal bone, nasopharynx, parotid gland, tongue base, and neck. Nine of the 23 patients with possible fifth nerve deficits had extracranial structural lesions that explained the symptoms; none of these nine, however, had typical trigeminal neuralgia. Of eight patients with peripheral seventh nerve abnormalities, two had positive findings on scans. Of five patients presenting with referred ear pain, three had carcinoma of the upper aerodigestive tract. The authors' experience suggests that patients at high risk for structural lesions responsible for cranial nerve deficits can be selected by clinical criteria. Protocols for each clinical setting are presented.

Kalovidouris, A.; Mancuso, A.A.; Dillon, W.



Update of Assessment of Survival in Head and Neck Cancer after Regional Recurrence  

PubMed Central

Objective. To evaluate site of regional recurrence in patients with squamous cell carcinoma of upper aerodigestive tract after neck dissection and the results of salvage treatment. Methods. 95 patients with regional recurrence as the first manifestation of relapse were selected between 943 patients who underwent neck dissection. We evaluated level and side of recurrence, as well disease control after salvage treatment. Results. Level II was the most frequent site of recurrence. Salvage treatment was performed in 51% of ipsilateral and in 75% of contralateral (nondissected neck) recurrences. Control of the disease 12 months after salvage surgery was 25% in the ipsilateral and 37% in contralateral recurrences. Conclusions. Cervical recurrences occur predominantly in level II. Relapse in level I is frequent only in oral cavity tumors and relapse in level V is rare. The neck recurrence carries a poor prognosis even among patients who underwent retreatment with curative intent.

Amar, Ali; Chedid, Helma Maria; Rapoport, Abrao; Dedivitis, Rogerio Aparecido; Cernea, Claudio Roberto; Brandao, Lenine Garcia; Curioni, Otavio Alberto



[Considerations concerning respiratory physiopathology in a case of total arhinia].  


The Authors describe their personal experience in a rare case of total arhinia in a young boy, now seven years old, whose psycho-physical development is normal and who is healthy except for recurrent conjunctivitis due to the absence of nasolacrimal ducts. The Authors consider the possibility that in the case of total absence of the nasal function, as in total arhinia, the oropharyngeal and laryngotracheobronchial mucosa may acquire those functional and defensive properties typically belonging to nasal mucosa. In the subject in question, in fact, functional respiratory and immunosecretory parameters are normal. On the other hand, being well known how problematic acquired severely compromised nasal functions are one would think that only in the case of congenital absence of the nose can the lower aerodigestive structures compensate successfully. In the Authors' opinion this clinic observation contradicts the widely held belief that nasal respiration is absolutely necessary from the moment of birth on. PMID:8036890

Galetti, R; Dallari, S; Bruzzi, M; Vincenzi, A; Galetti, G



Consumption of alcohol and risk of cancer among men: a 30 year cohort study in Lithuania.  


Studies have indicated hazardous consumption of large quantities of alcohol among adults in Lithuania. We assessed the associations of alcohol consumption at baseline with cancer incidence among men in a population-based cohort study, using Cox models adjusted for smoking, education and body mass index. Attained age was used as a time-scale. During follow-up (1978-2008) 1,698 men developed cancer. A higher amount of alcohol consumption (?140.1 g/week vs. 0.1-10.0 g/week) was positively associated with increased risk of total cancer [hazard ratio (HR) = 1.36, 95 % confidence interval (95 % CI) 1.11, 1.65], upper aerodigestive tract cancer (HR = 2.79, 95 % CI 1.23, 6.34) and alcohol-related cancers (i.e. oral cavity, pharynx, larynx, oesophagus, colorectal and liver cancer) (HR = 1.88, 95 % CI 1.25, 2.85). Compared to occasional drinkers (a few times/year), drinkers 2-7 times/week showed an increased risk of total (HR = 1.45, 95 % CI 1.16, 1.83), alcohol-related (HR = 1.83 95 % CI 1.14, 2.93) and other cancers (HR = 1.35, 95 % CI 1.04, 1.76). Our results showed no statistically significant associations between quantity of alcohol intake per one occasion and risk of cancer. About 13 % of total, 35 % of upper aerodigestive tract, 22 % of alcohol-related and 10 % of other cancer cases were due to alcohol consumption in this cohort of men. PMID:23700027

Everatt, Ruta; Tamosiunas, Abdonas; Virviciute, Dalia; Kuzmickiene, Irena; Reklaitiene, Regina




PubMed Central

Background Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. Methods Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center. Results In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were overrepresented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis. Conclusions Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease.

Bellamy, Christopher O.C.; DiMartini, Andrea M.; Ruppert, Kris; Jain, Ashok; Dodson, Forrest; Torbenson, Michael; Starzl, Thomas E.; Fung, John J.; Demetris, Anthony J.



Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells.  


The genotoxicity of phthalates, widely used plasticizers, has been shown previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non-tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human lymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non-tumor patients and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570). Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA-damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively. PMID:11301413

Kleinsasser, N H; Wallner, B C; Kastenbauer, E R; Weissacher, H; Harréus, U A



Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer.  


The occurrence of second primary tumors (SPTs) following adjuvant therapy for resected stages II and IIIa non-small cell lung cancer (NSCLC) was investigated. Data regarding SPTs were prospectively collected in all patients accrued to Eastern Cooperative Group Oncology E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). Four hundred eighty-eight patients were accrued to the study, 242 to the RT arm and 246 to the CRT arm. Median follow-up was 73 months. Thirty patients (6.1%) developed 33 SPTs, 20 in the RT arm and ten in the CRT arm. Ten SPTs occurred within the upper aerodigestive tract, six in the RT arm and four in the CRT arm. Twenty-three SPTs occurred in other organs, 17 in the RT arm and six in the CRT arm. Median time to detection of a SPT for those patients randomized to RT and CRT was 43 and 36 months, respectively. The incidence of SPTs was 1.8% per patient-year of follow-up. Excluding skin tumors, the relative risk of death following diagnosis of a SPT for patients randomized to the CRT arm as compared with those randomized to RT alone was 2.26 (95% confidence interval, 0.78-5.58, P=0.12). Patients are at risk for developing a SPT following resection of stages II and IIIa NSCLC. The majority of SPTs occur outside the aerodigestive tract. Following development of a non-skin SPT, the survival difference between patients who had received adjuvant CRT and those treated with adjuvant RT alone was not significant. PMID:14512191

Keller, Steven M; Vangel, Mark G; Wagner, Henry; Schiller, Joan; Herskovic, Arnold; Komaki, Ritsuko; Gray, Robert; Marks, Randolph S; Perry, Michael C; Livingston, Robert B; Johnson, David H



Pharyngeal airway protective reflexes are triggered before the maximum volume of fluid that the hypopharynx can safely hold is exceeded.  


Aerodigestive reflexes triggered by pharyngeal stimulation can protect the airways by clearing fluid from the pharynx. The objective of this study was to determine the relationship between the maximum capacity of fluid that can safely dwell in the hypopharynx [hypopharyngeal safe volume (HPSV)] before spilling into the larynx and the threshold volumes required to trigger pharyngoglottal closure reflex (PGCR), pharyngo-upper esophageal sphincter contractile reflex (PUCR), and reflexive pharyngeal swallow (RPS). Twenty-five healthy volunteers (mean age 24 yr, 8 males) were studied in the semi-inclined supine position. PGCR, PUCR, and RPS were elicited using techniques of concurrent upper esophageal sphincter manometry and pharyngo-laryngoscopy. The hypopharynx was then anesthetized to abolish RPS. HPSV was determined by infusing water in the pharynx, and perfusion was stopped when the infusate reached the superior margin of the interarytenoid fold. The threshold volumes for triggering PGCR, PUCR, and RPS by slow and rapid injections before pharyngeal anesthesia were 0.18 ± 0.02 and 0.09 ± 0.02 ml; 0.20 ± 0.020 and 0.13 ± 0.04 ml; and 0.61 ± 0.04 and 0.4 ± 0.06 ml, respectively. All of the above volumes were significantly smaller than the HPSV (0.70 ± 0.06 ml, P < 0.01) except for the threshold volume to elicit RPS during slow perfusion, which was not significantly different (P = 0.23). We conclude that pharyngeal aerodigestive reflexes are triggered by both slow and rapid pharyngeal perfusion of water at significantly smaller volumes than the maximum capacity of the hypopharynx to safely hold contents without spilling into the airway. These reflexes thereby aid in prevention of aspiration. PMID:21566013

Dua, Kulwinder; Surapaneni, Sri Naveen; Kuribayashi, Shiko; Hafeezullah, Muhammad; Shaker, Reza



Automating the expert consensus paradigm for robust lung tissue classification  

NASA Astrophysics Data System (ADS)

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.



A 13C-NMR study of exopolysaccharide synthesis in Rhizobium meliloti Su47 strain  

NASA Astrophysics Data System (ADS)

Metabolic pathways implied in the synthesis of succinoglycan produced by the Su47 strain of R. meliloti were evaluated by 13C-NMR spectroscopy after incubation with [1{-}13C] or [2{-}13C] glucose. The biosynthesis of this polymer by R. meliloti from glucose occurred by a direct polymerisation of the introduced glucose and by the pentose phosphate pathway. Les voies métaboliques impliquées dans la synthèse du succinoglycane produit par la souche Su47 de R. meliloti ont été évaluées par la spectroscopie de RMN du carbone 13 après incubation des cellules avec du [1{-}13C] ou [2{-}13C] glucose. La biosynthèse de ce polymère à partir du glucose se produit par polymérisation directe du glucose et par la voie des pentoses phosphate.

Tavernier, P.; Portais, J.-C.; Besson, I.; Courtois, J.; Courtois, B.; Barbotin, J.-N.



Durability of Three-Way Platinum and Rhodium Catalysts in Oxidizing, Reducing and Cycled Environments  

NASA Astrophysics Data System (ADS)

The three-way catalytic behaviour (CO, HC and NOx conversions and light-off temperatures) of MN/CeO2/Al2O3 (MN: Pt, Rh, Pt-Rh) catalysts, fresh and aged under severe oxidizing, reducing and cycled environments, has been analyzed. The bimetallic Pt-Rh catalyst resulted the most active among those tested. Le comportement catalytique (conversions de CO, HC et NOx et temperature d'ignition) de catalyseurs trois-voies MN/CeO2/Al2O3 (MN : Pt, Rh, Pt-Rh) frais et vieillis sous sévère conditions en environnement oxydant, réducteur et cyclique, a été analysé. Les résultats obtenus indiquent que parmi les catalyseurs étudiés, le bi- metallique Pt-Rh est le plus actif.

Botas, J. A.; Ferret, R.; Gutiérrez-Ortiz, M. A.; González-Velasco, J. R.



La pr?vention de l'infection par le virus respiratoire syncytial  

PubMed Central

L’infection par le virus respiratoire syncytial (VRS) est la principale cause d’infection des voies respiratoires inférieures chez les jeunes enfants et pour cette raison, bon nombre des prématurés et des enfants présentant d’autres facteurs de risque doivent être hospitalisés chaque année au Canada. Le palivizumab, un anticorps monoclonal anti-VRS, peut réduire le taux d’hospitalisation et la gravité de la maladie d’un petit groupe de prématurés ou de nourrissons à haut risque pendant leur première saison de VRS. Le présent document de principes contient une analyse des publications ainsi que des recommandations à l’intention des médecins canadiens au sujet de son utilisation chez les prématurés et les autres nourrissons à risque.

Samson, L



La pr?vention des infections par le virus respiratoire syncytial  

PubMed Central

RÉSUMÉ L’infection par le virus respiratoire syncytial (VRS) est la principale cause d’infections des voies respiratoires inférieures chez les jeunes enfants. Le palivizumab, un anticorps monoclonal anti-VRS, réduit le taux d’hospitalisation des enfants à haut risque mais est très coûteux. Le présent document de principes remplace les trois précédents documents de principes de la Société canadienne de pédiatrie sur le sujet et est mis à jour principalement pour traiter des récentes modifications aux lignes directrices de l’American Academy of Pediatrics dans le contexte canadien. Il contient une analyse des publications ainsi que des recommandations au sujet de l’utilisation du palivizumab chez les enfants à haut risque

Robinson, JL



Lesion quantification in oncological positron emission tomography: a maximum likelihood partial volume correction strategy.  


A maximum likelihood (ML) partial volume effect correction (PVEC) strategy for the quantification of uptake and volume of oncological lesions in 18F-FDG positron emission tomography is proposed. The algorithm is based on the application of ML reconstruction on volumetric regional basis functions initially defined on a smooth standard clinical image and iteratively updated in terms of their activity and volume. The volume of interest (VOI) containing a previously detected region is segmented by a k-means algorithm in three regions: A central region surrounded by a partial volume region and a spill-out region. All volume outside the VOI (background with all other structures) is handled as a unique basis function and therefore "frozen" in the reconstruction process except for a gain coefficient. The coefficients of the regional basis functions are iteratively estimated with an attenuation-weighted ordered subset expectation maximization (AWOSEM) algorithm in which a 3D, anisotropic, space variant model of point spread function (PSF) is included for resolution recovery. The reconstruction-segmentation process is iterated until convergence; at each iteration, segmentation is performed on the reconstructed image blurred by the system PSF in order to update the partial volume and spill-out regions. The developed PVEC strategy was tested on sphere phantom studies with activity contrasts of 7.5 and 4 and compared to a conventional recovery coefficient method. Improved volume and activity estimates were obtained with low computational costs, thanks to blur recovery and to a better local approximation to ML convergence. PMID:19673203

De Bernardi, Elisabetta; Faggiano, Elena; Zito, Felicia; Gerundini, Paolo; Baselli, Giuseppe



Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis  

PubMed Central

Background Tuberculosis (TB) accounts of much of the morbidity and mortality associated with HIV. We evaluate the cost-effectiveness of different strategies to actively screen for TB disease in HIV positive individuals, where isoniazid preventative therapy (IPT) is given to those screening negative, and use value of information analysis (VOI) to identify future research priorities. Methodology/ Principal Findings We built an individual sampling model to investigate the costs (2010 US Dollars) and consequences of screening for TB, and providing TB treatment or IPT in adults testing HIV positive in Sub-Saharan Africa. A systematic review and meta-analysis was conducted to assess performance of the nine different TB screening strategies evaluated. Probabilistic sensitivity analysis was conducted to incorporate decision uncertainty, and expected value of perfect information for the entire model and for groups of parameters was calculated. Screening all HIV infected individuals with sputum microscopy was the least costly strategy, with other strategies not cost-effective at WHO recommended thresholds. Screening those with TB symptoms with sputum microscopy and CXR would be cost-effective at a threshold ICER of $7,800 per quality-adjusted life year (QALY), but associated with significant uncertainty. VOI analysis suggests further information would be of value. Conclusions/ Significance Resource-constrained countries in sub-Saharan Africa wishing to scale up TB preventative services in their HIV infected populations should consider expanding laboratory facilities to enable increased screening for TB with sputum microscopy, whilst improved estimates of the TB prevalence in the population to be screened are needed, as it may influence the optimal strategy.

Maheswaran, Hendramoorthy; Barton, Pelham



Deformable planning CT to cone-beam CT image registration in head-and-neck cancer  

SciTech Connect

Purpose: The purpose of this work was to implement and validate a deformable CT to cone-beam computed tomography (CBCT) image registration method in head-and-neck cancer to eventually facilitate automatic target delineation on CBCT. Methods: Twelve head-and-neck cancer patients underwent a planning CT and weekly CBCT during the 5-7 week treatment period. The 12 planning CT images (moving images) of these patients were registered to their weekly CBCT images (fixed images) via the symmetric force Demons algorithm and using a multiresolution scheme. Histogram matching was used to compensate for the intensity difference between the two types of images. Using nine known anatomic points as registration targets, the accuracy of the registration was evaluated using the target registration error (TRE). In addition, region-of-interest (ROI) contours drawn on the planning CT were morphed to the CBCT images and the volume overlap index (VOI) between registered contours and manually delineated contours was evaluated. Results: The mean TRE value of the nine target points was less than 3.0 mm, the slice thickness of the planning CT. Of the 369 target points evaluated for registration accuracy, the average TRE value was 2.6{+-}0.6 mm. The mean TRE for bony tissue targets was 2.4{+-}0.2 mm, while the mean TRE for soft tissue targets was 2.8{+-}0.2 mm. The average VOI between the registered and manually delineated ROI contours was 76.2{+-}4.6%, which is consistent with that reported in previous studies. Conclusions: The authors have implemented and validated a deformable image registration method to register planning CT images to weekly CBCT images in head-and-neck cancer cases. The accuracy of the TRE values suggests that they can be used as a promising tool for automatic target delineation on CBCT.

Hou Jidong; Guerrero, Mariana; Chen, Wenjuan; D'Souza, Warren D. [Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, Maryland 21201 (United States); Department of Radiotherapy, Fujian Provincial Cancer Hospital, Fujian Medical University, 91 Maluding Fuma Road, Fuzhou, Fujian 350014 (China); Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, Maryland 21201 (United States)



"First pain" in humans: convergent and specific forebrain responses  

PubMed Central

Background Brief heat stimuli that excite nociceptors innervated by finely myelinated (A?) fibers evoke an initial, sharp, well-localized pain ("first pain") that is distinguishable from the delayed, less intense, more prolonged dull pain attributed to nociceptors innervated by unmyelinated (C) fibers ("second pain"). In the present study, we address the question of whether a brief, noxious heat stimulus that excites cutaneous A? fibers activates a distinct set of forebrain structures preferentially in addition to those with similar responses to converging input from C fibers. Heat stimuli at two temperatures were applied to the dorsum of the left hand of healthy volunteers in a functional brain imaging (fMRI) paradigm and responses analyzed in a set of volumes of interest (VOI). Results Brief 41°C stimuli were painless and evoked only C fiber responses, but 51°C stimuli were at pain threshold and preferentially evoked A? fiber responses. Most VOI responded to both intensities of stimulation. However, within volumes of interest, a contrast analysis and comparison of BOLD response latencies showed that the bilateral anterior insulae, the contralateral hippocampus, and the ipsilateral posterior insula were preferentially activated by painful heat stimulation that excited A? fibers. Conclusions These findings show that two sets of forebrain structures mediate the initial sharp pain evoked by brief cutaneous heat stimulation: those responding preferentially to the brief stimulation of A? heat nociceptors and those with similar responses to converging inputs from the painless stimulation of C fibers. Our results suggest a unique and specific physiological basis, at the forebrain level, for the "first pain" sensation that has long been attributed to A? fiber stimulation and support the concept that both specific and convergent mechanisms act concurrently to mediate pain.



Fiducial-less 2D-3D spine image registration using spine region segmented in CT image  

NASA Astrophysics Data System (ADS)

The target pose (position and orientation) of a spinal lesion can be determined using image registration of a pair of two-dimensional (2D) x-ray projection images and a pre-treatment three-dimensional (3D) CT image. This is useful for detecting, tracking and correcting for patient movement during image-guided spinal radiotherapy and radiosurgery. We recently developed a fiducial-less 2D-3D spine image registration that localizes spinal targets by directly tracking adjacent skeletal structures and thereby eliminates the need for implanted fiducials. Experience has shown this method to be robust under a wide range of clinical circumstances. However, image artifacts in digitally reconstructed radiographs (DRRs) that can be introduced by breathing during CT scanning or by other surrounding structures such as ribs have the negative effects on image registration performance. Therefore, we present an approach to eliminate the image artifacts in DRRs for a more robust registration. The spinal structures in the CT volume are approximately segmented in a semi-automatic way and saved as a volume of interest (VOI). The DRRs are then generated within the spine VOI for two orthogonal projections. During radiation treatment delivery, two X-ray images are acquired simultaneously in near real time. Then each X-ray image is registered with the DRR image to obtain 2D local displacements of skeletal structures. The 3D tumor position is calculated from the 2D displacements by 2D-to-3D back-projection and geometric transformation. Experiments on clinical data were conducted to evaluate the performance of the improved registration. The results showed that spine segmentation substantially improves image registration performance.

Fu, Dongshan; Wang, Hongwu; Maurer, Calvin R., Jr.; Kuduvalli, Gopinath



Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis  

NASA Astrophysics Data System (ADS)

Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

Ward, T.; Fleming, J. S.; Hoffmann, S. M. A.; Kemp, P. M.



Breast segmentation in MR images using three-dimensional spiral scanning and dynamic programming  

NASA Astrophysics Data System (ADS)

Magnetic resonance (MR) imaging has been widely used for risk assessment and diagnosis of breast cancer in clinic. To develop a computer-aided diagnosis (CAD) system, breast segmentation is the first important and challenging task. The accuracy of subsequent quantitative measurement of breast density and abnormalities depends on accurate definition of the breast area in the images. The purpose of this study is to develop and evaluate a fully automated method for accurate segmentation of breast in three-dimensional (3-D) MR images. A fast method was developed to identify bounding box, i.e., the volume of interest (VOI), for breasts. A 3-D spiral scanning method was used to transform the VOI of each breast into a single two-dimensional (2-D) generalized polar-coordinate image. Dynamic programming technique was applied to the transformed 2-D image for delineating the "optimal" contour of the breast. The contour of the breast in the transformed 2-D image was utilized to reconstruct the segmentation results in the 3-D MR images using interpolation and lookup table. The preliminary results on 17 cases show that the proposed method can obtain accurate segmentation of the breast based on subjective observation. By comparing with the manually delineated region of 16 breasts in 8 cases, an overlap index of 87.6% +/- 3.8% (mean +/- SD), and a volume agreement of 93.4% +/- 4.5% (mean +/- SD) were achieved, respectively. It took approximately 3 minutes for our method to segment the breast in an MR scan of 256 slices.

Jiang, Luan; Lian, Yanyun; Gu, Yajia; Li, Qiang



Performance evaluation of an automatic anatomy segmentation algorithm on repeat or four-dimensional CT images using a deformable image registration method  

PubMed Central

Purpose Auto-propagation of anatomical region-of-interests (ROIs) from the planning CT to daily CT is an essential step in image-guided adaptive radiotherapy. The goal of this study was to quantitatively evaluate the performance of the algorithm in typical clinical applications. Method and Materials We previously adopted an image intensity-based deformable registration algorithm to find the correspondence between two images. In this study, the ROIs delineated on the planning CT image were mapped onto daily CT or four-dimentional (4D) CT images using the same transformation. Post-processing methods, such as boundary smoothing and modification, were used to enhance the robustness of the algorithm. Auto-propagated contours for eight head-and-neck patients with a total of 100 repeat CTs, one prostate patient with 24 repeat CTs, and nine lung cancer patients with a total of 90 4D-CT images were evaluated against physician-drawn contours and physician-modified deformed contours using the volume-overlap-index (VOI) and mean absolute surface-to-surface distance (ASSD). Results The deformed contours were reasonably well matched with daily anatomy on repeat CT images. The VOI and mean ASSD were 83% and 1.3 mm when compared to the independently drawn contours. A better agreement (greater than 97% and less than 0.4 mm) was achieved if the physician was only asked to correct the deformed contours. The algorithm was robust in the presence of random noise in the image. Conclusion The deformable algorithm may be an effective method to propagate the planning ROIs to subsequent CT images of changed anatomy, although a final review by physicians is highly recommended.

Wang, He; Garden, Adam S.; Zhang, Lifei; Wei, Xiong; Ahamad, Anesa; Kuban, Deborah A.; Komaki, Ritsuko; O'Daniel, Jennifer; Zhang, Yongbin; Mohan, Radhe; Dong, Lei



In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese  

PubMed Central

Background Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives Our goal was to determine whether in vivo brain levels of ?-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure. Methods We used T1-weighted magnetic resonance imaging (MRI) to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate, and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. We used the MEGA-PRESS MRS sequence to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia [GABA-VOI (volume of interest)]. Results Seven of 10 exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p = 0.014) in the ratio of GABA to total creatine (GABA/tCr) in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%; p = 0.04) of NAA/tCr in frontal cortex that strongly correlated with cumulative Mn exposure (R = ?0.93; p < 0.001). Conclusions We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased NAA levels in the frontal cortex, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the noninvasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity.

Dydak, Ulrike; Jiang, Yue-Ming; Long, Li-Ling; Zhu, He; Chen, Jian; Li, Wen-Mei; Edden, Richard A.E.; Hu, Shuguang; Fu, Xue; Long, Zaiyang; Mo, Xue-An; Meier, Dieter; Harezlak, Jaroslaw; Aschner, Michael; Murdoch, James B.; Zheng, Wei



MR-based hypoxia measures in human glioma.  


Hypoxia plays a central role in tumor stem cell genesis and is related to a more malignant tumor phenotype, therapy resistance (e.g. in anti-angiogenic therapies) and radio-insensitivity. Reliable hypoxia imaging would provide crucial metabolic information in the diagnostic work-up of brain tumors. In this study, we applied a novel BOLD-based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients and investigated potential benefits and drawbacks. Forty-five glioma patients were examined preoperatively in a pilot study on a 3T MR scanner. rOEF was calculated from quantitative transverse relaxation rates (T2, T2*) and cerebral blood volume (CBV) using a quantitative BOLD approach. rOEF maps were assessed visually and by means of a volume of interest (VOI) analysis. In six cases, MRI-targeted biopsy samples were analyzed using HIF-1?-immunohistochemistry. rOEF maps could be obtained with a diagnostic quality. Focal spots with high rOEF values were observed in the majority of high-grade tumors but in none of the low-grade tumors. VOI analysis revealed potentially hypoxic tumor regions with high rOEF in contrast-enhancing tumor regions as well as in the non-enhancing infiltration zone. Systematic bias was found as a result of non-BOLD susceptibility effects (T2*) and contrast agent leakage affecting CBV. Histological samples demonstrated reasonable correspondence between MRI characteristics and HIF-1?-staining. The presented method of rOEF imaging is a promising tool for the metabolic characterization of human glioma. For the interpretation of rOEF maps, confounding factors must be considered, with a special focus on CBV measurements in the presence of contrast agent leakage. Further validation involving a bigger cohort and extended immuno-histochemical correlation is required. PMID:23918147

Tóth, Vivien; Förschler, Annette; Hirsch, Nuria M; den Hollander, Jürgen; Kooijman, Hendrik; Gempt, Jens; Ringel, Florian; Schlegel, Jürgen; Zimmer, Claus; Preibisch, Christine



Assessment of tumour response with (18)F-fluorodeoxyglucose positron emission tomography using three-dimensional measures compared to SUVmax--a phantom study.  


SUVmax is currently the most common semi-quantitative method of response assessment on FDG PET. By defining the tumour volume of interest (VOI), a measure of total glycolytic volume (TGV) may be obtained. We aimed to comprehensively examine, in a phantom setting, the accuracy of TGV in reflecting actual lesion activity and to compare TGV with SUVmax for response assessment. The algorithms for VOI generation from which TGV was derived included fixed threshold techniques at 50% of maximum (MAX50), 70% of maximum (MAX70), an adaptive threshold of 50% of (maximum + background)/2 (BM50) and a semi-automated iterative region-growing algorithm, GRAB. Comparison with both actual lesion activity and response scenarios was performed. SUVmax correlated poorly with actual lesion activity (r = 0.651) and change in lesion activity (r = 0.605). In a response matrix scenario SUVmax performed poorly when all scenarios were considered, but performed well when only clinically likely scenarios were included. The TGV derived using MAX50 and MAX70 algorithms performed poorly in evaluation of lesion change. The TGV derived from BM50 and GRAB algorithms however performed extremely well in correlation with actual lesion activity (r = 0.993 and r = 0.982, respectively), change in lesion activity (r = 0.972 and r = 0.963, respectively) and in the response scenario matrix. TGV(GRAB) demonstrated narrow confidence bands when modelled with actual lesion activity. Measures of TGV generated by iterative algorithms such as GRAB show potential for increased sensitivity of metabolic response monitoring compared to SUVmax, which may have important implications for improved patient care. PMID:18653927

Boucek, J A; Francis, R J; Jones, C G; Khan, N; Turlach, B A; Green, A J



Assessment of tumour response with 18F-fluorodeoxyglucose positron emission tomography using three-dimensional measures compared to SUVmax—a phantom study  

NASA Astrophysics Data System (ADS)

SUVmax is currently the most common semi-quantitative method of response assessment on FDG PET. By defining the tumour volume of interest (VOI), a measure of total glycolytic volume (TGV) may be obtained. We aimed to comprehensively examine, in a phantom setting, the accuracy of TGV in reflecting actual lesion activity and to compare TGV with SUVmax for response assessment. The algorithms for VOI generation from which TGV was derived included fixed threshold techniques at 50% of maximum (MAX50), 70% of maximum (MAX70), an adaptive threshold of 50% of (maximum + background)/2 (BM50) and a semi-automated iterative region-growing algorithm, GRAB. Comparison with both actual lesion activity and response scenarios was performed. SUVmax correlated poorly with actual lesion activity (r = 0.651) and change in lesion activity (r = 0.605). In a response matrix scenario SUVmax performed poorly when all scenarios were considered, but performed well when only clinically likely scenarios were included. The TGV derived using MAX50 and MAX70 algorithms performed poorly in evaluation of lesion change. The TGV derived from BM50 and GRAB algorithms however performed extremely well in correlation with actual lesion activity (r = 0.993 and r = 0.982, respectively), change in lesion activity (r = 0.972 and r = 0.963, respectively) and in the response scenario matrix. TGVGRAB demonstrated narrow confidence bands when modelled with actual lesion activity. Measures of TGV generated by iterative algorithms such as GRAB show potential for increased sensitivity of metabolic response monitoring compared to SUVmax, which may have important implications for improved patient care.

Boucek, J. A.; Francis, R. J.; Jones, C. G.; Khan, N.; Turlach, B. A.; Green, A. J.



Abnormal White Matter Integrity in Adolescents with Internet Addiction Disorder: A Tract-Based Spatial Statistics Study  

PubMed Central

Background Internet addiction disorder (IAD) is currently becoming a serious mental health issue around the globe. Previous studies regarding IAD were mainly focused on associated psychological examinations. However, there are few studies on brain structure and function about IAD. In this study, we used diffusion tensor imaging (DTI) to investigate white matter integrity in adolescents with IAD. Methodology/Principal Findings Seventeen IAD subjects and sixteen healthy controls without IAD participated in this study. Whole brain voxel-wise analysis of fractional anisotropy (FA) was performed by tract-based spatial statistics (TBSS) to localize abnormal white matter regions between groups. TBSS demonstrated that IAD had significantly lower FA than controls throughout the brain, including the orbito-frontal white matter, corpus callosum, cingulum, inferior fronto-occipital fasciculus, and corona radiation, internal and external capsules, while exhibiting no areas of higher FA. Volume-of-interest (VOI) analysis was used to detect changes of diffusivity indices in the regions showing FA abnormalities. In most VOIs, FA reductions were caused by an increase in radial diffusivity while no changes in axial diffusivity. Correlation analysis was performed to assess the relationship between FA and behavioral measures within the IAD group. Significantly negative correlations were found between FA values in the left genu of the corpus callosum and the Screen for Child Anxiety Related Emotional Disorders, and between FA values in the left external capsule and the Young's Internet addiction scale. Conclusions Our findings suggest that IAD demonstrated widespread reductions of FA in major white matter pathways and such abnormal white matter structure may be linked to some behavioral impairments. In addition, white matter integrity may serve as a potential new treatment target and FA may be as a qualified biomarker to understand the underlying neural mechanisms of injury or to assess the effectiveness of specific early interventions in IAD.

Qin, Lindi; Zhao, Zhimin; Xu, Jianrong; Lei, Hao



Noninvasive image derived heart input function for CMRglc measurements in small animal slow infusion FDG PET studies  

NASA Astrophysics Data System (ADS)

Absolute quantitation of the cerebral metabolic rate for glucose (CMRglc) can be obtained in positron emission tomography (PET) studies when serial measurements of the arterial [18F]-fluoro-deoxyglucose (FDG) input are available. Since this is not always practical in PET studies of rodents, there has been considerable interest in defining an image-derived input function (IDIF) by placing a volume of interest (VOI) within the left ventricle of the heart. However, spill-in arising from trapping of FDG in the myocardium often leads to progressive contamination of the IDIF, which propagates to underestimation of the magnitude of CMRglc. We therefore developed a novel, non-invasive method for correcting the IDIF without scaling to a blood sample. To this end, we first obtained serial arterial samples and dynamic FDG-PET data of the head and heart in a group of eight anaesthetized rats. We fitted a bi-exponential function to the serial measurements of the IDIF, and then used the linear graphical Gjedde-Patlak method to describe the accumulation in myocardium. We next estimated the magnitude of myocardial spill-in reaching the left ventricle VOI by assuming a Gaussian point-spread function, and corrected the measured IDIF for this estimated spill-in. Finally, we calculated parametric maps of CMRglc using the corrected IDIF, and for the sake of comparison, relative to serial blood sampling from the femoral artery. The uncorrected IDIF resulted in 20% underestimation of the magnitude of CMRglc relative to the gold standard arterial input method. However, there was no bias with the corrected IDIF, which was robust to the variable extent of myocardial tracer uptake, such that there was a very high correlation between individual CMRglc measurements using the corrected IDIF with gold-standard arterial input results. Based on simulation, we furthermore find that electrocardiogram-gating, i.e. ECG-gating is not necessary for IDIF quantitation using our approach.

Xiong, Guoming; Cumming, Paul; Todica, Andrei; Hacker, Marcus; Bartenstein, Peter; Böning, Guido



A minimally interactive method to segment enlarged lymph nodes in 3D thoracic CT images using a rotatable spiral-scanning technique  

NASA Astrophysics Data System (ADS)

Precise size measurement of enlarged lymph nodes is a significant indicator for diagnosing malignancy, follow-up and therapy monitoring of cancer diseases. The presence of diverse sizes and shapes, inhomogeneous enhancement and the adjacency to neighboring structures with similar intensities, make the segmentation task challenging. We present a semi-automatic approach requiring minimal user interactions to fast and robustly segment the enlarged lymph nodes. First, a stroke approximating the largest diameter of a specific lymph node is drawn manually from which a volume of interest (VOI) is determined. Second, Based on the statistical analysis of the intensities on the dilated stroke area, a region growing procedure is utilized within the VOI to create an initial segmentation of the target lymph node. Third, a rotatable spiral-scanning technique is proposed to resample the 3D boundary surface of the lymph node to a 2D boundary contour in a transformed polar image. The boundary contour is found by seeking the optimal path in 2D polar image with dynamic programming algorithm and eventually transformed back to 3D. Ultimately, the boundary surface of the lymph node is determined using an interpolation scheme followed by post-processing steps. To test the robustness and efficiency of our method, a quantitative evaluation was conducted with a dataset of 315 lymph nodes acquired from 79 patients with lymphoma and melanoma. Compared to the reference segmentations, an average Dice coefficient of 0.88 with a standard deviation of 0.08, and an average absolute surface distance of 0.54mm with a standard deviation of 0.48mm, were achieved.

Wang, Lei; Moltz, Jan H.; Bornemann, Lars; Hahn, Horst K.



Automatic pulmonary vessel segmentation in 3D computed tomographic pulmonary angiographic (CTPA) images  

NASA Astrophysics Data System (ADS)

Automatic and accurate segmentation of the pulmonary vessels in 3D computed tomographic angiographic images (CTPA) is an essential step for computerized detection of pulmonary embolism (PE) because PEs only occur inside the pulmonary arteries. We are developing an automated method to segment the pulmonary vessels in 3D CTPA images. The lung region is first extracted using thresholding and morphological operations. 3D multiscale filters in combination with a newly developed response function derived from the eigenvalues of Hessian matrices are used to enhance all vascular structures including the vessel bifurcations and suppress non-vessel structures such as the lymphoid tissues surrounding the vessels. At each scale, a volume of interest (VOI) containing the response function value at each voxel is defined. The voxels with a high response indicate that there is an enhanced vessel whose size matches the given filter scale. A hierarchical expectation-maximization (EM) estimation is then applied to the VOI to segment the vessel by extracting the high response voxels at this single scale. The vessel tree is finally reconstructed by combining the segmented vessels at all scales based on a "connected component" analysis. Two experienced thoracic radiologists provided the gold standard of pulmonary arteries by manually tracking the arterial tree and marking the center of the vessels using a computer graphical user interface. Two CTPA cases containing PEs were used to evaluate the performance. One of these two cases also contained other lung diseases. The accuracy of vessel tree segmentation was evaluated by the percentage of the "gold standard" vessel center points overlapping with the segmented vessels. The result shows that 97.3% (1868/1920) and 92.0% (2277/2476) of the manually marked center points overlapped with the segmented vessels for the cases without and with other lung disease, respectively. The results demonstrate that vessel segmentation using our method is not degraded by PE occlusion and the vessels can be accurately extracted.

Zhou, Chuan; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Patel, Smita; Cascade, Philip N.; Sahiner, Berkman; Wei, Jun; Ge, Jun; Kazerooni, Ella A.



Computerized detection of pulmonary embolism in computed tomographic pulmonary angiography (CTPA): improvement of vessel segmentation  

NASA Astrophysics Data System (ADS)

Vessel segmentation is a fundamental step in an automated pulmonary embolism (PE) detection system. The purpose of this study is to improve the segmentation scheme for pulmonary vessels affected by PE and other lung diseases. We have developed a multiscale hierarchical vessel enhancement and segmentation (MHES) method for pulmonary vessel tree extraction based on the analysis of eigenvalues of Hessian matrices. However, it is difficult to segment the pulmonary vessels accurately when the vessel is occluded by PEs and/or surrounded by lymphoid tissues or lung diseases. In this study, we developed a method that combines MHES with level set refinement (MHES-LSR) to improve vessel segmentation accuracy. The level set was designed to propagate the initial object contours to the regions with relatively high gray-level, high gradient, and high compactness as measured by the smoothness of the curvature along vessel boundaries. Two and eight CTPA scans were randomly selected as training and test data sets, respectively. Forty volumes of interest (VOI) containing "representative" vessels were manually segmented by a radiologist experienced in CTPA interpretation and used as reference standard. The results show that, for the 32 test VOIs, the average percentage volume error relative to the reference standard was improved from 31.7+/-10.9% using the MHES method to 7.7+/-4.7% using the MHES-LSR method. The correlation between the computer-segmented vessel volume and the reference standard was improved from 0.954 to 0.986. The accuracy of vessel segmentation was improved significantly (p<0.05). The MHES-LSR method may have the potential to improve PE detection.

Zhou, Chuan; Chan, Heang-Ping; Kuriakose, Jean W.; Chughtai, Aamer; Hadjiiski, Lubomir M.; Wei, Jun; Patel, Smita; Kazerooni, Ella A.



Influence and Compensation of Truncation Artifacts in MR-Based Attenuation Correction in PET/MR.  


The goal of this article is to quantify the influence of truncation artifacts in the magnetic resonance (MR)-based attenuation map (MRMap) on reconstructed positron emission tomography (PET) image volumes and to propose a new method for minimizing this influence. Methods: PET data sets of 20 patients investigated in a Philips Ingenuity PET/MR were reconstructed with and without applying two different methods for truncation compensation (TC1 vendor-provided, TC2 newly developed). In this patient group, the extent of truncation artifacts and quality of the truncation compensation (TC) was assessed visually in the MRMaps. In three additional patients MRMaps generated by algorithm TC2 could be compared to the ground truth of transmission-based attenuation maps obtained with a Siemens ECAT HR(+) scanner. The influence of truncation on regional SUVs in lesions, other hot structures (bladder, kidney, myocardium) and the arms was assessed in suitable volume of interests (VOI). Results: Truncation compensated MRMaps exhibited residual artifacts in the arms in 16 patients for algorithm TC1 and to a lesser extent in eight patients for algorithm TC2. Compared to the transmission-based attenuation maps algorithm TC2 slightly overestimated the size of the truncated arms by 0.3 cm in the radial direction. Without truncation compensation, VOIs located in the trunk showed an average SUVmax underestimation of less than 5.4% relative to the results obtained with TC2. Inside the patients' arms underestimations up to 46.5% were found. Conclusion: In the trunk, standardized uptake values (SUV) underestimations due to truncation artifacts in the MRMap are rather small. Inside the arms, severe SUV underestimations can occur. Therefore, reliable TC is mandatory and can be achieved by applying the newly developed algorithm TC2 which has yielded promising results so far. Implementation of the proposed method is straightforward and should be easily adaptable to other PET/MR systems. PMID:24186268

Schramm, G; Langner, J; Hofheinz, F; Petr, J; Lougovski, A; Beuthien-Baumann, B; Platzek, I; van den Hoff, J



Computer-aided detection of breast masses in digital breast tomosynthesis (DBT): improvement of false positive reduction by optimization of object segmentation  

NASA Astrophysics Data System (ADS)

DBT is a promising new imaging modality that may improve the sensitivity and specificity for breast cancer detection. However, DBT could only provide quasi-3D information with limited resolution along the depth (Z) direction because tomosynthesis only has limited angular information for reconstruction. Our purpose of this study is to develop a mass segmentation method for a computer-aided detection system in DBT. A data set of 50 two-view DBTs was collected with a GE prototype system. We reconstructed the DBTs using a simultaneous algebraic reconstruction technique (SART). Mass candidates including true and false masses were identified by 3D gradient field analysis. Two-stage 3D clustering followed by active contour segmentation was applied to a volume of interest (VOI) at each candidate location. We compared a fixed-Z approach, in which the Z dimension of the VOI was pre-determined, to an adaptive-Z approach, in which Z was determined by the object diameter (D) on the X-Y plane obtained from the first-stage clustering. We studied the effect of Z ranging from D to D+8 slices, centered at the central slice, in the second stage. Features were extracted on the individual slices of the segmented 3D object and averaged over all slices for both approaches. Linear discriminant analysis with stepwise feature selection was trained with a leave-one-case-out method to differentiate true from false masses in each feature space. With proper optimization of the adaptive-Z approach, the classification accuracy was significantly improved (p<0.0001) in comparison with the fixed-Z approach. The improved differentiation of true from false masses will be useful for false positive reduction in an automated mass detection system.

Wei, Jun; Chan, Heang-Ping; Sahiner, Berkman; Hadjiiski, Lubomir M.; Helvie, Mark A.; Zhou, Chuan; Lu, Yao



Proprietes de Transport Electronique DU Rutile Stoechiometrique  

NASA Astrophysics Data System (ADS)

Le rutile est un oxyde metallique qui presente beaucoup de similitudes avec certains perovskites notamment le titanate de barium ou de strontium. Il est comme ces derniers, compose d'un agencement d'octaedres d'oxygene centres sur l'atome de titane. Ces octaedres sont responsables de la forte polarisabilite de ces cristaux et de leur grande constante dielectrique. Leurs proprietes optiques, seuil d'absorption et spectre de phonons, sont par exemple forts semblables. La presente etude vise a determiner la nature du transport electronique dans le rutile stoechiometrique pur et d'en comparer les resultats avec les proprietes de certains perovskites. Nous determinerons par differentes mesures optoelectroniques les parametres caracteristiques des pieges et leur influence sur le transport des electrons et des trous. Les resultats de conductivite et de capacitance de meme que les spectres de photoconductivite dans nos echantillons ont mis en evidence la presence d'au moins cinq niveaux energetiques dans la bande interdite du rutile agissant comme pieges pour les electrons ou pour les trous et qui jouent un role de premiere importance dans le comportement electrique du rutile. Par la technique de charge transitoire, nous determinerons pour la premiere fois dans le rutile stoechiometrique la grandeur de la mobilite de derive des trous a la temperature ambiante soit 3,4 cm^2/V cdots et nous etablierons une borne superieure a la mobilite des electrons soit 0,1 cm^2 /Vcdots.

Keroack, Danielle


Melange a Quatre Ondes Degenere dans les Absorbants Saturables EN Milieu Mince  

NASA Astrophysics Data System (ADS)

Le melange a quatre ondes est utilise notamment pour determiner la duree des temps de reorientation moleculaire et mesurer la grandeur des susceptibilites nonlineaires du troisieme ordre. Nous avons mis en evidence les particularites du melange a quatre ondes degenere en milieu absorbant mince a l'aide du formalisme de l'optique nonlineaire et de l'approche holographique. Des experiences realisees avec des impulsions de 33 ps ont permis de caracteriser la cinetique de la nonlinearite en regime transitoire des molecules de rhodamine 6G incorporees dans des matrices d'alcool polyvinylique; un milieu aussi compose d'absorbants anisotropes, les molecules de rhodamine 6G en solution aqueuse et un autre forme d'absorbants isotropes, les films minces de cristaux de semiconducteur CdS_ {x}Se_{1-x} ont ete etudies. Nous avons observe pour ces trois milieux les signaux generes aux ordres superieurs par melange a quatre ondes degenere en milieu mince pour differentes conditions de polarisation.

O'Neill, Claire



A decision tree model to estimate the value of information provided by a groundwater quality monitoring network  

NASA Astrophysics Data System (ADS)

Nitrate pollution poses a health risk for infants whose freshwater drinking source is groundwater. This risk creates a need to design an effective groundwater monitoring network, acquire information on groundwater conditions, and use acquired information to inform management. These actions require time, money, and effort. This paper presents a method to estimate the value of information (VOI) provided by a groundwater quality monitoring network located in an aquifer whose water poses a spatially heterogeneous and uncertain health risk. A decision tree model describes the structure of the decision alternatives facing the decision maker and the expected outcomes from these alternatives. The alternatives include: (i) ignore the health risk of nitrate contaminated water, (ii) switch to alternative water sources such as bottled water, or (iii) implement a previously designed groundwater quality monitoring network that takes into account uncertainties in aquifer properties, pollution transport processes, and climate (Khader and McKee, 2012). The VOI is estimated as the difference between the expected costs of implementing the monitoring network and the lowest-cost uninformed alternative. We illustrate the method for the Eocene Aquifer, West Bank, Palestine where methemoglobinemia is the main health problem associated with the principal pollutant nitrate. The expected cost of each alternative is estimated as the weighted sum of the costs and probabilities (likelihoods) associated with the uncertain outcomes resulting from the alternative. Uncertain outcomes include actual nitrate concentrations in the aquifer, concentrations reported by the monitoring system, whether people abide by manager recommendations to use/not-use aquifer water, and whether people get sick from drinking contaminated water. Outcome costs include healthcare for methemoglobinemia, purchase of bottled water, and installation and maintenance of the groundwater monitoring system. At current methemoglobinemia and bottled water costs of 150 $/person and 0.6 $/baby/day, the decision tree results show that the expected cost of establishing the proposed groundwater quality monitoring network exceeds the expected costs of the uninformed alternatives and there is not value to the information the monitoring system provides. However, the monitoring system will be preferred to ignoring the health risk or using alternative sources if the methemoglobinemia cost rises to 300 $/person or the bottled water cost increases to 2.3 $/baby/day. Similarly, the monitoring system has value if the system can more accurately report actual aquifer concentrations and the public more fully abides by managers' recommendations to use/not use the aquifer. The system also has value if it will serve a larger population or if its installation costs can be reduced, for example using a smaller number of monitoring wells. The VOI analysis shows how monitoring system design, accuracy, installation and operating costs, public awareness of health risks, costs of alternatives, and demographics together affect the value of implementing a system to monitor groundwater quality.

Khader, A.; Rosenberg, D.; McKee, M.



Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and ??, ??, and ??/?? T-cell origin: a comprehensive clinicopathologic and phenotypic study.  


Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of ?? or ?? type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 ?? enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) ?,? and, in cases tested, ? negative (presumptive NK origin); 5% were TCR ??, 3% were TCR ??, 1% were TCR ??/??, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only ?? T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with ?? EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ?2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal ?? EATL. PMID:22314189

Pongpruttipan, Tawatchai; Sukpanichnant, Sanya; Assanasen, Thamathorn; Wannakrairot, Pongsak; Boonsakan, Paisarn; Kanoksil, Wasana; Kayasut, Kanita; Mitarnun, Winyou; Khuhapinant, Archrob; Bunworasate, Udomsak; Puavilai, Teeraya; Bedavanija, Anan; Garcia-Herrera, Adriana; Campo, Elias; Cook, James R; Choi, John; Swerdlow, Steven H



The economic value of remote sensing information: a case study of agricultural production and groundwater vulnerability using applied environmental science and hydrogeospatial methods  

NASA Astrophysics Data System (ADS)

William M. Forney1*, Richard L. Bernknopf1, Shruti K. Mishra2, Ronald P. Raunikar1. 1=Western Geographic Science Center, US Geological Survey, Menlo Park, California. 2=Contractor, Western Geographic Science Center, US Geological Survey, Menlo Park, California *=Contact author,, 650-329-4237. Does remote sensing information provide economic benefits to society and can those benefits be valued? Can resource management and policy be better informed by coupling past and present earth observations with groundwater nitrate measurements? Using an integrated assessment approach, the USGS's research applies an established conceptual framework to answer these questions as well as estimate the value of information (VOI) for remote sensing imagery. The approach uses moderate resolution land imagery (MRLI) data from the Landsat and Advanced Wide Field Sensor satellites that has been classified by the National Agricultural Statistics Service into the Cropland Data Layer (CDL). Within the constraint of the US Environmental Protection Agency's public health threshold for potable groundwater resources, we model the relationship between a population of the CDL's land uses and the evolution of nitrate (NO3-) contamination of aquifers in a case study region in northeastern Iowa. Using source data from the Iowa Department of Natural Resources and the USGS's National Water Quality Assessment Program, the approach uses multi-scaled, environmental science models to address dynamic, biophysical process models of nitrogen fate and transport at specific sites (wells) and at landscape scale (35 counties) in order to assess groundwater vulnerability. In addition to the ecosystem service of potable groundwater, this effort focuses on particular agricultural goods and land uses: corn, soybeans and livestock manure management. Results of this four-year study will be presented, including: 1) the integrated models of the assessment approach, 2) mapping the range of vulnerabilities across the region, and 3) considerations of improved nitrogen and crop management. Finally, utilizing both a situation where society does not have access to MRLI, and an enhanced land use scenario based on plausible, future regulatory and policy frameworks and continued availability of MRLI, estimates of the incremental increase in the MRLI's VOI are presented.

Forney, W.; Bernknopf, R. L.; Mishra, S.; Raunikar, R. P.



Pulmonary vessel segmentation utilizing curved planar reformation and optimal path finding (CROP) in computed tomographic pulmonary angiography (CTPA) for CAD applications  

NASA Astrophysics Data System (ADS)

Vessel segmentation is a fundamental step in an automated pulmonary embolism (PE) detection system. The purpose of this study is to improve the segmentation scheme for pulmonary vessels affected by PE and other lung diseases. We have developed a multiscale hierarchical vessel enhancement and segmentation (MHES) method for pulmonary vessel tree extraction based on the analysis of eigenvalues of Hessian matrices. However, it is difficult to segment the pulmonary vessels accurately under suboptimal conditions, such as vessels occluded by PEs, surrounded by lymphoid tissues or lung diseases, and crossing with other vessels. In this study, we developed a new vessel refinement method utilizing curved planar reformation (CPR) technique combined with optimal path finding method (MHES-CROP). The MHES segmented vessels straightened in the CPR volume was refined using adaptive gray level thresholding where the local threshold was obtained from least-square estimation of a spline curve fitted to the gray levels of the vessel along the straightened volume. An optimal path finding method based on Dijkstra's algorithm was finally used to trace the correct path for the vessel of interest. Two and eight CTPA scans were randomly selected as training and test data sets, respectively. Forty volumes of interest (VOIs) containing "representative" vessels were manually segmented by a radiologist experienced in CTPA interpretation and used as reference standard. The results show that, for the 32 test VOIs, the average percentage volume error relative to the reference standard was improved from 32.9+/-10.2% using the MHES method to 9.9+/-7.9% using the MHES-CROP method. The accuracy of vessel segmentation was improved significantly (p<0.05). The intraclass correlation coefficient (ICC) of the segmented vessel volume between the automated segmentation and the reference standard was improved from 0.919 to 0.988. Quantitative comparison of the MHES method and the MHES-CROP method with the reference standard was also evaluated by the Bland-Altman plot. This preliminary study indicates that the MHES-CROP method has the potential to improve PE detection.

Zhou, Chuan; Chan, Heang-Ping; Kuriakose, Jean W.; Chughtai, Aamer; Wei, Jun; Hadjiiski, Lubomir M.; Guo, Yanhui; Patel, Smita; Kazerooni, Ella A.



Secondary extramedullary plasmacytoma causing small bowel intussusception in a patient with multiple myeloma - A case report  

PubMed Central

INTRODUCTION Multiple myeloma is a monoclonal, immunoproliferative plasma-cell neoplasm of the B lymphoid cells. Extramedullary plasmacytoma is a type of plasma-cell neoplasm that can present as a primary tumour or secondary to another plasma-cell neoplasm, such as multiple myeloma. Secondary extramedullary plasmacytoma is usually noted in the advanced stages of the disease with ileum involvement being very rare. PRESENTATION OF CASE We report a rare case of a 58-year-old man, with known multiple myeloma, re-presenting with evidence of small bowel obstruction, secondary to an intussusception due to a malignant plasma cell deposit, which was successfully resected at laparotomy. Previous two similar admissions, prior to this index admission, failed to arrive at this difficult rare diagnosis. DISCUSSION Primary and secondary extramedullary plasmacytoma mainly affects the upper aero-digestive tract. Involvement of the ileum, as in this case, is a rare complication. Prognosis of secondary extramedullary plasmacytoma affecting the gastrointestinal tracts is unknown, due to the small number of cases reported in the literature, but suggestive of a poor prognosis. The role of surgery is often palliative to deal with resolvable life-threatening emergencies and where possible to prolong life. CONCLUSION The case adds to the current literature of the rare event of visceral secondary extramedullary plasmacytoma involving the gastrointestinal tract, in the course of multiple myeloma and highlights the need for a high index of suspicion for such uncommon complications, to avoid delay in diagnosis and treatment.

Ariyarathenam, Arun; Galvin, Nick; Akoh, Jacob A.



Radiotherapy Alone With Curative Intent in Patients With Stage I Extranodal Nasal-Type NK/T-Cell Lymphoma  

SciTech Connect

Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.

Li Yexiong, E-mail: [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Wang Hua; Jin Jing; Wang Weihu; Liu Qingfeng; Song Yongwen; Wang Zhaoyang; Qi Shunan; Wang Shulian; Liu Yueping; Liu Xinfan; Yu Zihao [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China)



Diagnostic Biopsy of Lymph Nodes of the Neck, Axilla and Groin: Rhyme, Reason or Chance?  

PubMed Central

INTRODUCTION Improving patient pathways of care is becoming increasingly important in the delivery of timely, appropriate surgical care. With this aim, we analysed the referral and management pathway of patients undergoing diagnostic superficial lymph node biopsy. PATIENTS AND METHODS A retrospective review of case notes of patients undergoing diagnostic superficial lymph node biopsy over 3 years, 1998–2000 at the Bradford Hospitals NHS Trust. Indication for surgical biopsy was based on clinical suspicion following assessment in the out-patient clinic for the majority, and arrangement of investigations as deemed appropriate. There were no clinical algorithms in use during the study period. RESULTS There was no evidence for the use of explicit protocols for referral or management. Biopsy was often delayed. Of 268 patients referred from primary care, referral was made to any of 14 hospital departments with 39% (105 of 268) attending more than one outpatient appointment, and 155 (41 of 268) attending more than one department. Eighteen percent (47 of 268) of patients were informed of their diagnosis within 6 weeks of referral and 42% (113 of 268) within 3 months of referral. Nine percent (24 of 268) underwent pre-operative fine needle aspiration cytology. Of patients with enlarged neck nodes, 29% (52/180) had examination of the upper aero-digestive tract. CONCLUSIONS The study supports the introduction of co-ordinated problem-based referral and management pathways for the management of patients with enlarged superficial lymph nodes supported by regular audits of practice.

Moor, James W; Murray, Patrick; Inwood, Jane; Gouldesbrough, David; Bem, Chris



Photodynamic therapy and the treatment of neoplastic diseases of the larynx, oral cavity, pharynx, and tracheobronchial tree  

NASA Astrophysics Data System (ADS)

Photodynamic therapy has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Thirty patients with neoplasia of the head and neck have been treated with PDT with follow-up to twenty nine months. Four patients with T3 and T4 carcinomas of the upper aerodigestive tract had a partial response. Eleven patients with T1 and T2 carcinomas of the larynx obtained a complete response and are disease free. Seven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and have remained disease free. Two patients with Kaposi's sarcoma of the oral cavity were treated. One obtained a complete response. Three patients with recurrent juvenile laryngotracheal papillomatosis obtained a complete response, but one recurred four months post-PDT. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however, limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations, and complications will be discussed.

Biel, Merrill A.



Photodynamic therapy and the treatment of neoplastic diseases of the larynx, pharynx, oral cavity, and tracheobronchial tree  

NASA Astrophysics Data System (ADS)

Photodynamic therapy (PDT) has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Fifty-three patients with neoplasia of the head and neck have been treated with PDT with follow-up to 40 months. Eight patients with T2-T4 carcinomas of the upper aerodigestive tract had a partial response. Eighteen patients with CIS and T1 carcinomas of the larynx obtained a complete response and are disease free. Eleven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and remain disease free. Two patients with Kaposi's sarcoma or the oral cavity were treated, one obtained a complete response. Five patients with juvenile laryngotracheobronchial papillomatosis obtained a complete response, but all recurred within six months of treatment. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations and complications are discussed.

Biel, Merrill A.



The pathology of head and neck tumors: the occult primary and metastases to the head and neck, Part 10.  


Metastases from carcinomas to the head and neck, either to lymph nodes or to extranodal sites, arise most often from known primary neoplasms. However, some are from a clinically inapparent neoplasm--the so-called occult primary. If the metastasis is an epidermoid carcinoma in a lymph node, the odds clearly favor the primary being in the upper aerodigestive tract. The success rate of discovery is variable, however, and a significant number of primaries remain undetected. Metastatic adenocarcinomas, to either nodal or extranodal sites, are most often from infraclavicular neoplasms. In general, the incidence of metastases to the head and neck from visceral primaries below the clavicle follows the general incidence of the primary cancer itself. Renal-cell carcinoma is the exception since its frequency of metastases to the head and neck exceeds the expected incidence in the general population. Branchiogenic carcinoma is more a conceptual than a literal clinicopathologic entity. The diagnosis should be made with reluctance and only after fulfillment of several rather stringent criteria. PMID:7239939

Batsakis, J G


The anatomic location of neck metastasis from occult squamous cell carcinoma.  


It has been axiomatic among head and neck surgeons that open biopsy of cervical nodes will jeopardize patients having squamous cell carcinoma. The inappropriate biopsy of a squamous cell carcinoma metastatic to a cervical node will statistically double both the subsequent rates of local recurrence and distant metastasis. There is no reliable method to clearly distinguish a cervical node involved with squamous cell carcinoma from adenopathy of other sources. Because of this, all patients with cervical adenopathy are evaluated with the time honored approach of careful visualization and palpation of the upper aerodigestive tract prior to open biopsy. The extent of this evaluation is often judgmental. A review of patients with cervical adenopathy of unknown origin and who had a tissue diagnosis, shows that node location is the most helpful parameter for predicting eventual histopathology. Nodes in the jugulodigastric, digestive, and anterior cervical regions have a probability of 19% and 12%, respectively, of being a squamous cell carcinoma. Multiple adenopathies in the supraclavicular and posterior cervical areas are frequently malignant (84% and 61% respectively), however, these are usually either lymphoma or infraclavicular metastasis. PMID:6784081

Johnson, J T; Newman, R K


Dual-Acquisition Extracranial Computed Tomographic Angiography-Enhanced Neck Computed Tomography before Transoral Laser Microsurgery in Head and Neck Cancer Patients. Preliminary results.  


Transoral laser microsurgery (TLM) is an alternative surgical technique for piecemeal endoscopic resection of mucosal-based aerodigestive tract tumors. Though uncommon, potentially catastrophic postoperative bleeding may occur with this technique secondary to vascular injury along invasive tumor inner margins. We describe our preliminary results using a preoperative dual-acquisition extracranial computed tomographic angiography (CTA)-enhanced neck computed tomographic (CT) imaging and postprocessing protocol developed to improve visualization of mucosal-based head and neck tumors and adjacent arterial branches with the objective of facilitating TLM surgery and reducing secondary bleeding complications. Twenty patients with known head and neck cancers anticipated for TLM resection were selected for a dual-acquisition CTA-CT scanning and postprocessing protocol. The mucosal-based pharyngeal tumors and peritumoral vessel enhancement were compared on matched CTA and enhanced neck CT axial images. Operative reports and clinical notes were retrospectively reviewed to identify patients in whom the TLM surgical approach was altered or changed to conventional open surgery as a result of presurgical CTA-CT findings. Enhancement of peritumoral vasculature was almost uniformly superior (19 of 20 patients) on extracranial CTA compared with enhanced neck CT images. In six candidates for TLM surgery (30%), CTA findings resulted in a change in surgical approach to improve intraoperative peritumoral vascular control. In this small pilot series, primary tumor-peritumoral vessel relationships delineated by the addition of extracranial CTA to preoperative enhanced neck CT frequently impacted the surgical approach and facilitated TLM planning. PMID:24059660

Weindling, S M; Salassa, J R; Casler, J D; Chellini, D L



Aggregatibacter actinomycetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization  

PubMed Central

Summary The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, is a common inhabitant of the human upper aerodigestive tract. The organism produces an RTX (Repeats in ToXin) toxin (LtxA) that kills human white blood cells. LtxA is believed to be a membrane-damaging toxin, but details of the cell surface interaction for this and several other RTX toxins have yet to be elucidated. Initial morphological studies suggested that LtxA was bending the target cell membrane. Because the ability of a membrane to bend is a function of its lipid composition, we assessed the proficiency of LtxA to release of a fluorescent dye from a panel of liposomes composed of various lipids. Liposomes composed of lipids that form nonlamellar phases were susceptible to LtxA-induced damage while liposomes composed of lipids that do not form non-bilayer structures were not. Differential scanning calorimetry demonstrated that the toxin decreased the temperature at which the lipid transitions from a bilayer to a nonlamellar phase, while 31P nuclear magnetic resonance studies showed that the LtxA-induced transition from a bilayer to an inverted hexagonal phase occurs through the formation of an isotropic intermediate phase. These results indicate that LtxA cytotoxicity occurs through a process of membrane destabilization.

Brown, Angela C.; Boesze-Battaglia, Kathleen; Du, Yurong; Stefano, Frank P.; Kieba, Irene R.; Epand, Raquel F.; Kakalis, Lazaros; Yeagle, Philip L.; Epand, Richard M.; Lally, Edward T.



Cancer of the head and neck.  

PubMed Central

Cancers of the upper aerodigestive tract, collectively known as head and neck cancers, arise from a multiplicity of sites. In the West, excess tobacco and alcohol consumption are the most important of the known predisposing factors; elsewhere in the world, notably in India and China, the aetiology, pattern of primary sites, and clinical behaviour are different. Clinically these tumours pose exceptional problems in management, and skilled multidisciplinary teams are necessary in order to achieve the highest level of service and research. Historically, surgery and radiotherapy have been the most important treatment modalities; chemotherapy is now increasingly employed but not yet fully established. Successful rehabilitation of patients with head and neck cancers requires access to high quality speech therapists and other support staff with training in functional pharyngeal disorders. Current research efforts are largely directed towards defining the proper role of chemotherapy and assessing the possible advantage of unconventional radiation approaches. In recent years the roles of primary, reconstructive, and salvage surgery have also become better defined. Many patients are suitable for randomisation into ongoing prospective clinical trials which have been specifically designed to address these issues. Images FIG 3 FIG 4 FIG 5

Tobias, J. S.




PubMed Central

SUMMARY At present, it is difficult to identify a gold standard for endoscopic staging of laryngeal cancer, especially considering the large number of endoscopic instruments available. We have coined the term multistep endoscopy to describe a method for staging laryngeal precancerous and neoplastic lesions that sequentially uses several endoscopic tools including high definition white light endoscopy (HDTV), stroboscopy and autofluorescence endoscopy. During the period from November 2007 to November 2009, 140 patients with a suspect laryngeal lesion underwent multistep endoscopy at the Department of Otorhinolaryngology at Martini Hospital in Turin. All patients were subjected to a series of endoscopic examinations in indirect laryngoscopy (white light endoscopy coupled to a HDTV camera, laryngostroboscopy, indirect autofluorescence) followed by white light endoscopy coupled to a HDTV camera and autofluorescence in direct microlaryngoscopy. The aim of the present prospective study was to evaluate the utility of multistep endoscopy in the diagnostic work-up of laryngeal lesions. Multistep endoscopy showed a higher sensitivity and "biological" predictive value in early cancer and precancerous lesions of the larynx (sensitivity, 97.9%; specificity, 90.5%) compared to individual endoscopic tools. It allows for better therapeutic planning of superficial lesions and more accurate orientation when performing mapping biopsies on diffuse lesions. In our opinion, more widespread use of indirect autofluorescence endoscopy during follow-up may be warranted to search for synchronous/metachronous second tumours of the upper aerodigestive tract.




Management of stridor in neonates and infants.  


Stridor is the sound caused by abnormal air passage into the lungs and can exist in different degrees and be caused by obstruction located anywhere in the extra-thoracic (nose, pharynx, larynx, trachea) or intra-thoracic airway (tracheobronchial tree). Stridor may be congenital or acquired, acute, intermittent or chronic. Laryngotracheal inflammation (croup) is the most common cause of acute stridor. Laryngotracheomalacia is the most common cause of congenital, chronic stridor. Stridor is a clinical sign and not a diagnosis. The golden standard in the workup of stridor is an upper and lower airway endoscopy under general anaesthesia. Endoscopic examination under general anaesthesia requires a multidisciplinary approach and close cooperation between anaesthesiologist, paediatrician, ENT surgeon and nursing staff. Following this procedure, a place in the intensive care unit should be available for those cases presenting with stridor in which a definite diagnosis could not yet be established. Although important, pre-endoscopy assessment including history, physical examination and radiological examination, is only a guide to the type and degree of pathology found during endoscopy. About 1 out of 10 infants are found to have lesions in more than one anatomical site of the upper aerodigestive tract. PMID:16363272

Claes, J; Boudewyns, A; Deron, P; Vander Poorten, V; Hoeve, H



Antiepidermal Growth Factor Receptor Therapy in Squamous Cell Carcinoma of the Head and Neck  

PubMed Central

Squamous cell carcinoma of head and neck (SCCHN) is the most common neoplasm of the upper aerodigestive tract. In this paper, we attempt to summarize the role and applications of the epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (moAbs) and tyrosine kinase inhibitors (TKIs) locally advanced as well as metastatic SCCHN. Targeted therapy in SCCHN is now incorporated in the first-line regimes for advanced disease. Novel targeted agents, including the EGFR antibody, cetuximab, have been approved for use as single agents or in combination with radiation therapy or chemotherapy in treatment of recurrent metastatic or locally advanced SCCHN. Refractory mechanisms that bypass the pathway of EGFR inhibitors activity are identified explaining resistance to targeted therapy. Strategies of cotargeting EGFR and other pathways are under investigation. Examples of targeted therapy being used include mammalian target of rapamycin (mtor) inhibitors, antivascular endothelial growth factor (VEGF) moAb, and other inhibitors. We will be focusing our paper on the preclinical and clinical aspects of EGFR inhibition in SCCHN and touch upon other targeted therapies in application.

Shaib, Walid; Kono, Scott; Saba, Nabil



Effects of radiation therapy in microvascular anastomoses  

SciTech Connect

The otolaryngologist, as a head and neck surgeon, commonly cares for patients with upper aerodigestive tract malignancies. Therapy of these neoplasms often requires wide excision. One standard reconstructive procedure utilizes pedicled regional flaps, both dermal and myodermal which have some disadvantages. The shortcomings of these pedicled regional flaps have led to the use of the vascularized free flap in certain cases. The occasional case may lead to catastrophe if microanastomoses fail when combined with radiation. Notwithstanding, many surgical series have reported success when radiation has been given. The present investigation was undertaken to assess the effects of radiation therapy on microvascular anastomoses when radiation is administered pre- or postoperatively or when nonradiated tissue is transferred to an irradiated recipient site. These effects were observed serially in an experimental rat model using a tubed superficial epigastric flap that adequately reflected tissue viability and vascular patency. The histologic changes were then noted over a three month period after completion of both radiation and surgery. This study adds credence to the observation of the lack of deleterious effects of radiation on experimental microvascular anastomotic patency whether the radiation is given before or after surgery or if radiated tissue is approximated to nonradiated vessels.

Fried, M.P.



Reconstruction after robotic head and neck surgery: when and why.  


The advancement of robotically assisted surgery during the last decade has seen a revolution in the approach to surgical oncologic resection, moving toward reducing patient morbidity without compromising oncologic outcomes. In no field has this been more dramatic than in the application of transoral robotic surgery (TORS), using the da Vinci surgical system for resecting tumors of the head and neck. This organ-preserving technique allows the surgeon to remove tumors of the upper aerodigestive tract without external incisions and potentially spare the patient adjuvant treatment. The introduction of TORS improves upon current transoral techniques to the oropharynx and supraglottis. The traditional conception of TORS is that it would be used for smaller tumors and defects would be permitted to heal by secondary intention; however, as head and neck surgeons pursue larger tumors robotically, robotic-assisted reconstruction has entered the paradigm. Given the relative infancy of these procedures, clear guidelines for when reconstruction is warranted do not exist. The current literature, thus far, has focused on feasibility, safety, and implement of the robot in reconstruction. We reviewed the current literature pertinent to TORS reconstruction focusing on patient selection, tumor size, and location. Furthermore, we briefly review our own experience of 20 TORS procedures involving robotic-assisted reconstructions. Finally, we provide an algorithmic approach to determining the need for reconstruction in a given patient. This focuses on four key criteria: tumor location, tumor extent, prior treatment, and patient-specific factors. PMID:22399257

Longfield, Evan A; Holsinger, F Christopher; Selber, Jesse C



[Treatment of glottal gap].  


Glottal gaps can be either physiological or pathological. The latter are multifactorial, predominantly organic in origin and occasionally functional. Organic causes include vocal fold paralysis or scarring, as well as a deficiency or excess of tissue. In addition to loss of the mucosal wave, the degree of hoarseness is primarily determined by the circumferential area of the glottal gap. It is thus important to quantify the extent of glottal insufficiency. Although a patient's symptoms form the basis for treatment decisions, these may be subjective and inadequately reflected by the results of auditory-perceptual evaluation, voice analysis and voice performance tests. The therapeutic approach should always combine phonosurgery with conventional voice therapy methods. Voice therapy utilises all the resources made available by the sphincter model of the aerodigestive tract and knowledge on the mechanism of voice production. The aim of phonosurgery is medialization, reconstruction or reinnervation by injection laryngoplasty or larynx framework surgery. These different methods can be combined and often applied directly after vocal fold surgery (primary reconstruction). In conclusion, the techniques described here can be effectively employed to compensate for glottal gaps. PMID:23407775

Voigt-Zimmermann, S; Arens, C



Light distributors for photodynamic therapy  

NASA Astrophysics Data System (ADS)

A brief overview is given of light distributors developed by our group in Lausanne for photodynamic therapy (PDT) of cancer. We focus on fiberoptic devices which have to a large extent been tested over the years in the clinic for PDT of the upper aerodigestive tract, the tracheobronchial tree, the esophagus, the uterus, and the skin. Both surface and interstitial light distributors are discussed. Several different physical principles for obtaining the desired light intensity distribution in tissue are demonstrated, including the use of specially shaped reflecting surfaces, light scattering and refraction by particles, the use of flexible highly reflecting balloons, controlled fiber core surface roughening, and microlenses. PDT can be improved using 'intelligent' light distributors, which permit the measurement of the light intensity reflected from the irradiated surface, as well as the dye fluorescence signals. Both are measured in situ and in real time during the treatment. The use of such devices, which can measure photobleaching kinetics, and enable one to adjust the light dose to the observed dye fluorescence signals, thus giving better PDT control, is discussed.

van den Bergh, Hubert; Mizeret, Jerome; Theumann, Jean-Francois; Woodtli, A.; Bays, R.; Robert, D.; Thielen, P.; Philippoz, J. M.; Braichotte, Daniel; Forrer, Martin; Savary, Jean-Francois; Monnier, Philippe; Wagnieres, Georges



Fine needle aspiration (FNA) cytology for diagnosis of cervical lymphadenopathy.  


Patients with cervical adenopathy suspicious for malignancy are often referred to the Otolaryngology Service for tissue diagnosis. Confirmation of nodal involvement by upper aero-digestive tract tumors (UADT) is best obtained by fine needle aspiration (FNA). Reported studies of FNA for lymphoma diagnosis have yielded conflicting results. Retrospective review of charts and pathology of 161 patients diagnosed with lymphomas yielded 53 patients with cervical adenopathy without apparent UADT. FNA's were performed on 28, and were repeated nine times, for a total of 37. Eleven had Hodgkin's disease and 17 other types of lymphomas. Seven of 37 specimens contained only blood; 15 contained lymphoid cells, nine of which were designated "reactive." Lymphoid cells designated as "atypical" or "suspicious for lymphoma" were found in 13 of the 37 aspirates. Two were diagnostic of lymphoma. Lymphoma was confirmed by histopathologic specimens in all patients, obtained 0-941 days (median 15, mean 73 days) after initial FNA. In lymphoma patients with cervical lymphadenopathy, FNA does not usually suffice for, and often leads to significant delays in diagnosis. PMID:22351165

Khillan, Ratesh; Sidhu, Gurinder; Axiotis, Constantine; Braverman, Albert S



Case of childhood laryngeal papillomatosis with metastatic carcinoma esophagus in adulthood  

PubMed Central

A young male patient was diagnosed to have laryngeal papillomas at the age of 3 years for which he underwent permanent tracheostomy and also multiple surgical and laser excision procedures. Then, later in life, the patient had progressive breathlessness and dysphagia. On examination, he had supraclavicular lymphadenopathy showing squamous carcinoma pathology. Since laryngeal papillomas have a high propensity to transform into laryngeal squamous cell carcinoma, he was first evaluated for laryngeal carcinoma which was negative. Esophagoscopy showed a growth in the esophagus, the biopsy of which was positive for squamous malignant cells. Patient was then started on palliative chemotherapy with combination of paclitaxel and carboplatin, and at progression with weekly nanoxel with stable disease. This is a rare case of childhood laryngeal papillomatosis progressing to metastatic esophageal carcinoma. This case has been presented to highlight the fact that patients with laryngeal papillomas are not only at high risk of progressing to laryngeal carcinoma but can also have other malignancies of the upper aerodigestive tract and lung. Most of them have been correlated to human papilloma virus (HPV), but in our patient HPV DNA was negative.

Shetty, Nishitha; Prabhash, Kumar; Joshi, Amit; Sayed, Suhail I.; Sharma, Shilpi; Noronha, Vanita; Deshmukh, Anuja; Chaukar, Devendra; Kane, S.; Gopal; D'cruz, Anil K.



Retinoic acid induces cells cultured from oral squamous cell carcinomas to become anti-angiogenic.  

PubMed Central

Retinoids have shown great promise as chemopreventive against the development of squamous cell carcinomas of the upper aerodigestive tract. However, the exact mechanism by which they block new tumors from arising is unknown. Here, we report that 13-cis- and all-trans-retinoic acid, used at clinically achievable doses of 10(-6) mol/L or less, can directly and specifically affect cell lines cultured from oral squamous cell carcinomas, inducing them to switch from an angiogenic to an anti-angiogenic phenotype. Although retinoic-acid-treated and untreated tumor cells make the same amount of interleukin-8, the major inducer of neovascularization produced by such tumor lines, they vary in production of inhibitory activity. Only the retinoic-acid-treated cells produce a potent angio-inhibitory activity that is able to block in vitro migration of endothelial cells toward tumor cell conditioned media and to halt neovascularization induced by such media in the rat cornea. Anti-angiogenic activity is induced in the tumor cells by low doses of retinoids in the absence of toxicity with a kinetics that suggest that it could be contributing to the effectiveness of the retinoids as chemopreventive agents. Images Figure 6

Lingen, M. W.; Polverini, P. J.; Bouck, N. P.



Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants.  


The complexity of carcinogenesis in squamous cell cancer (SCC) of the upper aerodigestive tract requires examining environmental risk factors, including mutagen sensitivities to xenobiotics. Three environmental, occupational, and habitual pollutants - dibutylphthalate (DBP), diisobutylphthalate (DiBP), and N'nitrosodiethylamine (NDELA) - were submitted to genotoxicity testing on mucosal biopsy specimens of tumor and nontumor patients in vitro. The single-cell microgel electrophoresis (Comet) assay was applied to detect DNA strand breaks in human epithelial cells of the pharynx and larynx from nontumor patients, patients with SCC of the oropharynx and patients with SCC of the larynx. Genotoxicity was found for DBP, DiBP, and NDELA in cells derived from nontumor and tumor patients. With respect to phthalates, Olive tail moment (OTM) levels were higher in patients with SCC of the oropharynx and SCC of the larynx (P < 0.01), the latter showing even more pronounced genotoxicity for DiBP. Testing epithelial cells of the patients with either oropharyngeal or laryngeal SCC for NDELA demonstrated results similar to the nontumor patients. Present findings indicate heterogeneous mutagen sensitivities to some but not all xenobiotics. PMID:10993555

Kleinsasser, N H; Weissacher, H; Kastenbauer, E R; Dirschedl, P; Wallner, B C; Harréus, U A



Aspartame, low-calorie sweeteners and disease: Regulatory safety and epidemiological issues.  


Aspartame is a synthetic sweetener that has been used safely in food for more than 30years. Its safety has been evaluated by various regulatory agencies in accordance with procedures internationally recognized, and decisions have been revised and updated regularly. The present review summarizes the most relevant conclusions of epidemiological studies concerning the use of low-calorie sweeteners (mainly aspartame), published between January 1990 and November 2012. In the Nurses' Health study and the Health Professionals Followup study some excess risk of Hodgkin lymphoma and multiple myeloma was found in men but not in women; no association was found with leukemia. In the NIH-AARP Diet and Health Study, there was no association between aspartame and haematopoietic neoplasms. US case-control studies of brain and haematopoietic neoplasms also showed no association. The NIH-AARP Diet and Health Study and case-control studies from California showed no association with pancreatic cancer, and a case-control study from Denmark found no relation with breast cancer risk. Italian case-control studies conducted in 1991-2008 reported no consistent association for cancers of the upper aerodigestive tract, digestive tract, breast, endometrium, ovary, prostate, and kidney. Low calorie sweeteners were not consistently related to vascular events and preterm deliveries. PMID:23891579

Marinovich, Marina; Galli, Corrado L; Bosetti, Cristina; Gallus, Silvano; La Vecchia, Carlo



Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma  

PubMed Central

Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. HNSCC has long been a treatment challenge because of the high rate of recurrences and of advanced disease at the time of diagnosis. Molecular identification of tissue biomarkers in diagnostic biopsy specimens may not only identify patients at risk for developing HNSCC but may also select patients that may benefit from more aggressive treatment modalities. Several biomarkers studied to date such as the proteins p53, cyclin D1, p16, Cox-2 enzyme, epidermal growth factor and vascular endothelial growth factor receptors, matrix metalloproteinases and the Fhit marker for genomic instability could be manipulated for the therapeutic benefit of these patients. This review presents the most updated information on molecular biomarkers with the greatest prognostic potential in HNSCC and discusses some factors that contribute to the controversy concerning their prognostic importance.

Thomas, Giovana R; Nadiminti, Hari; Regalado, Jacinto



Educational differences in cancer mortality among women and men: a gender pattern that differs across Europe  

PubMed Central

We used longitudinal mortality data sets for the 1990s to compare socioeconomic inequalities in total cancer mortality between women and men aged 30–74 in 12 different European populations (Madrid, Basque region, Barcelona, Slovenia, Turin, Switzerland, France, Belgium, Denmark, Norway, Sweden, Finland) and to investigate which cancer sites explain the differences found. We measured socioeconomic status using educational level and computed relative indices of inequality (RII). We observed large variations within Europe for educational differences in total cancer mortality among men and women. Three patterns were observed: Denmark, Norway and Sweden (significant RII around 1.3–1.4 among both men and women); France, Switzerland, Belgium and Finland (significant RII around 1.7–1.8 among men and around 1.2 among women); Spanish populations, Slovenia and Turin (significant RII from 1.29 to 1.88 among men; no differences among women except in the Basque region, where RII is significantly lower than 1). Lung, upper aerodigestive tract and breast cancers explained most of the variations between gender and populations in the magnitude of inequalities in total cancer mortality. Given time trends in cancer mortality, the gap in the magnitude of socioeconomic inequalities in cancer mortality between gender and between European populations will probably decrease in the future.

Menvielle, G; Kunst, A E; Stirbu, I; Strand, B H; Borrell, C; Regidor, E; Leclerc, A; Esnaola, S; Bopp, M; Lundberg, O; Artnik, B; Costa, G; Deboosere, P; Martikainen, P; Mackenbach, J P



Squamous carcinoma of the head and neck in the young adult.  


We present a series of 2305 previously untreated histologically proven squamous carcinomas of the mucosal surfaces of the upper aerodigestive tract managed by one of us in a 27-year period. 62 (2.7%) of the patients were aged 40 years or younger. The sex ratio between young and old patients was similar but, as expected, the younger patients were in better physical condition. Furthermore, 90% of young patients were treated, compared with only 78% of the older patients. Younger patients had a higher incidence of oropharyngeal tumours and lymph node metastases, but the proportion of poorly differentiated tumours, and stage T3-T4 tumours, was similar, as was the metastatic rate. The crude survival of the younger patients was 10% better than that of the older group, and adjusted (life-table) survival was 9% better, and this better survival in younger patients was significant when differing site incidence and N-stage were allowed for by multivariate analysis. The recurrence rate at the primary site was 19% in the younger patients and 15% in older patients, but this difference was not significant. The recurrence rate in cervical lymph nodes was similar in both age groups: 37% at 2 years in young patients and 38% in older patients. PMID:1555311

Clarke, R W; Stell, P M



Influenza and SARS-Coronavirus Activating Proteases TMPRSS2 and HAT Are Expressed at Multiple Sites in Human Respiratory and Gastrointestinal Tracts  

PubMed Central

The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.

Gierer, Stefanie; Danisch, Simon; Perin, Paula; Lucas, Jared M.; Nelson, Peter S.; Pohlmann, Stefan; Soilleux, Elizabeth J.



Polymeric implant materials for the reconstruction of tracheal and pharyngeal mucosal defects in head and neck surgery  

PubMed Central

The existing therapeutical options for the tracheal and pharyngeal reconstruction by use of implant materials are described. Inspite of a multitude of options and the availability of very different materials none of these methods applied for tracheal reconstruction were successfully introduced into the clinical routine. Essential problems are insufficiencies of anastomoses, stenoses, lack of mucociliary clearance and vascularisation. The advances in Tissue Engineering (TE) offer new therapeutical options also in the field of the reconstructive surgery of the trachea. In pharyngeal reconstruction far reaching developments cannot be recognized at the moment which would allow to give a prognosis of their success in clinical application. A new polymeric implant material consisting of multiblock copolymers was applied in our own work which was regarded as a promising material for the reconstruction of the upper aerodigestive tract (ADT) due to its physicochemical characteristics. In order to test this material for applications in the ADT under extreme chemical, enzymatical, bacterial and mechanical conditions we applied it for the reconstruction of a complete defect of the gastric wall in an animal model. In none of the animals tested either gastrointestinal complications or negative systemic events occurred, however, there was a multilayered regeneration of the gastric wall implying a regular structured mucosa. In future the advanced stem cell technology will allow further progress in the reconstruction of different kind of tissues also in the field of head and neck surgery following the principles of Tissue Engineering.

Rickert, Dorothee



Probe-based confocal laser endomicroscopy in head and neck malignancies: early preclinical experience  

NASA Astrophysics Data System (ADS)

Background: Malignancies of the upper aerodigestive tract (UADT) are conventionally diagnosed by white light endoscopy, biopsy and histopathology. Probe-based Confocal Laser Endomicroscopy (pCLE) is a novel non-invasive technique which offers in vivo surface and sub-surface imaging of tissue. It produces pictures of cellular architecture comparable to histology without the need for biopsy. It has already been successfully used in different clinical subspecialties to help in the diagnosis and treatment planning of inflammatory and neoplastic diseases. PCLE needs to be used in combination with specific or non-specific contrast agents. In this study we evaluated the potential use of pCLE in combination with non-specific and specific contrast agents to distinguish between healthy mucosa and invasive carcinoma. Methods: Tissue samples from healthy mucosa and squamous cell carcinoma of the head and neck were taken during surgery. After topical application of three different contrast agents, samples were examined using different pCLE-probes and a Confocal Laser Scanning Microscope (CLSM). Images were then compared to the corresponding histological slides and cryosections. Results: Initial results show that pCLE in combination with fluorophores allows visualization of cellular and structural components. Imaging of different layers was possible using three distinct pCLEprobes. Conclusion: pCLE is a promising non-invasive technique that may be a useful adjunct in the evaluation, diagnosis and treatment planning of head and neck malignancies.

Englhard, Anna; Girschick, Susanne; Mack, Brigitte; Volgger, Veronika; Gires, Oliver; Conderman, Christian; Stepp, Herbert; Betz, Christian Stephan



Penetrating neck trauma: a review of management strategies and discussion of the 'No Zone' approach.  


The evaluation and management of hemodynamically stable patients with penetrating neck injury has evolved considerably over the previous four decades. Algorithms developed in the 1970s focused on anatomic neck "zones" to distinguish triage pathways resulting from the operative constraints associated with very high or very low penetrations. During that era, mandatory endoscopy and angiography for Zone I and III penetrations, or mandatory neck exploration for Zone II injuries, became popularized, the so-called "selective approach." Currently, modern sensitive imaging technology, including computed tomographic angiography (CTA), is widely available. Imaging triage can now accomplish what operative or selective evaluation could not: a safe and noninvasive evaluation of critical neck structures to identify or exclude injury based on trajectory, the key to penetrating injury management. In this review, we discuss the use of CTA in modern screening algorithms introducing a "No Zone" paradigm: an evidence-based method eliminating "neck zone" differentiation during triage and management. We conclude that a comprehensive physical examination, combined with CTA, is adequate for triage to effectively identify or exclude vascular and aerodigestive injury after penetrating neck trauma. Zone-based algorithms lead to an increased reliance on invasive diagnostic modalities (endoscopy and angiography) with their associated risks and to a higher incidence of nontherapeutic neck exploration. Therefore, surgeons evaluating hemodynamically stable patients with penetrating neck injuries should consider departing from antiquated, invasive algorithms in favor of evidence-based screening strategies that use physical examination and CTA. PMID:23317595

Shiroff, Adam M; Gale, Stephen C; Martin, Niels D; Marchalik, Daniel; Petrov, Dmitriy; Ahmed, Hesham M; Rotondo, Michael F; Gracias, Vicente H



Traditional and modern uses of natural honey in human diseases: a review.  


Honey is a by-product of flower nectar and the upper aero-digestive tract of the honey bee, which is concentrated through a dehydration process inside the bee hive. Honey has a very complex chemical composition that varies depending on the botanical source. It has been used both as food and medicine since ancient times. Human use of honey is traced to some 8000 years ago as depicted by Stone Age paintings. In addition to important role of natural honey in the traditional medicine, during the past few decades, it was subjected to laboratory and clinical investigations by several research groups and it has found a place in modern medicine. Honey has been reported to have an inhibitory effect on around 60 species of bacteria, some species of fungi and viruses. Antioxidant capacity of honey is important in many disease conditions and is due to a wide range of compounds including phenolics, peptides, organic acids, enzymes, and Maillard reaction products. Honey has also been used in some gastrointestinal, cardiovascular, inflammatory and neoplastic states. This review covers the composition, physico-chemical properties and the most important uses of natural honey in human diseases. PMID:23997898

Eteraf-Oskouei, Tahereh; Najafi, Moslem



Pharmacokinetics of meso-(tetrahydroxyphenyl)chlorin (m-THPC) studied by fluorescence spectroscopy on early cancer of the cheek pouch mucosa of Golden Syrian hamsters  

NASA Astrophysics Data System (ADS)

Golden Syrian hamsters are evaluated as an animal model for phototherapy of early squamous cell carcinomas of the mucosa of the upper aerodigestive tract, the esophagus and the tracheobronchial tree. Carcinomas of this type are induced on the hamster cheek pouch mucosa by the application of the carcinogen 7,12 DMBA. For phototherapeutic experiments on the animals we utilized meso- (tetrahydoxyphenyl)chlorin (mTHPC). The same drug is currently in phase I, II clinical trials for ENT patients with superficial squamous cell carcinomas. By means of light induced fluorescence (LIF) we measured in vivo the kinetics of the uptake and removal of mTHPC in the normal and tumoral cheek mucosa and in the skin. The photodynamic therapy (PDT) reaction of the tissue after excitation of the photosensitizer by laser light at 652 nm was studied. Both pharmacokinetics and PDT efficacy are compared between animal model and clinical results with special emphasis on selectivity between normal and tumoral mucosa. These first experiments show that this tumor model in the hamster cheek pouch seems to be suitable for tests of a number of PDT variables of new photosensitizers preceding their clinical application as well as for optimization of the multiple parameters of clinical phototherapy.

Glanzmann, Thomas; Theumann, Jean-Francois; Braichotte, Daniel; Forrer, Martin; Wagnieres, Georges; van den Bergh, Hubert; Andrejevic, Snezana; Savary, Jean-Francois; Monnier, Philippe



Molecular heterogeneity in mucoepidermoid carcinoma: conceptual and practical implications.  


Mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy of the upper aerodigestive tract and tracheobronchial tree, is also known for its considerable cellular heterogeneity including epidermoid, intermediate and mucin producing cells. Despite this structural and cellular heterogeneity, MEC is uniquely characterized by a specific translocation t(11; 19) (q12; p13), resulting in a fusion between the MECT1 and the MAML2 genes. Although the incidence of this fusion in MEC varies, it is generally accepted that more than 50 % of this entity manifest the MECT1-MAML2. Fusion-positive cases showed significantly better survival than fusion-negative cases, suggesting that MECT1-MAML2 represents a specific prognostic molecular marker in MEC. We contend that fusion in MEC represents a distinct mechanism in the development of this entity. In that context, fusion positive MEC, regardless of grade, manifest a more stable genome and better clinical behaviour, while fusion negative MEC represent a distinctly different pathway characterized by marked genomic instability and relatively aggressive tumors. PMID:23459841

Bell, Diana; El-Naggar, Adel K



Cyclin D1 overexpression increases susceptibility to 4-nitroquinoline-1-oxide-induced dysplasia and neoplasia in murine squamous oral epithelium.  


The cyclin D1 oncogene is frequently amplified/overexpressed in oral squamous cell carcinomas. Mice with overexpression of cyclin D1 targeted to the stratified squamous epithelia of the tongue, esophagus, and forestomach develop a phenotype of epithelial dysplasia at these sites. In this study, we examined the effect of cyclin D1 overexpression on susceptibility of mice to carcinogen-induced tumorigenesis, using 4-nitroquinoline-1-oxide (4NQO), an established potent oral carcinogen in mice. Cyclin D1 overexpressing mice and nontransgenic littermates were administered 4NQO (20 or 50 parts per million (ppm) in the drinking water) for 8 wk and monitored for an additional 16 wk. Histopathological analyses of the tongue revealed significantly higher severity of dysplasia in the cyclin D1 overexpression mice, compared with nontransgenic controls and with untreated controls. Moreover, only the cyclin D1 overexpression mice developed neoplastic lesions in the oro-esophageal epithelia. Examination of the dysplastic and neoplastic lesions revealed abnormal proliferation. Our findings suggest that cyclin D1 overexpression enhances susceptibility to carcinogen-induced oral tumorigenesis. These results underscore the importance of cyclin D1 in the process of oral neoplastic development. Further, they emphasize the value of this transgenic model to study the pathogenesis of oral precancer and cancer and establish it as a model system to test candidate agents for chemoprevention of upper aero-digestive cancer. PMID:19263437

Wilkey, Jonathan F; Buchberger, Glenn; Saucier, Kirsten; Patel, Salony M; Eisenberg, Ellen; Nakagawa, Hiroshi; Michaylira, Carmen Z; Rustgi, Anil K; Mallya, Sanjay M



Highly Selective Infusions of Supradose Cisplatin for Cranial Base Malignancies  

PubMed Central

Treatment results for malignant skull base lesions may be improved with combined modality therapy. Using a novel drug infusion technique that capitalizes on the pharmacodynamic cisplatin-neutralizing properties of thiosulfate, 14 patients (6 untreated, 8 recurrent) received cisplatin (120 to 200 mg/m2 for 1 to 4 weeks × 2-4 cycles) as part of a multimodality treatment program. Histology included squamous cell carcinoma, 11 patients (8 upper aerodigestive tract, 3 cutaneous); sarcoma, 2 patients (malignant fibrous histiocytoma, synovial cell sarcoma); and salivary gland cancer, 1 patient. The lesions involved the lateral skull base (12 patients) and the anterior (2 patients). Dose intensities for cisplatin were between 33.3 and 200 mg/m2/wk. Major responses occurred in 9/14 patients (64.3%), 3 of whom had complete responses. Drug toxicity, occurring in 11 patients, was mild and there were no significant complications as a result of the infusions. Eleven patients subsequently underwent surgical resections. The mean survival time is 23.3 months. Eight patients are alive without disease, 2 alive with disease, and 4 are dead of disease. The effectiveness of this highly selective supradose cisplatin infusion technique and its low morbidity support continued investigations of its application to patients with cranial base malignancies.

Robbins, K. Thomas; Pellitteri, Phillip K.; Harris, Jeffrey P.; Hanchett, Catherine; Kerber, Charles; Vicario, Daniel



Is an aggressive approach justified in the management of an aggressive cancer-the squamous cell carcinoma of thyroid?  

PubMed Central

Background Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm, with less than 50 cases reported in the world literature. The prognosis is poor with a median survival of less than six months. The death is usually secondary to progression of local disease as distant metastases are rare. Case reports Three cases, two males and one female presenting with sudden increase in the size of long standing thyroid swellings and associated pressure effects on the aero-digestive tract are reported. Exhaustive clinical, endoscopic, and radiological examinations did not reveal any primary site of squamous-cell carcinoma as the likely source of the metastases, or of any contiguous spread from neighboring structures. Two cases were managed by combined modality therapy including curative surgery with radiotherapy and one by radiotherapy alone. Conclusion Primary squamous cell carcinoma is a rare malignancy with a poor outcome inspite of combined modality therapy. Out of three reported cases, two succumbed to their disease within less than one year. Aggressive surgery in the form of curative resection along with adjuvant radiotherapy is recommended, the tumor being chemo resistant.

Chintamani; Kulshreshtha, Pranjal; Singh, Jaiprakash; Sugandhi, Nidhi; Bansal, Anju; Bhatnagar, Dinesh; Saxena, Sunita



Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis  

PubMed Central

Mature natural killer (NK) cell neoplasms are classified by the World Health Organization into NK/T cell lymphoma, nasal type (NKTCL), aggressive NK-cell leukemia (ANKCL) and chronic lymphoproliferative disorders of NK-cells, the latter being considered provisionally. NKTCL and ANKCL are rare diseases, with higher prevalence in Asia, Central and South America. Most NKTCL present extranodal, as a destructive tumor affecting the nose and upper aerodigestive tract (nasal NKTCL) or any organ or tissue (extranasal NKTCL) whereas ANKCL manifests as a systemic disease with multiorgan involvement and naturally evolutes to death in a few weeks. The histopathological hallmark of these aggressive NK-cell tumors is a polymorphic neoplastic infiltrate with angiocentricity, angiodestruction and tissue necrosis. The tumor cells have cytoplasmatic azurophilic granules and usually show a CD45+bright, CD2+, sCD3-, cytCD3epsilon+, CD56+bright, CD16?/+, cytotoxic granules molecules+ phenotype. T-cell receptor genes are in germ-line configuration. Epstein-Barr virus (EBV) -encoded membrane proteins and early region EBV RNA are usually detected on lymphoma cells, with a pattern suggestive of a latent viral infection type II. Complex chromosomal abnormalities are frequent and loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. The rarity of the NK-cell tumors limits our ability to standardize the procedures for the diagnosis and clinical management and efforts should be made to encourage multi-institutional registries.



Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention  

PubMed Central

Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

Baumeister, Philipp; Reiter, Maximilian; Harreus, Ulrich



Changing trends in oesophageal endoscopy: a systematic review of transnasal oesophagoscopy.  


The safety, efficacy, and economic implications of using transnasal oesophagoscopy (TNE) are compared with conventional rigid or flexible oesophagoscopy for oesophageal disorders in otorhinolaryngology (ORL) clinics in this systematic review. Eleven electronic databases were searched for articles on transnasal oesophagoscopy. A total of 67 relevant titles were identified and 39 abstracts were screened of which 17 full- text articles were included in this report. There was fair level of evidence to suggest that TNE was effective for screening examination in patients with dysphagia, globus pharyngeus, and reflux symptoms and for detection of metachronous oesophageal carcinoma. TNE can also be used to biopsy suspicious lesions in the upper aerodigestive tract, placement of wireless pH capsule, transnasal balloon dilation of the oesophagus, secondary tracheoesophageal puncture, and management of foreign bodies. TNE was well tolerated and can be safely performed in an office setting with topical anaesthesia. Complications associated with TNE were mild and uncommon. There was evidence to suggest potential cost savings by performing TNE in the office setting compared with conventional investigation and examination for dysphagia. TNE may lead to a change in practice from investigation and treatment in the operating theatre or day care center to an office-based practice. PMID:23984101

Sabirin, Junainah; Abd Rahman, Maharita; Rajan, Philip



Alcohol as a cause of cancer.  

PubMed Central

This is a review of the epidemiologic literature on alcohol and risks of various cancers. Alcohol has consistently been related to risks of squamous cell carcinomas of the mouth, oral pharynx, larynx, and esophagus in multiple studies of varying design. The joint effects of alcohol and smoking are greater than additive, and are probably multiplicative, suggesting biological synergism. All major types of alcoholic beverages have been casually implicated in the genesis of these diseases. The influence of alcohol on risks of upper aerodigestive tract cancers may be greater in persons with marginal nutritional status than in better-nourished individuals. Alcohol also has been associated with an increased risk of adenocarcinomas of the esophagus, gastro-esophageal junction, and gastric cardia, but the relationship is not as strong as for squamous cell esophageal carcinomas. Alcohol and tobacco account for over 80% of the squamous carcinomas of the mouth, pharynx, larynx, and esophagus in the United States. Risks of cancers of the distal stomach, pancreas, colon, and rectum have not been consistently related to alcohol, although possible relationships between beer drinking and rectal cancer and between heavy use of alcohol and pancreatic cancer warrant further study. Studies of alcohol and liver cancer, in which the confounding influence of hepatitis B was considered, have yielded inconsistent results and should be replicated. An association between heavy alcohol use and breast cancer has been observed in most studies, even after controlling for known risk factors for breast cancer, and additional investigations of this issue are warranted.

Thomas, D B



Hypokalemia during the early phase of refeeding in patients with cancer  

PubMed Central

OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (?20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p?=?0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding.

Grasso, Simona; Ferro, Yvelise; Migliaccio, Valeria; Mazza, Elisa; Rotundo, Stefania; Pujia, Arturo; Montalcini, Tiziana



[Proton spectroscopy of the lower leg muscles before and after exercise].  


The aim of this study was to at tempt to assess the suitability of proton spectroscopy (1HMRS) in deter mining the metabolic state of the lower leg muscles in healthy volunteers before and after intense exercise. 30 healthy volunteers participated in the study, performed on a 1.5T MR scanner using a point-resolved spectroscopy (PRESS) sequence. VOI (Volume of Interest) was localized in the tibialis anterior and soleus muscle lower leg. The data were processed using GE spectroscopy tools. We analyzed on all MR spectra the following metabo lits: intramyocellular lipids (IMCL), extramyocellular lipids (EMCL), carnitine (Ct), creatine (Cr), choline (Cho), trimethylamines (TMA), glucose (Glc), taurine (Tau) and lactate (Lac). We compared the resultant intensity ratios using t - test. Based on statistical analysis of results, there was no si gnificant difference between average value of relative (WSS) (p<0.05) before and after exercise for either the tibialis anterior muscle or soleus muscle. Only the division of the research group into subgroups showed statistical differences. For the tibialis anterior (TA) showed an increase in the TMA subgroup of male group, volunteers whom doing sport occasionally and non smoking. Ct decrease in subgroup volunteers whom exercise time was exactly 20 minutes. For soleus muscle (SOL) increase IMCL(CH2) in subgroup of volunteers whom exercise time was exactly 20 minuts and non smoking. In the subgroup of volunteers doing sports professionally Ct increase after exercise. 1HMRS allows noninvasive studies of muscle metabolism before and after exercises. PMID:23944098

Karcz, Paulina; Urbanik, Andrzej



Molecular biological characteristics based Hierarchical Mumford-Shah Vector-Model for the delineation of biological target volumes corresponding to head and neck tumors.  


To more accurately and precisely delineate a biologic target volume (BTV) for the positron emission tomography (PET)-guided radiotherapy treatment planning, we proposed a novel Hierarchical Mumford-Shah Vector Model (HMSMv), where the image-vector was composed of the molecular biological characteristics such as contrast, busyness and the standard uptake value (SUV) of tumors. The BTV was delineated via the propagation of the level set flow of the proposed HMSMv. The propagation took place inside a ring-volume of interest (VOI) which was defined by an adaptive volume-growing algorithm based on the PET SUV, contrast and busyness of a tumor. Four patient studies were assessed and visually inspected by two radiation oncologists (Suyu Zhu and Zaijie Huang). Compared the resulting BTV with the gross target volume (GTV) of one patient study, the sensitivity, specificity and similarity were 92.28%, 87.29%, 79.28% respectively. Moreover, all of four BTVs were between the corresponding GTV and planning target volume (PTV). Most of the BTVs were between the GTV and the clinical target volume (CTV). The results demonstrated that the proposed method can delineate the BTVs of nasopharyngeal carcinomas more accurately and precisely than the manual delineation and also the threshold segmentation method with SUV of 2.5 as the threshold. The GTV, CTV, and PTV were manually delineated by the two radiation oncologists based on PET, CT and MRI images for the intensity modulated radiotherapy (IMRT) planning of the four patients. PMID:24110442

Liu, Guocai; Yang, Weili; Zhu, Suyu; Huang, Qiu; Huang, Zaijie; Wu, Haiyan; Liu, Min; Huang, Wenlin; Liu, Bin; Liu, Jinguang; Hu, Bingqiang; Mo, Yi; Zhang, Jiutang; Zeng, Biao; Yuan, Yuan; Peng, Xiang; Liu, Ke; Zhou, Jumei



Cone beam CT tumor vasculature dynamic study (Murine model)  

NASA Astrophysics Data System (ADS)

Tumor angiogenesis is the process by which new blood vessels are formed from the existing vessels in a tumor to promote tumor growth. Tumor angiogenesis has important implications in the diagnosis and treatment of various solid tumors. Flat panel detector based cone beam CT opens up a new way for detection of tumors, and tumor angiogenesis associated with functional CBCT has the potential to provide more information than traditional functional CT due to more overall coverage during the same scanning period and the reconstruction being isotropic resulting in a more accurate 3D volume intensity measurement. A functional study was conducted by using CBCT to determine the degree of the enhancement within the tumor after injecting the contrast agent intravenously. For typical doses of contrast material, the amount of enhancement is proportional to the concentration of this material within the region of interest. A series of images obtained at one location over time allows generation of time-attenuation data from which a number of semi-quantitative parameters, such as enhancement rate, can be determined. An in vivo mice study with and without mammo tumor was conducted on our prototype CBCT system, and half scan scheme is used to determine the time-intensity curve within the VOI of the mouse. The CBCT has an x-ray tube, a gantry with slip ring technology, and a 40×30 cm Varian Paxscan 4030CB real time FPD.

Yang, Dong; Ning, Ruola; Conover, David; Ricardo, Betancourt; Liu, Shaohua



Tracer kinetic model-driven registration for dynamic contrast-enhanced MRI time-series data.  


Dynamic contrast-enhanced MRI (DCE-MRI) time series data are subject to unavoidable physiological motion during acquisition (e.g., due to breathing) and this motion causes significant errors when fitting tracer kinetic models to the data, particularly with voxel-by-voxel fitting approaches. Motion correction is problematic, as contrast enhancement introduces new features into postcontrast images and conventional registration similarity measures cannot fully account for the increased image information content. A methodology is presented for tracer kinetic model-driven registration that addresses these problems by explicitly including a model of contrast enhancement in the registration process. The iterative registration procedure is focused on a tumor volume of interest (VOI), employing a three-dimensional (3D) translational transformation that follows only tumor motion. The implementation accurately removes motion corruption in a DCE-MRI software phantom and it is able to reduce model fitting errors and improve localization in 3D parameter maps in patient data sets that were selected for significant motion problems. Sufficient improvement was observed in the modeling results to salvage clinical trial DCE-MRI data sets that would otherwise have to be rejected due to motion corruption. PMID:17969122

Buonaccorsi, Giovanni A; O'Connor, James P B; Caunce, Angela; Roberts, Caleb; Cheung, Sue; Watson, Yvonne; Davies, Karen; Hope, Lynn; Jackson, Alan; Jayson, Gordon C; Parker, Geoffrey J M



[Examination of the optimum condition that determines contamination for three-dimensions chemical shift imaging].  


Magnetic resonance spectroscopy (MRS) is a useful tool for obtaining metabolic information non-invasively. However, low reducibility of MRS data, measuring biases caused by the operator, effects of relaxation time, and environmental contamination may sometimes become problematic. In this study, we examined contamination in echo time (TE) and the availability of outer volume suppression (OVS) by using the excitation and localization methods. In addition, we investigated the optimized condition for three-dimensions (3D)-chemical shift imaging (CSI) in gliomas. Contamination was dependent on resolution in the excitation and localization methods and on CSI resolution, but it was not dependent on TE. The additional installation of OVS and saturation pulse (SAT) corresponding to the target sites were extremely useful. There was concern about the influence of chemical shift, crosstalk, contamination, and no radio frequency (RF) uniformity in the marginal volume of interest (VOI). Metabolite distribution was deteriorated along the Z-axis but not in the X-Y plane. It, however, was improved by using a small voxel size in the Z-axis. PMID:22277818

Kikuchi, Chie; Inoue, Mitsuhiro



PIRATE: pediatric imaging response assessment and targeting environment  

NASA Astrophysics Data System (ADS)

By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho



La biogen?se des m?lanosomes  

PubMed Central

Les mélanocytes situés à la base de l’épiderme produisent des mélanosomes qui sont transférés aux kératinocytes pour assurer la pigmentation de l’épiderme et sa photoprotection contre les rayons ultraviolets. Les mélanosomes, organites apparentés aux lysosomes, sont le lieu de synthèse et de stockage d’un pigment, la mélanine. Leur formation dépend de protéines mélanosomales qui transitent par les voies de biosynthèse et d’endocytose et exploitent les mécanismes moléculaires du trafic intracellulaire. Les acteurs moléculaires impliqués dans le transport des protéines mélanosomales et la biogenèse des mélanosomes sont la cible de mutations dans des maladies génétiques accompagnées d’hypopigmentation comme l’albinisme et les maladies lysosomales. Les études menées sur les mélanocytes issus de souris modèles de ces maladies permettent de comprendre certaines des étapes-clés de la mélanogenèse ainsi que les dysfonctionnements associés à ces pathologies. De plus, décrypter la mélanogenèse facilite également la compréhension d’autres processus physiologiques, comme l’illustrent les similitudes inattendues avec l’amyloïdogenèse dans les maladies neurodégénératives.

Delevoye, Cedric; Giordano, Francesca; van Niel, Guillaume; Raposo, Graca



Quantitative Accuracy of Low-Count SPECT Imaging in Phantom and In Vivo Mouse Studies  

PubMed Central

We investigated the accuracy of a single photon emission computed tomography (SPECT) system in quantifying a wide range of radioactivity concentrations using different scan times in both phantom and animal models. A phantom containing various amounts of In-111 or Tc-99m was imaged until the activity had decayed close to background levels. Scans were acquired for different durations, employing different collimator pinhole sizes. VOI analysis was performed to quantify uptake in the images and the values compared to the true activity. The phantom results were then validated in tumour-bearing mice. The use of an appropriate calibration phantom and disabling of a background subtraction feature meant that absolute errors were within 12% of the true activity. Furthermore, a comparison of in vivo imaging and biodistribution studies in mice showed a correlation of 0.99 for activities over the 200?kBq to 5?MBq range. We conclude that the quantitative information provided by the NanoSPECT camera is accurate and allows replacement of dissection studies for assessment of radiotracer biodistribution in mouse models.

Finucane, Ciara M.; Murray, Iain; Sosabowski, Jane K.; Foster, Julie M.; Mather, Stephen J.



Temperature-modulated bioluminescence tomography  

NASA Astrophysics Data System (ADS)

It was recently reported that bioluminescent spectra can be significantly affected by temperature, which we recognize as a major opportunity to overcome the inherent illposedness of bioluminescence tomography (BLT). In this paper, we propose temperature-modulated bioluminescence tomography (TBT) to utilize the temperature dependence of bioluminescence for superior BLT performance. Specifically, we employ a focused ultrasound array to heat small volumes of interest (VOI) one at a time, and induce a detectable change in the optical signal on the body surface of a mouse. Based on this type of information, the BLT reconstruction can be stabilized and improved. Our numerical experiments clearly demonstrate the merits of our TBT with either noise-free or noisy datasets. Also, this idea is applicable in 2D bioluminescence imaging and computational optical biopsy (COB). We believe that our approach and technology represents a major step forward in the field of BLT, and has an important and immediate applicability in bioluminescence imaging of small animals in general.

Wang, Ge; Shen, Haiou; Cong, Wenxiang; Zhao, Shan; Wei, Guo Wei



Coupling hydrodynamic models and value of information for designing stage monitoring networks  

NASA Astrophysics Data System (ADS)

Because the collection of data in water systems is important for making informed decisions, monitoring networks are designed and installed in such systems. Traditionally, the design of hydrometric monitoring networks has been concentrated on measuring streamflow/precipitation at particular key (gauged) sites so that streamflow/precipitation can be estimated accurately at ungauged sites. Although many methods take into account a set of final users of the information, there appears to be no method that explicitly considers them in the mathematical formulation of the decision-making process. This paper presents a novel approach for designing monitoring networks in a water system using the concept of value of information (VOI). This concept takes into account three main factors: (1) the belief that the decision maker has about the state of the water system before having any information; (2) the consequences associated with the decision of having to choose among several possible management actions given the state of the water system; and (3) the evaluation and update of new information when it becomes available. The methodology uses a water level time series generated by a hydrodynamic model at every computational point, each one being a potential monitor site. The method is tested in a polder system in the Netherlands, where monitoring is required to make informed decisions about the operation of a set of hydraulic structures to reduce flood impacts.

Alfonso, Leonardo; Price, Roland



Pattern Formation and Turbulence in Convection, the Legacy of Henri B'enard.  

NASA Astrophysics Data System (ADS)

Just over a century ago a 26-year young physicist by the name of Henri B'enard handed in his Ph.D. thesis, entitled Les tourbillons cellulaires dans une nappe liquide, at the Ecole Normale Sup'erieure in Paris. In a fluid layer with a free upper surface and heated from below he observed and studied remarkably regular hexagonal patterns. Here I shall attempt to trace the developments in nonlinear physics, and especially in fluid mechanics, that have evolved from B'enard's seminal experiments. As a result of the work of many, including Lord Rayleigh, Harold Jeffries (Sir Harold), W.V.R. Malkus and G. Veronis, and especially Fritz Busse (2000 Fluid-Dynamics-Prize recipient) and his long-term collaborator Richard Clever, a remarkably detailed understanding of the nature of convection in a shallow fluid layer between two solid horizontal confining surfaces and heated from below had been gained by the early 1970's. The bifurcation to convection is stationary and occurs at a temperature difference (in dimensionless form represented by the Rayleigh number R) and a wave number k that are non-zero (Rayleigh, Jeffries). The bifurcation is supercritical to a pattern of rolls (Malkus and Veronis; Schl"uter, Lortz, and Busse). Above onset there is a finite range in the R-k plane, delimited by several interesting instabilities, over which the rolls are stable (Clever and Busse). This region, known now affectionately as the ``Busse Balloon", has been used during the last three decades to study both theoretically and experimentally numerous non-linear phenomena, including the role of thermal fluctuations near the bifurcation, the dynamics of pattern coarsening, various wave-number selection processes, spatio-temporal chaos, and spatially localized structures or ``pulses". In somewhat more recent times the range of R has been extended up to 10^14 times the critical value Rc= O(10^3) at onset and a richness of phenomena involving turbulent flows has been revealed and studied quantitatively. One of the particularly interesting issues amenable to study in this system has been the interaction between large-scale flow structures and the small-scale turbulent fluctuations; but there are many other aspects that have provided seemingly endless fascination for the researchers.

Ahlers, Guenter



Etude des defauts microscopiques et des proprietes optiques, electroniques et magnetiques du compose neodyme cerium oxyde de cuivre  

NASA Astrophysics Data System (ADS)

La presente these, qui combine des mesures de diffusion Raman, de transmission infrarouge, de conductivite hyperfrequence et d'interferometrie ultrasonore sur les composes Nd 2-xCexCuO 4, traite des defauts d'oxygene, ainsi que des proprietes optiques, electroniques et magnetiques de ces materiaux. Les resultats experimentaux obtenus sont correles avec plusieurs donnees experimentales disponibles dans la litterature. D'abord, la caracterisation des modes Raman et des niveaux d'energie de champ cristallin de l'ion Nd3+ au moyen de techniques optiques, en fonction du dopage en cerium et du contenu en oxygene, permettent de conclure a la presence de defauts lies a une non-stoechiometrie en oxygene dans ces composes. En effet, des excitations de champ cristallin assignees a des ions Nd3+ en sites irreguliers sont observees, en plus des bandes d'absorption associees aux ions Nd3+ en site regulier, dans les spectres correspondant aux multiplets 4I11/2, 4I13/2 et 4I 15/2 de l'ion Nd3+. Les resultats experimentaux indiquent que, contrairement a la croyance largement repandue, les oxygenes apicaux, bien que presents dans les echantillons dopes, ne sont pas enleves lors du processus de reduction des echantillons necessaire pour faire apparaitre la supraconductivite dans cette famille de cuprates. Au contraire, des lacunes d'oxygene, dont le type varie en fonction du dopage, sont creees lors de ce processus. En particulier, il est montre dans ce travail que la reduction des echantillons dopes de maniere optimale conduit a la creation de lacunes d'oxygene dans les plans CuO2. Les consequences de telles lacunes sont largement discutees. En outre, il est suggere que de telles lacunes sont responsables de la perte de l'ordre antiferromagnetique a longue portee des ions Cu2+. Finalement, l'interaction d'echange anisotrope Nd3+-Cu 2+ dans le compose nondope est caracterisee au moyen de la transmission infrarouge sous champ magnetique. L'eclatement des doublets de Kramers mesure experimentalement est compare, en fonction de l'intensite et de l'orientation du champ magnetique externe, a des calculs d'effet Zeeman. Alors, que les calculs d'effet Zeeman ne coincident pas avec les donnees experimentales pour un champ applique perpendiculairement aux plans CuO 2, ceux-ci sont en accord avec les resultats de transmission infrarouge pour des champs superieurs a 4 T appliques parallelement a ces plans, indiquant une suppression apparente de l'interaction d'echange anisotrope Nd3+-Cu 2+ dans de telles conditions. (Abstract shortened by UMI.)

Richard, Pierre


Genetic variants at 4q23 and 12q24 are associated with head and neck cancer risk in China.  


A recent genome-wide association study (GWAS) reported significant associations of several novel genetic variants with risk of upper aerodigestive tract (UADT) cancers including head and neck cancer (HNC) in Europeans. However, these findings have not been confirmed in other populations including Chinese. According to the findings from the GWAS and other publications, we genotyped six genetic variants (rs1494961, rs1229984, rs1789924, rs971074, rs4767364, and rs671) in a case-control study with 397 HNC cases and 900 controls in China, by using the TaqMan allelic discrimination assay. We found that rs1229984 at 4q23 significantly increased the risk of HNC [dominant model: adjusted odds ratio (OR)?=?1.34, 95% confidence interval (CI)?=?1.05-1.71; additive model: adjusted OR?=?1.24, 95% CI?=?1.04-1.50], while rs671 at 12q24 significantly decreased the risk of HNC (recessive model: adjusted OR?=?0.46, 95% CI?=?0.25-0.85). Furthermore, when these two loci were evaluated together by the number (0-4) of putative risk alleles (rs1229984 G and rs671 G), a significant locus-dosage effect was found between the groups and risk of HNC (Ptrend ?=?0.016). Compared with the "0-1" group, groups with "2" risk alleles and "3-4" risk alleles significantly increased the risk of HNC with adjusted ORs of 1.17 (95% CI?=?0.84-1.64) and 1.51 (95% CI?=?1.06-2.15), respectively. However, no significant association was detected between other four variants (rs1494961, rs1789924, rs971074, and rs4767364) and HNC risk. These findings suggest that rs1229984 at 4q23 and rs671 at 12q24 may serve as candidate markers for susceptibility to HNC in Chinese population. © 2012 Wiley Periodicals, Inc. PMID:22674868

Yuan, Hua; Ma, Hongxia; Lu, Feng; Yuan, Zhiyao; Wang, Ruixia; Jiang, Hongbing; Hu, Zhibin; Shen, Hongbing; Chen, Ning



Penetrating neck injuries: analysis of experience from a Canadian trauma centre  

PubMed Central

Objective To study the demographics and treatment outcome of penetrating neck injuries presenting to a major trauma centre in order to develop a treatment protocol. Design A case review. Setting A trauma centre at a tertiary care institution. Patients One hundred and thirty consecutive patients who had 134 neck wounds penetrating the platysma and presented to the trauma service between 1979 and 1997. Intervention Surgical exploration or observation alone. Main outcome measures The location of injury, patient management, number of significant injuries, duration of hospital stay and outcome. Results Injuries were caused by stab wounds in 124 patients (95%) and gunshot wounds in 6 (5%). The location of injury was zone I (lower neck) in 20 cases (15%), zone II (midportion of the neck) in 108 (81%) and zone III (upper neck) in 5 (4%). The location was not recorded in 1 case. Fifty patients were managed by observation alone and 80 were managed surgically. Neck exploration in 48 asymptomatic patients was negative in 32 (67%). Significant injuries, including major vascular (12), nerve (13) and aerodigestive tract (19) injuries, were identified in 34 patients. Two of the 130 patients (1.5%) died of major vascular injuries. Seventy-six percent of significant injuries, including all zone II major vascular injuries, were symptomatic on presentation. The mean (and standard deviation) hospital stay for asymptomatic patients treated with observation alone and surgical exploration was similar (3.5 [6.02] versus 4.3 [5.46] days respectively, p = 0.575). Long-term disability, all neurologic in nature, was documented in 3 patients managed by observation alone and 6 patients managed by surgical exploration. Conclusions Penetrating neck trauma, in particular stab wounds to zone II in asymptomatic patients, is associated with low morbidity and mortality. A selective management protocol with investigations directed by symptoms is the most appropriate approach for the patient population and resource base in this setting.

Nason, Richard W.; Assuras, George N.; Gray, Perry R.; Lipschitz, Jeremy; Burns, Charles M.



The reconstruction of the spheno-orbital region using latissimus dorsi flap and costal graft.  


To minimize complications in skull base surgery, it is necessary to separate intracranial structures from the upper aerodigestive tract with well-vascularized tissue. The majority of defects can be reconstructed using local flaps using pericranium, galea, or temporalis muscle. However, there are conditions that affect the suitability of the previously mentioned flaps, for example, previous surgical procedures or radiotherapy. Local flaps may also be inadequate to reconstruct particularly large defects. Extensive bony demolitions produce aesthetic deformities that need accurate reconstructions. Orbital wall defects have to be reconstructed to avoid complications such as the transmission of cerebral pulsation, bulbar dystopias, diplopia, and ophthalmoplegia. The microvascular latissimus dorsi flap is ideal in all these cases, and the use of a costal graft allows simultaneous reconstruction of bony defects. From January 2000 to January 2008, 17 patients have undergone surgical ablation of the spheno-orbital region and reconstruction with latissimus dorsi flap and costal grafts. The flap survival rate was 100%. One patient required revision of the venous anastomosis. No cerebrospinal fluid leak or intracranial infections have been detected. The only complications registered were dystopias in 6 patients and diplopia in 4; all of these spontaneously resolved within 2 months. The microvascular latissimus dorsi flap with costal graft is an effective method for the reconstruction of the spheno-orbital region when local flaps are not indicated. It has a negligible donor-site morbidity, an ideal vascular pedicle, and an easy harvesting technique. The costal graft allows the simultaneous reconstruction of the orbital walls, giving good results. PMID:23851876

Biglioli, Federico; Mortini, Pietro; Pedrazzoli, Marco; D'Alessandro, Luca; Bardazzi, Alessandro; Colletti, Giacomo



Clinical value of metabolic tumor volume by PET/CT in extranodal natural killer/T cell lymphoma.  


This study investigated whether metabolic tumor volume (MTV) by PET/CT as indicator of extent of lymphoma burden would be a prognostic factor in stage I(E)/II(E) extranodal natural killer/T cell lymphoma (ENKTCL). Eighty patients with stage I(E)/II(E) ENKTCL in the upper aerodigestive tract underwent PET/CT at diagnosis were enrolled and 32 patients received upfront radiotherapy (RTx). MTV was measured on PET/CT images by the extranodal region above SUV, 2.5. Receiver operating curve analyses indicated that an MTV of 35.2 cm(3) was the ideal cut-off to distinguish between low and high MTV groups. Clinical outcomes were compared according to several prognostic factors (age, stage, high performance status [PS], high International Prognostic Index, elevated lactate dehydrogenase [LDH], local tumor invasiveness [LTI], high MTV and up-front RT). High PS, elevated LDH, LTI, high MTV and upfront RT were associated with survivals. In multivariate analysis, high MTV (PFS, HR=4.170, 95% CI=1.714-10.147, p=0.002; OS, HR=4.102, 95% CI=1.617-10.408, p=0.003) and up-front RT (PFS, HR=0.410, 95%CI=0.178-0.946, p=0.037; OS, HR=0.365, 95% CI=0.152-0.872, p=0.023) were significant independent prognostic factors. Upfront RTx and extent of tumor burden, as measured by the MTV, had significant prognostic value in patients with ENKTCL. PMID:23040533

Song, Moo-Kon; Chung, Joo-Seop; Shin, Ho-Jin; Moon, Joon-Ho; Ahn, Jae-Sook; Lee, Ho-Sup; Lee, Sang-Min; Lee, Gyeong-Won; Kim, Seong-Jang; Lee, Seok-Mo



Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers  

PubMed Central

Purpose Increased levels of cyclooxygenase-2 and prostaglandin E2 (PGE2) have been observed in tobacco-related malignancies of the upper aerodigestive tract. Moreover, exposure to tobacco smoke can stimulate the synthesis of PGE2. Recent evidence suggests that urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE2 production. In this study, we investigated whether levels of urinary PGE-M were increased in smokers and in patients with head and neck squamous cell carcinoma (HNSCC). Experimental Design Fifty-eight HNSCC cases and 29 age- and gender-matched healthy controls were prospectively enrolled in the study. A detailed smoking history and single void urine specimen were obtained from each participant. Levels of urinary PGE-M were quantified in a blinded fashion using mass spectrometry and compared with smoking history and tumor status. Results Adjusted for case-control matching, median urinary PGE-M levels were significantly higher in ever smokers (15.7 ng/mg creatinine) compared with never smokers (9.9 ng/mg creatinine) for the entire study population (n = 87, P = 0.005). Concentrations of urinary PGE-M were nearly doubled in ever smokers (15.2 ng/mg creatinine) versus never smokers (7.8 ng/mg creatinine) among healthy controls (P = 0.001). Higher PGE-M levels were observed in current versus former smokers and in those with greater pack-year exposure. A significant difference in amounts of PGE-M was not observed in patients with HNSCC versus healthy controls. Conclusions Increased levels of urinary PGE-M were observed in smokers. Urinary PGE-M may have use as a noninvasive biomarker of the effects of tobacco smoke exposure.

Gross, Neil D.; Boyle, Jay O.; Morrow, Jason D.; Williams, Myles K.; Moskowitz, Chaya S.; Subbaramaiah, Kotha; Dannenberg, Andrew J.; Duffield-Lillico, Anna J.



Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.  


Responses to the genotoxic effect of bleomycin in lymphocytes of blood cultures, expressed as the average number of chromatid breaks per cell (b/c), varied from less than 0.20 to more than 2.00 in 335 normal individuals. More than 11% of the subjects tested showed a b/c rate above 1.00 and more than 22% showed a b/c rate above 0.80. These individuals are considered sensitive to this radiomimetic drug. The distributional profile of bleomycin responses of the control individuals appears to be representative of the normal human population. In patients with cancers of the colon (83), upper aerodigestive tract (head/neck) (77), and lung (71), the frequencies of subjects in the hypersensitive class were found to be between 40 and 50%, and the response profiles were distinctly different from those of the control population. On the other hand, in a group of elderly cigarette smokers, who exhibited no symptoms of lung cancer, the bleomycin sensitivity profile was significantly skewed toward the more resistant stratum, with only one hypersensitive case among 56 individuals tested (1.78%). The sensitivity profile of patients with breast cancer (82) was similar to that of the control population. Our data suggest that: (1) mutagen sensitivity may play an important role in carcinogenesis of organs and tissues that have direct contact with the external environment (respiratory, digestive, and integumentary systems); (2) it appears to have no significant influence on carcinogenesis of tissues that are not directly exposed to the environment (e.g., breast, brain); and (3) it also has little impact on carcinogenesis in individuals with a hereditary predisposition to cancer (e.g., retinoblastoma, Gardner's syndrome). Development of more effective and precise test systems for carcinogen sensitivity is highly desirable for identification of persons at risk. PMID:2466800

Hsu, T C; Johnston, D A; Cherry, L M; Ramkissoon, D; Schantz, S P; Jessup, J M; Winn, R J; Shirley, L; Furlong, C



Consensus recommendations for management of head and neck cancer in Asian countries: A review of international guidelines.  


Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients. PMID:23830839

D'cruz, A; Lin, T; Anand, A K; Atmakusuma, D; Calaguas, M J; Chitapanarux, I; Cho, B C; Goh, B C; Guo, Y; Hsieh, W S; Hu, C; Kwong, D; Lin, J C; Lou, P J; Lu, T; Prabhash, K; Sriuranpong, V; Tang, P; Vu, V V; Wahid, I; Ang, K K; Chan, A T



Combination of Anti-IGF-1R Antibody A12 and Ionizing Radiation in Upper Respiratory Tract Cancers  

SciTech Connect

Purpose: The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers. Methods and Materials: Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25-2 mg x 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis, and vascular endothelial growth factor expression at Days 1 and 6 after start of treatment. Results: A12 enhanced the radiosensitivity of HN5 and FaDu head-and-neck carcinomas in vitro (p < 0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner, with enhancement factors ranging from 1.2 to 1.8 (p < 0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (p < 0.05) and vascular endothelial growth factor expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted until 6 days from the start of treatment and in increased necrosis at Day 1 (p < 0.01, respectively). Combined treatment with A12 and radiation resulted in additive or subadditive growth delay in H460 or A549 xenografts, respectively. Conclusions: The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aerodigestive tract cancers.

Riesterer, Oliver; Yang Qiuan; Raju, Uma; Torres, Mylin; Molkentine, David; Patel, Nalini; Valdecanas, David; Milas, Luka [Department of Experimental Radiation Oncology, University of Texas M.D. Anderson, Cancer Center, Houston, TX (United States); Ang, K. Kian, E-mail: kianang@mdanderson.or [Department of Radiation Oncology, University of Texas M.D. Anderson, Cancer Center, Houston, TX (United States)



Chronic Cigarette Smoke Extract Treatment Selects For Apoptotic Dysfunction and Mitochondrial mutations in Minimally Transformed Oral Keratinocytes  

PubMed Central

Cigarette smoke demonstrates a carcinogenic effect through chronic exposure, not acute exposures. However, current cell line models study only the acute effects of cigarette smoke. Using a cell line model, we compared the effects of acute versus chronic cigarette-smoke-extract (CSE) on mitochondria in minimally-transformed oral keratinocytes (OKF6). OKF6 cells were treated with varying concentrations of CSE for 6-months. Cells were analyzed monthly by flow cytometry for mitochondrial-membrane-potential (MMP), cytochrome-c release, caspase-3 activation and viability after CSE-exposure. At each time point the same assays were performed after 24hrs of valinomycin (MMP depolarizing agent) treatment. The mitochondrial-DNA of chronically CSE-treated cells was sequenced. After 6-months of CSE-treatment, the cells were increasingly resistant to CSE-mediated and valinomycin induced cell death. In addition, chronic CSE-treatment caused chronic depolarization of MMP, cytochrome c release, and caspase activation. Cells grown in the presence of only CSE vapor also exhibited the same resistance and chronic baseline apoptotic activation. Mitochondrial DNA sequencing found that chronic CSE treated cells had more amino acid changing mitochondrial mutations than acutely treated cells. CSE treatment of normal cells select for apoptotic dysfunction as well as mitochondrial mutations. These findings suggest that chronic tobacco exposure induce carcinogenesis via selection of apoptosis resistance and mitochondrial mutation in addition to previously known genotoxic effects that were found by acute treatments. Chronic models of tobacco exposure on upper aerodigestive epithelia may be more insightful than models of acute exposure in studying head and neck carcinogenesis

Chang, Steven S.; Jiang, Wei Wen; Smith, Ian; Glazer, Chad; Sun, Wen-Yue; Mithani, Suhail; Califano, Joseph A.



Socioeconomic inequalities in alcohol related cancer mortality among men: to what extent do they differ between Western European populations?  

PubMed Central

We aim to study socioeconomic inequalities in alcohol related cancers mortality (upper aero-digestive tract (UADT) (oral cavity, pharynx, larynx, oesophagus) and liver) in men and to investigate whether the contribution of these cancers to socioeconomic inequalities in cancer mortality differs within Western Europe. We used longitudinal mortality datasets including causes of death. Data were collected during the 1990s among men aged 30–74 years in 13 European populations (Madrid, the Basque region, Barcelona, Turin, Switzerland (German and Latin part), France, Belgium (Walloon and Flemish part, Brussels), Norway, Sweden, Finland). Socioeconomic status was measured using the educational level declared at the census at the beginning of the follow-up period. We conducted Poisson regression analyses and used both relative (Relative index of inequality (RII)) and absolute (mortality rates difference) measures of inequality. For UADT cancers, the RII’s were above 3.5 in France, Switzerland (both parts) and Turin whereas for liver cancer they were the highest (around 2.5) in Madrid, France and Turin. The contribution of alcohol related cancer to socioeconomic inequalities in cancer mortality was 29–36% in France and the Spanish populations, 17–23% in Switzerland and Turin, and 5–15% in Belgium and the Nordic countries. We did not observe any correlation between mortality rates differences for lung and UADT cancers, confirming that the pattern found for UADT cancers is not only due to smoking. This study suggests that alcohol use substantially influences socioeconomic inequalities in male cancer mortality in France, Spain and Switzerland but not in the Nordic countries and nor in Belgium.

Menvielle, Gwenn; Kunst, Anton E.; Stirbu, Irina; Borrell, Carme; Bopp, Matthias; Regidor, Enrique; Heine Strand, Bj?rn; Deboosere, Patrick; Lundberg, Olle; Leclerc, Annette; Costa, Giuseppe; Chastang, Jean-Francois; Esnaola, Santiago; Martikainen, Pekka; Mackenbach, Johan P.



Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine.  


The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of the TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations (1) stabilize the immunogenic structural properties of VLPs and (2) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites. PMID:21640778

Velasquez, Lissette S; Shira, Samantha; Berta, Alice N; Kilbourne, Jacquelyn; Medi, Babu M; Tizard, Ian; Ni, Yawei; Arntzen, Charles J; Herbst-Kralovetz, Melissa M



Bone marrow transplantation for infantile ceramidase deficiency (Farber disease).  


Infantile ceramidase deficiency (Farber disease) is an uncommon, progressive lysosomal storage disease characterized by multiple ceramide-containing nodules (lipogranulomata) in the subcutaneous tissue and upper aerodigestive tract, painful periarticular swelling, psychomotor retardation, and varying degrees of ocular, pulmonary or hepatic involvement. Management of Farber disease has been limited to symptomatic supportive care, and few affected infants survive beyond 5 years of age. We performed an allogeneic bone marrow transplant (BMT) from an HLA-identical heterozygous sister in a 9.5-month-old female with minimally symptomatic Farber disease who received a pre-transplant regimen of busulfan and cyclophosphamide. Ceramidase activity in peripheral blood leukocytes increased from 6% before transplant to 44% (donor heterozygote level) by 6 weeks after BMT. By 2 months after transplant, the patient's subcutaneous lipogranulomata, pain on joint motion, and hoarseness had resolved. Despite modest gains in cognitive and language development, hypotonia and delayed motor skills persisted. Gradual loss of circulating donor cells with autologous hematopoietic recovery occurred; VNTR analyses showed 50% donor DNA in peripheral blood cells at 8.5 months after BMT and only 1% at 21 months after transplant. Interestingly, leukocyte ceramidase activity consistently remained in the heterozygous range despite attrition of donor cells in peripheral blood. This novel observation indicates ongoing hydrolase production by non-circulating donor cells, possibly in the mononuclear phagocytic system, and uptake by recipient leukocytes. Although lipogranulomata and hoarseness did not recur, the patient's neurological and neurocognitive status progressively declined. She died 28 months after BMT (age 37.5 months) with pulmonary insufficiency caused by recurrent aspiration pneumonias. Allogeneic BMT improves the peripheral manifestations of infantile ceramidase deficiency, but may not prevent the progressive neurological deterioration, even when carried out in minimally symptomatic patients. PMID:10967581

Yeager, A M; Uhas, K A; Coles, C D; Davis, P C; Krause, W L; Moser, H W



Curcumin inhibits carcinogen and nicotine-induced Mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma.  


Curcumin appears to be a safe, bioactive food compound that is a potential chemopreventive for patients at a high risk for head and neck squamous cell carcinoma (HNSCC). Identification and validation of intermediate endpoints is an important step in evaluating chemopreventive agents. AKT/MTOR pathway biomarkers are intrinsic to the carcinogenic process as well as the mechanism of intervention with curcumin. Antiproliferative effects of curcumin were assayed in 9 HNSCC and a keratinocyte cell line. Nicotine, a genotoxic alkaloid involved in tobacco addiction, forms DNA adducts and has been implicated in upper aerodigestive tract cancer promotion. The antiproliferative effects of curcumin were associated with inhibition of the AKT/MTOR pathway in presence and absence of nicotine, which also induced this pathway. Curcumin was highly effective at suppressing growth of SCC40 xenografts and its activity is associated with modulation of MTOR's downstream target pS6. Curcumin at 15 mg significantly increased survival (286 ± 37 vs. 350 days) in the 4NQO carcinogenic model survival study. A major cause of lethal progression of HNSCC is local regional migration and invasion of malignant cells, and curcumin significantly inhibited cancer cell migration and invasion in vitro and in vivo where downregulation of pS6 was associated with a significant decrease in MMP-9. This is the first study to demonstrate that curcumin inhibits the adverse effects of nicotine by blocking nicotine-induced activation of the AKT/MTOR pathway in HNSCC, which retards cell migration. These studies indicate that inhibiting the AKT/MTOR pathway with curcumin may be useful as an oral chemopreventive agent. PMID:20851953

Clark, Cheryl A; McEachern, Matthew D; Shah, Shivang H; Rong, Youhua; Rong, Xiaohua; Smelley, Christopher L; Caldito, Gloria C; Abreo, Fleurette W; Nathan, C O




PubMed Central

SUMMARY Snoring is caused by vibrating anatomical structures in the upper aerodigestive tract. It can be treated surgically and non-surgically, although resective procedures are associated with high postoperative morbidity and failure rate. We describe a new non-resective surgical procedure called the velo-uvulo-pharyngeal lift in which the soft palate is lifted, shortened, advanced and stiffened by means of permanent threads anchored to fibro-osseous attachments at the level of the posterior nasal spine and both pterygoid hamuli. Four adult patients (median age 44.5 years; range 42-65) affected by snoring and mild obstructive sleep apnoea-hypopnoea syndrome (apneoa-hypopnoea index, AHI < 20) requiring septal surgery under general anesthesia also underwent velo-uvulo-pharyngeal lift. There were no significant intra- or post-operative complications, and all of the patients reported immediate snoring relief. The main complaints were slight pain and a sensation of local fullness, both of which spontaneously disappeared within two days. The subjective clinical improvement in snoring was confirmed during post-operative follow-up (median 15.5 months; range 6-25), as was the stable reshaping of the soft velo-uvulo-pharyngeal tissues and enlargement of the mesopharyngeal space. There was also a decrease in daytime sleepiness. Our preliminary results suggest that velo-uvulo-pharyngeal lift is a simple, cost-effective and minimally invasive means of widening the mesopharyngeal space in snoring patients with or without mild sleep apnoea-hypopnoea syndrome. The widening of the mesopharyngeal space prevents contact-induced wall vibrations and its inspiratory obstruction causing hypopnoea and apnoea. It can also be combined with other procedures if indicated.




Neck masses: diagnostic analysis of 630 cases in Turkish population.  


Neck masses can be classified into three main categories: congenital, inflammatory and neoplastic. Our aim was to determine the distribution of diagnosis in patients who were followed-up for a neck mass and had undergone surgery for diagnostic indications. Six hundred and thirty cases referred to the Otorhinolaryngology and Head Neck Surgery Department of Haseki Research and Training Hospital between January 2005 and February 2012 with a neck mass who underwent excisional or incisional biopsy to establish a histopathologic diagnosis were retrospectively evaluated. Patients with a diagnosis of upper aerodigestive tract malignancy were excluded from the study. As well as the patients with thyroid masses were excluded. Only unknown primary neck masses were included in the study. The neck masses were categorized as inflammatory (33.49 %), congenital (18.9 %) or neoplastic (47.6 %). Neoplastic masses were either benign (51 %) or malignant (49 %) tumors. The most common causes were tuberculous lymphadenitis (40.28 %) among inflammatory masses, thyroglossal duct cysts (32.77 %) among congenital masses, pleomorphic adenoma (22.33 %) among benign neoplastic masses, and lymphoma (20 %) among malignant neoplastic masses. The most common types of mass were congenital in the 0-20 year age group, benign neoplastic in 21-40-year-old and malignant neoplastic in the >40-year group. Any neck mass, especially in an elderly patient, should be managed with caution as a considerable proportion may be malignant. In children and adolescents, a neck mass requiring surgery is most likely to be congenital. Tuberculosis should be considered as a cause of a neck mass due to a long-term inflammatory process in a developing country. PMID:23525652

Balikci, H H; Gurdal, M M; Ozkul, M H; Karakas, M; Uvacin, O; Kara, N; Alp, A; Ozbay, I



An observational study to assess changes in social inequality in smoking-attributable upper aero digestive tract cancer mortality among Canadian males between 1986 and 2001  

PubMed Central

Background Tobacco and low socioeconomic status have been acknowledged as potential risk factors for upper aero-digestive tract (UADT) cancers in North America. In context of reducing adult male smoking prevalence (by over 50%), in the past few decades in Canada, this study tried to document changes in smoking-attributable UADT cancer mortality rates, among Canadian males of different social strata, between 1986 and 2001. Methods The contribution of smoking to UADT cancer mortality was estimated indirectly by using lung cancer mortality as an indicator of the accumulated mortality from smoking in a population. This method was applied to UADT cancer death rates of 35–69 year old socially stratified males. Data, stratified by neighborhood income quintile, could be obtained from Statistics Canada, for four census years, 1986, 1991, 1996, and 2001. Results A total of 2704 male deaths were analyzed. Between 1986 and 2001, UADT cancer deaths reduced by 30% (32 to 22 per 100,000) but the proportion of these deaths attributable to smoking reduced much more, by 41% (22 to 13 per 100,000). In the span of fifteen years, absolute social inequality (measured by rate difference between the highest and the lowest stratum) in smoking-attributable male UADT cancer mortality in Canada reduced by 47% and relative social inequality (measured by rate ratios) reduced by 9%. Conclusion The present analyses reveal that between 1986 and 2001, smoking-attributable UADT cancer mortality rates among adult males (35–69 years) in Canada reduced in all social strata and the social inequalities in these rates have narrowed. Analysis of more current data will be of interest to confirm these trends.



BerEp4, Cytokeratin 14, and Cytokeratin 17 Immunohistochemical Staining Aid in Differentiation of Basaloid Squamous Cell Carcinoma From Basal Cell Carcinoma With Squamous Metaplasia.  


Context.-Basaloid squamous cell carcinoma (bSCC) is an uncommon variant of squamous cell carcinoma, which may overlap histologically with basal cell carcinoma with squamous metaplasia (BCCm). Objective.-To aid in the differentiation of these neoplasms using immunohistochemical staining because of the worse prognosis associated with bSCC. Design.-Using immunohistochemical techniques, we investigated BerEp4, cytokeratin 17 (CK17), and cytokeratin 14 (CK14) protein expression in 25 cases of bSCC (8 cutaneous [32%], 12 aerodigestive tract [48%], and 5 lymph node metastases [20%]) and 43 cases of BCCm (39 cutaneous [91%], and 4 metastases [9%]). An immunoreactivity score was assigned using the percentage of tumor cells staining and the pattern of expression. Interobserver agreement for 2 independent pathologists was assessed using a ? coefficient. Results.-The mean percentage of staining was significantly higher in BCCm, compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK14, P < .001; unpaired t test), with 58% of BCCm cases (25 of 43) displaying diffuse staining for all markers, and nearly all (98%; 42 of 43) displaying diffuse staining for CK17 and CK14. In contrast, no bSCC cases (0%) displayed diffuse staining for all 3 markers, and only 8% (2 of 25) displayed diffuse staining for CK17 and CK14. High interobserver agreement was determined. Conclusions.-BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of either CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in BCCm and bSCC diagnosis. PMID:24168496

Linskey, Katy R; Gimbel, Devon C; Zukerberg, Lawrence R; Duncan, Lyn M; Sadow, Peter M; Nazarian, Rosalynn M



Cannabinoids and cancer: causation, remediation, and palliation.  


This review discusses three different associations between cannabinoids and cancer. First, it assesses evidence that smoking of cannabis preparations may cause cancers of the aerodigestive and respiratory system. There have been case reports of upper-respiratory-tract cancers in young adults who smoke cannabis, but evidence from a few epidemiological cohort studies and case-control studies is inconsistent. Second, there is mixed evidence on the effects of THC and other cannabinoids on cancers: in some in vitro and in vivo studies THC and some synthetic cannabinoids have had antineoplastic effects, but in other studies THC seems to impair the immune response to cancer. As yet there is no evidence that THC or other cannabinoids have anticancer effects in humans. Third, Delta(9)-tetrahydrocannabinol (THC) may treat the symptoms and side-effects of cancer, and there is evidence that it and other cannabinoids may be useful adjuvant treatments that improve appetite, reduce nausea and vomiting, and alleviate moderate neuropathic pain in patients with cancer. The main challenge for the medical use of cannabinoids is the development of safe and effective methods of use that lead to therapeutic effects but that avoid adverse psychoactive effects. Furthermore, medical, legal, and regulatory obstacles hinder the smoking of cannabis for medical purposes. These very different uses of cannabinoids are in danger of being confused in public debate, especially in the USA where some advocates for the medical use of cannabinoids have argued for smoked cannabis rather than pharmaceutical cannabinoids. We review the available evidence on these three issues and consider their implications for policy. PMID:15629274

Hall, Wayne; Christie, MacDonald; Currow, David



Altered expression of SIRT gene family in head and neck squamous cell carcinoma.  


Head and neck squamous cell carcinoma (HNSCC) include a group of malignant neoplasms that arise from the upper aerodigestive tract and represent the seventh most common cause of cancer-related death. The overall 5-year survival rates have not significantly improved for decades in spite of the advances in the field of oncology and surgery, encouraging further research on factors that might modify disease prognosis. The silent information regulator (SIR) genes (Sirtuins) play key roles in cellular stress and are associated with aging-related diseases including cancer. Currently, seven human sirtuin (SIRT1-7) genes have been identified, but the roles of SIRT genes in HNSCC are still uncertain. Therefore, in this study, we used real-time quantitative reverse transcription-polymerase chain reaction to investigate the expressions of the seven SIRT genes in human HNSCC tissues to assess the changes in cancerous and noncancerous parts and the correlation with different tumor behaviors. Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous tissues (all p<0.01). The expression levels of SIRT1, SIRT2, SIRT3, SIRT5, and SIRT7 showed downregulation in advanced stages in respect to early stages (p<0.05). These results indicate that the downregulation of SIRT genes expression may contribute to the development of cancer and trigger the neoplastic disease to more advanced stages. Our study indicates that SIRT genes expression could help in the diagnosis and represent a prognostic biomarker in HNSCC. PMID:23475622

Lai, Chi-Chih; Lin, Pai-Mei; Lin, Sheng-Fung; Hsu, Cheng-Hsien; Lin, Hsin-Ching; Hu, Ming-Luen; Hsu, Cheng-Ming; Yang, Ming-Yu



Intranasal delivery of Norwalk virus-like particles formulated in an in-situ gelling, dry powder vaccine  

PubMed Central

The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in-situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations 1.) stabilize the immunogenic structural properties of VLPs and 2.) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in-situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites.

Velasquez, Lissette S.; Shira, Samantha; Berta, Alice N.; Kilbourne, Jacquelyn; Medi, Babu M.; Tizard, Ian; Ni, Yawei; Arntzen, Charles J.; Herbst-Kralovetz, Melissa M.




PubMed Central

Purpose The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers. Methods and Materials Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25–2 mg × 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis and VEGF expression at days 1 and 6 after start of treatment. Results A12 enhanced the radiosensitivity of HN5 and FaDu head and neck carcinomas in vitro (p<0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner with enhancement factors ranging from 1.2 to 1.8 (p<0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (P<0.05) and VEGF expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted till 6 days from the start of treatment and in increased necrosis at day 1 (p<0.01, respectively). Combined treatment with A12 and radiation resulted in additive or sub-additive growth delay in H460 or A549 xenografts, respectively. Conclusions The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aero-digestive tract cancers.




Mortality among male and female smokers in Sweden: a 33 year follow up  

PubMed Central

STUDY OBJECTIVE—It is still unclear if men and women are equally susceptible to the hazards of tobacco smoking. The objective of this study was to examine smoking related mortality among men and women.?DESIGN—In 1963 a questionnaire concerning tobacco smoking habits was sent out to a random sample from the 1960 Swedish census population. Date and cause of death have been collected for the deceased in the cohort through 1996.?SETTING—Sweden.?PARTICIPANTS—The survey included a total of 27 841 men and 28 089 women, aged 18-69 years. The response rate was 93.1% among the men and 95.4% among the women.?MAIN RESULTS—After adjustment for age and place of residence positive associations were found between cigarette smoking and mortality from ischaemic heart disease, aortic aneurysm, bronchitis and emphysema, cancer of the lung, upper aerodigestive sites, bladder, pancreas in both men and women, but not from cerebrovascular disease. When the effect of amount of the cigarette consumption was considered, female smokers displayed, for example, slightly higher relative death rates from ischaemic heart disease. However, no statistically significant gender differential in relative mortality rates was observed for any of the studied diseases.?CONCLUSIONS—Women and men in this Swedish cohort seem equally susceptible to the hazards of smoking, when the gender differential in smoking characteristics is accounted for. Although the cohort under study is large, there were few female smokers in the high consuming categories and the relative risk estimates are therefore accompanied by wide confidence intervals in these categories.???Keywords: smoking; cause specific mortality

Nilsson, S; Carstensen, J; Pershagen, G



A method for energy window optimization for quantitative tasks that includes the effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT imaging  

NASA Astrophysics Data System (ADS)

Quantitative Yttrium-90 (90Y) bremsstrahlung single photon emission computed tomography (SPECT) imaging has shown great potential to provide reliable estimates of 90Y activity distribution for targeted radionuclide therapy dosimetry applications. One factor that potentially affects the reliability of the activity estimates is the choice of the acquisition energy window. In contrast to imaging conventional gamma photon emitters where the acquisition energy windows are usually placed around photopeaks, there has been great variation in the choice of the acquisition energy window for 90Y imaging due to the continuous and broad energy distribution of the bremsstrahlung photons. In quantitative imaging of conventional gamma photon emitters, previous methods for optimizing the acquisition energy window assumed unbiased estimators and used the variance in the estimates as a figure of merit (FOM). However, for situations, such as 90Y imaging, where there are errors in the modeling of the image formation process used in the reconstruction there will be bias in the activity estimates. In 90Y bremsstrahlung imaging this will be especially important due to the high levels of scatter, multiple scatter, and collimator septal penetration and scatter. Thus variance will not be a complete measure of reliability of the estimates and thus is not a complete FOM. To address this, we first aimed to develop a new method to optimize the energy window that accounts for both the bias due to model-mismatch and the variance of the activity estimates. We applied this method to optimize the acquisition energy window for quantitative 90Y bremsstrahlung SPECT imaging in microsphere brachytherapy. Since absorbed dose is defined as the absorbed energy from the radiation per unit mass of tissues in this new method we proposed a mass-weighted root mean squared error of the volume of interest (VOI) activity estimates as the FOM. To calculate this FOM, two analytical expressions were derived for calculating the bias due to model-mismatch and the variance of the VOI activity estimates, respectively. To obtain the optimal acquisition energy window for general situations of interest in clinical 90Y microsphere imaging, we generated phantoms with multiple tumors of various sizes and various tumor-to-normal activity concentration ratios using a digital phantom that realistically simulates human anatomy, simulated 90Y microsphere imaging with a clinical SPECT system and typical imaging parameters using a previously validated Monte Carlo simulation code, and used a previously proposed method for modeling the image degrading effects in quantitative SPECT reconstruction. The obtained optimal acquisition energy window was 100-160 keV. The values of the proposed FOM were much larger than the FOM taking into account only the variance of the activity estimates, thus demonstrating in our experiment that the bias of the activity estimates due to model-mismatch was a more important factor than the variance in terms of limiting the reliability of activity estimates.

Rong, Xing; Du, Yong; Frey, Eric C.



Use of a beta microprobe system to measure arterial input function in PET via an arteriovenous shunt in rats  

PubMed Central

Background Kinetic modeling of physiological function using imaging techniques requires the accurate measurement of the time-activity curve of the tracer in plasma, known as the arterial input function (IF). The measurement of IF can be achieved through manual blood sampling, the use of small counting systems such as beta microprobes, or by derivation from PET images. Previous studies using beta microprobe systems to continuously measure IF have suffered from high background counts. Methods In the present study, a light-insensitive beta microprobe with a temporal resolution of up to 1 s was used in combination with a pump-driven femoral arteriovenous shunt to measure IF in rats. The shunt apparatus was designed such that the placement of the beta microprobe was highly reproducible. The probe-derived IF was compared to that obtained from manual sampling at 5-s intervals and IF derived from a left ventricle VOI in a dynamic PET image of the heart. Results Probe-derived IFs were very well matched to that obtained by "gold standard" manual blood sampling, but with an increased temporal resolution of up to 1 s. The area under the curve (AUC) ratio between probe- and manually derived IFs was 1.07 ± 0.05 with a coefficient of variation of 0.04. However, image-derived IFs were significantly underestimated compared to the manually sampled IFs, with an AUC ratio of 0.76 ± 0.24 with a coefficient of variation of 0.32. Conclusions IF derived from the beta microprobe accurately represented the IF as measured by blood sampling, was reproducible, and was more accurate than an image-derived technique. The use of the shunt removed problems of tissue-background activity, and the use of a light-tight probe with minimal gamma sensitivity refined the system. The probe/shunt apparatus can be used in both microprobe and PET studies.



Diagnostic power of default mode network resting state fMRI in the detection of Alzheimer's disease.  


Functional magnetic resonance imaging (fMRI) of default mode network (DMN) brain activity during resting is recently gaining attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. The aim of this study was to determine which method of data processing provides highest diagnostic power and to define metrics to further optimize the diagnostic value. fMRI was acquired in 21 healthy subjects, 17 subjects with mild cognitive impairment and 15 patients with Alzheimer's disease (AD) and data evaluated both with volumes of interest (VOI)-based signal time course evaluations and independent component analyses (ICA). The first approach determines the amount of DMN region interconnectivity (as expressed with correlation coefficients); the second method determines the magnitude of DMN coactivation. Apolipoprotein E (ApoE) genotyping was available in 41 of the subjects examined. Diagnostic power (expressed as accuracy) of data of a single DMN region in independent component analyses was 64%, that of a single correlation of time courses between 2 DMN regions was 71%, respectively. With multivariate analyses combining both methods of analysis and data from various regions, accuracy could be increased to 97% (sensitivity 100%, specificity 95%). In nondemented subjects, no significant differences in activity within DMN could be detected comparing ApoE ?4 allele carriers and ApoE ?4 allele noncarriers. However, there were some indications that fMRI might yield useful information given a larger sample. Time course correlation analyses seem to outperform independent component analyses in the identification of patients with Alzheimer's disease. However, multivariate analyses combining both methods of analysis by considering the activity of various parts of the DMN as well as the interconnectivity between these regions are required to achieve optimal and clinically acceptable diagnostic power. PMID:20541837

Koch, Walter; Teipel, Stephan; Mueller, Sophia; Benninghoff, Jens; Wagner, Maxmilian; Bokde, Arun L W; Hampel, Harald; Coates, Ute; Reiser, Maximilian; Meindl, Thomas



Lumbar vertebral body bone microstructural scaling in small to medium-sized strepsirhines.  


Bone mass, architecture, and tissue mineral density contribute to bone strength. As body mass (BM) increases any one or combination of these properties could change to maintain structural integrity. To better understand the structural origins of vertebral fragility and gain insight into the mechanisms that govern bone adaptation, we conducted an integrative analysis of bone mass and microarchitecture in the last lumbar vertebral body from nine strepsirhine species, ranging in size from 42 g (Microcebus rufus) to 2,440 g (Eulemur macaco). Bone mass and architecture were assessed via µCT for the whole body and spherical volumes of interest (VOI). Allometric equations were estimated and compared with predictions for geometric scaling, assuming axial compression as the dominant loading regime. Bone mass, microarchitectural, and vertebral body geometric variables predominantly scaled isometrically. Among structural variables, the degree of anisotropy (Tb.DA) was the only parameter independent of BM and other trabecular architectural variables. Tb.DA was related to positional behavior. Orthograde primates had higher average Tb.DA (1.60) and more craniocaudally oriented trabeculae while lorisines had the lowest Tb.DA (1.25), as well as variably oriented trabeculae. Finally, lorisines had the highest ratio of trabecular bone volume to cortical shell volume (?3x) and while there appears to be flexibility in this ratio, the total bone volume (trabecular + cortical) scales isometrically (BM(1.23) , r(2) = 0.93) and appears tightly constrained. The common pattern of isometry in our measurements leaves open the question of how vertebral bodies in strepsirhine species compensate for increased BM. PMID:23355518

Fajardo, Roberto J; Desilva, Jeremy M; Manoharan, Rajaram K; Schmitz, James E; Maclatchy, Laura M; Bouxsein, Mary L



Modifications de l'expression des gènes GST-? et p53 dans des lignées tumorales cellulaires humaines O.R.L. après irradiation gamma : induction, études cellulaires et moléculaires  

NASA Astrophysics Data System (ADS)

Cell sub-populations surviving to high radiation doses were selected. The KBm survival part was obtained by exposure to a mutagenic agent and irradiation, FaDum results of a progressive irradiation of FaDu. A semi-quantitative RT-PCR analysis revealed a significant overexpression of GST-? and p53 genes for KBm and FaDum cell lines that remained stable for 18 months. The SF2, ?, ?, and MID parameters, determined by clonogenic assays, show no modifications of radiosensitivity. The variations of expression observed are not correlated to a radiosensitivity variation. The overexpression of GST-? and p53 does not seem to be a radiosensitivity marker. Nous avons isolé des sous-populations de 2 lignées cellulaires humaines (KB et FaDu) de carcinomes des voies aéro-digestives supérieures survivant à de fortes doses d'irradiation. La fraction survivante KBm a été obtenu après exposition à un agent mutagène et à une irradiation, FaDum résulte de l'irradiation progressive de FaDu. Une analyse par RT-PCR semi-quantitative nous a permis de mettre en évidence une surexpression significative des gènes GST-? et p53 pour les souches KBm et FaDum analysées après 18 mois de culture. Les paramètres, ?, ?, SF2, MID, déterminés par essais clonogéniques, n'indiquent pas de modification de la radiosensibilité. Les variations d'expression observées ne sont donc pas corrélées à une variation de radiosensibilité. La surexpression des gènes GST-? et p53 ne semble pas constituer un marqueur de radiosensibilité.

Dubessy, C.; Merlin, J. L.; Marchal, C.



The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging.  


Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's ¹H MR spectroscopy (¹H-MRS) signal, reducing sensitivity to changes. While single-voxel ¹H-MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1-mm³ resolution MRI into GM, WM and CSF masks that were co-registered with the MRSI grid to yield their partial volumes in approximately every 1 cm³ spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i- metabolite's GM and WM concentrations C(i) (GM) , C(i) (WM) . With the voxels' GM and WM volumes as independent coefficients, the over-determined system of equations was solved for the global averaged C(i) (GM) and C(i) (WM) . Trading off local concentration differences offers three advantages: (i) higher sensitivity due to combined data from many voxels; (ii) improved specificity to WM versus GM changes; and (iii) reduced susceptibility to partial volume effects. These improvements made no additional demands on the protocol, measurement time or hardware. Applying this approach to 18 volunteered 3D MRSI sets of 480 voxels each yielded N-acetylaspartate, creatine, choline and myo-inositol C(i) (GM) concentrations of 8.5?±?0.7, 6.9?±?0.6, 1.2?±?0.2, 5.3?±?0.6 mM, respectively, and C(i) (WM) concentrations of 7.7?±?0.6, 4.9?±?0.5, 1.4?±?0.1 and 4.4?±?0.6mM, respectively. We showed that unaccounted voxel WM or GM partial volume can vary absolute quantification by 5-10% (more for ratios), which can often double the sample size required to establish statistical significance. PMID:22714729

Tal, Assaf; Kirov, Ivan I; Grossman, Robert I; Gonen, Oded



New design for an endo-esophageal probe intended for the ablation of cardiac muscle in the left-atrium: A parametric simulation study  

NASA Astrophysics Data System (ADS)

A parametric simulation study was carried out to establish optimal dimensions of endo-esophageal devices intended to treat the atrial fibrillation (AF). The devices are spherical-surface sections truncated at 15 mm (depth of 4 mm) and cut in concentric-rings each composed of independently driven sectors. The number of independent elements (N) was minimized for different values of ratio of amplitude of secondary lobe over main lobe (E) of 0.35, 0.4, 0.45 and 0.5 and for a volume of interest (VOI) of 24×27×28 mm3 (located at 23.5 mm from the center of the device), which is large enough to contain all the targets identified in the Visible Human Project Male specimen. Operating at 1 MHz, E and N were calculated in function of the element size and focal length (F). After keeping values of F and normalized dimensions of the independent elements in terms of wavelength, higher frequencies were considered: 1.25 and 1.5 MHz. Lesion formation in the heart chamber showed that the twelve configurations were able to produce the typical lesion used to treat the AF while preserving surrounding structures. For an exposure of 5 s and maximal temperature of 70 Â?C, the average (s.d.) acoustical intensity at transducer surface varied from 22.3(5.8)W/cm2 for a device with F = 98 mm at 1 MHz to 9.2(2.1)W/cm2 for a device with F = 186 mm at 1.5 MHz, while requiring 319 and 1158 elements, respectively, and achieving values of E of 0.5 and 0.41, respectively.

Pichardo, Samuel; Hynynen, Kullervo



Regional Amyloid Deposition in Amnestic Mild Cognitive Impairment and Alzheimer's Disease Evaluated by [18F]AV-45 Positron Emission Tomography in Chinese Population  

PubMed Central

Background To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) subjects with [18F]AV-45 positron emission tomography (PET). Materials and Methods [18F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [18F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed. Results The global cortical [18F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p?=?0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment. Conclusions Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [18F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [18F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects.

Hsiao, Ing-Tsung; Kuo, Hung-Chou; Hsu, Wen-Chuin; Chuang, Wen-Li; Kung, Mei-Ping; Wey, Shiaw-Pyng; Hsieh, Chia-Ju; Wai, Yau-Yau; Yen, Tzu-Chen; Huang, Chin-Chang



Dynamic PET with 18F-Deoxyglucose (FDG) and quantitative assessment with a two-tissue compartment model reflect the activity of glucose transporters and hexokinases in patients with colorectal tumors  

PubMed Central

Dynamic PET (dPET) with 18F-Deoxyglucose (FDG) provides quantitative information about distribution of the tracer in a predefined volume over time. A two-tissue compartment model can be used to obtain quantitative data regarding transport of FDG into and out of the cells, phosphorylation and dephosphorylation rate of intracellular FDG, and fractional blood volume in the target volume, also named vessel density. Aim of the study was the correlation of glucose transporters expression and hexokinases with the corresponding compartment parameters.Patients with colorectal tumors were examined with dynamic PET prior to surgery. Afterwards, tumor samples were obtained during surgery and gene expression was assessed using gene arrays. The dynamic PET data were evaluated to quantify the parameters of a two tissue compartment model for colorectal tumors using a Volume-of-Interest (VOI) technique. A multiple correlation/regression analysis was performed using glucose transporters as independent variables and k1 as the dependent variable. A correlation of r=0.7503 (p=0.03) was obtained for the transporters SLC2A1, SLC2A2, SLC2A4, SLC2A8, SLC2A9, SLC2A10 and k1. The correlation of r=0.7503 refers to an explained variance of data of 56.30 %, therefore more than 50 % of data changes are associated with the gene expression. An analysis of the hexokinases HK1-HK3 and k3 revealed a correlation coefficient of r=0.6093 (p=0.04), which is associated with an explained variance of 37.12 %. Therefore, parameters k1 and k3 reflect gene activity. The results demonstrate that k1 and k3 of the two-tissue compartment model are correlated with glucose transporters and hexokinases.

Strauss, Ludwig G; Koczan, Dirk; Klippel, Sven; Pan, Leyun; Willis, Stefan; Sachpekidis, Christos; Dimitrakopoulou-Strauss, Antonia



Dose efficiency consideration for volume-of-interest breast imaging using x-ray differential phase-contrast CT  

NASA Astrophysics Data System (ADS)

The newly developed differential phase-contrast (DPC) imaging technique has attracted increasing interest among researchers. In a DPC system, the self-imaging effect and the phase-stepping method are implemented through three gratings to manifest phase contrast, and differentiated phase images can be obtained. An important advantage of this technique is that hospital-grade x-ray tubes can be used, allowing much higher x-ray output power and faster image processing than with micro-focus in-line phase-contrast imaging. A DPC-CT system can acquire images from different view angles along a circular orbit, and tomographic images can be reconstructed. However, the principle of DPC imaging requires multiple exposures to compute any differentiated phase image at each view angle, which raises concerns about radiation exposure via x-ray dose. Computer simulations are carried out to study the dose efficiency for DPC-CT for volume-of-interest breast imaging. A conceptual CBCT/DPC-CT hybrid imaging system and a numerical breast phantom are designed for this study. A FBP-type reconstruction algorithm is optimized for the VOI reconstruction. Factors including the x-ray flux and detector pixel size are considered and their effects on reconstruction image quality in terms of noise level and contrast-to-noise ratio are investigated. The results indicate that with a pixel size of 20 microns and a dose level of 5.7mGy, which is equivalent to the patient dose of a two-view mammography screening or a dedicated CBCT breast imaging scan, much better tissue contrast and spatial resolution can be achieved using the DPC-CT technique. It is very promising for possible application at pathology-level in vivo study for human breasts.

Cai, Weixing; Ning, Ruola



Using normalization 3D model for automatic clinical brain quantative analysis and evaluation  

NASA Astrophysics Data System (ADS)

Functional medical imaging, such as PET or SPECT, is capable of revealing physiological functions of the brain, and has been broadly used in diagnosing brain disorders by clinically quantitative analysis for many years. In routine procedures, physicians manually select desired ROIs from structural MR images and then obtain physiological information from correspondent functional PET or SPECT images. The accuracy of quantitative analysis thus relies on that of the subjectively selected ROIs. Therefore, standardizing the analysis procedure is fundamental and important in improving the analysis outcome. In this paper, we propose and evaluate a normalization procedure with a standard 3D-brain model to achieve precise quantitative analysis. In the normalization process, the mutual information registration technique was applied for realigning functional medical images to standard structural medical images. Then, the standard 3D-brain model that shows well-defined brain regions was used, replacing the manual ROIs in the objective clinical analysis. To validate the performance, twenty cases of I-123 IBZM SPECT images were used in practical clinical evaluation. The results show that the quantitative analysis outcomes obtained from this automated method are in agreement with the clinical diagnosis evaluation score with less than 3% error in average. To sum up, the method takes advantage of obtaining precise VOIs, information automatically by well-defined standard 3-D brain model, sparing manually drawn ROIs slice by slice from structural medical images in traditional procedure. That is, the method not only can provide precise analysis results, but also improve the process rate for mass medical images in clinical.

Lin, Hong-Dun; Yao, Wei-Jen; Hwang, Wen-Ju; Chung, Being-Tau; Lin, Kang-Ping



3D hierarchical geometric modeling and multiscale FE analysis as a base for individualized medical diagnosis of bone structure.  


This paper describes a new alternative for individualized mechanical analysis of bone trabecular structure. This new method closes the gap between the classic homogenization approach that is applied to macro-scale models and the modern micro-finite element method that is applied directly to micro-scale high-resolution models. The method is based on multiresolution geometrical modeling that generates intermediate structural levels. A new method for estimating multiscale material properties has also been developed to facilitate reliable and efficient mechanical analysis. What makes this method unique is that it enables direct and interactive analysis of the model at every intermediate level. Such flexibility is of principal importance in the analysis of trabecular porous structure. The method enables physicians to zoom-in dynamically and focus on the volume of interest (VOI), thus paving the way for a large class of investigations into the mechanical behavior of bone structure. This is one of the very few methods in the field of computational bio-mechanics that applies mechanical analysis adaptively on large-scale high resolution models. The proposed computational multiscale FE method can serve as an infrastructure for a future comprehensive computerized system for diagnosis of bone structures. The aim of such a system is to assist physicians in diagnosis, prognosis, drug treatment simulation and monitoring. Such a system can provide a better understanding of the disease, and hence benefit patients by providing better and more individualized treatment and high quality healthcare. In this paper, we demonstrate the feasibility of our method on a high-resolution model of vertebra L3. PMID:21193070

Podshivalov, L; Fischer, A; Bar-Yoseph, P Z



Impact of metal artefacts due to EEG electrodes in brain PET/CT imaging  

NASA Astrophysics Data System (ADS)

The goal of this study is to investigate the impact of electroencephalogram (EEG) electrodes on the visual quality and quantification of 18F-FDG PET images in neurological PET/CT examinations. For this purpose, the scans of 20 epilepsy patients with EEG monitoring were used. The CT data were reconstructed with filtered backprojection (FBP) and with a metal artefact reduction (MAR) algorithm. Both data sets were used for CT-based attenuation correction (AC) of the PET data. Also, a calculated AC (CALC) technique was considered. A volume of interest (VOI)-based analysis and a voxel-based quantitative analysis were performed to compare the different AC methods. Images were also evaluated visually by two observers. It was shown with simulations and phantom measurements that from the considered AC methods, the MAR-AC can be used as the reference in this setting. The visual assessment of PET images showed local hot spots outside the brain corresponding to the locations of the electrodes when using FBP-AC. In the brain, no abnormalities were observed. The quantitative analysis showed a very good correlation between PET-FBP-AC and PET-MAR-AC, with a statistically significant positive bias in the PET-FBP-AC images of about 5-7% in most brain voxels. There was also good correlation between PET-CALC-AC and PET-MAR-AC, but in the PET-CALC-AC images, regions with both a significant positive and negative bias were observed. EEG electrodes give rise to local hot spots outside the brain and a positive quantification bias in the brain. However, when diagnosis is made by mere visual assessment, the presence of EEG electrodes does not seem to alter the diagnosis. When quantification is performed, the bias becomes an issue especially when comparing brain images with and without EEG monitoring.

Lemmens, Catherine; Montandon, Marie-Louise; Nuyts, Johan; Ratib, Osman; Dupont, Patrick; Zaidi, Habib



Evaluating the evolution of the Red River system based on in situ U-Pb dating and Hf isotope analysis of zircons  

NASA Astrophysics Data System (ADS)

The Red River originates from SW China and SE Tibet and has a total length >1000 km. In this study, we present new U-Pb dating and Hf isotopic analysis of zircon grains, from both modern and paleoriver sands in order to constrain the provenance of the modern river and to decipher drainage evolution through time. Our data show that the Yangtze and Songpan Garze blocks are the most important sources for sediment, although this material is mostly reworked via younger sedimentary rocks in the upper reaches of the Red River. Sands in the Da River and to a lesser extent the Lo River have zircon ages indicating that they are minor contributors to the net flow, consistent with rock uplift, which is strongest in the upper reaches of the Red River, rather than precipitation being the primary control on erosion. Sediments eroded from the metamorphic rocks along the Red River Fault Zone appear to have made a greater contribution during the Miocene. Zircon ages suggest that the Red River flowed north of the Day Nui Con Voi in the Middle-Late Miocene. The Red River appears to have had a largely stable provenance since at least the Late Miocene. Upper Miocene sedimentary rocks NE of the Red River indicate the presence of a separate, large river in the Late Miocene. Hf isotope data indicate that the Irrawaddy River was never part of the Red River system. Although we do not exclude the Salween, Mekong, and Yangtze rivers from having been part of the Red River, any connection must have been pre-Middle Miocene.

van Hoang, Long; Wu, Fu-Yuan; Clift, Peter D.; Wysocka, Anna; Swierczewska, Anna



Crush-2: Communicating research through a science-art collaboration  

NASA Astrophysics Data System (ADS)

Historically, the Earth's environment and dynamics have influenced and inspired the arts. Art in turn is a powerful vehicle for expression of the natural world. It lends itself to public presentation in many forms and appeals to a diverse audience. Science-art collaborations provide a unique opportunity to connect with the public by taking science out of the classroom and into museums, galleries and public spaces. Here we investigate the use of contemporary digital sound-art in communicating geoscience research to the general public through the installation Crush-2. Crush-2, is an interactive sound-art installation exploring the microscopic forces released during the crushing of rock. Such processes have a strong influence on the sliding behaviour and hence earthquake potential of active faults. This work is a collaboration between sound artist and composer Natasha Barrett (Oslo) and geoscientists Karen Mair (University of Oslo), Alexandre Schubnel (Ecole Normale Superieure, Paris) and Steffen Abe (RWTH Aachen). Using a sonification technique, Barrett has assigned sound recorded from rocks, of different pitches, timbres and durations, to individual fracturing events produced in our 3D fault fragmentation models and laboratory rock breaking experiments. In addition, ultrasonic acoustic emissions recorded directly in the laboratory are made audible for our hearing and feature in the work. The installation space comprises a loudspeaker array and sensor enabled helmet with wireless headphones. By wearing the helmet, moving and listening, the audience explores an artistic interpretation of the scientific data in physical space. On entering the space, one is immediately immersed in a 3D cacophony of sound. Sustained or intermittent pings, burrs, plops and tingles jostle for position in our heads whilst high pitched delicate cascades juxtapose with deep thunder like rumbles. Depending on the user's precise path through the soundscape, the experience changes accordingly, so every visitor has a unique sound adventure. The experience is intensely engaging, playful and yet a little unsettling and provides a truly unique way to explore our scientific data and present geoscience research to the public. Crush-2 has featured in an exhibition on Sonic Interaction Design at the Norwegian Museum of Science, Technology and Medicine, Oslo, Norway (27 May - 21 August 2011) and forms part of a solo exhibition by Barrett at Galleri ROM, Oslo in fall 2011. Visitor feedback from the Museum exhibition suggests that users were initially attracted to the exhibit by its interactive 'hands-on' nature and dramatic sounds, but as they 'explored' the soundspace, became curious to ask questions about the underlying science. The concept of using sound rather than visual gives an unusual and therefore highly memorable experience. This science-art collaboration provides a novel and highly enjoyable way to present our work to the public - that is particularly attractive to youngsters. Visitors to this poster presentation will be able to explore the Crush-2 soundscape using a laptop and headphone interactive mode.

Mair, K.; Barrett, N.; Schubnel, A. J.; Abe, S.



Contribution a l'etude du comportement de dalles de ponts en beton arme de barres en PRF soumises a des charges concentrees simulant les charges de roues  

NASA Astrophysics Data System (ADS)

Au cours des dernieres annees, la deterioration des structures en beton arme a pris une ampleur sans precedent, et ce, malgre le fait que leur duree de vie en service initialement prevue est loin d'etre atteinte. La corrosion de l'armature d'acier est un des principaux facteurs reduisant la duree de vie des ponts en beton arme d'acier. Par ailleurs, l'armature en materiaux composites de polymeres renforces de fibres (PRF) constitue une solution a l'armature metallique afin de pallier au probleme de la corrosion d'acier et a la deterioration des structures en beton arme. Aussi, les barres d'armature en materiaux composites de PRF possedent une resistance en traction elevee (environ 2 a 6 fois la limite elastique de l'acier d'armature conventionnel), ce qui leur permet de constituer un renforcement structural attrayant pour les structures en beton. Le comportement d'elements structuraux en beton arme de barres en PRF est different de ceux en beton arme de barres d'acier. En effet, les barres en PRF possedent un module d'elasticite relativement plus faible que celui de l'acier et ont des proprietes d'adherence differentes de celles des barres d'acier. L'utilisation des barres d'armature en PRF pour armer les dalles de tabliers de ponts se concretise de plus en plus avec l'avancement des recherches dans ce domaine. La recherche entamee dans le cadre de cette these s'inscrit dans un programme de travaux realises au sein de la Chaire de recherche CRSNG/Industrie sur les Materiaux composites novateurs en PRF pour les infrastructures au departement de genie civil a l'Universite de Sherbrooke. Le comportement de membrures en beton arme de PRF soumis a des sollicitations mecaniques constitue un des principaux axes de recherche. Dans le cadre de cette these, une serie d'essais a ete effectuee sur huit dalles de ponts a confinement interne a grande echelle. Les parametres des essais comprennent: (1) l'epaisseur de la dalle, (2) le type et le taux d'armature transversale de l'assemblage inferieur, (3) la resistance en compression du beton, et (4) le taux d'armature dans les autres directions (armatures transversale et longitudinale de l'assemblage superieur et l'armature longitudinale de l'assemblage inferieur). Lors des essais de chargement, les dalles ont ete supportees par deux poutrelles metalliques espacees de 2000 mm centre a centre et soumises a une charge statique concentree sur une aire de contact de 600 mm x 250 mm afin de simuler une charge de camion (87,5 kN--CL-625) et ce conformement au code Canadien sur le calcul des ponts routiers [CAN/CSA-S6-06]. Aussi, une analyse numerique du comportement des dalles testees sous charges est faite a l'aide d'un logiciel d'elements finis ADINA version 8.2. Les essais ont montre que toutes les dalles testees ont rompu par poinconnement, peu importe le parametre etudie. Aussi, une epaisseur de dalle de 175 mm repond aux exigences du Canadien sur le calcul des ponts routiers [CAN/CSA-S6-06]. Par ailleurs, les resultats ont montre que la resistance en compression du beton est un parametre qui influe sur la deflexion, les deformations dans les barres et l'ouverture de fissures. Enfin, les resultats des analyses numeriques effectuees corroborent avec ceux obtenus experimentalement. Mots cles. Dalle de ponts en beton, armature de PRF, charges statiques, flexion, deformations, poinconnement, elements finis.

Bouguerra, Kheireddine


Mesures experimentales de l'impact des revetements hydrophobeset superhydrophobes sur la trainee et la portance d'un profil aerodynamique propre et glace  

NASA Astrophysics Data System (ADS)

Ce projet, realise a la demande du Laboratoire International des Materiaux Antigivre, a pour but de mesurer et definir experimentalement l'impact de revetements hydrophobes sur les coefficients de trainee et de portance d'un profil NACA 0012. Pour ce faire, la balance aerodynamique du LIMA devait tout d'abord etre amelioree afin d'offrir une sensibilite suffisante pour realiser le projet. Plusieurs ameliorations ont ete faites, comme le changement des cellules de charge, la diminution du nombre de cellules de charge, le changement du cadre de la balance, etc. Une fois ces ameliorations terminees, la reproductibilite, l'exactitude et la sensibilite ont ete valides afin de s'assurer de la fiabilite des resultats offerts par la balance. Pour les angles d'attaque etudies avec les revetements, soient -6° et 0°, la balance a une reproductibilite de +/-2,06% a 360 000 de nombre de Reynolds. Pour valider la sensibilite, des essais a -6° et 0° d'angle d'attaque et des nombres de Reynolds de 360 000 et 500 000 ont ete faits avec des papiers sables. Les resultats de ces essais ont permis de, tracer des courbes de tendances du coefficient de trainee du NACA 0012 en fonction de la rugosite de surface et d'etablir la valeur de la sensibilite de la balance a +/-8 mu m. Cinq revetements populaires ont ete choisis pour l'experimentation, soient le Wearlon, le Staclean, le Hirec, le Phasebreak ainsi que le Nusil. Les revetements sont soumis aux memes conditions experimentales que les papiers sables, et une rugosite equivalente est trouvee par extrapolation des resultats. Cependant, les rugosites equivalentes de surfaces different entre -6° et 0°. Les essais avec le Staclean et le Hirec donnent des coefficients de trainee equivalent a ceux avec l'aluminium, alors que le Wearlon, le Nusil et le Phasebreak donnent une augmentation du coefficient de trainee de 13%, 17% et 25% respectivement par rapport a l'aluminium. Pour les coefficients de portance, la balance ne detecte pas l'effet des revetements, ni des papiers sables, sur la force de portance ce qui signifie qu'il entre dans l'insensibilite de la balance. La derniere etape experimentale consistait a mesurer l'impact des revetements sur la formation de la glace ainsi que sur l'evolution des coefficients de trainee et de portance du NACA 0012 en fonction de l'accumulation de glace sur celui-ci. Le Wearlon a ete choisi comme revetement en raison de sa grande popularite. Des essais a -5°C et -20°C ont ete faits et les resultats ont montres que le Wearlon n'apporte pas d'effet benefique au NACA 0012 en conditions d'accumulations de glace. L'augmentation du coefficient de trainee du profil muni du Wearlon debutait plus rapidement que sur l'aluminium et de l'eau gelait legerement plus loin vers l'arriere du profil pendant les essais, ce qui n'est pas souhaitable. Le coefficient de trainee est superieur d'environ 13% pour le Wearlon par rapport a l'aluminium pendant toute l'accumulation de glace, ce qui correspond au meme ecart lorsque la glace n'est pas en cause. Pour le coefficient de portance, les resultats ne peuvent etre utilises pour une raison qui doit etre investiguee.

Villeneuve, Eric


Archean Pb Isotope Evolution: Implications for the Early Earth.  

NASA Astrophysics Data System (ADS)

The U-Pb isotope system provides us with a powerful tool for understanding the chemical evolution of the Earth. Pb isotopes in Archean rocks, however, have not been widely utilized because U mobility makes initial Pb isotope ratios from old silicate rocks difficult, if not impossible, to determine. Galenas in syngenetic volcanogenic massive sulfide (VMS) deposits, however, provide snapshots of initial Pb ratios because their Pb isotopic composition is time invariant at their formation (U/Pb=0). The Pb isotopic record from galenas from rocks of all age have been utilized for over 70 years to answer a wide range of scientific problems beginning with Al Nier's pioneering work analyzing Pb isotopes in the 1930's but are no longer widely used by the isotopic community because they have been produced by older TIMS techniques. We have begun a re-examination of Archean Pb by an extensive analysis of over 100 galena samples from Archean VMS deposits throughout the Superior and Slave Provinces in Canada as well as from other VMS deposits in Finland, South Africa and Western Australia. The goal of this work is to provide modern, high precision measurements and update an old, but venerable, Pb isotopic data set. We feel these data provide important constraints on not only the Pb isotopic evolution of the Earth, but planetary differentiation and recycling processes operating in the first 2 b.y. of Earth's history. Our analytical techniques include dissolving the Pb sulfide minerals, purifying them with ion chromatography, and analyzing them using MC-ICPMS at both Washington State University (Neptune) and Ecole Normale Superieure in Lyon, France (Nu). All Pb solutions are doped with Tl in order to correct for mass fractionation. In this abstract we report preliminary galena Pb isotope data from 6 VMS deposits in the Abitibi greenstone belt: Chibougamu, Matagami, Noranda, Normetal, Timmins, and Val d"Or. These deposits are all approximately 2.7 Ga in age but in detail vary from 2.728 Ga (Normetal) to 2.70 Ga (Noranda). The Pb isotopic compositions from these galenas, when normalized to a common age of 2.7 Ga, define a highly linear array in 207Pb/204Pb vs. 206Pb/204Pb. This array is nearly coincident with the 2.7 Ga geochron with a slope that corresponds to an age of ~4.4 Ga and with an extraordinary large range of 207Pb/204Pb, about the same magnitude as modern MORB. These data have important implications for the evolution of the Archean mantle. First, the slope of the Abitibi Pb-Pb array and its coincidence with the 2.7 Ga geochron suggests widespread U-Pb differentiation within the first hundred million years of Earth's history. This may have been due to either core formation or silicate/melt differentiation due to widespread melting of the mantle (e.g., formation of a magma ocean). Second, variations in ? in the Abitibi mantle and the subsequent Pb isotopic heterogeneities, whatever their cause, have not been significantly changed from 4.4 until 2.7 Ga. This implies that changes in ? in the Abitibi mantle source between 4.4 and 2.7 Ga, such as would be caused by crust extraction or recycling of older crust into this region of the mantle, were insufficient to destroy the original ? variations created at 4.4 Ga. Therefore, it appears that this portion of the mantle had essentially remained isolated and undisturbed from the early Hadean until the late Archean.

Vervoort, J. D.; Thorpe, R.; Albarede, F.; Blichert-Toft, J.



Conservative management of esophageal perforation after a fall  

PubMed Central

INTRODUCTION Esophageal perforation in the setting of blunt trauma is rare, and diagnosis can be difficult due to atypical signs and symptoms accompanied by distracting injury. PRESENTATION OF CASE We present a case of esophageal perforation resulting from a fall from height. Unexplained air in the soft tissues planes posterior to the esophagus as well as subcutaneous emphysema in the absence of a pneumothorax on CT aroused clinical suspicions of an injury to the aerodigestive tract. The patient suffered multiple injuries including bilateral first rib fractures, C6 lamina fractures, C4–C6 spinous process fractures, a C7 right transverse process fracture with associated ligamentous injury and cord contusion, multiple comminuted nasal bone fractures, and a right verterbral artery dissection. Esophageal injury was localized using a gastrograffin esophagram to the cervical esophagus and was most likely secondary to cervical spine fractures. Because there were no clinical signs of sepsis and the esophagram demonstrated a contained rupture, the patient was thought to be a good candidate for a trial of conservative management consisting of broad spectrum intravenous antibiotics, oral care with chlorhexadine gluconate, NPO, and total parenteral nutrition. No cervical spine fixation or procedure was performed during this trial of conservative management. The patient was received another gastrograffin esophagram on hospital day 14 and demonstrated no evidence of contrast extravasation. DISCUSSION Early diagnosis and control of the infectious source are the cornerstones to successful management of esophageal perforation from all etiologies. Traditionally, esophageal perforation relied on a high index of clinical suspicion for early diagnosis, but the use of CT scan for has proved to be highly effective in diagnosing esophageal perforation especially in patients with atypical presentations. While aggressive surgical infection control is paramount in the majority of esophageal perforations, a select subset of patients can be successfully managed non-operatively. CONCLUSION In the setting of blunt trauma, esophageal perforation is rare and is associated with a high morbidity. In select patients who do not show any clinical signs of sepsis, contained perforations can heal with non-operative management consisting of broad spectrum antibiotics, strict oral hygiene, NPO, and total parenteral nutrition.

Delos Reyes, Arthur P.; Clancy, Christopher; Lach, Joseph; Olorunto, William A.; Williams, Mallory



Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?  

PubMed Central

Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach’s “acid mantle” against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H+/K+-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H2RAs should be used as the preferred agents over PPIs.

Fohl, Alexander L; Regal, Randolph E



Ear, nose and throat injuries at Bugando Medical Centre in northwestern Tanzania: a five-year prospective review of 456 cases  

PubMed Central

Background Injuries to the ear, nose and throat (ENT) regions are not uncommon in clinical practice and constitute a significant cause of morbidity and mortality in our setting. There is dearth of literature on this subject in our environment. This study was conducted to describe the causes, injury pattern and outcome of these injuries in our setting and proffer possible preventive measures. Methods This was a descriptive prospective study of patients with ear, nose and throat injuries managed at Bugando Medical Centre between May 2007 and April 2012. Ethical approval to conduct the study was sought from relevant authorities. Statistical data analysis was performed using SPSS computer software version 17.0. Results A total of 456 patients were studied. The median age of patients at presentation was 18 years (range 1 to 72 years). The male to female ratio was 2:1. The commonest cause of injury was foreign bodies (61.8%) followed by road traffic accidents (22.4%). The ear was the most common body region injured accounting for 59.0% of cases. The majority of patients (324, 71.1%) were treated as an outpatient and only 132(28.9%) patients required admission to the ENT wards after definitive treatment. Foreign body removal and surgical wound debridement were the most common treatment modalities performed in 61.9% and 16.2% of cases respectively. Complication rate was 14.9%. Suppurative otitis media (30.9%) was the commonest complication in the ear while traumatic epistaxis (26.5%) and hoarseness of voice (11.8%) in the aero-digestive tract were commonest in the nose and throat. The overall median length of hospital stay for in-patients was 8 days (range 1 to 22 days). Patients who developed complications and those who had associated injuries stayed longer in the hospital (P?



Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4 - the AdAPT Method  

PubMed Central

Background Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [ptrend]?=?2.5×10?3). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76–0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url:

Johansson, Mattias; Roberts, Angus; Chen, Dan; Li, Yaoyong; Delahaye-Sourdeix, Manon; Aswani, Niraj; Greenwood, Mark A.; Benhamou, Simone; Lagiou, Pagona; Holcatova, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V.; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S.; Conway, David I.; Znaor, Ariana; Healy, Claire M.; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Fabianova, Eleonora; Mates, Ioan Nicolae; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wunsch-Filho, Victor; Eluf-Neto, Jose; Boffetta, Paolo; Franceschi, Silvia; Herrero, Rolando; Fernandez Garrote, Leticia; Talamini, Renato; Boccia, Stefania; Galan, Pilar; Vatten, Lars; Thomson, Peter; Zelenika, Diana; Lathrop, Mark; Byrnes, Graham; Cunningham, Hamish; Brennan, Paul; Wakefield, Jon; Mckay, James D.



Regional, disease specific patterns of smoking-attributable mortality in 2000  

PubMed Central

Background: Smoking has been causally associated with increased mortality from several diseases, and has increased considerably in many developing countries in the past few decades. Mortality attributable to smoking in the year 2000 was estimated for adult males and females, including estimates by age and for specific diseases in 14 epidemiological subregions of the world. Methods: Lung cancer mortality was used as an indirect marker of the accumulated hazard of smoking. Never-smoker lung cancer mortality was estimated based on the household use of coal with poor ventilation. Estimates of mortality caused by smoking were made for lung cancer, upper aerodigestive cancer, all other cancers, chronic obstructive pulmonary disease (COPD), other respiratory diseases, cardiovascular diseases, and selected other medical causes. Estimates were limited to ages 30 years and above. Results: In 2000, an estimated 4.83 million premature deaths in the world were attributable to smoking, 2.41 million in developing countries and 2.43 million in industrialised countries. There were 3.84 million male deaths and 1.00 million female deaths attributable to smoking. 2.69 million smoking attributable deaths were between the ages of 30–69 years, and 2.14 million were 70 years of age and above. The leading causes of death from smoking in industrialised regions were cardiovascular diseases (1.02 million deaths), lung cancer (0.52 million deaths), and COPD (0.31 million deaths), and in the developing world cardiovascular diseases (0.67 million deaths), COPD (0.65 million deaths), and lung cancer (0.33 million deaths). The share of male and female deaths and younger and older adult deaths, and of various diseases in total smoking attributable deaths exhibited large inter-regional heterogeneity, especially in the developing world. Conclusions: Smoking was an important cause of global mortality in 2000, affecting a large number of diseases. Age, sex, and disease patterns of smoking-caused mortality varied greatly across regions, due to both historical and current smoking patterns, and the presence of other risk factors that affect background mortality from specific diseases.

Ezzati, M; Lopez, A



Cutaneous signs of systemic disease.  


Commonly used dermatologic eponyms and characteristic skin signs are enormously helpful in guiding a diagnosis, even though they may not be pathonemonic. They include, on the nails, Aldrich-Mees' lines (syn.: Mees' lines), Beau's lines, Muehrcke's lines, Terry's nails, and half and half nails, often associated, respectively, with arsenic poisoning, acute stress or systemic illness, severe hypertension, liver disease and uremia, and, around the nails, Braverman's sign, associated with collagen-vascular disease. Elsewhere, one may see the Asboe-Hansen and Nikolsky's signs, indicative of the pemphigus group of diseases, Auspitz's sign, a classic finding in psoriasis, Borsieri's and Pasita's signs, seen in early scarlet fever, the butterfly rash, indicative of systemic lupus erythematosus, and the buffalo hump, seen in Cushing's disease and also in the more common corticosteroid toxicity. Gottron's papules and the heliotrope rash are signs of dermatomyositis. Janeway's lesions and Osler's nodes are seen in bacterial endocarditis. A Dennie-Morgan fold under the eye is seen in association with atopic disease. Koplik's spots are an early sign of rubeola. Fitzpatrick's sign is indicative of a benign lesion (dermatofibroma), whereas Hutchinson's sign is indicative of a malignant one (subungual melanoma). Petechiae are seen in many diseases, including fat embolization, particularly from a large bone fracture following trauma. Palpable purpura is indicative of leukocytoclastic vasculitis, and is an early, critical sign in Rickettsial diseases, including Rocky Mountain Spotted Fever, which must be diagnosed and treated early. Hyperpigmentation of areolae and scars is seen in Addison's disease. Acanthosis nigricans may indicate internal cancer, especially stomach cancer, whereas Bazex's syndrome occurs in synchrony with primary, usually squamous cancer, in the upper aerodigestive tract or metastatic cancer in cervical lymph nodes. Perioral pigmented macules or one or more cutaneous sebaceous neoplasms may be a sign of the Peutz-Jeghers or Muir-Torre syndrome, respectively, both associated also with intestinal polyps that have a malignant potential. Telangiectasiae in the perioral region may be associated with similar lesions internally in Osler-Weber-Rendu disease. Kerr's sign is indicative of spinal cord injury and Darier's sign of mastocytosis. Post proctoscopic periobital purpura (PPPP) is a phenomenon observed in some patients with systemic amyloidosis. Koebner's isomorphic response refers to the tendency of an established dermatosis, such as psoriasis, to arise in (a) site(s) of trauma, whereas Wolf's isotrophic response refers to a new dermatosis, such as tinea, not yet seen in the patient, arising in (a) site(s) of a former but different dermatosis, such as zoster. PMID:21855727

Patel, Laju M; Lambert, Phelps J; Gagna, Claude E; Maghari, Amin; Lambert, W Clark


Joint and independent effects of alcohol drinking and tobacco smoking on oral cancer: a large case-control study.  


Alcohol drinking and tobacco smoking are assumed to have significant independent and joint effects on oral cancer (OC) development. This assumption is based on consistent reports from observational studies, which, however, overestimated the independent effects of smoking and drinking, because they did not account for the interaction effect in multivariable analyses. This case-control study sought to investigate the independent and the joint effects of smoking and drinking on OC in a homogeneous sample of adults. Case patients (N?=?1,144) were affected by invasive oral/oropharyngeal squamous cell carcinoma confirmed histologically, diagnosed between 1998 and 2008 in four hospitals of São Paulo (Brazil). Control patients (N?=?1,661) were not affected by drinking-, smoking-associated diseases, cancers, upper aero-digestive tract diseases. Cumulative tobacco and alcohol consumptions were assessed anamnestically. Patients were categorized into never/ever users and never/level-1/level-2 users, according to the median consumption level in controls. The effects of smoking and drinking on OC adjusted for age, gender, schooling level were assessed using logistic regression analysis; Model-1 did not account for the smoking-drinking interaction; Model-2 accounted for this interaction and included the resultant interaction terms. The models were compared using the likelihood ratio test. According to Model-1, the adjusted odds ratios (ORs) for smoking, drinking, smoking-drinking were 3.50 (95% confidence interval -95CI, 2.76-4.44), 3.60 (95CI, 2.86-4.53), 12.60 (95CI, 7.89-20.13), respectively. According to Model-2 these figures were 1.41 (95CI, 1.02-1.96), 0.78 (95CI, 0.48-1.27), 8.16 (95CI, 2.09-31.78). Analogous results were obtained using three levels of exposure to smoking and drinking. Model-2 showed statistically significant better goodness-of-fit statistics than Model-1. Drinking was not independently associated with OC, while the independent effect of smoking was lower than expected, suggesting that observational studies should be revised adequately accounting for the smoking-drinking interaction. OC control policies should focus on addictive behaviours rather than on single lifestyle risk factors. PMID:23874521

Ferreira Antunes, José Leopoldo; Toporcov, Tatiana Natasha; Biazevic, Maria Gabriela Haye; Boing, Antonio Fernando; Scully, Crispian; Petti, Stefano